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1

Crispen's Five Antivirus Rules.  

ERIC Educational Resources Information Center

Explains five rules to protect computers from viruses. Highlights include commercial antivirus software programs and the need to upgrade them periodically (every year to 18 months); updating virus definitions at least weekly; scanning attached files from email with antivirus software before opening them; Microsoft Word macro protection; and the…

Crispen, Patrick Douglas

2000-01-01

2

Crispen's Five Antivirus Rules.  

ERIC Educational Resources Information Center

Provides rules for protecting computers from viruses, Trojan horses, or worms. Topics include purchasing commercial antivirus programs and keeping them updated; updating virus definitions weekly; precautions before opening attached files; macro virus protection in Microsoft Word; and precautions with executable files. (LRW)

Crispen, Patrick Douglas

2000-01-01

3

Avast Free Antivirus  

NSDL National Science Digital Library

Avast Free Antivirus has been around for sometime, and this latest edition has some notable new features. Perhaps the most significant change here is the very helpful user interface, which includes a new tabbed section and a context sensitive help menu. Visitors can also use the real-time shields to protect against spyware and viruses originating from hundreds of sources. This version is compatible with computers running Windows 2000 and newer.

4

Securing anti-virus software with virtualization  

US Patent & Trademark Office Database

The subject disclosure relates to systems and methods that secure anti-virus software through virtualization. Anti-virus systems can be maintained separate from user applications and operating system through virtualization. The user applications and operating system run in a guest virtual machine while anti-virus systems are isolated in a secure virtual machine. The virtual machines are partially interdependent such that the anti-virus systems can monitor user applications and operating systems while the anti-virus systems remain free from possible malicious attack originating from a user environment. Further, the anti-virus system is secured against zero-day attacks so that detection and recovery may occur post zero-day.

2012-11-06

5

Game analysis on the market entry decisions into the mobile antivirus industry  

Microsoft Academic Search

The mobile antivirus software market is still at its early stage but many companies have entered this market. After analyzing the motivation of the antivirus companies, we find that the mobile antivirus market is not mature enough for so many companies to enter today. We use a game theoretical approach to examine the competition of mobile antivirus software providers. It

Weiguo Ye; Feida Lin

2009-01-01

6

Evolution of Computer Virus Concealment and AntiVirus Techniques: A Short Survey  

Microsoft Academic Search

This paper presents a general overview on evolution of concealment methods in computer viruses and defensive techniques employed by anti-virus products. In order to stay far from the anti-virus scanners, computer viruses gradually improve their codes to make them invisible. On the other hand, anti-virus technologies continually follow the virus tricks and methodologies to overcome their threats. In this process,

Babak Bashari Rad; Maslin Masrom; Suhaimi Ibrahim

2011-01-01

7

Impact of anti-virus software on computer virus dynamical behavior  

NASA Astrophysics Data System (ADS)

The impact of anti-virus software on the spreading of computer virus is investigated via developing a mathematical model in this paper. Considering the anti-virus software may not be effective, as it may be an outdated version, and then the computers may be infected with a reduced incidence rate. According to the method of next generation matrix, the basic reproduction number is derived. By introducing appropriate Lyapunov function and the Routh stability criterion, acquiring the stability conditions of the virus-free equilibrium and virus equilibrium. The effect of anti-virus software and disconnecting rate on the spreading of virus are also analyzed. When combined with the numerical results, a set of suggestions are put forward for eradicating virus effectively.

Sun, Mei; Li, Dandan; Han, Dun; Jia, Changsheng

2014-05-01

8

Effect of anti-virus software on infectious nodes in computer network: A mathematical model  

NASA Astrophysics Data System (ADS)

An e-epidemic model of malicious codes in the computer network through vertical transmission is formulated. We have observed that if the basic reproduction number is less than unity, the infected proportion of computer nodes disappear and malicious codes die out and also the malicious codes-free equilibrium is globally asymptotically stable which leads to its eradication. Effect of anti-virus software on the removal of the malicious codes from the computer network is critically analyzed. Analysis and simulation results show some managerial insights that are helpful for the practice of anti-virus in information sharing networks.

Mishra, Bimal Kumar; Pandey, Samir Kumar

2012-07-01

9

Coping with Computer Viruses: General Discussion and Review of Symantec Anti-Virus for the Macintosh.  

ERIC Educational Resources Information Center

Discusses computer viruses that attack the Macintosh and describes Symantec AntiVirus for Macintosh (SAM), a commercial program designed to detect and eliminate viruses; sample screen displays are included. SAM is recommended for use in library settings as well as two public domain virus protection programs. (four references) (MES)

Primich, Tracy

1992-01-01

10

The effect of computer virus occurrence and virus threat level on antivirus companies' financial performance  

Microsoft Academic Search

Computer virus incidents jumped 140 percent from May 2000 to May 20011. The international computer security association labs 8th annual survey has determined that 1.2 million computer virus incidents occurred in more than 900,000 computers in the year 20022. The antivirus market place has grown by 31 percentage revenue growth from 2001 to 20023. Even though enterprises are dedicating more

John R. Harrald; Sonia A. Schmitt; Sunil Shrestha

2004-01-01

11

PAPAIN DIGESTION FRAGMENTS OF HUMAN IGM GLOBULINS  

PubMed Central

Papain digestion of two Waldenström IgM globulins produced a high amount of small peptides and resulted in the formation of two end products, the Fabµ and Fcµ fragments. The Fcµ fragment is characterized by a fast electrophoretic mobility, a high content in carbohydrate, and a high molecular weight. It was demonstrated that this fragment is made of heavy chain pieces belonging to several disulfide-linked monomeric subunits, presumably representing the carboxy-terminal end of the µ-chains. Fc fragments from the two macroglobulins could not be distinguished immunologically. An appreciable proportion of IgM molecules apparently underwent degradation without the formation of a stable Fc fragment. An Fc-like fragment, analogous to the reduced Fc fragment, was obtained at early stages of papain digestion of the IgM subunits. The Fabµ fragment, with slow and individually distinct electrophoretic mobility, bears many physicochemical and immunological similarities to the Fab? fragment. It consists of one light chain and one Fd piece, both of which were isolated. The interaction of these two constituents was demonstrated by gel diffusion studies. Fab fragments of both IgM globulins were resolved into two subpopulations with different electric charges. In addition to these fragments, intermediary split products were observed at early stages of the degradation process, together with a high yield of small peptides mainly derived from the papain-sensitive region of the heavy chains. Immunologic data strongly suggested that this segment of µ-chains is situated between the Fd piece and the portion included in the Fc fragment. Several experiments indicated the importance of conformational antigenic specificity in both Fab and Fc regions of the IgM globulins.

Mihaesco, Constantin; Seligmann, Maxime

1968-01-01

12

The IGM Project: Searching For IGM Emission Over 0  

Microsoft Academic Search

I discuss several experimental projects underway or proposed designed to discover and map emission from the IGM. The Cosmic Web Imager (CWI) is a ground-based high resolution spectrometer designed to detect low surface brightness emission from redshifted Lyman alpha, OVI and CIV at Palomar and Keck Observatories, over 2IGM emission

Christopher D. Martin; M. Matuszewski; S. Rahman; P. Morrissey; A. Moore; D. Schiminovich; B. Milliard; S. Frank; J. Deharveng; C. Peroux

2011-01-01

13

Clinical and Immunological Features in IgM Deficiency  

Microsoft Academic Search

Background: IgM deficiency is a dysgammaglobulinemia characterized by isolated low levels of serum IgM. Patients with IgM deficiency may exhibit various clinical manifestations. However, IgM deficiency still remains to be explored with regard to diagnosis and treatment. Methods: Through a retrospective chart review, we investigated the clinical and immunological features of 15 symptomatic adult IgM-deficient patients who were referred to

Leman Yel; Srinivasan Ramanuja; Sudhir Gupta

2009-01-01

14

Interferon-alpha for IgM nephropathy?  

PubMed

Immunoglobulin M (IgM) nephropathy is an idiopathic glomerulonephritis characterized by mesangial deposits of IgM. IgM nephropathy presenting with proteinuria, especially nephrotic syndrome, frequently is steroid-dependent or steroidresistant and associated with reaching endstage renal disease after a 15-year follow-up. Because no long-term effective treatment is known for patients with IgM nephropathy, there is a clear need for therapeutic alternatives. We describe a patient with IgM nephropathy represented by recurrence of nephrotic syndrome who achieved longterm remission with interferon-alpha sustained treatment. PMID:23380390

Liu, Sha; Zhang, Dongliang; Zhang, Qidong; Liu, Wenhu

2014-08-01

15

Pediatric Selective IgM Immunodeficiency  

PubMed Central

Objective. Limited information exists on features of pediatric Selective IgM immunodeficiency (SIgMID). Previously published pediatric cases and 2 new cases are reviewed. Methods. English literature from PubMed and references from relevant articles were reviewed. Previously reported cases and 2 new cases from an allergy/immunology practice were analyzed. Results. Forty-nine reported cases of SIgMID presented with respiratory infections (77.6%), gastrointestinal disease (16.3%), skin disease (12.2%), and meningitis (8.2%). Mean serum IgM level was 16.5 ± 13.8 mg/dL. Two patients were identified with SIgMID among 6300 active pediatric patients (0.03%) presenting with asthma, vasomotor rhinitis, and recurrent respiratory infections. In the 51 cases reported, none developed lymphoproliferative disease nor evolved into panhypogammaglobulinemia; four fatalities were reported. Conclusions. The prevalence of SIgMID in our pediatric population was 0.03%. In general, respiratory infections are the common comorbid conditions. Death and autoimmune disease are uncommon complications of pediatric SIgMID.

Goldstein, Marc F.; Goldstein, Alex L.; Dunsky, Eliot H.; Dvorin, Donald J.; Belecanech, George A.; Shamir, Kfir

2008-01-01

16

Methods for Purifying and Detecting IgM Antibodies.  

National Technical Information Service (NTIS)

Methods and kits for purifying and detecting IgM antibodies employ binding substances which are Borellia burgdorferi cells, or cellular or extracellular components obtained or derived therefrom and which bind to this class of antibodies. The binding subst...

D. W. Dorward E. D. Huguenel G. Davis C. F. Garon

1992-01-01

17

Protective Roles of Natural IgM Antibodies  

PubMed Central

Antibodies are a vital part of the armamentarium of the adaptive immune system for the fine-tuning of the recognition and response to foreign threats. However, in health there are some types of antibodies that instead recognize self-antigens and these contribute to the enhancement of primitive innate functions. This repertoire of natural IgM antibodies is postulated to have been selected during immune evolution for their contributions to critical immunoregulatory and housekeeping properties. The clearance of dying cells is one of the most essential responsibilities of the immune system, which is required to prevent uncontrolled inflammation and autoimmunity. In the murine immune system, natural IgM antibodies that recognize apoptotic cells have been shown to enhance the phagocytic clearance of dead and dying cells and to suppress innate immune signaling pathways. In the mouse, natural IgM are often the products of B-1 cell clones that arise during immune development without an absolute requirement for exogenous antigenic stimulation. In patients with systemic lupus erythematosus, IgM autoantibodies, which bind to neo-epitopes on apoptotic cells, have been demonstrated to be present at significantly higher levels in patients with lower disease activity and with less severe organ damage. While certain specificities of IgM autoantibodies correlate with protection from lupus renal disease, others may convey protective properties from lupus-associated atherosclerotic cardiovascular disease. New and unexpected insights into the functional roles of IgM antibodies are still emerging, especially regarding the functions of natural antibodies. Herein, we review recent progress in our understanding of the potential roles of natural IgM autoantibodies in the regulation of immune homeostasis and for protection from autoimmune and inflammatory diseases.

Gronwall, Caroline; Vas, Jaya; Silverman, Gregg J.

2012-01-01

18

Factors predicting transformation of asymptomatic IgM monoclonal gammopathy.  

PubMed

We evaluated the risk of transformation of asymptomatic immunoglobulin (Ig) M monoclonal gammopathy (aIgM MG) into symptomatic lymphoproliferative disease in 287 patients all analyzed for bone marrow histopathology and immunophenotyping. This series included 201 patients with IgM MG of undetermined significance (IgM MGUS) and 86 with smoldering Waldenström's macroglobulinemia (sWM). After a median of 50 months (range, 12-322 months), 32 cases of aIgM-MG (11.1%) evolved into symptomatic malignant lymphoproliferative disease, as follows: symptomatic WM (n=26), non-Hodgkin lymphoma (n=6). The cumulative transformation percentage at 5 and 10 years was 8% and 19.5%, respectively. The parameters significantly correlated with evolution were, at univariate analysis, BM lymphoplasmacytic infiltration, high erythrocyte sedimentation rate, serum MC, serum IgM size, and serum IgA size. Among patients with aIgM-MG, those at high risk of evolution were patients with sWM, a distinct entity with serum IgM monoclonal protein?3 g/dL and/or ?10% bone marrow lymphoplasmacytic infiltration. PMID:21454196

Greco, Antonino; Tedeschi, Alessandra; Varettoni, Marzia; Nichelatti, Michele; Paris, Laura; Ricci, Francesca; Vismara, Eleonora; Morra, Enrica

2011-02-01

19

Genetics Home Reference: X-linked hyper IgM syndrome  

MedlinePLUS

... PubMed Recent literature OMIM Genetic disorder catalog Conditions > X-linked hyper IgM syndrome On this page: Description ... names Glossary definitions Reviewed April 2013 What is X-linked hyper IgM syndrome? X-linked hyper IgM ...

20

The Legacy HST Data Set of IGM Spectroscopy  

NASA Astrophysics Data System (ADS)

We propose to analyze the E230M STIS spectra of 9 quasars to derive physical properties of the Lyman alpha forest lines in the redshift range z=0.9 to 1.6. These quasars were originally observed to measure deuterium in metal line systems or to study the detailed kinematics of metal absorption lines systems to compare to ground based studies. To date, no analysis of the Lyman alpha forest has been published for these spectra. We will combine the archive data with data of 7 other quasars we have observed ourselves with the E230M, and two quasars with published line lists, to derive the properties of the IGM. The spectra will be reduced, coadded, continua fit, lines identified and Voigt profiles fit to Lyman alpha forest lines using techniques and code developed for our previous work. The physical characteristics of the final sample will be compared to the expected properties derived from analysis of simulations of the IGM. Comparison between the properties at z~1 and those at higher redshifts accessible from the ground can test whether structure in the Lyman alpha forest is evolving in the manner predicted by gravitational instability theories. We will combine the HST absorption data with deep multiband imaging and galaxy redshifts from ground-based programs underway to study the evolution of the IGM and its relationship to the evolution of star-formation in galaxies.

Bechtold, Jill

2004-07-01

21

Understanding the IGM Absorbers with Numerical Simulations of the WHIM  

NASA Astrophysics Data System (ADS)

The total baryon content of the universe can be deduced both from observations of the cosmic microwave background, and the observed Deuterium to Hydrogen ratio {D/H} through the theory of big-bang nucleosynthesis. Though observations can account for all of the baryons at high redshift, roughly half the baryons are referred to as``missing'' in the low redshift universe since they are not observed in known baryonic structureslike galaxies, clusters, and the Lyman-alpha forest. Cosmological simulations predict that the missing baryons can be found in acosmic web of sheets and filaments that thread the halos, in the ``warm-hot intergalactic medium'' {WHIM} phase {10^5 - 10^7K}. The WHIM gas should be detectable in Ly-alpha or Ly-beta {10^4 K gas} and in shock-heated gas{10^5 - 10^6 K} in Ly-alpha and OVI absorption. Ultraviolet {UV} spectroscopy with the Far Ultraviolet Spectroscopic Explorer {FUSE} and HST has detected IGM absorbers in various metal species and HI along lines of sight to bright quasars that are likely associated with gas in the WHIM phase. This gas may account for the bulk of the missing baryons in the low redshift universe. Using Enzo hydro/N-body grid-based cosmology simulations, we will determine whether there is a unique interpretation given the current IGM absorber observations, and how new observations may provide strong tests of these theories. We propose to, with a suite of high-resolution Enzo simulations and novel analysis techniques, characterize the UV absorbers, and to model observational metrics to compare with the data. In particular, we study the metal diffusion throughout the IGM using various prescriptions for star formation, galaxy formation and thermaland chemical feedback, and study the numerical convergence of these algorithms.;

Hallman, Eric

2009-07-01

22

Comparison of PanBio Dengue Duo Igm and IgG Capture ELISA and Venture Technologies Dengue IgM and IgG Dot Blot  

Microsoft Academic Search

Background: A number of commercial ELISA for dengue diagnosis have recently become available, though direct comparison between these assays have not been published. Objectives: The Venture Technologies Dengue IgM and IgG Dot Blot assays and the PanBio Dengue Duo IgM and IgG Capture ELISA were compared. StudyDesign: Paired sera from patients with dengue (n=20) and Japanese encephalitis (JE, n=10), and

A. J. Cuzzubbo; D. W. Vaughn; A. Nisalak; T. Solomon; S. Kalayanarooj; J. Aaskov; N. M. Dung; P. L. Devine

2000-01-01

23

Targeting cell surface ?2-microglobulin by pentameric IgM antibodies  

PubMed Central

Summary Monoclonal antibodies (mAbs) specific for human ?2-microglobulin (?2M) have been shown to induce tumour cell apoptosis in haematological and solid tumours via recruiting major histocompatibility complex (MHC) class I molecules into and excluding cytokine receptors from the lipid rafts. Based on these findings, we hypothesized that IgM anti-?2M mAbs might have stronger apoptotic effects because of their pentameric structure. Our results showed that, compared with IgG mAbs, IgM anti-?2M mAbs exhibited stronger tumouricidal activity in vitro against different tumour cells, including myeloma, mantle cell lymphoma, and prostate cancer, and in vivo in a human-like xenografted myeloma mouse model without damaging normal tissues. IgM mAb-induced apoptosis is dependent on the pentameric structure of the mAbs. Disrupting pentameric IgM into monomeric IgM significantly reduced their ability to induce cell apoptosis. Monomeric IgM mAbs were less efficient at recruiting MHC class I molecules into and exclusion of cytokine receptors from lipid rafts, and at activating the intrinsic apoptosis cascade. Thus, we developed and validated the efficacy of anti-?2M IgM mAbs that may be utilized in the clinical setting and showed that IgM anti-?2M mAbs may be more potent than IgG mAbs at inducing tumour apoptosis.

Cao, Yabing; Lan, Yongsheng; Qian, Jianfei; Zheng, Yuhuan; Hong, Sungyoul; Li, Haiyan; Wang, Michael; Kwak, Larry W.; Lin, Dongyu; Yang, Jing; Yi, Qing

2011-01-01

24

Relation of carotid plaque with natural IgM antibodies in patients with systemic lupus erythematosus.  

PubMed

Noninvasive carotid measurements have proven value in the estimation of future cardiovascular (CV) outcomes in systemic lupus erythematosus (SLE). Natural IgM-antibodies to phosphorylcholine (PC) epitopes can enhance apoptotic-cell clearance and induce anti-inflammatory pathways. Herein, we show that subclinical CV disease, as detected by carotid ultrasound, in a cross-sectional SLE cohort was associated with lower levels of IgM anti-PC, as well as lower levels of the ratio of IgM anti-PC/total IgM, compared to patients without plaque (p=0.004 and p=0.02, respectively). The IgM anti-PC/total IgM association remained significant after adjusting for age, cholesterol and hypertension. Adiponectin and sE-selectin were significantly elevated in patients with plaque, and statistical models showed that combining adiponectin, sE-selectin and IgM anti-PC/total IgM was better for predicting plaque than either test alone. These results support the hypothesis that IgM-natural autoantibodies may inhibit atherogenesis, and confirm the utility of IgM anti-PC levels as a biomarker for subclinical CV disease. PMID:24704464

Grönwall, Caroline; Reynolds, Harmony; Kim, June K; Buyon, Jill; Goldberg, Judith D; Clancy, Robert M; Silverman, Gregg J

2014-07-01

25

Spitzer Observations of Stephan's Quintet -- IGM Dust and Gas in a Multi-galaxy Collision  

Microsoft Academic Search

Stephan's Quintet (SQ) is the most famous and well studied compact group of galaxies. Spectacular activity is triggered by interactions between member galaxies and various constituents of the intragroup medium (IGM), including a ~40 kpc large scale-shock and IGM starbursts more than 20 kpc away from any neighboring galaxy centers. Our new Spitzer IRS (SH, LH, and SL) and MIPS

C. K. Xu; P. N. Appleton; M. Dopita; Y. Gao; N. Y. Lu; C. Popescu; W. T. Reach; J. Sulentic; R. Tuffs; M. Yun

2008-01-01

26

Monoclonal IgM from patients with peripheral demyelinating neuropathies cross-react with bacterial polypeptides.  

PubMed Central

Human monoclonal IgM associated with a demyelinating peripheral neuropathy often feature a distinct antibody activity directed against a glucuronyl sulphate epitope shared by myelin-associated glycoprotein (MAG), nerve glycolipids and low molecular weight peripheral nerve polypeptides. Earlier studies showed that these IgM use a diverse repertoire of VH and VL genes which exhibit somatic mutations, possibly indicative of an antigen-driven process. Here, we investigated whether such monoclonal IgM may react with environmental bacterial antigens. We found that six patients' sera and purified monoclonal IgM, as well as IgM from supernatants of three clonal anti-MAG-secreting cell lines reacted with unique 90-100 kD polypeptides from extracts of two out of 10 bacterial species. Purified MAG was able to inhibit this reactivity. These results indicate molecular mimicry as a possible mechanism of this immunomediated neuropathy and associated clonal lymphoid disease. Images Fig. 1 Fig. 2

Brouet, J C; Mariette, X; Gendron, M C; Dubreuil, M L

1994-01-01

27

Anti-GD2-like IgM autoreactivity in multiple sclerosis patients.  

PubMed

Seric IgM autoreactivity in 100 multiple sclerosis (MS) and 106 control (70 of whom had other neurological diseases) patients was assessed either by immunohistochemistry on normal human CNS tissue or to GD2, GD1a, GD3 by ELISA and thin layer chromatography (TLC) techniques. By double immunohistochemistry, we found that 44% of the total MS population showed seric IgM reactivity to oligodendrocytes and myelin, this finding being particularly frequent in patients with secondary progressive MS. In the non-MS cohort, positive signals were seen only in one patient. In all cases, extraction of lipids from CNS sections abolished the immunoreactivity. Among the gangliosides investigated by ELISA, anti-GD2-like IgM autoantibodies were detected in the serum of 30% of MS patients, a subgroup of whom (below 10%) reacted also with GD1a and/or GD3. More than 85% of MS cases with anti-GD2-like IgM immunoreactivity by ELISA showed also IgM antioligodendrocyte/myelin staining by immunohistochemistry. However, no immunostaining in MS sera was observed when gangliosides were resolved by TLC. A positive correlation with neurological disability was observed, as the Expanded Disability Status Scale of MS patients with anti-GD2-like IgM autoreactivity by ELISA was significantly worse than seronegative MS cases. The results of the present study enforce the role of glycolipids as potential autoantigens and of IgM autoantibodies in MS pathogenesis. PMID:16764343

Marconi, S; Acler, M; Lovato, L; De Toni, L; Tedeschi, E; Anghileri, E; Romito, S; Cordioli, C; Bonetti, B

2006-06-01

28

Levels of IgM and IgA circulating immune complexes in dogs with leishmaniasis.  

PubMed

The concentrations of IgM and IgA circulating immune complexes (CIC) were determined in 82 dogs with naturally acquired leishmania infection and in a control group of 25 healthy dogs. The mean serum IgM and IgA CIC concentration in infected dogs were significantly (IgM; P < 0.004; IgA; P < 0.000) higher than in the control group. An increase in IgM and IgA CIC concentration was found in 47.6 and 95.1%, respectively, of the leishmania-infected dogs. The serum IgM and IgA CIC concentrations in infected dogs showing hypercreatininaemia were not statistically higher than those of sick dogs with normal creatininaemia. When hypercreatininaemia (> or = 1.30 mg/dl) was used as an indicator for CIC disease, the positive predictive value obtained with 0.368 for IgM CIC and 0.894 for IgA CIC, indicating that renal function impairment was associated with the high serum IgM and IgA CIC concentrations in 36.8 and 89.4%, respectively, of the infected dogs. PMID:9673577

Margarito, J M; Lucena, R; López, R; Molleda, J M; Martín, E; Ginel, P J

1998-06-01

29

The new ParaDIgm: IgM from bench to clinic  

PubMed Central

The inaugural IgM event entitled “The new ParaDIgm: IgM from bench to clinic” brought together the increasingly active and growing IgM antibody community to discuss recent advances and challenges facing the discovery and development of IgM antibody therapies and technologies. Researchers, clinicians and biomanufacturing experts delivered 21 talks on the basic science and isolation of IgM, upstream and downstream development, and formulation and clinical development of the molecules. Participants networked around topics aimed at exploring the full potential of IgM antibodies. The meeting was held at DECHEMA Gesellschaft für Chemische Technik und Biotechnologie e. V. (Society for Chemical Engineering and Biotechnology), a non-profit scientific and technical society based in Frankfurt am Main, Germany. The meeting was sponsored by Patrys, Laureate Biopharma, Bio-Rad Laboratories, BIA Separations, Percivia and the Bio Affinity Company (BAC). The second New ParaDIgm: IgM from bench to clinic meeting, will be held on April 23–24, 2013 in Frankfurt, Germany.

Hanala, Sherif

2012-01-01

30

IgM expression in paraffin sections distinguishes follicular lymphoma from reactive follicular hyperplasia  

PubMed Central

The trapping of IgM-containing immune complexes (ICs) by follicular dendritic cells (FDCs) serves as an important step in promoting germinal center (GC) formation. Thus, the deposition of IgM-containing ICs on FDCs can be detected by antibodies recognizing IgM. The present investigation provides the first comprehensive report on the IgM staining pattern in follicular lymphoma (FL, n = 60), with comparisons to reactive follicular hyperplasias (RFH, n = 25), demonstrating that immunohistochemical staining for IgM in paraffin-embedded sections seems to be an additional tool for differentiating between FL and RFH. In RFH, IgM highlighted processes of FDCs, with stronger and more compact staining in light than in dark zones, with occasional very dim staining of GC B cells. In FL, IgM expression patterns were of three types. Pattern I (38 cases) stained tumor cells within neoplastic follicles, with no staining of FDCs. Pattern II (15 cases) stained neither tumor cells nor FDCs. Pattern III (7 cases) stained tumor cells with (3 cases) or without (4 cases) IgM expression; however, variable and attenuated IgM expression was observed on FDCs in each case. Interestingly, significant numbers of IgD+ mantle cells were preserved around the neoplastic follicles in these 7 cases. The data suggested that a complete or considerable loss of IgM expression in FDCs, reflecting the loss of IgM-containing ICs in FDCs, is a typical feature of FL. Increased IgM expression by GC B cells can also serve as an indicator of immunophenotypic abnormality in FL.

Zheng, Yuanyuan; Zhou, Xiaoge; Xie, Jianlan; Zhu, Hong; Zhang, Shuhong; Zhang, Yanning; Wei, Xuejing; Yue, Bing

2014-01-01

31

Expression and glycoengineering of functionally active heteromultimeric IgM in plants.  

PubMed

IgM antibodies are an important player of the human's innate defense mechanisms and increasingly have gained interest as therapeutics. Although the expression of IgM antibodies in mammalian cell culture is established, this approach remains costly and alternative methods have not been developed yet. Plants have a proven record for the production of therapeutically relevant recombinant proteins. However, whether they are able to express proteins like IgM antibodies, which range among the most complex human proteins, remains unknown so far. Here we report the in planta generation of the functionally active monoclonal antitumor IgM PAT-SM6 (SM6). SM6 efficiently accumulates in plant leaves and assembles correctly into heterooligomers (pentamers and hexamers). Detailed glycosylation analysis exhibited complex and oligomannosidic N-glycans in a site-specific manner on human-serum IgM and on plant- and human-cell-line-produced SM6. Moreover, extensive in planta glycoengineering allowed the generation of SM6 decorated with sialylated human-type oligosaccharides, comparable to plasma-derived IgM. A glycosylated model of pentameric IgM exhibits different accessibility of the glycosylation sites, explaining site-specific glycosylation. Biochemical and biophysical properties and importantly biological activities of plant-derived SM6 glycoforms are comparable to the human-cell-derived counterparts. The in planta generation of one of the most complex human proteins opens new pathways toward the production of difficult-to-express proteins for pharmaceutical applications. Moreover, the generation of IgMs with a controlled glycosylation pattern allows the study of the so far unknown contribution of sugar moieties to the function of IgMs. PMID:24706782

Loos, Andreas; Gruber, Clemens; Altmann, Friedrich; Mehofer, Ulrich; Hensel, Frank; Grandits, Melanie; Oostenbrink, Chris; Stadlmayr, Gerhard; Furtmüller, Paul G; Steinkellner, Herta

2014-04-29

32

Expression and glycoengineering of functionally active heteromultimeric IgM in plants  

PubMed Central

IgM antibodies are an important player of the human’s innate defense mechanisms and increasingly have gained interest as therapeutics. Although the expression of IgM antibodies in mammalian cell culture is established, this approach remains costly and alternative methods have not been developed yet. Plants have a proven record for the production of therapeutically relevant recombinant proteins. However, whether they are able to express proteins like IgM antibodies, which range among the most complex human proteins, remains unknown so far. Here we report the in planta generation of the functionally active monoclonal antitumor IgM PAT-SM6 (SM6). SM6 efficiently accumulates in plant leaves and assembles correctly into heterooligomers (pentamers and hexamers). Detailed glycosylation analysis exhibited complex and oligomannosidic N-glycans in a site-specific manner on human-serum IgM and on plant- and human-cell-line–produced SM6. Moreover, extensive in planta glycoengineering allowed the generation of SM6 decorated with sialylated human-type oligosaccharides, comparable to plasma-derived IgM. A glycosylated model of pentameric IgM exhibits different accessibility of the glycosylation sites, explaining site-specific glycosylation. Biochemical and biophysical properties and importantly biological activities of plant-derived SM6 glycoforms are comparable to the human-cell–derived counterparts. The in planta generation of one of the most complex human proteins opens new pathways toward the production of difficult-to-express proteins for pharmaceutical applications. Moreover, the generation of IgMs with a controlled glycosylation pattern allows the study of the so far unknown contribution of sugar moieties to the function of IgMs.

Loos, Andreas; Gruber, Clemens; Altmann, Friedrich; Mehofer, Ulrich; Hensel, Frank; Grandits, Melanie; Oostenbrink, Chris; Stadlmayr, Gerhard; Furtmuller, Paul G.; Steinkellner, Herta

2014-01-01

33

Transcriptional Heterogeneity of IgM+ Cells in Rainbow Trout (Oncorhynchus mykiss) Tissues  

PubMed Central

Two major classes of B lymphocytes have been described to date in rainbow trout: IgM+ and IgT+ cells. IgM+ cells are mainly localized in the spleen, peripheral blood and kidney but are also found in other tissues. However, differences among IgM+ cell populations attending to its location are poorly defined in fish. Thus, the aim of this work was to characterize the expression of different immune molecules such as chemokine receptors, Toll-like receptors (TLRs) and transcription factors on sorted IgM+ lymphocytes from different rainbow trout tissues. IgM+ populations from blood, spleen, kidney, gills, intestine and liver were isolated by cell sorting and the constitutive levels of transcription of these genes evaluated by real-time PCR. To further characterize B cells, we identified an MS4A sequence. In humans, the MS4A family includes several genes with immune functions, such as the B cell marker CD20 or FcR?. Subsequently, we have also evaluated the mRNA levels of this MS4A gene in the different IgM+ populations. The relevant differences in transcriptional patterns observed for each of these IgM+ populations analyzed, point to the presence of functionally different tissue-specific B cell populations in rainbow trout. The data shown provides a pattern of genes transcribed in IgM+ B cells not previously revealed in teleost fish. Furthermore, the constitutive expression of all the TLR genes analyzed in IgM+ cells suggests an important role for these cells in innate immunity.

Abos, Beatriz; Castro, Rosario; Pignatelli, Jaime; Luque, Alfonso; Gonzalez, Lucia; Tafalla, Carolina

2013-01-01

34

IgM Promotes the Clearance of Small Particles and Apoptotic Microparticles by Macrophages  

PubMed Central

Background Antibodies are often involved in enhancing particle clearance by macrophages. Although the mechanisms of antibody-dependent phagocytosis have been studied for IgG in greater detail, very little is known about IgM-mediated clearance. It has been generally considered that IgM does not support phagocytosis. Recent studies indicate that natural IgM is important to clear microbes and other bioparticles, and that shape is critical to particle uptake by macrophages; however, the relevance of IgM and particle size in their clearance remains unclear. Here we show that IgM has a size-dependent effect on clearance. Methodology/Principal Findings We used antibody-opsonized sheep red blood cells, different size beads and apoptotic cells to determine the effect of human and mouse IgM on phagocytosis by mouse alveolar macrophages. Our microscopy (light, epifluorescence, confocal) and flow cytometry data show that IgM greatly enhances the clearance of small particles (about 1–2 micron) by these macrophages. There is an inverse relationship between IgM-mediated clearance by macrophages and the particle size; however, macrophages bind and internalize many different size particles coated with IgG. We also show that IgM avidly binds to small size late apoptotic cells or bodies (2–5 micron) and apoptotic microparticles (<2 µm) released from dying cells. IgM also promotes the binding and uptake of microparticle-coated beads. Conclusions/Significance Therefore, while the shape of the particles is important for non-opsonized particle uptake, the particle size matters for antibody-mediated clearance by macrophages. IgM particularly promotes the clearance of small size particles. This finding may have wider implications in IgM-mediated clearing of antigens, microbial pathogens and dying cells by the host.

Litvack, Michael L.; Post, Martin; Palaniyar, Nades

2011-01-01

35

Hidden 19S IgM rheumatoid factor in adults with juvenile rheumatoid arthritis onset.  

PubMed Central

Forty-eight adult patients with juvenile rheumatoid arthritis (JRA) (onset before age 16 years) were evaluated at the age of 17 years or more for the presence of hidden 19S IgM rheumatoid factors (RF), i.e., 19S IgM RF that can be detected by the complement-dependent haemolytic assay in the IgM-containing fraction after separation of the serum by acid gel filtration. The average age of the patients was 25.3 years. The mean duration of disease was 16.5 years. Thirty-two of 48 patients (67%) showed the presence of hidden 19S IgM RF in their serum. Disease activity correlated with hidden RF titres in 62% (55/88) of the evaluations. The results indicate that patients with seronegative JRA onset continue to have significant titres of hidden 19S IgM RF in their sera into early adulthood.

Speiser, J C; Moore, T L; Weiss, T D; Baldassare, A R; Ross, S C; Osborn, T G; Dorner, R W; Zuckner, J

1985-01-01

36

IgM Promotes the Clearance of Small Particles and Apoptotic Microparticles by Macrophages  

Microsoft Academic Search

BackgroundAntibodies are often involved in enhancing particle clearance by macrophages. Although the mechanisms of antibody-dependent phagocytosis have been studied for IgG in greater detail, very little is known about IgM-mediated clearance. It has been generally considered that IgM does not support phagocytosis. Recent studies indicate that natural IgM is important to clear microbes and other bioparticles, and that shape is

Michael L. Litvack; Martin Post; Nades Palaniyar; Ben Ko

2011-01-01

37

Purification and molecular characterization of IgM in olive barb, Puntius Sarana.  

PubMed

In the present article, immunoglobulin (Ig) of Puntius sarana (a vulnerable medium carp species) was purified by affinity chromatography, characterized, and identified as only IgM type with a native molecular weight of 879 kDa having one heavy (88 kDa) and one light (26 kDa) chain. Further, the developed rabbit antisera against IgM was found to be quite specific to P. sarana IgM and used in ELISA to measure the antibody titer in P. sarana at different time periods, against an antigen (hemocyanin) injection with and without adjuvant. The antibody titer was significantly higher in most of the time periods in both groups, however, the adjuvant-treated group showed higher antibody titer at days 43 and 90, compared to non adjuvant-treated group. Further, the partial IgM sequence was amplified and its expression level was checked during ontogenesis. The IgM transcript was detected from unfertilized egg stage to 4 days post fertilization (dpf) and again reappeared at 21 dpf whereas during infection with Aeromonas hydrophila, significantly marked up-regulation of the gene was observed at 12 hr, 24 hr, and 7 days post-infection time periods indicating the role of IgM during early embryonic time period as well as during bacterial pathogenesis. PMID:24654823

Das, Abhilipsa; Sahoo, Pramoda Kumar; Mohanty, Jyotirmaya; Garnayak, Sushil Kumar

2014-01-01

38

Study of IgM aggregation in serum of patients with macroglobulinemia.  

PubMed

The effect of solvent conditions on the aggregation of IgM in serum specimens from patients with macroglobulinemia was studied by a turbidimetric procedure. Aggregation of IgM varied considerably among the samples and was affected by a number of experimental parameters. In general, IgM aggregation was more pronounced under acidic conditions and in solvents with low ionic strength. The presence of water-miscible organic solvents also promoted aggregation. Based on these studies, it was concluded that the major force involved in the formation of immunoglobulin aggregates in the serum of patients with macroglobulinemia was electrostatic, rather than hydrophobic, interactions. A number of additives known to prevent protein aggregation were evaluated for their effectiveness in inhibiting IgM aggregation. The only additives that were shown to inhibit or reduce IgM aggregation were charged molecules, such as arginine, sodium chloride, ethylenediamintetraacetic acid and quaternary ammonium beta-cyclodextrin. Some of these charged additives were also effective in dissociating the IgM aggregates once they were formed, even in the presence of detergent. PMID:11071070

Sharma, L; Baker, J; Brooks, A M; Sharma, A

2000-08-01

39

Platelet antibodies of the IgM class in immune thrombocytopenic purpura  

SciTech Connect

The clinical course and response to therapy of patients with immune thrombocytopenic purpura (ITP) are not completely determined by the level of IgG present on the platelet surface. It is possible that antibodies of other immunoglobulin classes also play a role in platelet destruction in some of these patients. Therefore, the authors studied 175 patients with ITP for the presence of IgM anti-platelet antibodies using radiolabeled polyclonal or monoclonal anti-IgM. They observed that 57% of patients with clinical ITP had increased levels of IgM on their platelets, compared with normal controls and patients with thrombocytopenia who did not have ITP. They obtained similar results using either radiolabeled polyclonal or monoclonal anti-IgM, reagents whose integrity was first characterized using erythrocytes coated with defined amounts of IgM antibody. Among patients with increased platelet-IgM there was a significant correlation both with the presence of increased platelet-C3 as well as the amount of platelet-C3. The authors demonstrated the presence of warm-reacting IgM anti-platelet antibodies in the plasma of two of these patients who were further studied. These studies demonstrate the presence of warm-reacting IgM anti-platelet antibodies in some patients with ITP. They suggest that the binding of complement to platelets by IgM antibodies may initiate platelet clearance as well as enhance the effect of IgG antibodies in ITP.

Cines, D.B.; Wilson, S.B.; Tomaski, A.; Schreiber, A.D.

1985-04-01

40

Complement-Activating IgM Enhances the Humoral but Not the T Cell Immune Response in Mice  

PubMed Central

IgM antibodies specific for a certain antigen can enhance antibody responses when administered together with this antigen, a process believed to require complement activation by IgM. However, recent data show that a knock-in mouse strain, C?13, which only produces IgM unable to activate complement, has normal antibody responses. Moreover, the recently discovered murine IgM Fc receptor (FcµR or TOSO/FAIM3) was shown to affect antibody responses. This prompted the re-investigation of whether complement activation by specific IgM is indeed required for enhancement of antibody responses and whether the mutation in Cµ13 IgM also caused impaired binding to FcµR. The results show that IgM from Cµ13 and wildtype mice bound equally well to the murine FcµR. In spite of this, specific C?13 IgM administered together with sheep red blood cells or keyhole limpet hemocyanine was a very poor enhancer of the antibody and germinal center responses as compared with wildtype IgM. Within seconds after immunization, wildtype IgM induced deposition of C3 on sheep red blood cells in the blood. IgM which efficiently enhanced the T-dependent humoral immune response had no effect on activation of specific CD4+ T cells as measured by cell numbers, cell division, blast transformation, or expression of the activation markers LFA-1 and CD44 in vivo. These observations confirm the importance of complement for the ability of specific IgM to enhance antibody responses and suggest that there is a divergence between the regulation of T- and B-cell responses by IgM.

Ding, Zhoujie; Bergman, Anna; Rutemark, Christian; Ouchida, Rika; Ohno, Hiroshi; Wang, Ji-Yang; Heyman, Birgitta

2013-01-01

41

Comparison between five methods for the separation of IgM.  

PubMed

Five serum fractionation methods were examined with regard to their suitability for use in the demonstration of specific IgM antibodies. It was found that Protein A - Sepharose CL - 4B chromatography leads to higher IgM recovery than absorption with whole Staphylococcus aureus (58% as opposed to 40%). It is also cheaper, since this absorbent can be reused. Contamination with 2-5% IgG and about 70% IgA is encountered with both methods. Quaternary aminoethyl (QAE) - Sephadex chromatography gives excellent IgM recovery (97%) and its cost and execution time are the lowest. IgG and IgA residues are 2% and 53% respectively. Ultrafiltration results in poorer recovery of IgM (31%). However, the sample volume can be brought back to its initial value, or concentrated still further. IgG and IgA residues are 2% and 14%. The cost of the method and the time needed for its execution are relatively high. Gel chromatography is the only method to give a completely IgG- and IgA-free IgM fraction. The percentage of IgM recovered varies in accordance with the ratio between the volume of the sample and that of the column. Very high values may be obtained, but at the expense of heavy dilution. The cost is low, but the method requires a considerable amount of time. In short, none of the five methods is clearly superior to the others. Whether or not a given method is chosen will thus depend on the relative importance attached to the percentage of IgM recovered, the presence or otherwise of IgA, sample dilution, cost, and rapidity of execution. PMID:6865795

Negro Ponzi, A; Cerio, E; Angeretti, A; Bossolasco, M V; Martinetto, P

1983-04-01

42

Natural IgM: Beneficial Autoantibodies for the Control of Inflammatory and Autoimmune Disease.  

PubMed

Natural IgM are highly represented in the circulation at birth, and these often autoreactive antibodies have been postulated to have innate-like properties and play crucial roles in apoptotic cell clearance, tissue homeostasis, and immune modulation. This review summarizes the known properties of these IgM autoantibodies, and the evidence that these anti-apoptotic cell IgM natural antibodies can regulate inflammatory responses through ancient pathways of the innate immune system that first arose long before the initial emergence of the adaptive immune system. While the regulatory contributions of these natural IgM autoantibodies are certainly not an essential and fundamental component of host defenses, these provide an additional layer to further protect the host. More importantly, these IgM antibody responses are highly inducible and their up-regulation can be a powerful means for the host to survive in a setting of chronic inflammation. The observed beneficial clinical associations for cardiovascular disease and autoimmunity, as well as opportunities for potential therapeutic implications are discussed. PMID:24691998

Grönwall, Caroline; Silverman, Gregg J

2014-07-01

43

Comparison between DOT EIA IgM and Widal Test as early diagnosis of typhoid fever.  

PubMed

A recently developed DOT enzyme immunoassay known as "Typhidot" for detecting IgM antibody against 50 KDa OMP antigen of Salmonella typhi, was evaluated on 100 clinically suspected typhoid fever cases and 40 age-sex matched controls, in the Department of Microbiology, Mymensingh Medical College during, the period from June 2006 to July 2007. Blood culture, Widal test, and DOT EIA for IgM test were performed in all patients. Among 100 clinically suspected typhoid fever cases, 35 were subsequently confirmed on the basis of positive blood culture for S. typhi and/or significant rising titre of Widal test. The DOT EIA IgM test could produce results within 1 hour. The result of the DOT EIA IgM test showed a good diagnostic value for typhoid fever. The sensitivity, specificity, positive and negative predictive value of the test was found as 91.42%, 90.00%, 88.88% and 92.30% respectively. On the other hand corresponding values for Widal test were of 42.85%, 85.00%, 71.42% and 62.96% respectively. Thus, The DOT EIA IgM seems to be a practical alternative to Widal test for early diagnosis of typhoid fever. PMID:19182742

Begum, Z; Hossain, M A; Musa, A K; Shamsuzzaman, A K; Mahmud, M C; Ahsan, M M; Sumona, A A; Ahmed, S; Jahan, N A; Alam, M; Begum, A

2009-01-01

44

Determination of anti-HBsAg IgM monoclonal antibodies in cell culture media by perfusion immunoassay  

Microsoft Academic Search

A rapid, specific, perfusion immunoassay for active anti-HBsAg monoclonal IgM is described. The immunoassay requires less than 3.5 min per sample. The precision was found to be 3.6% at an IgM concentration of 17 ?g\\/ml. A detection limit of 1 ?g\\/ml IgM in culture media was determined. Assay results were found to correlate very well with standard size exclusion chromatography

John M. Brackett; Kristen L. Cousineau; Hongqi Wang; Ananth V. Annapragada; Odin D. Cabal; Gary S. Gall; Bruce Peterson; W. Gerard Robey

1997-01-01

45

The stimulation of IgM rheumatoid factor from human B lymphocytes by rheumatoid arthritis complement-activating immune complexes.  

PubMed Central

Immune complexes from rheumatoid arthritis (RA IC) and Hodgkin's disease (HD IC) sera were separated on an anti-C3g affinity column and their ability to stimulate the production of IgM and IgM RF by normal and RA B lymphocytes tested in a culture system in vitro. RA IC stimulated IgM production of which up to 91.3% had IgM RF activity. HD IC were incapable of stimulating the production of IgM and IgM RF. The stimulation of IgM and IgM RF production by RA IC required de novo protein synthesis. Both RA IC and HD IC were capable of significantly inhibiting (from 47.6 to 72.0%) pokeweed mitogen (PWM)-induced and goat F(ab)2 antihuman mu-induced B lymphocyte proliferation. Thus it is proposed that IC present in human pathological sera may regulate immunoglobulin production by an effect on B lymphocyte proliferation while some may, in addition, be capable of inducing IgM RF production from such cells.

Lorber, M; Samuel, D; Amlot, P; Panayi, G S

1988-01-01

46

Importance of specific IgM antibodies in 116 patients with various stages of syphilis.  

PubMed Central

We tested 222 serum samples obtained from 51 patients presenting with syphilis, before and after treatment; 117 from 65 patients with a history of syphilis (114) or yaws (3); 77 from 71 patients with no evidence of syphilis; and 1117 serologically negative serum samples. Our tests included the IgM fluorescent treponemal antibody absorbed (IgM-FTA-ABS) and solid phase haemadsorption assay (SPHA) techniques. According to the stage of development of syphilis, IgM antibodies were found in 83-100% of the serum samples. This permitted a precise diagnosis to be made and cure assessed. As IgM antibodies were absent in serum from patients with healed syphilis, resolved syphilis could be distinguished from developing syphilis. The sensitivity (92%) of the IgM-FTA-ABS test was comparable with that of the SPHA (96%), but the SPHA was more specific (97.4%) than the IgM-FTA-ABS test (89.61%).

Merlin, S; Andre, J; Alacoque, B; Paris-Hamelin, A

1985-01-01

47

Diagnostic and prognostic significance of the IgM antibody to the Hepatitis delta virus  

SciTech Connect

The IgM class antibody to the hepatitis delta virus (HDV) was determined in different clinical categories of hepatitis B surface antigen carriers infected by the HDV (positive in the test for total antibody to HDV). The IgM antibody was found at high titers in each 70 patients with inflammatory liver disease and at a low titer in one six patients with inactive cirrhosis; it was not found in eight carriers with normal liver histology. Testing for Igm antibody to HDV distinguishes hepatitis B surface antigen carriers who have underlying inflammatory HDV liver disease from those with past HDV infection and provides prognostic information on the course of chronic HDV hepatitis.

Farci, P.; Gerin, J.L.; Aragona, M.; Lindsey, I.; Crivelli, O.; Balestrieri, A.; Smedile, A.; Thomas, H.C.; Rizzetto, M.

1986-03-21

48

High frequency of false positive IgM immunoblots for Borrelia burgdorferi in clinical practice.  

PubMed

Although it is known that two-tier serologic testing for Lyme disease may be associated with false positive results on the IgM immunoblot, this problem has never been systematically studied in the clinical practice setting. In a retrospective investigation of patients referred to the private adult practice of an Infectious Diseases physician for possible for Lyme disease, 50 of 182 patients (27.5%, 95% CI: 21.1-34.6) were found to have a false positive IgM immunoblot. 78.0% of these patients had received unnecessary antibiotic therapy. False positive results were not restricted to any single commercial laboratory. Research on alternative testing strategies that eliminate the IgM immunoblot entirely is warranted. PMID:22369185

Seriburi, V; Ndukwe, N; Chang, Z; Cox, M E; Wormser, G P

2012-12-01

49

Antagonism of cannabinoid receptor 2 pathway suppresses IL-6-induced immunoglobulin IgM secretion  

PubMed Central

Background Cannabinoid receptor 2 (CB2) is expressed predominantly in the immune system, particularly in plasma cells, raising the possibility that targeting the CB2 pathway could yield an immunomodulatory effect. Although the role of CB2 in mediating immunoglobulin class switching has been reported, the effects of targeting the CB2 pathway on immunoglobulin secretion per se remain unclear. Methods Human B cell line SKW 6.4, which is capable of differentiating into IgM-secreting cells once treated with human IL-6, was employed as the cell model. SKW 6.4 cells were incubated for 4 days with CB2 ligands plus IL-6 (100 U/ml). The amount of secreted IgM was determined by an ELISA. Cell proliferation was determined by the 3H-Thymidine incorporation assay. Signal molecules involved in the modulation of IgM secretion were examined by real-time RT-PCR and Western blot analyses or by using their specific inhibitors. Results We demonstrated that CB2 inverse agonists SR144528 and AM630, but not CB2 agonist HU308 or CB1 antagonist SR141716, effectively inhibited IL-6-induced secretion of soluble IgM without affecting cell proliferation as measured by thymidine uptake. SR144528 alone had no effects on the basal levels of IgM in the resting cells. These effects were receptor mediated, as pretreatment with CB2 agonist abrogated SR144528-mediated inhibition of IL-6 stimulated IgM secretion. Transcription factors relevant to B cell differentiation, Bcl-6 and PAX5, as well as the protein kinase STAT3 pathway were involved in the inhibition of IL-6-induced IgM by SR144528. Conclusions These results uncover a novel function of CB2 antagonists and suggest that CB2 ligands may be potential modulators of immunoglobulin secretion.

2014-01-01

50

Hyper IgM immunodeficiency. A primary dysfunction of B lymphocyte isotype switching.  

PubMed Central

Immunological evaluations (lymphocyte markers, B cell differentiation, T cell function) were performed on peripheral blood mononuclear cells from four individuals with hyper IgM immunodeficiency. Number, proportion, and proliferation of T lymphocytes and T lymphocyte subpopulations were relatively normal in affected individuals. The percentage and number of B cells expressing surface IgM and IgD were either normal or elevated in both blood and lymph nodes. However, surface IgG- and IgA-bearing B lymphocytes were completely absent. In vitro stimulation of blood lymphocytes with both T cell-dependent and T-cell independent polyclonal B cell activators resulted in normal numbers of IgM plasma cells and IgM secretion in cultures, but failed to induce any IgG- or IgA-producing cells. This failure of isotype switching was intrinsic to the B cell population and did not involve aberrant T cell help or suppression. Therefore, individuals with this disorder possess an intrinsic B cell dysfunction that is not related to abnormal T cell regulation.

Levitt, D; Haber, P; Rich, K; Cooper, M D

1983-01-01

51

IgM characterization directly performed in crude culture supernatants by a new simple electrophoretic method.  

PubMed

A new electrophoretic technique for the qualitative and quantitative analyses of IgM isoforms and fragments has been developed. IgMs which are more complex than many other recombinantly expressed immunoglobulins are characterized by their high molecular weighted active forms and many additional isoforms and fragments in the molecular range between 25 and 1200kDa. To analyze the multimers, isoforms and fragments simultaneously a high-resolution method, which enables sufficient migration and separation is required. Furthermore, this method should be appropriate to analyze IgMs in crude culture supernatants as well as purified samples. Simple sample preparation avoiding unspecific protein loss has been established. Currently no standard method to analyze all of them accordingly is available. The IgM-SDS-PAGE investigated for this purpose includes all these aspects. The combination of simple sample preparation and the application of precast gels make this electrophoretic method suitable for research but also quality control. The selective quantification of the multimers and the relative isoform distribution were performed by sensitive Sypro Ruby staining obtaining reliable and reproducible data in clone screening and process development which has been demonstrated by recombinantly expressed IgMs with significantly different isoform pattern. PMID:20493871

Vorauer-Uhl, Karola; Wallner, Jakob; Lhota, Gabriele; Katinger, Hermann; Kunert, Renate

2010-07-31

52

Mechanisms underlying acquired von Willebrand syndrome associated with an IgM paraprotein.  

PubMed

Acquired von Willebrand (vW) syndrome is a rare bleeding disorder which is frequently associated with immunological, malignant or cardiovascular disorders. The underlying pathomechanisms, particularly in patients with IgM monoclonal gammopathies, often remain unknown. We report a patient with indolent small B-cell lymphoma (immunocytoma) and plasmacytic differentiation with an IgM kappa paraprotein who was admitted with retroperitoneal haematoma. Medical history and coagulation testing were consistent with acquired vW syndrome. vW immunohistochemistry showed normal cytoplasmic labelling of endothelial cells and megakaryocytes, whereas the lymphomatous infiltrate was negative. Acquired vW syndrome due to adsorption of vW factor on malignant cells was thus excluded. In the multimeric analysis, all multimers were present similar to that in type 1 vW syndrome, but the triplet structures were blurred. The bands on serum immunofixation electrophoresis were also atypically broadened, which suggested complex formation between the IgM and vW factor. Immunoprecipitation studies showed that the 176-kDa proteolytic fragment of vW factor co-precipitated with the IgM paraprotein in the patient but not in the controls, suggesting a specific interaction between vW factor and the paraprotein in the patient. The patient required surgery and was successfully managed by chemotherapy consisting of rituximab and fludarabin as well as plasma exchange. PMID:19572993

Mayerhofer, M; Haushofer, A; Kyrle, P A; Chott, A; Müllner, C; Quehenberger, P; Worel, N; Traby, L; Eichinger, S

2009-09-01

53

Baryonic Content in the Warm-Hot IGM at Low Redshift  

NASA Technical Reports Server (NTRS)

Baryons are 4.5% of the universe's mass/energy density; only 10% of these are in stars, galaxies, and clusters. At low-redshift 90% of baryons are in the IGM, 30% in Ly-alpha forest, but most are in hot gas (10(exp 5-7) K) produced by shocks during structure formation. O VI 1032-38 A are the best tracers of this gas. The distribution of O VI absorbers observed by FUSE rises as N(sup -2+/-0.2, down to 10(exp 13)/sq cm. Integrated to logN=13, 7% of baryons reside in the O VI-bearing IGM at 10% solar metallicity, T approx. 10(exp 5.5) K. At redshift z<0.1 metals have been transported less than 800/h kpc from L* galaxies and 200/h kpc from 0.1 L* galaxies. The steepness of dN/dz means that low-N absorbers contribute an equal mass of hot IGM as higher N gas. The total mass of O VI-bearing gas in the IGM depends on determining the turnover in dN/dz at low N(O VI). Future observations by FUSE are needed to reach lower N and to reduce the uncertainty in the dN/dz power law.

Sonneborn, George; Shull, M.; Danforth, C.; Moos, W.

2007-01-01

54

Spitzer Observations of Stephan's Quintet -- IGM Dust and Gas in a Multi-galaxy Collision  

Microsoft Academic Search

Stephan's Quintet (SQ) is the most famous and well studied compact group of galaxies. The rich literature archive of multi-wavelength data reveal one of the most fascinating pictures in the universe. We see a complex web of interactions between member galaxies and various constituents of the intragroup medium (IGM) which, in turn, have triggered spectacular activities such as a 40

C. K. Xu; Ph. Appleton; M. Dopita; Y. Gao; N. Y. Lu; C. Popescu; W. Reach; R. Tuffs; J. Sulentic; M. Yun

2005-01-01

55

Analysis of functional epitopes on the dengue 2 envelope (E) protein using monoclonal IgM antibodies.  

PubMed

Forty-two hybridomas secreting IgM antibody against dengue virus were derived from spleen cells of dengue 2 infected mice. Antibody from 27 of these recognised the E protein of this virus. Of the 22 antibodies which neutralised dengue 2, only two cross-reacted with other flaviviruses. These 22 antibodies recognised three discrete domains on dengue virions. Competitive binding studies with IgG monoclonal antibodies suggested that two of the three domains were recognised by both IgG and IgM antibodies and that there were two additional domains which may be recognised exclusively by either IgG or IgM antibodies. IgM antibodies reacting with domains recognised by IgG antibodies that enhanced infection of susceptible cells by dengue 2, had no enhancing properties. None of the IgM antibodies activated the serum complement system after reacting with dengue 2 virions. PMID:7541621

Jianmin, Z; Linn, M L; Bulich, R; Gentry, M K; Aaskov, J G

1995-01-01

56

IgM Repertoire Biodiversity is Reduced in HIV-1 Infection and Systemic Lupus Erythematosus  

PubMed Central

Background: HIV-1 infection or systemic lupus erythematosus (SLE) disrupt B cell homeostasis, reduce memory B cells, and impair function of IgG and IgM antibodies. Objective: To determine how disturbances in B cell populations producing polyclonal antibodies relate to the IgM repertoire, the IgM transcriptome in health and disease was explored at the complementarity determining region 3 (CDRH3) sequence level. Methods: 454-deep pyrosequencing in combination with a novel analysis pipeline was applied to define populations of IGHM CDRH3 sequences based on absence or presence of somatic hypermutations (SHM) in peripheral blood B cells. Results: HIV or SLE subjects have reduced biodiversity within their IGHM transcriptome compared to healthy subjects, mainly due to a significant decrease in the number of unique combinations of alleles, although recombination machinery was intact. While major differences between sequences without or with SHM occurred among all groups, IGHD and IGHJ allele use, CDRH3 length distribution, or generation of SHM were similar among study cohorts. Antiretroviral therapy failed to normalize IGHM biodiversity in HIV-infected individuals. All subjects had a low frequency of allelic combinations within the IGHM repertoire similar to known broadly neutralizing HIV-1 antibodies. Conclusion: Polyclonal expansion would decrease overall IgM biodiversity independent of other mechanisms for development of the B cell repertoire. Applying deep sequencing as a strategy to follow development of the IgM repertoire in health and disease provides a novel molecular assessment of multiple points along the B cell differentiation pathway that is highly sensitive for detecting perturbations within the repertoire at the population level.

Yin, Li; Hou, Wei; Liu, Li; Cai, Yunpeng; Wallet, Mark Andrew; Gardner, Brent Paul; Chang, Kaifen; Lowe, Amanda Catherine; Rodriguez, Carina Adriana; Sriaroon, Panida; Farmerie, William George; Sleasman, John William; Goodenow, Maureen Michels

2013-01-01

57

B Cell Activating Factor Inhibition Impairs Bacterial Immunity by Reducing T Cell-Independent IgM Secretion  

PubMed Central

B cell activating factor of the tumor necrosis factor family (BAFF) is an essential survival factor for B cells and has been shown to regulate T cell-independent (TI) IgM production. During Ehrlichia muris infection, TI IgM secretion in the spleen was BAFF dependent, and antibody-mediated BAFF neutralization led to an impairment of IgM-mediated host defense. The failure of TI plasmablasts to secrete IgM was not a consequence of alterations in their generation, survival, or early differentiation, since all occurred normally in infected mice following BAFF neutralization. Gene expression characteristic of plasma cell differentiation was also unaffected by BAFF neutralization in vivo, and except for CD138, plasmablast cell surface marker expression was unaffected. IgM was produced, since it was detected intracellularly, and impaired secretion was not due to a failure to express the IgM secretory exon. Addition of BAFF to plasmablasts in vitro rescued IgM secretion, suggesting that BAFF signaling can directly regulate secretory processes. Our findings indicate that BAFF signaling can modulate TI host defense by acting at a late stage in B cell differentiation, via its regulation of terminal plasmablast differentiation and/or IgM secretion.

Jones, Derek D.; Jones, Maura; DeIulio, Gregory A.; Racine, Rachael; MacNamara, Katherine C.

2013-01-01

58

[Clinical and laboratory features of four cases with IgM multiple myeloma].  

PubMed

Objective To improve the understanding of the clinical and laboratory features of the IgM multiple myeloma (MM). Methods The clinical data of four cases of IgM MM patients were collected, their clinical and laboratory features were summarized and analyzed. Results Four patients met the criteria of IgM MM. They were all male. The age at the diagnosis ranged from 54 to 69 years. The primary symptoms included bone pain, hyperviscosity and bleeding. Three cases had ?-chain and only one case had ?-chain. They were all staged ?A according to the Durie-Salmon staging system (DSS). One case staged ?and three cases staged ? according to the international staging system (ISS). The average value of IgM, hemoglobin, serum calcium, creatinine and the proportion of bone marrow plasma cells were 83.6 (52.9-111.0) g/L, 79.5? (61.0-105.0) g/L, 3.20(2.11-6.00) mmol/L, 104.3 (56.0-171.0) ?mol/L and 0.558 (0.290-0.775), respectively. Bone destruction was found in 3 cases. Immunophenotypes of bone marrow plasma cells were analyzed in 3 patients. Results showed that these cells expressed CD38 and CD138, and did not express CD19, CD20 and CD117. Chromosome and fluorescence in situ hybridization (FISH) analysis were carried out in 4 cases and found that all of them had IgH translocations and 1q21 amplification, 2 cases had 13q and 17p deletion, and 3 cases had t(11;14). Three patients received bortezomib-based regimens as induction therapy and reached partial response (PR) - very good partial response (VGPR). Followed up to November 30, 2012, the median progress-free survival (PFS) and overall survival (OS) of the 4 cases were only 6.0 (2.5-7.0) months and 17.5 (2.5-27.0) months, respectively. Conclusions IgM MM is very rare and is no more than 0.5% in all types of MM. IgM MM have frequent t(11;14) and amp(1q21). Bortezomib-based regimens are effective for it, however, the disease progresses rapidly and has poor prognosis. PMID:23668209

Fan, Jian-ling; Fu, Wei-jun; Shi, Hao-tian; Zhou, Fan; Yuan, Zhen-gang; Zhang, Chun-yang; Wei, Wei; Ye, Fei; Zhang, Hui; Hou, Jian

2013-04-01

59

A selective defect in IgM antigen receptor synthesis and transport causes loss of cell surface IgM expression on tolerant B lymphocytes.  

PubMed Central

To explore the biochemical basis for maintaining immunological tolerance by functional inactivation of self-reactive B lymphocytes, transgenic mice carrying rearranged anti-lysozyme immunoglobulin transgenes and a lysozyme transgene were used as a source of large numbers of tolerant self-reactive B cells. Antigen receptors of the IgD isotype were expressed at normal levels on tolerant B cells, contained the heterodimeric MB1/B29 signalling component of the receptor complex and were structurally indistinguishable from IgD on nontolerant B cells. In contrast, cell surface expression of IgM receptor complexes on tolerant B cells was greatly reduced, despite normal expression of mRNA encoding the receptor components. Three-fold fewer immunoreactive mu heavy chains were detectable after a short period of biosynthetic labelling and the immunoreactive mu chains produced were paired with kappa light chains and assembled normally into intact receptor complexes containing the MB1/B29 heterodimer. Nascent IgM receptor complexes nevertheless failed to be processed into an endoglycosidase H-resistant form in the tolerant B cells and thus appeared to be selectively blocked in their transport from the endoplasmic reticulum to the medial Golgi. These findings demonstrate that intracellular trafficking of antigen receptor complexes is regulated by exposure to receptor stimuli at the cell surface causing a long-lasting decrease in surface receptor expression on tolerant B cells. Images

Bell, S E; Goodnow, C C

1994-01-01

60

Functional affinity of IgM rheumatoid factor in patients with rheumatoid arthritis and other autoimmune diseases.  

PubMed Central

The functional affinity of IgM rheumatoid factors (RF) was measured in 31 patients with rheumatoid arthritis (RA), 24 with systemic lupus erythematosus (SLE), 13 with Sjögren's syndrome (SS), and in 13 seropositive healthy individuals. The functional affinity of IgM RF from patients with RA was significantly lower than in the other clinical groups studied. In addition, there was a significant inverse correlation between functional affinity and titre of IgM RF in all the groups. These results suggest that the usual mechanisms of affinity based selective pressure (somatic diversification and antigen selection) may operate differently for autoantibodies to serum antigens such as IgG.

Rath, S; Hogben, D N; Devey, M E

1988-01-01

61

Circulating monoclonal IgM lambda cryoglobulin with collagen type I affinity in vasculitis.  

PubMed Central

A previously fit 66-years-old male primarily presented symptoms compatible with Henock-Schönlein's purpura, from which he seemingly recovered. Shortly hereafter he relapsed with an IgM lambda essential monoclonal cryoglobulinemia type I, presenting a systemic, necrotizing vasculitis, with low titer of circulating immune complexes and complement consumption. Glucocorticoid treatment and plasmapheresis did not prevent an ultimately lethal course. An indirect immunoperoxidase technique showed that the cryo-IgM bound to the interstitial connective tissue corresponding to the localization of collagen type I. In addition it bound to affinity purified human procollagen type I. These results indicate, that the IgM lambda of the proband was an autoantibody with collagen type I specificity. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5

Clemmensen, I; Jensen, B A; H?lund, B; Kappelgaard, E; Neilsen, H

1986-01-01

62

O -acetyl sialic acid specific IgM in childhood acute lymphoblastic leukaemia  

Microsoft Academic Search

Initial studies have revealed an enhanced surface expression of O-acetylated sialoglycoconjugates (O-AcSGs) on lymphoblasts concomitant with high titres of IgG in childhood Acute Lymphoblastic Leukaemia (ALL) (Mandal C, Chatterjee M, Sinha D, Br J Haematol 110, 801–12, 2000). In our efforts to identify disease specific markers for ALL, we have affinity-purified IgM directed against O-AcSGs that reacts with three disease

Santanu Pal; Mitali Chatterjee; Dilip Kumar Bhattacharya; Santu Bandhyopadhyay; Chhabinath Mandal; Chitra Mandal

2001-01-01

63

Synthesis of IgM, IgG and IgA in rheumatoid arthritis  

Microsoft Academic Search

We studied the production of immunoglobulins by lymphocytes separated from the blood of 15 rheumatoid arthritis (RA) patients, of 12 patients suffering from other connective tissue diseases (CTD), and of 18 healthy controls. The production of IgM, IgG and IgA in pokeweed-mitogen-stimulated cultures was measured by counting the number of plaque-forming cells (PFC) and by determining the concentration of secreted

K Poikonen; M Oka; T Möttönen; I Jokinen; H Arvilommi

1982-01-01

64

Serum Free Light Chain Only Myeloma with Cytoplasmic IgM  

PubMed Central

In the past decade, the serum free light chain (FLC) immunoassays have become widely available enabling greater sensitivity in the diagnosis and management of monoclonal light chain diseases. Here, we describe a rare case of serum free light chain only myeloma with cytoplasmic IgM. A 75-year-old woman presented with a progressively worsening lumbosacral pain. FDG PET/CT images showed increased FDG uptake in the sacral mass, vertebral bodies, and ribs. Laboratory data found hypogammaglobulinemia and the bone marrow aspirate revealed only 2.2% of plasma cells. The serum and urine protein electrophoresis did not detect a monoclonal band. However, the serum FLC immunoassays reported an abnormal kappa/lambda ratio (0.001) indicating the presence of monoclonal lambda FLC. The sacral tumor biopsy revealed proliferation of plasma cells and immunohistochemical staining showed that the plasma cells were positive for CD138, IgM, and lambda light chain but negative for CD20. This case may have previously been described as a nonsecretory IgM myeloma but recently would be identified as free light chain only myeloma. The immunohistochemical and genetic features of the clonal plasma cells in free light chain only myeloma need to be further investigated to better understand the relevance and incidence of this myeloma type.

Ebana, Hideaki; Nakamura, Ken-ichi; Nozawa, Yoshihiro; Seki, Ritsuko

2014-01-01

65

A patterned recombinant human IgM guides neurite outgrowth of CNS neurons  

PubMed Central

Matrix molecules convey biochemical and physical guiding signals to neurons in the central nervous system (CNS) and shape the trajectory of neuronal fibers that constitute neural networks. We have developed recombinant human IgMs that bind to epitopes on neural cells, with the aim of treating neurological diseases. Here we test the hypothesis that recombinant human IgMs (rHIgM) can guide neurite outgrowth of CNS neurons. Microcontact printing was employed to pattern rHIgM12 and rHIgM22, antibodies that were bioengineered to have variable regions capable of binding to neurons or oligodendrocytes, respectively. rHIgM12 promoted neuronal attachment and guided outgrowth of neurites from hippocampal neurons. Processes from spinal neurons followed grid patterns of rHIgM12 and formed a physical network. Comparison between rHIgM12 and rHIgM22 suggested the biochemistry that facilitates anchoring the neuronal surfaces is a prerequisite for the function of IgM, and spatial properties cooperate in guiding the assembly of neuronal networks.

Xu, Xiaohua; Wittenberg, Nathan J.; Jordan, Luke R.; Kumar, Shailabh; Watzlawik, Jens O.; Warrington, Arthur E.; Oh, Sang-Hyun; Rodriguez, Moses

2013-01-01

66

Comparative biochemical characterization of a human IgM produced in both ascites and in vitro cell culture  

SciTech Connect

Researchers have conducted a comparative analysis of a monoclonal human IgM obtained from cells cultured in nude-mouse ascites and from the same cells cultured in a bioreactor. We studied the glycosylation of the IgMs using lectin blotting and high-pH anion-exchange chromatography with pulsed amperometric detection (HPAE-PAD), and we also developed reverse phase liquid chromatography (RPLC) peptide maps of the IgM samples. The HPAE-PAD data indicate that the samples differ in both the type and distribution of oligosaccharides present on the IgMs. In addition, the proteins differ in their solubility behavior and in their RPLC peptide maps. We conclude that the method of cell culture of capable of significantly altering the characteristics of the glycoprotein product. 27 refs., 5 figs.

Monica, T.J.; Goochee, C.F.; Maiorella, B.L. (Stanford Univ., CA (United States))

1993-04-01

67

[Chronic sensory ataxic neuropathy associated with IgM antibody against b-series gangliosides including GD1b].  

PubMed

We described a 62-year-old man with a 10 years history of chronic sensory ataxic neuropathy. His laboratory investigations revealed elevated serum IgM with IgM kappa paraproteinemia, IgM antibody against b-series gangliosides including GD3, GD2, GD1b, GT1b, GQ1b, GQ1b alpha, and high titer of cold agglutinin. The clinical and serological features in our patient were compatible with the diagnosis of CANOMAD (chronic ataxic neuropathy with ophthalmoplegia, M-protein, agglutination, and disialosyl antibodies), proposed by Willison et al. IgM antibody against b-series gangliosides including GD1b appeared to play an essential role in developing autoimmune sensory ataxic neuropathy. PMID:10614164

Susuki, K; Koga, M; Yuki, N; Johkura, K; Kuroiwa, Y

1999-09-01

68

Specific Recognition of Protein Carboxy-Terminal Sequences by Natural IgM Antibodies in Normal Serum  

Microsoft Academic Search

Our previous study indicated that normal serum contains complement-fixing natural IgM antibodies reacting with a large variety of randomly generated protein carboxy-termini. Here we show that the “carboxy-terminal” IgM (C-IgM) antibodies specifically react with short peptide sequences located immediately at the protein carboxy-terminus. The specificity of C-IgM–peptide interactions is tentatively defined by three to four amino acid residues. All carboxy-terminal

Alex V. Sokoloff; Ildiko Bock; Guofeng Zhang; Sara Hoffman; James Dama; James J. Ludtke; Anne M. Cooke; Jon A. Wolff

2001-01-01

69

An anti-mumps IgM antibody level in the serum of idiopathic sudden sensorineural hearing loss  

Microsoft Academic Search

Purpose: measurement of anti-IgM antibody for mumps enables us to diagnose silent mumps infection. From the viewpoint of prophylactic medicine, we examined the incidence of silent mumps infection in idiopathic sudden sensorineural hearing loss (ISSNHL) by measurement of anti-mumps IgM antibody. Materials and methods: serum level of anti-mumps IgM antibody was evaluated by EIA method in 69 ISSNHL cases. Results:

Satoshi Fukuda; Eiji Chida; Tsutomu Kuroda; Masaaki Kashiwamura; Yukio Inuyama

2001-01-01

70

Double diffusion and ELISA for the detection of IgG and IgM antibodies against Micropolyspora faeni.  

PubMed

Fifty-eight sera of subjects with suspected farmer's lung disease (FLD) were tested by double immunodiffusion and ELISA for the detection of IgG and IgM antibodies against Micropolyspora faeni. By comparing the two methods, we obtained a high concordance of results for IgG, but not so high for IgM. ELISA is therefore a sensitive and specific test in determining antibody concentration. PMID:3122606

Fasani, F; Bossi, A; Caramia, V

1987-12-01

71

Chronic ataxic neuropathies associated with anti-GD1b IgM antibodies: response to IVIg therapy  

Microsoft Academic Search

Objective:To determine the responses to treatment of patients with chronic sensory ataxic neuropathy associated with anti-GD1b IgM antibodies.Methods:Patients with chronic sensory ataxic neuropathy associated with anti-GD1b IgM antibodies followed in our department for at least 12 months between 2001 and 2008 were identified and studied retrospectively. Patients were tested at regular intervals using the INCAT disability score. Patients whose disability

S Attarian; J Boucraut; A M Hubert; D Uzenot; E Delmont; A Verschueren; J Franques; J P Azulay; J Pouget

2010-01-01

72

The acquisition of narrow binding specificity by polyspecific natural IgM antibodies in a semi-physiological environment.  

PubMed

Natural IgM antibodies (Abs) play an important role in clearing pathogens, enhancing immune responses, and preventing autoimmunity. However, the molecular mechanisms that mediate the functions of natural IgM Abs are understood only to a limited degree. This shortcoming is largely due to the fact that isolated natural IgM Abs are commonly polyspecific and recognize a variety of antigens (Ags) with no apparent structural homology. It is generally believed that polyspecificity is an inherent property of natural Abs. However, there is increasing evidence that polyspecificity may be induced by mild denaturing conditions. In this study, we compared the specificity of three polyspecific IgM Abs in conventional buffers and undiluted sera deficient in immunoglobulins. All three Abs lost their polyspecificity in serum. They no longer reacted with conventional screening Ags, including hapten-BSA conjugates, ssDNA, thyroglobulin and myosin, but fully retained their reactivity with cognate peptide Ags selected from a T7 phage library. The acquisition of narrow specificity by polyspecific IgM in serum was also observed with muscle tissue sections used as a source of endogenous Ags. The loss of polyspecificity by different Abs was apparently dependent on the presence of different serum constituents. The results of this study suggest that the seemingly inherent polyspecificity of many natural IgM Abs may be largely an in vitro phenomenon related to the lack of normal serum components in the medium. Potential mechanisms underlying the loss of polyreactivity are discussed. PMID:17983656

Chu, Qili; Ludtke, James J; Subbotin, Vladimir M; Blockhin, Andrey; Sokoloff, Alex V

2008-03-01

73

The acquisition of narrow binding specificity by polyspecific natural IgM antibodies in a semi-physiological environment  

PubMed Central

Natural IgM antibodies (Abs) play an important role in clearing pathogens, enhancing immune responses, and preventing autoimmunity. However, the molecular mechanisms that mediate the functions of natural IgM Abs are understood only to a limited degree. This shortcoming is largely due to the fact that isolated natural IgM Abs are commonly polyspecific and recognize a variety of antigens (Ags) with no apparent structural homology. It is generally believed that polyspecificity is an inherent property of natural Abs. However, there is increasing evidence that polyspecificity may be induced by mild denaturing conditions. In this study, we compared the specificity of three polyspecific IgM Abs in conventional buffers and undiluted sera deficient in immunoglobulins. All three Abs lost their polyspecificity in serum. They no longer reacted with conventional screening Ags, including hapten-BSA conjugates, ssDNA, thyroglobulin and myosin, but fully retained their reactivity with cognate peptide Ags selected from a T7 phage library. The acquisition of narrow specificity by polyspecific IgM in serum was also observed with muscle tissue sections used as a source of endogenous Ags. The loss of polyspecificity by different Abs was apparently dependent on the presence of different serum constituents. The results of this study suggest that the seemingly inherent polyspecificity of many natural IgM Abs may be largely an in vitro phenomenon related to the lack of normal serum components in the medium. Potential mechanisms underlying the loss of polyreactivity are discussed.

Chu, Qili; Ludtke, James J.; Subbotin, Vladimir M.; Blockhin, Andrey; Sokoloff, Alex V.

2008-01-01

74

Performance characteristics of the Euroimmun enzyme-linked immunosorbent assay kits for Brucella IgG and IgM.  

PubMed

Brucella IgG and IgM ELISA kits manufactured by Euroimmun (Lubeck, Germany) were evaluated in a reference laboratory setting. Intraassay coefficient of variation (CV) values were < or =10% for positive sera and < or =12% for negative sera; interassay CVs were < or =12% for positive sera and < or =20% for negative sera. The tube agglutination test (TAT) was performed on 51 sera exhibiting various ELISA reactivity profiles. All 18 sera negative for both IgG and IgM by ELISA were TAT negative (titer <1:80), whereas 31 (94%) of 33 sera positive for IgG and/or IgM were TAT positive; the 2 discordant sera were IgG positive IgM negative by ELISA. None of 41 sera from healthy laboratory employees were ELISA IgG positive, whereas 1 (2%) of 41 was ELISA IgM positive. Similarly, 0 of 149 potentially cross-reactive sera (containing rheumatoid factor or antibodies to selected Gram-negative bacteria) was ELISA IgG positive, whereas 4 (3%) of 149 were ELISA IgM positive. These findings demonstrate the acceptable performance of the Euroimmun ELISAs for Brucella antibodies. PMID:19748418

Prince, Harry E; Lopez, Janice; Yeh, Cindy; Tablante, Joselita; Morgan, Joseph; Kaneko, Beverly; Duffey, Paul

2009-10-01

75

Cloning, expression and evaluation of diagnostic potential of recombinant capsid protein based IgM ELISA for chikungunya virus.  

PubMed

The resurgence of chikungunya virus in the form of unprecedented explosive epidemic with unusual clinical severity after a gap of 32 years is a point of major public health concern. Definitive diagnosis is critical in differentiating the disease, especially in dengue endemic areas. The immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA) is widely used for diagnosis of chikungunya infection. However IgM ELISA based on whole virus antigen is associated with biohazard risk. The present study describes the development and evaluation of recombinant capsid protein based indirect IgM antibody capture micro plate enzyme linked immunosorbent assay (ELISA) for rapid and accurate diagnosis of chikungunya infection. The gene coding for capsid protein was cloned in frame with GST tag in pET41a+ vector and expressed in E. coli followed by purification with affinity chromatography. The comparative evaluation of in-house chikungunya IgM ELISA vis-a-vis commercially available SD ELISA kit with 90 chikungunya suspected acute phase human patient serum samples revealed 97% accordance. The overall sensitivity and specificity of the reported capsid protein based IgM ELISA was 100% and 95% respectively with 96% PPV and 100% NPV. These findings clearly demonstrated the usefulness of the recombinant capsid protein based CHIKV IgM ELISA for reliable clinical diagnosis of CHIKV infection in human patient. PMID:24681089

Priya, Raj; Khan, Mohsin; Rao, M Kameswara; Parida, Manmohan

2014-07-01

76

Murine Visceral Leishmaniasis: IgM and Polyclonal B-Cell Activation Lead to Disease Exacerbation  

PubMed Central

In visceral leishmaniasis, the draining lymph node (DLN) is the initial site for colonization and establishment of infection after intradermal transmission by the sand fly vector; however, little is known about the developing immune response within this site. Using an intradermal infection model, which allows for parasite visceralization, we have examined the ongoing immune responses in the DLN of BALB/c mice infected with L. infantum. Although not unexpected, at early times post-infection there is a marked B cell expansion in the DLN, which persists throughout infection. However, the characteristics of this response were of interest; as early as day 7 post-infection, polyclonal antibodies (TNP, OVA, chromatin) were observed and the levels appeared comparable to the specific anti-leishmania response. Although B-cell-deficient JHD BALB/c mice are relatively resistant to infection, neither B-cell-derived IL-10 nor B-cell antigen presentation appear to be primarily responsible for the elevated parasitemia. However, passive transfer and reconstitution of JHD BALB/c with secretory immunoglobulins, (IgM or IgG; specific or non-specific immune complexes) results in increased susceptibility to L. infantum infection. Further, JHD BALB/c mice transgenetically reconstituted to secrete IgM demonstrated exacerbated disease in comparison to wild type BALB/c mice as early as 2 days post-infection. Evidence suggests that complement activation (generation of C5a) and signaling via the C5aR (CD88) is related to the disease exacerbation caused by IgM rather than cytokine levels (IL-10 or IFN-?). Overall these studies indicate that polyclonal B cell activation, which is known to be associated with human visceral leishmaniasis, is an early and intrinsic characteristic of disease and may represent a target for therapeutic intervention.

Deak, Eszter; Jayakumar, Asha; Wing Cho, Ka; Goldsmith-Pestana, Karen; Dondji, Blaise; Lambris, John D.; McMahon-Pratt, Diane

2010-01-01

77

Production and characterization of monoclonal antibodies to IgM of Pacific herring (Clupea pallasii).  

PubMed

Pacific herring (Clupea pallasii) have a central role in the North Pacific ecosystem as a forage fish species and are natural reservoirs of several important finfish pathogens, including Viral hemorrhagic septicemia virus (VHSV). Here, we report the identification of the gene encoding the immunoglobulin mu (IgM) heavy chain, as well as the development and characterization of monoclonal antibodies (MAbs) that specifically react with Pacific herring IgM. Pacific herring immunoglobulin was purified and consisted of heavy and light chains of approximately 80 and 25 kDa. Three hybridoma clones were initially identified by ELISA as reactive with purified immunoglobulin but only one clone was able to detect an 80 kDa protein in Pacific and Atlantic herring (Clupea harengus) whole plasma by denaturing western blot. However, all three MAbs were able to precipitate an 80 kDa protein from Pacific herring and LCMS sequencing of peptide fragments derived from this protein matched the predicted amino acid sequence of the cloned, heavy chain gene. In addition, two of the MAbs stained cells within the putative lymphocyte gates for the spleen, anterior kidney and posterior kidney but were not reactive for myeloid/granulocyte gates, which is consistent with these MAbs reacting with surface IgM? B-cells. To our knowledge, this is the first report of IgM-related gene sequences and anti-IgM monoclonal antibodies from any member of the family Clupeidae. The antibodies produced in this study are critical for achieving our long-term goal of conducting serological surveillance to assess pathogen exposure in natural populations of Pacific herring. PMID:22771742

Purcell, Maureen K; Bromage, Erin S; Silva, Jessica; Hansen, John D; Badil, Samantha M; Woodson, James C; Hershberger, Paul K

2012-09-01

78

Early Detection of NSCLC with scFv Selected against IgM Autoantibody  

PubMed Central

Survival of patients with lung cancer could be significantly prolonged should the disease be diagnosed early. Growing evidence indicates that the immune response in the form of autoantibodies to developing cancer is present before clinical presentation. We used a phage-displayed antibody library to select for recombinant scFvs that specifically bind to lung cancer-associated IgM autoantibodies. We selected for scFv recombinant antibodies reactive with circulating IgM autoantibodies found in the serum of patients with early stage lung adenocarcinoma but not matched controls. Discriminatory performance of 6 selected scFvs was validated in an independent set of serum from stage 1 adenocarcinoma and matching control groups using two independent novel methods developed for this application. The panel of 6 selected scFvs predicted cancer based on seroreactivity value with sensitivity of 0.8 and specificity of 0.87. Receiver Operative Characteristic curve (ROC) for combined 6 scFv has an AUC of 0.88 (95%CI, 0.76–1.0) as determined by fluorometric microvolume assay technology (FMAT) The ROC curve generated using a homogeneous bridging Mesa Scale Discovery (MSD) assay had an AUC of 0.72 (95% CI, 0.59–0.85). The panel of all 6 antibodies demonstrated better discriminative power than any single scFv alone. The scFv panel also demonstrated the association between a high score - based on seroreactivity - with poor survival. Selected scFvs were able to recognize lung cancer associated IgM autoantibodies in patient serum as early as 21 months before the clinical presentation of disease. The panel of antibodies discovered represents a potential unique non-invasive molecular tool to detect an immune response specific to lung adenocarcinoma at an early stage of disease.

Pedchenko, Tetyana; Mernaugh, Ray; Parekh, Dipti; Li, Ming; Massion, Pierre P.

2013-01-01

79

Production and characterization of monoclonal antibodies to IgM of Pacific herring (Clupea pallasii)  

USGS Publications Warehouse

Pacific herring (Clupea pallasii) have a central role in the North Pacific ecosystem as a forage fish species and are natural reservoirs of several important finfish pathogens, including Viral hemorrhagic septicemia virus (VHSV). Here, we report the identification of the gene encoding the immunoglobulin mu (IgM) heavy chain, as well as the development and characterization of monoclonal antibodies (MAbs) that specifically react with Pacific herring IgM. Pacific herring immunoglobulin was purified and consisted of heavy and light chains of approximately 80 and 25 kDa. Three hybridoma clones were initially identified by ELISA as reactive with purified immunoglobulin but only one clone was able to detect an 80 kDa protein in Pacific and Atlantic herring (Clupea harengus) whole plasma by denaturing western blot. However, all three MAbs were able to precipitate an 80 kDa protein from Pacific herring and LCMS sequencing of peptide fragments derived from this protein matched the predicted amino acid sequence of the cloned, heavy chain gene. In addition, two of the MAbs stained cells within the putative lymphocyte gates for the spleen, anterior kidney and posterior kidney but were not reactive for myeloid/granulocyte gates, which is consistent with these MAbs reacting with surface IgM+ B-cells. To our knowledge, this is the first report of IgM-related gene sequences and anti-IgM monoclonal antibodies from any member of the family Clupeidae. The antibodies produced in this study are critical for achieving our long-term goal of conducting serological surveillance to assess pathogen exposure in natural populations of Pacific herring.

Purcell, Maureen K.; Bromage, Erin S.; Silva, Jessica; Hansen, John D.; Badil, Samantha M.; Woodson, James C.; Hershberger, Paul K.

2012-01-01

80

Rituximab therapy in chronic inflammatory demyelinating polyradiculoneuropathy with anti-SGPG IgM antibody.  

PubMed

We report a patient with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who showed high titers of anti-sulfated glucuronyl paragloboside (SGPG) IgM antibody without M-protein in serum. The patient was resistant to corticosteroids and immunosuppressants, but after administration of rituximab, clinical symptoms improved and the patient remained in a stable state for approximately 10 months. Rituximab may be a potent therapeutic option for refractory cases of CIDP irrespective of detectable M-protein in either serum or urine. PMID:16814550

Gono, Takahisa; Matsuda, Masayuki; Shimojima, Yasuhiro; Ishii, Wataru; Yamamoto, Kanji; Morita, Hiroshi; Hashimoto, Takao; Susuki, Keiichiro; Yuki, Nobuhiro; Ikeda, Shu-ichi

2006-07-01

81

IgG, IgA and IgM by formylated rocket immunoelectrophoresis.  

PubMed

Formylated rocket electrophoresis has been investigated as a means of measuring the serum immunoglobulins IgG, IgA, and IgM. This procedure is simpler to carry out than carbamylation. Comparison of formylated rocket results with those from the automated immunoprecipitin (A.I.P.) system and single radial immunodiffusion (S.R.D.) gives correlation coefficients of 0.92 to 0.98 and reproducibility comparable with the AI.P. system and better than S.R.D. The procedure is recommended for use in laboratories when the number of requests for immunoglobulins does not warrant a specific protein analyser. PMID:15637933

Slater, L

1975-01-01

82

Destructive arthritis in a patient with chikungunya virus infection with persistent specific IgM antibodies  

PubMed Central

Background Chikungunya fever is an emerging arboviral disease characterized by an algo-eruptive syndrome, inflammatory polyarthralgias, or tenosynovitis that can last for months to years. Up to now, the pathophysiology of the chronic stage is poorly understood. Case presentation We report the first case of CHIKV infection with chronic associated rheumatism in a patient who developed progressive erosive arthritis with expression of inflammatory mediators and persistence of specific IgM antibodies over 24 months following infection. Conclusions Understanding the specific features of chikungunya virus as well as how the virus interacts with its host are essential for the prevention, treatment or cure of chikungunya disease.

2009-01-01

83

IgM in a Human Neuropathy Related to Paraproteinemia Binds to a Carbohydrate Determinant in the Myelin-Associated Glycoprotein and to a Ganglioside  

Microsoft Academic Search

The IgM in three patients with paraproteinemia and peripheral neuropathy was shown to bind to human myelin-associated glycoprotein (MAG) that had been purified to homogeneity by gel filtration on Sepharose CL-6B. The antigenic determinant reacting with the IgM from all three patients was in the carbohydrate part of the MAG molecule. In addition, the IgM from the same three patients

Amjad A. Ilyas; Richard H. Quarles; Tracy D. Macintosh; Michael J. Dobersen; Bruce D. Trapp; Marinos C. Dalakas; Roscoe O. Brady

1984-01-01

84

Lansoprazole increases serum IgG and IgM in H. pylori-infected patients.  

PubMed

Proton-pump inhibitors have been reported to influence the human immune system, we therefore evaluated the effect of lansoprazole, a proton-pump inhibitor, on humoral immunity. Patients with gastric ulcer received lansoprazole 30 mg/day for 8 weeks, and serum immunoglobulins were evaluated before and upon completion of the treatment. There were 79 patients with gastric ulcer; 51 were H. pylori-infected and 28 were H. pylori-uninfected. Eighteen patients positive for H. pylori were receiving at least one non-steroidal anti-inflammatory drug, and 12 patients negative for H. pylori received one non-steroidal anti-inflammatory drug. H. pylori-infected patients showed significant increases in serum immunoglobulins G and M 8 weeks after the start of lansoprazole treatment (P<0.001 for IgG and P<0.01 for IgM), but uninfected patients did not. Even when H. pylori-infected patients receiving a non-steroidal anti-inflammatory drug or low-dose aspirin were analyzed separately, these increases were seen (P<0.001 for IgG and P<0.005 for IgM). Lansoprazole elevated serum levels of immunoglobulins G and M in gastric ulcer patients with H. pylori infection, particularly in those receiving non-steroidal anti-inflammatory drugs. Deducing from these observations, lansoprazole might alter the Th1 shift in the immune response induced by H. pylori infection. PMID:17346441

Matsukawa, Y; Kurosaka, H; Kato, K; Hayashi, I; Minekawa, K; Arakawa, Y; Sawada, S

2007-01-01

85

Cold-induced precipitation of a monoclonal IgM: a negative activation enthalpy reaction.  

PubMed

Cold-induced precipitation of a monoclonal IgM cryoglobulin isolated from a patient with Waldenström's macroglobulinemia was observed to have a negative activation enthalpy. The rate of the reaction increased, as the temperature decreased. Differential scanning calorimetry of the monoclonal IgM showed precipitation as an inverted peak during a downward temperature scan. The transition temperature was between 14 and 15 °C and was possibly concentration dependent. At temperatures below the transition the precipitation was best described by second-order kinetics. The difference in change in enthalpy between precipitation and disassociation suggests that cold-induced precipitation had a fast precipitation stage followed by a slower consolidation reaction. Negligible curvature of the Eyring plot suggested the precipitation reaction was dominated by van der Waal forces and hydrogen bonding. Conversely, during an upward temperature scan, disassociation was observed as a positive enthalpy peak. This reaction had two stages, a reaction undoing consolidation followed by heat-induced disassociation that had first-order kinetics. PMID:23240622

Meliga, Stefano C; Farrugia, William; Ramsland, Paul A; Falconer, Robert J

2013-01-17

86

Gravity changes during animal development affect IgM heavy-chain transcription and probably lymphopoiesis.  

PubMed

Our previous research demonstrated that spaceflight conditions affect antibody production in response to an antigenic stimulation in adult amphibians. Here, we investigated whether antibody synthesis is affected when animal development occurs onboard a space station. To answer this question, embryos of the Iberian ribbed newt, Pleurodeles waltl, were sent to the International Space Station (ISS) before the initiation of immunoglobulin heavy-chain expression. Thus, antibody synthesis began in space. On landing, we determined the effects of spaceflight on P. waltl development and IgM heavy-chain transcription. Results were compared with those obtained using embryos that developed on Earth. We find that IgM heavy-chain transcription is doubled at landing and that spaceflight does not affect P. waltl development and does not induce inflammation. We also recreated the environmental modifications encountered by the embryos during their development onboard the ISS. This strategy allowed us to demonstrate that gravity change is the factor responsible for antibody heavy-chain transcription modifications that are associated with NF-?B mRNA level variations. Taken together, and given that the larvae were not immunized, these data suggest a modification of lymphopoiesis when gravity changes occur during ontogeny. PMID:22993194

Huin-Schohn, Cécile; Guéguinou, Nathan; Schenten, Véronique; Bascove, Matthieu; Koch, Guillemette Gauquelin; Baatout, Sarah; Tschirhart, Eric; Frippiat, Jean-Pol

2013-01-01

87

Enteroviral meningoencephalitis as a complication of X-linked hyper IgM syndrome.  

PubMed

We describe 5 children from 2 families with mutations in the CD40 ligand (CD40L) gene leading to absent expression of CD40L on activated CD4 cells. All subjects presented with interstitial pneumonia with low serum IgG and normal serum IgM. One child had normal and one child had elevated serum IgA. Four had confirmed Pneumocystis carinii pneumonia. In spite of intravenous immunoglobulin treatment yielding therapeutic serum immunoglobulin levels, 3 children had enteroviral encephalitis. When assessed by flow cytometry, the 3 surviving affected male children had absent CD40L expression on activated CD4(+) T cells. The affected children from both families were shown to have the same single nucleotide insertion (codon 131) resulting in frameshift and early termination within exon 4 (extracellular domain). This observation demonstrates that persistent enteroviral infection is not only observed in X-linked agammaglobulinemia but may also occur in patients with X-linked hyper IgM syndrome. PMID:10228294

Cunningham, C K; Bonville, C A; Ochs, H D; Seyama, K; John, P A; Rotbart, H A; Weiner, L B

1999-05-01

88

Retrospective analysis of dengue specific IgM reactive serum samples  

PubMed Central

Objective To conduct a retrospective analysis of dengue cases in Kolkata, on the basis of presence of anti-dengue IgM in their sera and presence or absence of anti-dengue IgG and dengue specific Non structural 1 (NS1) antigen in each of the serum sample. Methods Sample was tested quantitatively employing ELISA technique, using Biorad test kits, with a view to get a more comprehensive picture of dengue in an urban endemic area and also to evaluate individual cases. Results This reconstructed study revealed that of those 91 dengue cases, 70.3% (64) and 29.7% (27) were suffering from secondary and primary dengue respectively, showing that number of secondary dengue cases were much more than that of primary dengue cases with a possibility of emergence of DHF. A small proportion of cases 18.7% (17) were reactive for NS1. The duration of fever in NS1 antigen positive cases varied between 5 and 7 days. Of 17 NS1 reactive cases, 10 (10.9%) and 7 (7.7%) were suffering from secondary and primary dengue respectively. Conclusions Early detection of primary and secondary dengue cases would be facilitated by utilizing all three parameters (NS1 antigen, anti-dengue IgM and IgG) helping to evaluate, monitor and treat a dengue case effectively.

Bhattacharya, Nemai; Bandyopadhyay, Bhaswati; Bhattacharjee, Indranil; Mukherjee, Hiranmoy; Talukdar, Srabani; Mondal, Ruby; Pramanick, Netai; Chandra, Goutam; Hati, Amiya K.

2013-01-01

89

Competitive adsorption-desorption of IgM monomers-dimers on silica and modified silica surfaces.  

PubMed

Understanding competitive adsorption-desorption of proteins onto surfaces is an important area of research in food processing and biomedical engineering. Here, we demonstrate, how electrospray-differential mobility analysis that has been traditionally used for characterizing bionanoparticles, can be used for quantifying complex competitive adsorption-desorption of oligomeric proteins or multiprotein systems using monomers and dimers of IgM as a model example onto silica and modified silica surfaces. Using ES-DMA, we show that IgM dimers show a preference to stay adsorbed to different surfaces although monomers adsorb more easily and desorption rates of monomers and dimers of IgM are surface-type-dependent and are not significantly affected by shear. We anticipate that this demonstration will make ES-DMA a popular "label-free" method for studying multicomponent multi-oligomeric protein adsorption to different surfaces in the future. PMID:23628202

Guha, Suvajyoti; Wayment, Joshua; Rastogi, Vinayak; Li, Mingdong; Tarlov, Michael J; Zachariah, Michael R

2013-07-15

90

The Majority of Human Memory B Cells Recognizing RhD and Tetanus Resides in IgM+ B Cells  

PubMed Central

B cell memory to T cell–dependent (TD) Ags are considered to largely reside in class-switched CD27+ cells. However, we previously observed that anti-RhD (D) Igs cloned from two donors, hyperimmunized with D+ erythrocytes, were predominantly of the IgM isotype. We therefore analyzed in this study the phenotype and frequency of D- and tetanus toxoid–specific B cells by culturing B cells in limiting dilution upon irradiated CD40L-expressing EL4.B5 cells and testing the culture supernatant. Most Ag-specific B cells for both TD Ags were found to reside in the IgM-expressing B cells, including CD27? B cells, in both hyperimmunized donors and nonhyperimmunized volunteers. Only shortly after immunization a sharp increase in Ag-specific CD27+IgG+ B cells was observed. Next, B cells were enriched with D+ erythrocyte ghosts and sorted as single cells. Sequencing of IGHV, IGLV, IGKV, and BCL6 genes from these D-specific B cell clones demonstrated that both CD27?IgM+ and CD27+IgM+ B cells harbored somatic mutations, documenting their Ag-selected nature. Furthermore, sequencing revealed a clonal relationship between the CD27?IgM+, CD27+IgM+, and CD27+IgG+ B cell subsets. These data strongly support the recently described multiple layers of memory B cells to TD Ags in mice, where IgM+ B cells represent a memory reservoir which can re-enter the germinal center and ensure replenishment of class-switched memory CD27+ B cells from Ag-experienced precursors.

Della Valle, Luciana; Dohmen, Serge E.; Verhagen, Onno J. H. M.; Berkowska, Magdalena A.; Vidarsson, Gestur

2014-01-01

91

Anti-?-glucose-based glycan IgM antibodies predict relapse activity in multiple sclerosis after the first neurological event  

PubMed Central

Background There is no specific serum-based biomarker for the diagnosis or prognosis of relapsing-remitting multiple sclerosis (RRMS). Objective We investigated whether levels of IgM antibodies to Glc(?1,4)Glc(?) (GAGA4) or to a panel of four glucose-based glycans could differentiate MS from other neurological diseases (OND) or predict risk of early relapse following first presentation (FP) of RRMS. Methods Retrospective analysis of 440 sera samples of three cohorts: A) FP-RRMS (n = 44), OND (n = 44); B) FP-RRMS (n = 167), OND (n = 85); and C) FP (n = 100). Anti-GAGA4 IgM levels were measured by enzyme immunoassay in cohort-A and cohort-B. Cohort-C IgM antibodies to glucosebased glycan panel were measured by immunofluorescence. Results FP-RRMS had higher levels of anti-GAGA4 IgM than OND patients (cohort-A, P = 0.01; cohort-B, P = 0.0001). Sensitivity and specificity were 27% and 97% for cohort-A; and 26% and 90% for cohort-B, respectively. In cohort-C, 58 patients experienced early relapse (<24 months), 31 had late relapse (?24 months), and 11 did not experience second attack during follow-up. Kaplan– Meier curves demonstrated decrease in time to next relapse for patients positive for the antibody panel (P = 0.02, log rank). Conclusions Serum anti-GAGA4 IgM discerns FP-RRMS patients from OND patients. Higher levels of serum anti-?-glucose IgM in FP patients predict imminent early relapse.

Freedman, MS; Laks, J; Dotan, N; Altstock, RT; Dukler, A; Sindic, CJM

2009-01-01

92

Enzyme immunoassay for detection of immunoglobulin M (IgM) and IgG antibodies to Mycoplasma pneumoniae.  

PubMed Central

An enzyme immunoassay (EIA) for detection of immunoglobulin M (IgM) and IgG antibodies to Mycoplasma pneumoniae was developed. The EIA was evaluated on the basis of results in the M. pneumoniae complement fixation (MPCF) test and the cold agglutinin test. Serum samples from 430 patients with respiratory infections of known or unknown etiology, from 91 healthy children and adults and from 20 patients with rheumatoid factor, were investigated. By the criteria chosen for positive diagnostic EIA values, we found that the combined measurement of specific IgM and IgG gave a specificity of 99.7% and a sensitivity of 97.8%. If only IgM antibodies were measured, the specificity was 100% and the sensitivity was 88%. For IgG alone the specificity was 99.7%, but the sensitivity was only 46% because of the high EIA cutoff value chosen for IgG. We found no false positives among serum samples from patients with non-M. pneumoniae respiratory infection of known etiology, and there were no false IgM positives due to rheumatoid factor. In some cases the IgM EIA results became positive earlier in the course of illness than the MPCF titer. While children and teenagers responded predominantly with IgM antibodies, patients older than 40 years often had an IgG response only (56% of cases), probably because of reinfection. We conclude that this EIA is a good alternative to the combined MPCF and cold agglutinin tests in the diagnosis of M. pneumoniae infection.

Uldum, S A; Jensen, J S; S?ndergard-Andersen, J; Lind, K

1992-01-01

93

Generation of a novel high-affinity monoclonal antibody with conformational recognition epitope on human IgM.  

PubMed

As IgM is the first isotype of antibody which appears in blood after initial exposure to a foreign antigen in the pattern of primary response, detection, and quantification of this molecule in blood seems invaluable. To approach these goals, generation, and characterization of a highly specific mAb (monoclonal antibody) against human IgM were investigated. Human IgM immunoglobulins were used to immunize Balb/c mice. Spleen cells taken from the immunized animals were fused with SP2/O myeloma cells using PEG (polyethylene glycol, MW 1450) as fusogen. The hybridomas were cultured in HAT containing medium and supernatants from the growing hybrids were screened by enzyme-linked immunosorbent assay (ELISA) using plates coated with pure human IgM and the positive wells were then cloned at limiting dilutions. The best clone designated as MAN-1, was injected intraperitoneally to some Pristane-injected mice. Anti-IgM mAb was purified from the animals' ascitic fluid by protein-G sepharose followed by DEAE-cellulose ion exchange chromatography. MAN-1 interacted with human IgM with a very high specificity and affinity. The purity of the sample was tested by SDS-PAGE and the affinity constant was measured (K(a) = 3.5 x 10(9)M(-1). Immunoblotting and competitive ELISA were done and the results showed that the harvested antibody recognizes a conformational epitope on the mu chain of human IgM and there was no cross-reactivity with other subclasses of immunoglobulins. Furthermore, isotyping test was done and the results showed the subclass of the obtained mAb which was IgG(1)kappa. PMID:20162378

Sarikhani, Sina; Mirshahi, Manouchehr; Gharaati, Mohammad Reza; Mirshahi, Tooran

2010-11-01

94

The clinical and laboratory features of chronic sensory ataxic neuropathy with anti-disialosyl IgM antibodies.  

PubMed

The clinical and laboratory phenotype of a paraproteinaemic neuropathy syndrome termed chronic sensory ataxic neuropathy with anti-disialosyl IgM antibodies is described in a series of 18 cases. Previous single case reports have outlined some features of this syndrome. All 18 cases were defined by the presence of serum IgM antibodies which react principally with NeuAc (alpha2-8)NeuAc(alpha2-3)Gal-configured disialosyl epitopes common to many gangliosides including GDlb, GD3, GTlb and GQlb. In 17 out of 18 cases, the serum contained benign IgM paraproteins, and in four of these cases at least two IgM paraproteins were present. The IgM antibodies were also cold agglutinins in 50% of cases. The clinical picture comprised a chronic neuropathy with marked sensory ataxia and areflexia, and with relatively preserved motor function in the limbs. In addition, 16 out of 18 cases had motor weakness affecting oculomotor and bulbar muscles as fixed or as relapsing-remitting features. When present in their entirety, these clinical features have been described previously under the acronym CANOMAD: chronic ataxic neuropathy, ophthalmoplegia, IgM paraprotein, cold agglutinins and disialosyl antibodies. This distribution of clinical features is reminiscent of Miller Fisher syndrome, in which acute-phase anti-disialylated ganglioside IgG antibodies are found. Clinical electrophysiology and nerve biopsy show both demyelinating and axonal features. A partial response to intravenous immunoglobulin and other treatments is reported in some cases. PMID:11571215

Willison, H J; O'Leary, C P; Veitch, J; Blumhardt, L D; Busby, M; Donaghy, M; Fuhr, P; Ford, H; Hahn, A; Renaud, S; Katifi, H A; Ponsford, S; Reuber, M; Steck, A; Sutton, I; Schady, W; Thomas, P K; Thompson, A J; Vallat, J M; Winer, J

2001-10-01

95

Teleost Fish Mount Complex Clonal IgM and IgT Responses in Spleen upon Systemic Viral Infection  

PubMed Central

Upon infection, B-lymphocytes expressing antibodies specific for the intruding pathogen develop clonal responses triggered by pathogen recognition via the B-cell receptor. The constant region of antibodies produced by such responding clones dictates their functional properties. In teleost fish, the clonal structure of B-cell responses and the respective contribution of the three isotypes IgM, IgD and IgT remain unknown. The expression of IgM and IgT are mutually exclusive, leading to the existence of two B-cell subsets expressing either both IgM and IgD or only IgT. Here, we undertook a comprehensive analysis of the variable heavy chain (VH) domain repertoires of the IgM, IgD and IgT in spleen of homozygous isogenic rainbow trout (Onchorhynchus mykiss) before, and after challenge with a rhabdovirus, the Viral Hemorrhagic Septicemia Virus (VHSV), using CDR3-length spectratyping and pyrosequencing of immunoglobulin (Ig) transcripts. In healthy fish, we observed distinct repertoires for IgM, IgD and IgT, respectively, with a few amplified ? and ? junctions, suggesting the presence of IgM- and IgT-secreting cells in the spleen. In infected animals, we detected complex and highly diverse IgM responses involving all VH subgroups, and dominated by a few large public and private clones. A lower number of robust clonal responses involving only a few VH were detected for the mucosal IgT, indicating that both IgM+ and IgT+ spleen B cells responded to systemic infection but at different degrees. In contrast, the IgD response to the infection was faint. Although fish IgD and IgT present different structural features and evolutionary origin compared to mammalian IgD and IgA, respectively, their implication in the B-cell response evokes these mouse and human counterparts. Thus, it appears that the general properties of antibody responses were already in place in common ancestors of fish and mammals, and were globally conserved during evolution with possible functional convergences.

Castro, Rosario; Jouneau, Luc; Pham, Hang-Phuong; Bouchez, Olivier; Giudicelli, Veronique; Lefranc, Marie-Paule; Quillet, Edwige; Benmansour, Abdenour; Cazals, Frederic; Six, Adrien; Fillatreau, Simon; Sunyer, Oriol; Boudinot, Pierre

2013-01-01

96

Association between haptoglobin and IgM levels and the clinical progression of caseous lymphadenitis in sheep  

PubMed Central

Background Sheep caseous lymphadenitis (CLA), caused by Corynebacterium pseudotuberculosis (Cp), is associated with direct economic losses and presents significant zoonotic potential. Despite the importance of the disease, a satisfactory vaccine model has not been developed. Thus, this study aimed to investigate the association between haptoglobin (Hp) and IgM levels and the clinical progression of CLA in primarily infected sheep and in sheep immunized with Cp- secreted antigens adjuvanted with Quillaja saponaria saponins. These animals were kept with CLA-positive sheep to simulate natural exposure that occurs in field conditions. During the experiment, the Hp and IgM levels were monitored for 21 days, and the development of internal CLA lesions was investigated through necropsies on day182 post-immunization. Results Primarily infected sheep in Group 2 (inoculated with 2x105 Cp virulent strain) had higher Hp values between the first and ninth days post inoculation (PI) than sheep in Group 1 (control; P?IgM titers than the control group around the ninth and eleventh days PI (P?IgM levels and clinical progression: sheep with high IgM titers had 100.0% less risk of having CLA abscesses than animals with low IgM levels (Odds ratio?=?0.000, P?IgM were predictive of a lower risk of CLA lesion development. Because the immunogen used in this study induced a high production of both Hp and IgM, Q. saponaria saponin should be considered a promising candidate in vaccine formulations against sheep CLA.

2013-01-01

97

Complementary innate (anti-A-specific) IgM emerging from ontogenic O-GalNAc-transferase depletion: (Innate IgM complementarity residing in ancestral antigen completeness).  

PubMed

The murine and the human genome have global properties in common. So the murine anti-A-specific complementary IgM and related human innate isoagglutinin represent developmental, 2-mercaptoethanol-sensitive, complement-binding glycoproteins, which do not arise from any measurable environmentally-induced or auto- immune response. The murine anti-A certainly originates from a cell surface- or cell adhesion molecule, which in the course of germ cell development becomes devoid of O-GalNAc-transferase and is released into the circulation. In human sera the enzyme occurs exclusively in those of blood group A- and AB subjects, while in group O(H) an identically encoded protein lets expect an opposite function and appears in conjunction with a complementary anti-A reactive glycoprotein. Since O-glycosylations rule the carbohydrate metabolism in growth and reproduction processes, we propose that the ancestral histo-(blood)-group A molecule arises in the course of O-GalNAc-glycosylations of glycolipids and protein envelops at progenitor cell surfaces. Germ cell development postulates embryonic stem cell fidelity, which is characterised by persistent production of ?-linked O-GalNAc-glycans. They are determined by the A-allele within the human, "complete" histo (blood) group AB(O) structure that in early ontogeny is hypothesised to be synthesised independently from the final phenotype. The structure either passes "completely" through the germline, in transferase-secreting mature tissues becoming the "complete" phenotype AB, or disappears in exhaustive glycotransferase depletion from the differentiating cell surfaces and leaves behind the "incomplete" blood group O-phenotype, which has released a transferase- and O-glycan-depleted, complementary glycoprotein (IgM) into the circulation. The process implies, that in humans the different blood phenotypes evolve from a "complete" AB(O) molecular complex in a distinct enzymatic and/or complement cascade suggesting O-glycanase involvements. While the murine and human oocyte zona pellucida express identical O-glycans, the human phenotype O might be explainable by the kinetics of the murine ovarian O-GalNAc glycan synthesis and the complementary anti-A released in parallel. The maturing murine ovary may provide insight into encoding of the physiologically superior ?-linked GalNAc ancestral epitope that becomes essential in reproduction as well as in tissue renewal events. According to recent reports, O-GalNAc-transferase-determined blood group A suggests superiority in human female fertility and was called even "protective". So the minor fertility of blood-group-O females may reside in a critical timing in developmental shifting of enzyme functions affecting the formation of GalNAc-determined hormone receptors on the way to maturation. Experiments that had inserted an oocyte genome into a somatic one to generate pluripotent stem cells, might elucidate a developmental dilemma by testing oocytes from different blood group AB donors donors. Perhaps they will unmask the molecular basis of an evolutionary trend, while stem cell generation itself capitalises on the enzymatically-advantaged, lineage-maintaining (histo) blood group A-allele, which guaranties ancestral functional completeness. PMID:24290972

Arend, Peter

2014-04-01

98

Binding properties of goat IgM anti-dinitrophenyl antibodies.  

PubMed Central

Goats immunized over 2 months with low doses of 1 mg/kg of dinitrophenylated Salmonella typhimurium responded with low levels of anti-DNP antibodies restricted to the IgM class. The purified antibodies show low association constants (Ka between 10(4) of 10(5) l/M), a high degree of homogeneity (heterogeneity indices alpha between 0.7 and 0.9) and ten combining sites when tested against dinitrophenyl-lysine as ligand by equilibrium dialysis. These binding properties remained unchanged during the whole immune response. When after 9 months the animals received the same immunogen and DNP-BGG, the anti-DNP antibody response included antibodies in the IgG class. Images Figure 3

Congy, N; Mihaesco, C

1978-01-01

99

Studies on the specificities of two IgM lambda cold agglutinins  

PubMed Central

The reactions of two monoclonal IgM lambda cold agglutinins, Sch and Sher, have been studied in detail with human and animal erythrocyte antigens. Although they were unusual in having lambda and not kappa polypeptide chains, they could be assigned to the anti I and anti-Pr1 groups of cold agglutinins. The findings with serum Sher indicated that the Pr1 antigen may be more complex than previously thought. The occurrence of unexpectedly large numbers of specificities among monoclonal anti-I, anti-i and anti-Pr antibodies is discussed and it is suggested that each monoclonal antibody may recognize only a limited portion of a complex red cell antigen.

Roelcke, D.; Ebert, W.; Feizi, Ten

1974-01-01

100

Leaky IGM at z=6 or Lyman Alpha Galaxy at z=5?  

NASA Astrophysics Data System (ADS)

We propose to image the z=6.4 quasar SDSS J1148+5251 with the ACS using a narrow-band ramp filter in the Lyman Beta Gunn-Peterson absorption trough. The observations will distinguish between two possible explanations for several weak emission features seen in a long-exposure Keck spectrum. Either there are high-ionization bubbles in the IGM at z=6 that allow light from the quasar to leak through the Lyman Beta forest, or there is an intervening Lyman alpha emitting galaxy at z=5 {as suggested by C IV absorption at the same redshift.} If there is a galaxy, it may be associated with a lensing mass concentration at z=5.

White, Richard

2003-07-01

101

[Evaluation of the commercial ELISA test-systems of different formats to detect specific IgM and IgG in the measles patients sera].  

PubMed

Nine commercial kits of "captured" and "indirect" format ELISA assay for the detection of specific IgM and IgG in sera of patients with measles were compared to each other. 72 sera specimens from typical medium-severity cases from a measles outbreak (2010) were collected on the 5-6th day after the rash onset. IgM was detected with "capture" tests (Vecto-Measles IgM, Vector Best, Measles IgM capture EIA, Microimmune Ltd) close to 100% of cases, irrespectively to the age and the initial vaccination status of the patients. The IgM result was negative in 23.6% by average while investigating using "indirect" format tests (Enzygnost Anti-Measles Virusll/IgM, Siemens; Anti-Measles Viruses ELISA (IgM), Eurominimum, Virion-Serion IgM (GmbH). These cases were in adults, the majority of which had 1-2 vaccinations in the past. The analysis of the presented data shows high correlation connection between the tests used and high confidence level for OD IgM and IgG of the sera of the patients with the primary and secondary immune response. PMID:24640171

Mamaeva, T A; Naumova, M A; Zheleznova, N V; Lipskaia, G Iu; Mulders, M; Featherstone, D A

2013-01-01

102

A clinical and neurobiological case of IgM NMDA receptor antibody associated encephalitis mimicking bipolar disorder.  

PubMed

Autoimmune encephalitis associated with IgG antibodies to the N-methyl-d-aspartic acid receptor subunit NR1 (NMDAR) presents with neurological symptoms, such as seizures, and especially psychiatric symptoms, such as hallucinations, psychosis, agitation and anxiety. To date, however, the pathological relevance of IgM NMDAR antibodies remains elusive. Here, we describe clinical, neuroradiological and neurobiological findings of a 28-year-old male presenting with IgM NMDAR antibodies coincident with autoimmune encephalitis characterized by symptoms of bipolar disorder. After repeated steroid treatment, cognitive and psychiatric abnormalities improved and no NMDAR antibody was detectable. Using primary neuronal cultures, we demonstrate that patient's serum containing IgM NMDAR antibodies reduced the detection of NMDAR on neuronal cells and decreased cell survival. Although NMDAR encephalitis with IgG antibodies is increasingly recognized and diagnosed, atypical presentations with NMDAR antibodies with immunoglobulin subclasses other than IgG pose a diagnostic and therapeutic challenge. Further clinical and neurobiological studies are needed to study the pathophysiological relevance of IgM NMDAR antibodies. PMID:23246244

Choe, Chi-Un; Karamatskos, Evangelos; Schattling, Benjamin; Leypoldt, Frank; Liuzzi, Gianpiero; Gerloff, Christian; Friese, Manuel A; Mulert, Christoph

2013-07-30

103

Characterization of IgA and IgM binding and internalization by surface-expressed human Fc?/? receptor.  

PubMed

The Fc?/? receptor (Fc?/?R) is an unusual Fc receptor in that it binds to two different antibody isotypes, IgA and IgM. This receptor is of interest because it is thought to be involved in the capture of IgA- and IgM-immune complexes and antigen presentation. To further characterize this receptor, we were able to stably express human Fc?/?R on the surface of the 293T cell line. Using this system, we determined the affinity of the interactions of the receptor with IgA and IgM, which led to novel insights including the important finding that IgM polymers can bind to human Fc?/?R in the absence of J chain. This is in contrast to the polymeric immunoglobulin receptor (pIgR), which requires the presence of J chain to bind to polymeric IgA and IgM. The dissociation constants (K(d)) of all of the different human IgA isotypes and allotypes for human Fc?/?R were determined, and we show that the N-linked glycans on IgA1 are not required for binding to the receptor. In addition, we demonstrate that IgA can be rapidly internalized by human Fc?/?R in the presence of cross-linking antibody. PMID:21632111

Yoo, Esther M; Trinh, K Ryan; Lim, Hana; Wims, Letitia A; Morrison, Sherie L

2011-09-01

104

Observations on the patterns of blood IgM levels in the populations of endemic and nonendemic sleeping sickness areas in Kenya  

PubMed Central

Increased levels of serum immunoglobulin M (IgM) may be related to a wide range of antigenic stimuli provided by a variety of infections to which people are repeatedly exposed. Most, if not all, of the natural antibodies against bacterial and cellular antigens have been found to belong to the IgM class. It is known that IgM levels in the blood increase in trypanosomiasis but it is not possible to demonstrate trypanosomes in all persons who show raised IgM levels in serological surveys in an endemic sleeping sickness area. Although survey data are limited, this paper discusses the usefulness of IgM tests as an aid to the detection of Trypanosoma rhodesiense infections.

Binz, G.; Watson, H. J. C.

1972-01-01

105

Generation, characterization and in vivo biological activity of two distinct monoclonal anti-PEG IgMs.  

PubMed

PEGylation, the attachment of polyethylene glycol (PEG) to nanocarriers and proteins, is a widely accepted approach to improving the in vivo efficacy of the non-PEGylated products. However, both PEGylated liposomes and PEGylated proteins reportedly trigger the production of specific antibodies, mainly IgM, against the PEG moiety, which possibly leads to a reduction in safety and therapeutic efficacy of the PEGylated products. In the present study, two monoclonal anti-PEG IgMs - HIK-M09 via immunization with an intravenous injection of PEGylated liposomes (SLs) and HIK-M11 via immunization with a subcutaneous administration of PEGylated ovalbumin (PEG-OVA) were successfully generated. The generated IgMs showed efficient reactivity to mPEG2000 conjugated to 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine (DSPE), PEGylated liposome (SL) and PEG-OVA. It appears that HIK-M09 recognizes ethoxy (OCH2CH2) repeat units along with a terminal motif of PEG, while HIK-M11 recognizes only ethoxy repeat units of PEG. Such unique properties allow HIK-M09 to bind with dense PEG. In addition, their impact on the in vivo clearance of the PEGylated products was investigated. It was found that the generated ant-PEG IgMs induced a clearance of SL as they were intravenously administered with SL. Interestingly, the HIK-M11, generated by PEG-OVA, induced the clearance of both SL and PEG-OVA, while the HIK-M09, generated by SL, induced the clearance of SL only. We here revealed that the presence of serum anti-PEG IgM and the subsequent binding of anti-PEG IgM to the PEGylated products are not necessarily related to the enhanced clearance of the products. It appears that subsequent complement activation following anti-PEG IgM binding is the most important step in dictating the in vivo fate of PEGylated products. This study may have implications for the design, development and clinical application of PEGylated products and therapeutics. PMID:24632081

Hashimoto, Yosuke; Shimizu, Taro; Mima, Yu; Abu Lila, Amr S; Ishida, Tatsuhiro; Kiwada, Hiroshi

2014-05-15

106

A T-cell subpopulation committed to help B cells for immune responses restricted to IgM type.  

PubMed Central

Immune responses againt bovine serum albumin by chicken were dependent upon thymus-derived cells. Thirty-five of seventy chickens that had been neonatally thymectomized and subsequently immunized with bovine serum albumin produced IgM antibodies, but not IgG antibodies, against the antigen. T cells (IgM-T cells) of such chickens were able to help B cells to produce IgM antibody responses but were not able to help them to switch IgM- to IgG-antibody responses. Helper activity of the IgM-T cells was much less susceptible to the cytotoxic effect of anti-thymus cell serum and complement than was that of normal T cells. The introduction of the IgM-T cells into normal chickens at the same time as the initiation of immunization of the chickens did not affect immune responses by them at all, indicating the absence of suppressor T cells in the IgM-T cell preparations. Injection of chicken thymus factor into immunodeficient chickens transplanted with normal B cells and IgM-T cells developed the capability to help B cells to switch IgM- to IgG-antibody responses. On the basis of these findings the authors propose the existence of helper T cells which are characterized by peripheralization in early periods of ontogeny, the possession of helper activity for only IgM-antibody responses, the lack of helper activity for the switch from IgM- to IgG-antibody responses and relative insusceptibility to the cytotoxic effect of anti-thymus cell serum and complement.

Naito, I; Bito, Y

1980-01-01

107

High Seroprevalence of Mycoplasma pneumoniae IgM in Acute Q Fever by Enzyme-Linked Immunosorbent Assay (ELISA)  

PubMed Central

Q fever is serologically cross-reactive with other intracellular microorganisms. However, studies of the serological status of Mycoplasma pneumoniae and Chlamydophila pneumoniae during Q fever are rare. We conducted a retrospective serological study of M. pneumoniae and C. pneumoniae by enzyme-linked immunosorbent assay (ELISA), a method widely used in clinical practice, in 102 cases of acute Q fever, 39 cases of scrub typhus, and 14 cases of murine typhus. The seropositive (57.8%, 7.7%, and 0%, p<0.001) and seroconversion rates (50.6%, 8.8%, and 0%, p<0.001) of M. pneumoniae IgM, but not M. pneumoniae IgG and C. pneumoniae IgG/IgM, in acute Q fever were significantly higher than in scrub typhus and murine typhus. Another ELISA kit also revealed a high seropositivity (49.5%) and seroconversion rate (33.3%) of M. pneumoniae IgM in acute Q fever. The temporal and age distributions of patients with positive M. pneumoniae IgM were not typical of M. pneumoniae pneumonia. Comparing acute Q fever patients who were positive for M. pneumoniae IgM (59 cases) with those who were negative (43 cases), the demographic characteristics and underlying diseases were not different. In addition, the clinical manifestations associated with atypical pneumonia, including headache (71.2% vs. 81.4%, p=0.255), sore throat (8.5% vs. 16.3%, p=0.351), cough (35.6% vs. 23.3%, p=0.199), and chest x-ray suggesting pneumonia (19.3% vs. 9.5%, p=0.258), were unchanged between the two groups. Clinicians should be aware of the high seroprevalence of M. pneumoniae IgM in acute Q fever, particularly with ELISA kits, which can lead to misdiagnosis, overestimations of the prevalence of M. pneumoniae pneumonia, and underestimations of the true prevalence of Q fever pneumonia.

Lai, Chung-Hsu; Chang, Lin-Li; Lin, Jiun-Nong; Chen, Wei-Fang; Kuo, Li-Li; Lin, Hsi-Hsun; Chen, Yen-Hsu

2013-01-01

108

Monomeric (7S) IgM found in the serum of rheumatoid arthritis patients share idiotypes with pentameric (19S) monoclonal rheumatoid factors.  

PubMed Central

Serum from some seropositive (RF+) rheumatoid arthritis (RA) patients contains relatively high concentrations of monomeric (7S) IgM molecules. Seven S IgM molecules fail to bind the Fc portion of IgG, unlike 19S IgM RFs that bind aggregated IgG in classical RF assays. Some pentameric IgM RFs are marked by crossreactive idiotypes (RCRI) defined by prototypic monoclonal RFs. In previous studies, we observed that a proportion of pokeweed mitogen (PWM) induced plasma cells from RA patients' blood lymphocytes express the major RCRI as assayed by indirect immunofluorescence with polyclonal anti-RCRI antibodies. In this study, 7S IgM obtained from three different RF+ RA patients inhibits specific anti-RCRI intracytoplasmic staining of PWM induced RF+ RA-derived plasma cells. These 7S molecules also block polyclonal anti-RCRI antibodies from reacting with red blood cells bearing 7S IgM molecules from RF+ patients with RA or Waldenstrom's macroglobulinemia. We conclude that some 7S IgM molecules in the serum of RF+ RA patients are marked by the major RCRI idiotype and are related to 19S monoclonal and polyclonal RFs.

Bonagura, V R; Mendez, L; Agostino, N; Pernis, B

1987-01-01

109

IgM autoantibodies to distinct apoptosis-associated antigens correlate with protection from cardiovascular events and renal disease in patients with SLE.  

PubMed

Emerging evidence suggests that there are IgM-autoantibodies that may play protective roles in SLE. While IgM are often considered polyreactive, we postulate that there are distinct sets of IgM-autoantibodies of defined autoreactive specificities relevant to different features of SLE. We examined the relationships between levels of IgM natural autoantibodies (NAbs) to apoptosis-associated phosphorylcholine (PC) or malondialdehyde (MDA) antigens, with lupus-associated autoantibodies and features of disease, in 120 SLE patients. IgM anti-PC was significantly higher in patients with low disease activity and less organ damage determined by the SELENA-SLEDAI, the physician's evaluation and the SLICC damage score. Furthermore, IgM anti-PC was significantly higher in patients without cardiovascular events. In contrast, IgM anti-cardiolipin and IgM anti-dsDNA were significantly higher in patients without renal disease. These results support the hypothesis that some IgM autoantibodies are part of a natural immune repertoire that provide homeostatic functions and protection from certain clinical lupus features. PMID:22297166

Grönwall, Caroline; Akhter, Ehtisham; Oh, Cheongeun; Burlingame, Rufus W; Petri, Michelle; Silverman, Gregg J

2012-03-01

110

The sensitivity and specificity of Lassa virus IgM by ELISA as screening tool at early phase of Lassa fever infection  

PubMed Central

Background: Early diagnosis, prompt treatment, and disease containment are vital measures in the management of Lassa fever (LF), a lethal and contagious arenaviral hemorrhagic disease prevalent in West Africa. Lassa Virus (LAV)-specific Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) test, the gold standard for diagnosis, is unavailable in most centers. Serologic detection of LAV IgM is a more accessible tool and this work was to investigate its adequacy as an early marker for LF. Patients and Methods: A prospective case–control study conducted July 2007-March 2011 in a tertiary referral health center in Nigeria. Blood samples for test and control were evaluated for Lassa specific antigens and IgM using RT-PCR (primers S36+ and LVS 339) and indirect ELISA (Lassa Nucleo-protein (NP)-Antigen) respectively. RT-PCR outcome was used as standard to test for the sensitivity and specificity of IgM. Results: Of the 37 confirmed cases of LF infection by RT-PCR, 21 (57%) were IgM positive. Amongst the 35 confirmed negative cases (control group), eight were IgM positive. The diagnostic sensitivity and specificity of the IgM assay were 57% and 77% respectively. The negative and positive predictive values of the IgM serological assay were 63% and 72%, respectively, while the efficiency of the test was 67%. Conclusion: The specificity and sensitivity of IgM as a screening tool for early detection of LF appear weak and, hence, the need for a reliable LF “rapid screening kit” since RT-PCR is unavailable in most centers. In the interim, “high clinical index of suspicion,” irrespective of IgM status, requires urgent referral to confirmatory centers.

Ibekwe, Titus S.; Nwegbu, Maxwell M.; Asogun, Daniel; Adomeh, Donatus I.; Okokhere, Peter O.

2012-01-01

111

Natural IgM and innate immune collectin SP-D bind to late apoptotic cells and enhance their clearance by alveolar macrophages in vivo.  

PubMed

Innate immune collectin surfactant protein D (SP-D) and natural immunoglobulin M (IgM) are two soluble proteins. These opsonic proteins are good candidates for enhancing late apoptotic cell clearance. However, effects of these proteins on late apoptotic cell clearance in the lungs are not clearly established. We have recently shown that SP-D can bind several immunoglobulin isotypes, including IgM. Here we hypothesized that IgM and SP-D bind to late apoptotic cells and enhance their clearance from the lungs. We show that IgM and SP-D bind to late apoptotic secondary necrotic cells, and that IgM and SP-D either co-localize to the same regions or to different regions of late apoptotic Jurkat T cells. Mouse alveolar macrophages internalized late apoptotic cells, in vivo. We induced lung inflammation in mice using LPS and show that airway IgM and SP-D levels and the clearance of late apoptotic cells by alveolar macrophages increases under these conditions. We then coated late apoptotic cells with IgM, SP-D, or both and instilled them into the mouse airways. We found that alveolar macrophages internalize IgM- and SP-D-coated late apoptotic cells more effectively than uncoated late apoptotic cells, in vivo. None of these conditions cause inflammation in the naïve lungs. Therefore, these data suggest that both IgM and SP-D effectively opsonize late apoptotic cells and directly enhance their clearance by alveolar macrophages in the lungs. PMID:21035192

Litvack, Michael L; Djiadeu, Pascal; Renganathan, Sri Dushyaanthan Sri; Sy, Sarah; Post, Martin; Palaniyar, Nades

2010-01-01

112

Interactions of a nonneutralizing IgM antibody and complement in parainfluenza virus neutralization.  

PubMed

While many viruses activate the complement cascade directly, this is generally not a neutralizing event in the absence of antibody. We used a nonneutralizing IgM monoclonal antibody to parainfluenza virus type 3 (PIV3) hemagglutinin-neuraminidase (HN) to explore the role of antibody in complement-dependent neutralization of PIV3. Neither the antibody nor nonimmune guinea pig serum (GPS) neutralized PIV3 significantly, but a more than 100-fold reduction in titer was found when antibody and GPS were combined. Heat-inactivated GPS or GPS lacking either of two different complement proteins were all inactive with or without antibody. Specific repletion of the deficient sera with highly purified complement proteins restored neutralizing activity, indicating an absolute requirement for the classical pathway of complement activation and lytic terminal complement components, and viral lysis was confirmed by electron microscopy. The presence of antibody before complement activation was essential; later addition had no effect. Spontaneous complement activation by PIV3 occurred via the classical pathway in the absence of antibody. Addition of antibody did not alter the overall rate or extent of complement component C3 binding to PIV3 in these experiments. We conclude that certain nonneutralizing antibodies may support complement-dependent PIV3 neutralization by facilitating viral lysis. This process does not, however, involve enhanced activation through the C3 step. Lysis may require antibody-dependent localization of the membrane attack complex or reorganization of the viral envelope structures to facilitate attack complex insertion and lysis. PMID:2849234

Vasantha, S; Coelingh, K L; Murphy, B R; Dourmashkin, R R; Hammer, C H; Frank, M M; Fries, L F

1988-12-01

113

A recombinant protein-based enzyme immunoassay for IgM antibody to human cytomegalovirus.  

PubMed

The reliability of an enzyme-linked immunosorbent assay (ELISA) which used recombinant antigen to detect human cytomegalovirus IgM was studied. Serum samples from each of 283 children aged 5 +/- 2 years were studied. In all samples the anti-IgM antibodies were investigated with the ELISA techniques Enzygnost (Behring) and ETI-Cito (Sorin) which were both based on whole viral particles, and OPUS (Behring) based on recombinant antigen. Of the samples, 254 (89.4%) were negative with all three tests. The 29 remaining samples were positive with one or two of the three techniques. The diagnostic efficacy of Enzygnost, ETI-Cito and OPUS, respectively, was for sensitivity of 50%, 66.7% and 50%, and for specificity of 100%, 95.6% and 96%, respectively. The results with each of the three ELISAs did not differ widely and their diagnostic efficacy was similar. The method based on recombinant antigen was not found to be more effective than tests based on whole viral particles. PMID:9697339

Gutiérrez, J; Rodríguez, M; Pardal, J; Piédrola, G; Maroto, M C

1998-01-01

114

Comparison of four commercial IgM and IgG ELISA kits for diagnosing brucellosis.  

PubMed

Brucellosis is a worldwide zoonotic disease that often requires serology for diagnosis. The serum agglutination test is the gold standard assay, but ELISAs are used by many laboratories. Many commercial ELISAs are available, but few studies have compared their performance. This study compared the ability of four commercially available ELISA kits (from Bio-Quant, Immuno-Biological Laboratories - America, Vircell and Euroimmun) to diagnose brucellosis in patients from Egypt and the USA. The sensitivities for all kits tested, except the Vircell kit, were >90%, whilst the specificities were variable, with the Bio-Quant assay having a specificity of <40%. Detection of IgG antibody was more sensitive than detection of IgM antibody for diagnosing brucellosis cases, but the specificity was comparable. Overall, there was good agreement between all of the kits except for the Bio-Quant kit. None of the diagnostic assays was 100% reliable for diagnosing brucellosis; therefore, serology results need to be considered in tandem with patient history, clinical signs and other test results. PMID:21835974

Fadeel, Moustafa Abdel; Hoffmaster, Alex R; Shi, Jianrong; Pimentel, Guillermo; Stoddard, Robyn A

2011-12-01

115

Viral infections and IgM autoantibodies to cytoplasmic intermediate filaments.  

PubMed Central

Seventy-four out of 113 sera from patients with infectious hepatitis, chickenpox, measles and mumps reacted with both smooth muscle and cytoplasmic filaments in cultured fibroblasts and neuroblastoma. Five out of eighty-five control sera also reacted in this way. That the cytoplasmic structures are intermediate filaments was suggested by their rearrangement into coils of perinuclear filaments in colchicine- or vinblastine-treated fibroblasts, but not in cytochalasin B-treated cells. The idenity of these structures was confirmed by the demonstration that the same structures reacted with the post-viral sera and a rabbit and human anti-intermediate filament antibody. Immunoabsorption studies showed that twenty-seven out of thirty-two positive sera were neutralised by skeletin, the intermediate filament protein from smooth muscle. In all but one of the sera, the antibody was IgM. Antibody titres fell in the second specimen in eleven out of fourteen pairs of acute and convalescent sera. The association between viral infections and autoantibodies suggest that production of antibodies suggests that production of antibody to intermediate filaments may be initiated by viruses.

Toh, B H; Yildiz, A; Sotelo, J; Osung, O; Holborow, E J; Kanakoudi, F; Small, J V

1979-01-01

116

Transport models for secretory IgA and secretory IgM.  

PubMed Central

At least seven models have been proposed for the epithelial transport of IgA, and each model presents particular features which are not generally appreciated. Much of the confusion in this field has been caused by the many conflicting reports about the cellular origin of the secretory component (SC) and the mode in which it is expressed by secretory epithelial cells. The transport model proposed in 1973-74 on the basis of test-tube experiments and immunohistochemical studies has now gained considerable support from observations made on both normal and neoplastic living epithelial cells According to this model, the J ("joining') chain and SC represent "the lock and key' in the selective external translocation of both dimeric IgA and pentameric IgM through serous-type secretory epithelial cell. Incorporation of J chains into these two Ig isotypes during their production in gland-associated immunocytes induces a configurational fit (binding site) allowing them to combine by specific non-covalent interactions with SC in the plasma membrance of the epithelial cell. After being formed on the basolateral surface of the cell, the SC-IgA and SC-IgM complexes are transported in cytoplasmic vesicles to the gland lumen along with some free SC. Covalent stabilization of human secretory IgA during this process depends on unique possibilities for disulphide-exchange reactions and is not an inherent feature of the transport model.

Brandtzaeg, P

1981-01-01

117

Toxic effects of chlorpyrifos on lysozyme activities, the contents of complement C3 and IgM, and IgM and complement C3 expressions in common carp (Cyprinus carpio L.).  

PubMed

Chlorpyrifos is one of the organophosphate pesticides widely used in agricultural practices throughout world. It has resulted in a series of toxicological and environmental problems, such as impacts on many non-target aquatic species, including fish. In the present study, toxic effects of chlorpyrifos on lysozyme activities, contents of IgM and complement C3, and the expressions of IgM and complement C3 at mRNA level in common carp were evaluated by acute exposure of 15 (1/10 LC50) or 75?gL(-1) (1/2 LC50) of chlorpyrifos for 7d. The results of acute toxicity tests showed that the 96h-LC50 of chlorpyrifos for common carp was determined to be 149?gL(-1). We also found that chlorpyrifos promoted lysozyme activities at the earlier stages of exposure but inhibited it at the late stages in the serum, hepatopancreas, and spleen of common carp. Furthermore, it was observed that chlorpyrifos-exposure decreased IgM contents in fish serum and spleen while increased it in kidney. No obvious change was found in the contents of complement C3 in fish spleen, while a slight increase of complement C3 was observed in fish serum and kidney after 1d of chlorpyrifos-exposure. In addition, the results of quantitative real-time PCR showed that IgM and complement C3 expressions were up-regulated at the earlier stage of exposure but down-regulated at later stage. Our results indicate that chlorpyrifos causes immunotoxicity to common carp. PMID:23769463

Li, Xiaoyu; Liu, Li; Zhang, Yaning; Fang, Qian; Li, Yuanyuan; Li, Yuanlong

2013-09-01

118

Natural IgM Anti-leucocyte Autoantibodies (IgM-ALA) Regulate Inflammation Induced by Innate and Adaptive Immune Mechanisms.  

PubMed

Little is known about the function of natural IgM autoantibodies, especially that of IgM anti-leukocyte autoantibodies (IgM-ALA). Natural IgM-ALA are present at birth and characteristically increase during inflammatory and infective conditions. Our prior clinical observations and those of other investigators showing fewer rejections in renal and cardiac allografts transplanted into recipients with high levels of IgM-ALA led us to investigate whether IgM-ALA regulate the inflammatory response. In this review, we show that IgM, in physiologic doses, inhibit pro-inflammatory cell function in-vitro. We also show in an IgM knockout murine model, with intact B cells and regulatory T cells, that there is more severe inflammation and loss of function in the absence of IgM after renal ischemia reperfusion injury and cardiac allograft rejection. Replenishing IgM in IgM knockout mice or increasing the levels of IgM-ALA in wild-type B6 mice significantly attenuated the inflammation in both of these inflammatory models that involve IFN-? and IL-17. The protective effect on renal ischemia reperfusion injury Is mediated by IgM ALA as protection was lost when using IgM pre-adsorbed with leukocytes to remove IgM-ALA. We provide data to show that the anti-inflammatory effect of IgM is mediated, in part, by inhibiting TLR-4-induced NF-?B translocation into the nucleus and inhibiting differentiation of activated T cells into Th-1 and Th-17 cells. In additional studies, we also show that intra-peritoneal administration of IgM prevents NOD mice from developing autoimmune insulitis which also involves Th-1 and Th-17 cells. These observations highlight the importance of IgM-ALA in regulating excess inflammation mediated by both innate and adaptive immune mechanisms and where the inflammatory response involves Th-17 cells that are not effectively regulated by T regs, B regs, and IL-10. IgM-ALA may in part regulate inflammation by altering dendritic cell function, as dendritic cells pre-treated in-vitro with polyclonal IgM protected mice from renal IRI. The latter findings may have relevance for cell-based therapy. PMID:24711004

Lobo, Peter I; Brayman, Kenneth L; Okusa, Mark D

2014-07-01

119

Mouse IgM Fc receptor, FCMR, promotes B cell development and modulates antigen-driven immune responses  

PubMed Central

FCMR, a Fc receptor specific for pentameric IgM, is expressed at high levels by B cells. Although circulating IgM has profound effects on responses to pathogens, autoimmunity and B cell homeostasis, the biologic consequences of its binding to FCMR are poorly understood. We interrogated FCMR contributions to B cell function by studying mice lacking FCMR. FCMR transcripts are expressed at different levels by various B cell subsets. FCMR-deficient mice have reduced numbers of developing B cells, splenic FO and peritoneal B-2 cells, but increased levels of peritoneal B-1a cells and autoantibodies. Following immunization, germinal center B cell and plasma cell numbers are increased. FCMR-deficient B cells are sensitive to apoptosis induced by BCR ligation. Our studies demonstrate that FCMR is required for B cell differentiation and homeostasis, the prevention of autoreactive B cells and responsiveness to antigenic challenge.

Choi, Seung-Chul; Wang, Hongsheng; Tian, Linjie; Murakami, Yousuke; Shin, Dong-Mi; Borrego, Francisco; Morse, Herbert C.; Coligan, John E.

2012-01-01

120

[The treatment of Waldenström macroglobulinemia and the therapy of diseases caused by monoclonal IgM gammaglobulin].  

PubMed

Waldenström macroglobulinemia is defined by the presence of IgM type monoclonal immunoglobulin and histologi cal prove of lymphoplasmocytary lymphoma in the bone marrow. Alkylating cytostatic drugs, chlorambucil or cyclofosfamide in monotherapy have been typically used for its treatment. Similarly to other lymphoproliferative diseases with a low degree of aggressiveness, purine analogues (fludarabine and 2-chlordeoxyadenosine) have a faster treatment response and a higher number of treatment responses, especially if administered in combination with alkylating drugs. The monoclonal antibody rituximab (R) also brings considerable improvement to patients suffering from the disease. It is good for cytopenic patients on monotherapy, and for non-cytopenic patients, in combination with other drugs, both with R-CHOP and with a purine analogue and an alkylating cytostatic drug. In recent years, new drugs for the treatment of this disease have been tested (bortezomib, thalidomid, revlimid and others). High-dose chemotherapy with autologous transplantation has a higher treatment response rate than classical chemotherapy. It is recommended in case of insufficient effect of conventional treatment or early relaps. Young patients with suitable profile and insufficient response to conventional treatment can also qualify for allogenic transplantation; graft response against the disease has been observed in almost all patients who underwent allogenic transplantation. However, treatment is often necessary also in diseases caused by IgM monoclonal immunoglobulin, irrespective of it being formed by a malignant or a benign clone, because the characteristics of IgM monoclonal immunoglobulin may endanger the patient's integrity. The article provides an overview of treatment options for Waldenström macroglobulinemia and diseases caused by monoclonal IgM. PMID:18390120

Adam, Z; Scudla, V; Krejcí, M; Korístek, Z

2008-01-01

121

Sensorimotor demyelinating neuropathy with IgM antibody against gangliosides GD1a, GT1b and GM3  

Microsoft Academic Search

We report a patient with sensorimotor demyelinating neuropathy with high-titer IgM antibody against gangliosides GD1a, GT1b and GM3. The patient was a 65-year-old male who was hospitalized with chief complaints of muscular weakness of all limbs and numbness of the hands and feet. Nerve-conduction studies revealed reduced conduction velocities of the motor nerves with increased temporal dispersion and loss of

Kotaro Mizutani; Nobuyuki Oka; Susumu Kusunoki; Ryuji Kaji; Takahiro Mezaki; Ichiro Akiguchi; Hiroshi Shibasaki

2001-01-01

122

Analysis of the interaction of monoclonal antibodies with surface IgM on neoplastic B-cells  

Microsoft Academic Search

In vitro studies identified three Burkitts lymphoma cell lines, Ramos, MUTU-I and Daudi, that were growth inhibited by anti-IgM antibody. However, only Ramos and MUTU-I were sensitive to monoclonal antibodies (mAb) recognizing the Fc region of surface IgM (anti-Fc?). Experiments using anti-Fc? mAb (single or non-crossblocking pairs), polyclonal anti-? Ab, and hyper-crosslinking with a secondary layer of Ab, showed that

M S Cragg; L Zhang; R R French; M J Glennie; Cragg

1999-01-01

123

FUSE Observations of He II Absorption in the IGM Toward HE2347-4342: Opacity and Fluctuations  

Microsoft Academic Search

We use the FUSE far-ultraviolet (912-1187 Å) spectrum of the z=2.885 QSO HE2347-4342 (Kriss et al. 2000, AAS abstract) to obtain information about the He II opacity of the intergalactic medium (IGM) and its fluctuations over the redshift interval z = 2.1 - 2.8. The dataset comes from approximately 400 ks of exposure obtained during orbital night, and the spectrum

J. M. Shull; M. Giroux; J. Tumlinson; J. Kriss; L. Cowie; A. Songaila; W. Zheng; H. W. Moos; W. Oegerle; A. Davidsen; S. Friedman; J. Kruk; J. Hutchings; D. Morton; R. Green; E. Jenkins; J.-M. Deharveng

2000-01-01

124

Identification of Plasmodium falciparum var1CSA and var2CSA domains that bind IgM natural antibodies  

Microsoft Academic Search

Malaria in pregnancy is responsible for maternal anaemia, low-birth-weight babies and infant deaths. Plasmodium falciparum infected erythrocytes are thought to cause placental pathology by adhering to host receptors such as chondroitin sulphate A (CSA). CSA binding infected erythrocytes also bind IgM natural antibodies from normal human serum, a process that may facilitate placental adhesion or promote immune evasion. The parasite

Jean-Philippe Semblat; Ahmed Razaa; Sue A. Kyes; J. Alexandra Rowe

2006-01-01

125

Human IgM paraproteins demonstrate shared reactivity between Campylobacter jejuni lipopolysaccharides and human peripheral nerve disialylated gangliosides  

Microsoft Academic Search

IgM paraproteins from patients with CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, M-protein, agglutination, anti-disialosyl antibodies) react with NeuAc(?2–8)NeuAc epitopes on a wide range of gangliosides including GQ1b, GT1a, GD1b and GD3. The tissue distribution of reactive antigens in human peripheral nerve has not been addressed in detail. In addition, the origin of these antibodies is unknown. Here we report that purified

Bart C Jacobs; Graham M O'Hanlon; Elvera G Breedland; Jean Veitch; Pieter A van Doorn; Hugh J Willison

1997-01-01

126

Analysis of the human VH gene repertoire. Differential effects of selection and somatic hypermutation on human peripheral CD5(+)/IgM+ and CD5(-)/IgM+ B cells.  

PubMed Central

To analyze the immunoglobulin repertoire of human IgM+ B cells and the CD5(+) and CD5(-) subsets, individual CD19(+)/ IgM+/CD5(+) or CD5(-) B cells were sorted and non-productive as well as productive VH gene rearrangements were amplified from genomic DNA and sequenced. In both subsets, the VH3 family was overrepresented largely as a result of preferential usage of a small number of specific individual family members. In the CD5(+) B cell subset, all other VH families were found at a frequency expected from random usage, whereas in the CD5(-) population, VH4 appeared to be overrepresented in the nonproductive repertoire, and also negatively selected since it was found significantly less often in the productive compared to the nonproductive repertoire; the VH1 family was significantly diminished in the productive rearrangements of CD5(-) B cells. 3-23/DP-47 was the most frequently used VH gene segment and was found significantly more often than expected from random usage in productive rearrangements of both CD5(+) and CD5(-) B cells. Evidence for selection based on the D segment and the JH gene usage was noted in CD5(+) B cells. No differences were found between the B cell subsets in CDR3 length, the number of N-nucleotides or evidence of exonuclease activity. Somatically hypermutated VHDJH rearrangements were significantly more frequent and extensive in CD5(-) compared to CD5(+) IgM+ B cells, indicating that IgM+ memory B cells were more frequent in the CD5(-) B cell population. Of note, the frequency of specific VH genes in the mutated population differed from that in the nonmutated population, suggesting that antigen stimulation imposed additional biases on the repertoire of IgM+ B cells. These results indicate that the expressed repertoire of IgM+ B cell subsets is shaped by recombinational bias, as well as selection before and after antigen exposure. Moreover, the influences on the repertoires of CD5(+) and CD5(-) B cells are significantly different, suggesting that human peripheral blood CD5(+) and CD5(-) B cells represent different B cell lineages, with similarities to murine B-1a and B-2 subsets, respectively.

Brezinschek, H P; Foster, S J; Brezinschek, R I; Dorner, T; Domiati-Saad, R; Lipsky, P E

1997-01-01

127

Mutations of CD40 gene cause an autosomal recessive form of immunodeficiency with hyper IgM  

PubMed Central

CD40 is a member of the tumor necrosis factor receptor superfamily, expressed on a wide range of cell types including B cells, macrophages, and dendritic cells. CD40 is the receptor for CD40 ligand (CD40L), a molecule predominantly expressed by activated CD4+ T cells. CD40/CD40L interaction induces the formation of memory B lymphocytes and promotes Ig isotype switching, as demonstrated in mice knocked-out for either CD40L or CD40 gene, and in patients with X-linked hyper IgM syndrome, a disease caused by CD40L/TNFSF5 gene mutations. In the present study, we have identified three patients with an autosomal recessive form of hyper IgM who fail to express CD40 on the cell surface. Sequence analysis of CD40 genomic DNA showed that one patient carried a homozygous silent mutation at the fifth base pair position of exon 5, involving an exonic splicing enhancer and leading to exon skipping and premature termination; the other two patients showed a homozygous point mutation in exon 3, resulting in a cysteine to arginine substitution. These findings show that mutations of the CD40 gene cause an autosomal recessive form of hyper IgM, which is immunologically and clinically undistinguishable from the X-linked form.

Ferrari, Simona; Giliani, Silvia; Insalaco, Antonella; Al-Ghonaium, Abdulaziz; Soresina, Anna R.; Loubser, Michael; Avanzini, Maria A.; Marconi, Massimo; Badolato, Raffaele; Ugazio, Alberto G.; Levy, Yves; Catalan, Nadia; Durandy, Anne; Tbakhi, Abdelghani; Notarangelo, Luigi D.; Plebani, Alessandro

2001-01-01

128

Long-term response to rituximab and fludarabine combination in IgM anti-myelin-associated glycoprotein neuropathy.  

PubMed

We report the clinical response and biological effects of treatment with rituximab and fludarabine (RF) in five patients with IgM anti-myelin-associated glycoprotein (MAG) demyelinating neuropathy. Between November 2006 and October 2009, four men and one woman aged 52-85 years received intravenous rituximab at 375 mg/m(2) on day 1 and oral fludarabine at 40 mg/m(2) /day from days 1 to 5, in a treatment cycle that was repeated every month for up to 6 months. Two patients had IgM monoclonal gammopathy of undetermined significance and three low tumor mass Waldenstrom's macroglobulinemia. Four patients showed a major hematological response with a decrease in anti-MAG titer in three and clearing in one. One patient did not respond. For the responding patients, symptoms and electrophysiological parameters improved significantly. No patient relapsed at post-RF treatment follow-up (12-45 months), and no toxicity was reported. The combination of RF induced significant responses in IgM anti-MAG demyelinating neuropathies, without toxicity. Clinical improvements were correlated to hematological and immunological results. PMID:22003932

Gruson, Berengere; Ghomari, Kamel; Beaumont, Marie; Garidi, Reda; Just, Alain; Merle, Philippe; Merlusca, Lavinia; Marolleau, Jean P; Royer, Bruno

2011-09-01

129

PDGF is Required for Remyelination-Promoting IgM Stimulation of Oligodendrocyte Progenitor Cell Proliferation  

PubMed Central

Background Promotion of remyelination is a major goal in treating demyelinating diseases such as multiple sclerosis (MS). The recombinant human monoclonal IgM, rHIgM22, targets myelin and oligodendrocytes (OLs) and promotes remyelination in animal models of MS. It is unclear whether rHIgM22-mediated stimulation of lesion repair is due to promotion of oligodendrocyte progenitor cell (OPC) proliferation and survival, OPC differentiation into myelinating OLs or protection of mature OLs. It is also unknown whether astrocytes or microglia play a functional role in IgM-mediated lesion repair. Methods We assessed the effect of rHIgM22 on cell proliferation in mixed CNS glial and OPC cultures by tritiated-thymidine uptake and by double-label immunocytochemistry using the proliferation marker, Ki-67. Antibody-mediated signaling events, OPC differentiation and OPC survival were investigated and quantified by Western blots. Results rHIgM22 stimulates OPC proliferation in mixed glial cultures but not in purified OPCs. There is no proliferative response in astrocytes or microglia. rHIgM22 activates PDGF?R in OPCs in mixed glial cultures. Blocking PDGFR-kinase inhibits rHIgM22-mediated OPC proliferation in mixed glia. We confirm in isolated OPCs that rHIgM22-mediated anti-apoptotic signaling and inhibition of OPC differentiation requires PDGF and FGF-2. We observed no IgM-mediated effect in mature OLs in the absence of PDGF and FGF-2. Conclusion Stimulation of OPC proliferation by rHIgM22 depends on co-stimulatory astrocytic and/or microglial factors. We demonstrate that rHIgM22-mediated activation of PDGF?R is required for stimulation of OPC proliferation. We propose that rHIgM22 lowers the PDGF threshold required for OPC proliferation and protection, which can result in remyelination of CNS lesions.

Watzlawik, Jens O.; Warrington, Arthur E.; Rodriguez, Moses

2013-01-01

130

Diagnosis of recent primary rubella virus infections: significance of glycoprotein-based IgM serology, IgG avidity and immunoblot analysis.  

PubMed

Reliable serodiagnosis of rubella virus (RV) infections requires discrimination of specific IgM induced by primary rubella from persistent, reactivated or non-specific IgM reactivity. Sera from 130 pregnant women with recent or past RV infection/vaccination, persistent IgM or negative rubella serology, 26 patients with other acute infections and 5 patients with rheumatoid factor-positivity were analyzed for RV-specific IgM by ELISA coated with whole-virus lysate or native glycoprotein, followed by determination of IgG avidity and E2-specific IgG using lysate-coated ELISA and non-reducing immunoblot. Compared to a reference ?-capture IgM ELISA, the sensitivity for diagnosing recent rubella infection/vaccination was 90.0% and 100% for the lysate-based and glycoprotein-based IgM ELISA, respectively. With respect to women with past RV infections or negative histories of RV infection/vaccination, both assays were 97.5-100% specific, whereas for patients with other acute infections the glycoprotein substrate provided a specificity of 92.3% compared to only 80.8% using whole-virus antigen. Analyzing anti-RV IgG avidity and anti-E2 IgG reactivity allowed the time point of primary infection to be determined unambiguously in >86% of samples. In conclusion, using RV glycoprotein antigen improves the specificity of indirect IgM ELISA. In cases of RV-specific IgM reactivity, recent primary rubella infection can be confirmed or excluded efficiently by specific IgG avidity and immunoblot analysis. PMID:21513745

Wandinger, Klaus-Peter; Saschenbrecker, Sandra; Steinhagen, Katja; Scheper, Thomas; Meyer, Wolfgang; Bartelt, Uwe; Enders, Gisela

2011-06-01

131

Natural IgM and innate immune collectin SPD bind to late apoptotic cells and enhance their clearance by alveolar macrophages in vivo  

Microsoft Academic Search

Innate immune collectin surfactant protein D (SP-D) and natural immunoglobulin M (IgM) are two soluble proteins. These opsonic proteins are good candidates for enhancing late apoptotic cell clearance. However, effects of these proteins on late apoptotic cell clearance in the lungs are not clearly established. We have recently shown that SP-D can bind several immunoglobulin isotypes, including IgM. Here we

Michael L. Litvack; Pascal Djiadeu; Sri Dushyaanthan Sri Renganathan; Sarah Sy; Martin Post; Nades Palaniyar

132

Semiquantitative anti-HBc IgM detection in children with chronic hepatitis B: a long-term follow-up study.  

PubMed

Serum anti-HBc IgM titres were monitored monthly by a semiquantitative method in 14 children with HBeAg positive chronic hepatitis B followed up for 18-65 months. All patients, but one, were treated with alfa-interferon (IFN) at different times. On the whole, 12 flare-up episodes were observed and 7 patients cleared HBV-DNA and seroconverted to anti-HBe. Seroconversion occurred only in patients with pretreatment anti-HBc IgM index greater than 0.15 and serum HBV-DNA concentration below 100 pg/ml; the pretreatment alanine aminotransferase (ALT) value was not predictive of response. Combining anti-HBc IgM results and serum HBV-DNA levels observed during the pre-IFN period allowed a precise identification of patients who were likely to respond to IFN therapy. Patients who seroconverted to anti-HBe showed a progressive reduction in serum anti-HBc IgM titres within 6 months. Interestingly, one child, in whom HBV-DNA reappeared and who reconverted to HBeAg 7 months after treatment, showed no anti-HBc IgM decrease after the transient clearance of HBV-DNA and anti-HBe seroconversion. Semiquantitative anti-HBc IgM detection is a useful tool in the decision making process for children with chronic hepatitis B. PMID:7561786

Gaeta, G B; Nardiello, S; Pizzella, T; Russo, G; Maisto, A; Sardaro, C; Galanti, B; Giusti, G

1995-07-01

133

Administration of RRR-?-tocopherol to pregnant mares stimulates maternal IgG and IgM production in colostrum and enhances vitamin E and IgM status in foals.  

PubMed

This study assessed the effect of a vitamin E supplement given to pregnant mares on immunoglobulins (Ig) levels in foals. In addition, the fatty acid (FA) content and composition of the mares' milk was assessed. Milk ?-tocopherol concentrations were compared between pregnant Danish Warmblood mares (n = 17) given a daily oral supplement of 2500 international units (IU) RRR-?-tocopherol in the last 4 weeks of pregnancy and a group of unsupplemented mares (n = 17) receiving 170-320 IU vitamin E daily originating from the feed. Milk ?-tocopherol was higher in supplemented mares (36.7, 12.4 and 9.8 ?mol/l respectively) in relation to control mares (13.1, 6.4 and 5.8 ?mol/l on days 1, 2 and 3 respectively; p < 0.001). Milk IgG was higher on days 2 and 3 post-partum (PP) in supplemented mares (1.03 and 0.73 mg/ml respectively) in relation to control mares (0.79 and 0.56 mg/ml respectively; p < 0.05). Milk IgM was higher on days 2 and 3 post-partum (PP) in supplemented mares (0.19 and 0.17 mg/ml) in relation to control mares (0.13 and 0.11 mg/ml respectively; p < 0.05). Plasma ?-tocopherol in foals was higher from supplemented mares on days 1, 2 and 3 (5.7, 14.8 and 19.2 ?mol/l respectively) in relation to foals from control mares (3.6, 6.1 and 7.6 respectively; p < 0.001). Foal plasma IgM was higher from supplemented mares on day 3 (0.50 mg/ml) in relation to foals from control mares (0.32 mg/ml; p < 0.001). The total FA content in milk was highest on day 1 (21.6 g FA/kg milk) in relation to days 2 and 3 (13.6 and 13.5 g FA/kg milk respectively; p < 0.001). In conclusion, a daily oral supplement of 2500 IU RRR-?-tocopherol increased ?-tocopherol content in mare milk and foal plasma, IgG and IgM in mare milk and IgM in foal plasma. PMID:20796079

Bondo, T; Jensen, S K

2011-04-01

134

Serum carbohydrate-binding IgM are present in Vietnamese striped catfish (Pangasianodon hypophthalmus) but not in North African catfish (Clarias gariepinus).  

PubMed

Pangasianodon hypophthalmus serum was fractionated by affinity chromatography on 12 different Sepharose-carbohydrate columns and proteins eluted by the corresponding sugar. Binding to the affinity matrices is dependent on Ca(2+) ions. Upon gel filtration using Superose-12, essentially one fraction was obtained, eluting as a protein with a molecular mass of about 900 kDa. SDS-PAGE in reducing conditions revealed the presence of large (72 kDa) subunits (H-chains) and one up to three small (24, 26 and/or 28-29 kDa) subunits (L-chains). The isolated proteins were shown to be IgM since they bind monoclonal anti-P. hypophthalmus IgM antibodies. Rabbit polyclonal anti-galactose-binding IgM only cross-react with some sugar-binding IgM. The H-chains of the anti-carbohydrate IgM are glycosylated. Circular dichroism studies revealed that the IgMs have an "all-?" type of structure, and that Ca(2+) ions, though essential for carbohydrate-binding activity, are not required for the structural integrity of the molecules. In non-reducing SDS-PAGE, only monomers and halfmers were obtained, showing that there are no disulfide bonds linking the monomers, and that a disulfide bond connecting both H-chains within one monomer is only present in 45% of the molecules. Both the monomers and the halfmers display molecular mass heterogeneity which is indicative for redox forms at the level of the intradomain disulfide bonds. The native carbohydrate-binding IgMs agglutinate erythrocytes from different animals, as well as fish pathogenic bacteria. Similar proteins could not be isolated from another catfish, Clarias gariepinus. PMID:21911003

Giang, Duong Thi Huong; Van Driessche, Edilbert; Beeckmans, Sonia

2012-02-01

135

Simultaneous expression of Borrelia OspA and OspC and IgM response in cerebrospinal fluid in early neurologic Lyme disease.  

PubMed Central

Lyme disease is the major tick-borne disease, caused by Borrelia burgdorferi (Bb). Neurological involvement is common in all stages. In vivo expression of Bb antigens (Ags) and the immune response to them has not been well investigated in the cerebrospinal fluid (CSF). Upregulation of outer surface protein (Osp) C and concomitant downregulation of OspA before tick inoculation of the spirochete has been reported in skin and blood in animals. CSF OspA Ag in early disease suggests otherwise in CSF. Early Ag expression and IgM response in human CSF was investigated here. Paired CSF and serum was collected from 16 early, predominantly erythema migrans Lyme disease patients with neurologic problems, 13 late Lyme disease patients, and 19 other neurologic disease (OND) controls. Samples were examined for IgM reactivity to recombinant Bb-specific Osps using ELISA and immunoblot. Of 12 early Lyme disease patients with neurologic involvement with both CSF and serum IgM against OspC, 7 (58%) had IgM to OspA (n = 5) or OspB (n = 2) that was restricted to the CSF, not serum. Overall, 12 of 16 (75%) of these early Lyme disease patients with neurologic involvement had CSF and serum IgM against OspC. Only 3 of 13 (23%) late Lyme disease patients and none of 19 OND controls had CSF IgM directed against OspC. In conclusion, in CSF, OspC and OspA can be coexpressed, and IgM response to them occurs in early Lyme disease patients with neurologic involvement. This biologic finding may also provide a discriminating marker for CNS infection in Lyme disease.

Schutzer, S E; Coyle, P K; Krupp, L B; Deng, Z; Belman, A L; Dattwyler, R; Luft, B J

1997-01-01

136

A randomised clinical trial comparing interferon-? and intravenous immunoglobulin in polyneuropathy associated with monoclonal IgM  

PubMed Central

OBJECTIVES—The polyneuropathy associated with a monoclonal IgM directed to the myelin associated glycoprotein (MAG) is a specific entity with a putative causal link between the IgM and the neuropathy. The small benefit offered by alkylating agents or plasma exchanges in these patients justifies the search for alternative treatments.?METHODS—A 12 month multicentre, prospective, randomised, open clinical trial was carried out comparing intravenous immunoglobulin (IVIg; 2g/kg and then 1 g/kg every three weeks) and recombinant interferon-? (IFN-?; 3 MU/m2 subcutaneously three times weekly). The main end point was a clinical neuropathy disability score (CNDS) after six months of treatment. Twenty patients were enrolled; 10 were assigned to IVIg and 10 to IFN-?. ?RESULTS—At six months, one out of 10 patients treated with IVIg had a CNDS improvement of more than 20% whereas eight out of 10 patients treated with IFN-? had such an improvement (P=0.005). The mean CNDS worsened by 2.3 (SD 7.6) (8%) in the IVIg group whereas it improved by 7.5 (SD 11.1) (31%) in the IFN-? group (P=0.02). This improvement persisted after 12 months and was mainly related to an improvement of the sensory component (P=0.02) whereas the motor component was unchanged (P=0.39). Electrophysiological data did not show improvement of motor nerve conduction velocities whereas sensory nerve conduction velocities improved in the upper limbs. A decrease in the level of the monoclonal IgM was seen in two patients treated with IFN-?. At the end of the treatment, antibody activity to MAG was still detected in the serum of all patients.?CONCLUSION—IVIg, as used in this study, did not improve patients with polyneuropathy and monoclonal IgM. By contrast, although its mechanism of action remains to be fully elucided, IFN-? was effective in eight out of 10 patients at six months.??

Mariette, X.; Chastang, C.; Louboutin, J.; Leger, J.; Clavelou, P.; Brouet, J.

1997-01-01

137

IgG, IgM and IgA antibodies against the novel polyprotein in active tuberculosis  

PubMed Central

Background The present study was aimed to evaluate whether IgG, IgM and IgA antibodies levels detected against a novel Mycobacterium tuberculosis polyprotein 38 F-64 F (with 38 F being the abbreviation for 38kD-ESAT6-CFP10 and 64 F for Mtb8.4-MPT64-TB16.3-Mtb8) are suitable for diagnosing active tuberculosis, and for monitoring the efficacy of chemotherapy on TB patients. Methods In this study, a total of 371 active TB patients without treatment were selected and categorized into S+/C+?group (n?=?143), S-/C+?group (n?=?106) or S-/C- group (n?=?122). A series of serum samples were collected from 82 active TB patients who had undergone anti-TB chemotherapy for 0–6 months at one month interval. Humoral responses (IgG, IgM and IgA) were determined for the novel Mycobacterium tuberculosis polyprotein using indirect ELISA methods in all of serum samples. Results For S+/C+, S-/C+?and S-/C- active tuberculosis patients before anti-TB chemotherapy, the sensitivities of tests based on IgG were 65.7%, 46.2% and 52.5% respectively; the sensitivities based on IgM were 21.7%, 24.5% and 18.9%; and the sensitivities based on IgA were 25.2%, 17.9% and 23.8%. By combination of three isotypes, for all active tuberculosis patients, the test sensitivity increased to 70.4% with the specificity being 91.5%. After anti-TB chemotherapy, there were no significant differences between groups with different courses of anti-TB chemotherapy. Conclusions The novel Mycobacterium tuberculosis polyprotein 38 F-64 F represents potential antigen suitable for measuring IgG, IgM and IgA antibodies. However, the serodiagnostic test based on the 38 F-64 F polyprotein appears unsuitable for monitoring the efficacy of chemotherapy.

2014-01-01

138

Evidence that human autoimmune thrombocytopenia mediated by both immunoglobulin isotypes IgM and IgG is an independent disease entity.  

PubMed

Autoimmune thrombocytopenic purpura (AITP) is a bleeding disorder caused by clonally restricted self-reactive antibodies with specificity for platelet glycoproteins. Anti-platelet autoantibodies in AITP mainly belong to the IgG class. The occurrence of anti-platelet autoantibodies of the IgM isotype has been reported, and AITP is partially mediated by antibodies of both isotypes, IgM and IgG. Using a technique of quantitative immunoblotting of immunoglobulins on self-tissues, followed by multiparametric statistical analysis of the data, we here demonstrate that patients with IgM- and IgG-mediated AITP are readily discriminated from patients with IgM-mediated AITP as well as from patients with IgG-mediated AITP at the basis of self-reactive antibody repertoires of isotypes IgM and IgG toward non-platelet antigens of human origin. Our data suggest that, in view of the important physiological functions of self-reactive antibody repertoires, human AITP mediated by both immunoglobulin isotypes IgG and IgM may be an independent disease entity. The role of autoantibody isotype for the pathophysiology of AITP might currently be underestimated, and diagnostic and therapeutic procedures in AITP might profit from considering autoantibody isotype more carefully. PMID:16146538

Stahl, Dorothea; Hoemberg, Marc; Cassens, Uwe; Pachmann, Ulrich; Sibrowski, Walter

2005-10-01

139

Concomitance of IgM and IgG anti-dsDNA Antibodies Does Not Appear to Associate to Active Lupus Nephritis  

PubMed Central

Previous reports proposed that the IgM anti-dsDNA antibody is protective for lupus nephritis. In this cross-sectional study, we aimed to compare clinical features of systemic lupus erythematosus (SLE) patients positive for IgG anti-dsDNA alone with those presenting both IgG and IgM anti-dsDNA. Anti-dsDNA antibodies, urinary examination and complement levels were assessed in the day of appointment. IgG and IgM anti-dsDNA antibodies were detected by indirect immunofluorescence. Fifty-eight SLE patients (93.1% female, 81% European-derived, mean age 42.8±14.7 years, mean duration of disease 10.9±8 years) positive for IgG anti-dsDNA entered the study. Of those, 15 were also positive for the IgM anti-dsDNA isotype. The group with both isotypes showed significant less frequency of active nephritis (sediment changes and proteinuria) when compared to patients with IgG anti-dsDNA alone (6.7% versus 34.9%, p=0.046). These data suggest a nephroprotective role for IgM anti-dsDNA and a distinct biologic behavior for this isotype in SLE.

Keiserman, Briele; Ronchetti, Maria Rita; Monticielo, Odirlei Andre; Keiserman, Mauro Waldemar; Staub, Henrique Luiz

2013-01-01

140

Functional properties of isotype-switched immunoglobulin M (IgM) and IgG monoclonal antibodies to Pseudomonas aeruginosa lipopolysaccharide.  

PubMed Central

Controversy exists regarding isotype-related differences in the antibacterial and protective properties of lipopolysaccharide (LPS)-specific antibodies of the immunoglobulin M (IgM) class and various IgG subclasses. To clarify this issue, a murine hybridoma secreting IgM monoclonal antibody (MAb) specific for the O polysaccharide of Pseudomonas aeruginosa serogroup O6 LPS was class switched, by sib selection, to produce an IgG3 MAb with identical specificity and variable region heavy and light chain nucleotide sequences. This IgG3-secreting cell line was further switched to the production of O-specific, variable region-identical IgG1, IgG2b, and IgG2a MAbs. Functional comparisons of these LPS-specific IgM and IgG MAb isotypes revealed similar LPS binding, opsonic, and protective activities. Relatively minor isotype-related differences in levels of efficiency of MAb-mediated, complement-dependent opsonophagocytic killing (IgM > IgG2a > IgG3 > IgG2b > > IgG1) were not associated with corresponding differences in in vivo functions. These findings, in conjunction with previously published data, support a cautious approach to generic conclusions regarding the immunotherapeutic superiority of LPS-specific antibodies belonging to either the IgM or IgG class or to a particular IgG subclass.

Pollack, M; Koles, N L; Preston, M J; Brown, B J; Pier, G B

1995-01-01

141

A Case of IgM Deficiency with B Cell Deficiency Detected by ABO Discrepancy in a Patient with Acute Osteomyelitis  

PubMed Central

ABO discrepancy refers to an inconsistency between red cell and serum typings and has various causes, including hypogammaglobulinemia. IgM deficiency is a rare disorder that may accompany several conditions such as infection and autoimmune disorders. Here, we describe a case of IgM deficiency discovered during the evaluation of an ABO discrepancy in a 16-yr-old Korean boy. ABO blood grouping showed that while his cell type was O+, serum typing detected only anti-A (3+). Anti-B was not detectable at room temperature but was graded at 1+ at 4?. ABO genotyping revealed an O/O genotype. His serum IgG, IgA, and IgM concentrations were 770 mg/dL (reference range: 800-1,700 mg/dL), 244 mg/dL (reference range: 100-490 mg/dL), and 13.5 mg/dL (reference range: 50-320 mg/dL), respectively. He was diagnosed with acute osteomyelitis on the basis of clinical presentation and imaging studies. The symptoms gradually improved within 3 weeks of treatment. However, the ABO discrepancy and IgM deficiency persisted even 6 months after recovery and lymphocyte subset analysis revealed CD19+ B cell deficiency. To the best of our knowledge, IgM deficiency detected by ABO discrepancy in a patient with acute osteomyelitis has not been reported before.

Jung, Chae Lim; Cha, Mi-Kyung

2013-01-01

142

The effects of IgM rheumatoid factor on EAM and EAG rosette formation with Fc receptor-bearing lymphoid cells.  

PubMed

IgM rheumatoid factors (IgM-RF) and IgM from normal donors (IgM-C) were tested for their effects on rosette formation of Fc receptor (FcR)-bearing lymphoid cells with IgM- or IgG-coated bovine red blood cells (EAM or EAG). All cell populations tested bearing FcR for IgG (FcRG) showed reduced numbers of EAG rosettes formed in the presence of IgM-RF; IgM-C had no effect on EAG rosette formation with FcRG-bearing cells. T cells or L cells bearing FcRM showed reduced numbers of EAM rosettes in the presence of any IgM preparation. In addition, IgM-RF facilitated EAG-rosette formation with TM cells. These studies confirm that native IgM can bind to FcRM, blocking EAM rosettes, and that IgM-RF can modulate the binding of an IgG-containing immune complex to FcR-bearing cells. PMID:6604529

Emmons, R P; Davis, J S; Moretta, L

1983-09-01

143

False-positive IgM for CMV in pregnant women with autoimmune disease: a novel prognostic factor for poor pregnancy outcome.  

PubMed

Our aims were to assess the frequency of false-positive IgM antibodies for cytomegalovirus in pregnant women with autoimmune diseases and in healthy women (controls) and to determine their relationship with pregnancy outcome. Data from 133 pregnancies in 118 patients with autoimmune diseases and from 222 pregnancies in 198 controls were assessed. When positive IgM for cytomegalovirus was detected, IgG avidity, cytomegalovirus isolation and polymerase chain reaction for CMV-DNA in maternal urine and amniotic fluid samples were performed in order to identify primary infection or false positivity. A statistically significantly higher rate of false-positive IgM was found in pregnancies with autoimmune diseases (16.5%) in comparison with controls (0.9%). A worse pregnancy outcome was observed among patients with autoimmune disease and false cytomegalovirus IgM in comparison with those without false positivity: earlier week of delivery (p = 0.017), lower neonatal birth weight (p = 0.0004) and neonatal birth weight percentile (p = 0.002), higher rate of intrauterine growth restriction (p = 0.02) and babies weighing less than 2000 g (p = 0.025) were encountered. The presence of false cytomegalovirus IgM in patients with autoimmune diseases could be used as a novel prognostic index of poor pregnancy outcome: it may reflect a non-specific activation of the immune system that could negatively affect pregnancy outcome. Lupus (2010) 19, 844-849. PMID:20305050

De Carolis, S; Santucci, S; Botta, A; Garofalo, S; Martino, C; Perrelli, A; Salvi, S; Degennaro, Va; de Belvis, Ag; Ferrazzani, S; Scambia, G

2010-06-01

144

IFN-?-Producing CD4+ T Cells Promote Generation of Protective Germinal Center-Derived IgM+ B Cell Memory against Salmonella Typhi.  

PubMed

Abs play a significant role in protection against the intracellular bacterium Salmonella Typhi. In this article, we investigated how long-term protective IgM responses can be elicited by a S. Typhi outer-membrane protein C- and F-based subunit vaccine (porins). We found that repeated Ag exposure promoted a CD4(+) T cell-dependent germinal center reaction that generated mutated IgM-producing B cells and was accompanied by a strong expansion of IFN-?-secreting T follicular helper cells. Genetic ablation of individual cytokine receptors revealed that both IFN-? and IL-17 are required for optimal germinal center reactions and production of porin-specific memory IgM(+) B cells. However, more profound reduction of porin-specific IgM B cell responses in the absence of IFN-?R signaling indicated that this cytokine plays a dominant role. Importantly, mutated IgM mAbs against porins exhibited bactericidal capacity and efficiently augmented S. Typhi clearance. In conclusion, repeated vaccination with S. Typhi porins programs type I T follicular helper cell responses that contribute to the diversification of B cell memory and promote the generation of protective IgM Abs. PMID:24778443

Perez-Shibayama, Christian; Gil-Cruz, Cristina; Pastelin-Palacios, Rodolfo; Cervantes-Barragan, Luisa; Hisaki, Emiliano; Chai, Qian; Onder, Lucas; Scandella, Elke; Regen, Tommy; Waisman, Ari; Isibasi, Armando; Lopez-Macias, Constantino; Ludewig, Burkhard

2014-06-01

145

Differential diagnosis of IgM MGUS and WM according to B-lymphoid infiltration by morphology and flow cytometry.  

PubMed

The distinction between IgM monoclonal gammopathy of undetermined significance (MGUS), asymptomatic Waldenstrom's macroglobulinemia (WM; aWM), and symptomatic WM (sWM) relies on two features: the presence of infiltration by lymphoplasmacytic lymphoma in the bone marrow (BM) biopsy and the existence of signs or symptoms attributable to the disease. Nevertheless, some patients lack a BM biopsy or it is not conclusive for diagnosis. In this study we have investigated 94 patients with IgM monoclonal gammopathies, in which a BM trephine biopsy and morphological and flow cytometry (FCM) evaluation of BM aspirate were available at diagnosis. We found a clear correlation between BM infiltration of B-lymphocytes assessed by morphology and by FCM with a Pearson correlation of 0.62 (P<.001). Moreover, in the absence of a BM trephine biopsy, the cut-off points that would help in the differential diagnosis between MGUS, aWM, and sWM would be 20% for morphology and 5% for FCM, both assessed in the BM aspirate. PMID:21454201

Ocio, Enrique M; del Carpio, Daniel; Caballero, Álvaro; Alonso, Jennifer; Paiva, Bruno; Pesoa, Roberto; Villaescusa, Teresa; López-Anglada, Lucía; Vidriales, Belén; García-Sanz, Ramón

2011-02-01

146

Association between IgM anticardiolipin antibodies and deep venous thrombosis in patients without systemic lupus erythematosus.  

PubMed

Patients with systemic lupus erythematosus (SLE) are at risk of developing deep venous thrombosis (DVT). Should anticardiolipin antibodies (aCL) be detectable, this risk is significantly raised, particularly when these autoanti-bodies are cofactor-dependent. We conducted a cross-sectional study of consecutive unselected outpatients referred for clinical suspicion of DVT, as an attempt to address the following questions: firstly, were aCL antibodies associated with DVT in non-SLE patients? Secondly, was this association related to the cofactor dependence? From March 1992 to February 1994, 208 patients were enrolled in the study. Venography was positive in 110 patients (DVT patients), while the diagnosis of DVT could not be confirmed in the remaining 98 (referred to as disease controls). ACL was measured by ELISA, for IgG and IgM isotypes in two ways: fetal calf serum or bovine serum albumin were used as blocking agents to distinguish between cofactor-dependent and cofactor-independent antibodies. Positive aCL was defined as optical density (OD) values greater than the 95th percentile of OD distribution of 60 healthy controls. We found a high frequency of positive IgG aCL antibodies in both DVT patients and in disease controls (25.5 vs 23.5%). We suggest an association between IgM aCL and DVT. This association was, however, not dependent on the cofactor requirement. PMID:9229365

Oger, E; Lernyer, C; Dueymes, M; Le Moigne, E; Bressolette, L; Escoffre, M; Youinou, P; Mottier, D

1997-01-01

147

Autocrine IL-10 promotes human B-cell differentiation into IgM- or IgG-secreting plasmablasts.  

PubMed

B-cell-derived interleukin-10 (IL-10) is known to act in a paracrine fashion to suppress inflammation. Here, we show that IL-10 also acts in an autocrine manner to regulate the differentiation of activated human B cells. We report that IL-10 expression is not restricted to a dedicated B-cell subset, but is induced transiently in peripheral human naïve, memory, and CD5(+) B cells alike upon activation. Global transcriptome comparison of activated human B cells, secreting IL-10 or not, identified 138 differentially regulated genes, most of which were associated with differentiation into antibody-secreting cells and reflecting autocrine IL-10 signaling. We monitored the differentiation of IL-10-secreting B cells and determined the effect of IL-10-blocking antibodies against its autocrine and paracrine signaling. IL-10 signaling promoted the differentiation of activated IL-10-secreting B cells into IgM- or IgG-secreting cells, but was dispensable for IgA secretion. Our data imply that B-cell-derived IL-10 not only suppresses immune reactions via paracrine mechanisms, but can also contribute to the differentiation of IL-10-secreting B cells into IgM- and IgG-secreting plasmablasts through both autocrine and paracrine signaling. PMID:24643722

Heine, Guido; Drozdenko, Gennadiy; Grün, Joachim R; Chang, Hyun-Dong; Radbruch, Andreas; Worm, Margitta

2014-06-01

148

Transferrin-immune complex disease: a potentially overlooked gammopathy mediated by IgM and IgG.  

PubMed

The combination of marked hypersideremia, hypertransferrinemia, and monoclonal gammopathy of underdetermined significance (MGUS) should alert clinicians to the possible presence of an anti-transferrin immunoglobulin, an uncommon acquired disorder also defined as transferrin-immune complex disease (TICD). The authors have previously described a case of TICD with 100% transferrin saturation and liver iron overload. However, the findings in the few cases so far reported are heterogeneous, and the presence of high transferrin saturation and liver iron overload is not universal. In this article, the authors have described the identification of two additional patients with anti-transferrin monoclonal gammopathy, hypersideremia, and hypertransferrinemia, but with incomplete transferrin saturation and no hepatic iron overload. The autoantibodies were purified by using transferrin as affinity bait and characterized. One subject showed a high-titer monoclonal anti-transferrin IgM with a ?-type light chain. This finding is the first observation of IgM autoantibodies against transferrin. The other patient developed the disease after pregnancy. In this study, monoclonal antibody was an IgG mounting a ?-type light chain with altered molecular weight. These results highlight that transferrin might induce the development of a monoclonal immune response of different classes and specificity. The identification, in a single hematologic center, of three different subjects with anti-transferrin monoclonal gammopathy suggests that the disease probably represents a still underdiagnosed condition. From a clinical standpoint, these patients must be followed up both as MGUS and as hemochromatosis. PMID:23913829

Forni, Gian Luca; Pinto, Valeria; Musso, Marco; Mori, Marco; Girelli, Domenico; Caldarelli, Ilaria; Borriello, Adriana; Ragione, Fulvio Della

2013-12-01

149

Analysis of the interaction of monoclonal antibodies with surface IgM on neoplastic B-cells  

PubMed Central

In vitro studies identified three Burkitts lymphoma cell lines, Ramos, MUTU-I and Daudi, that were growth inhibited by anti-IgM antibody. However, only Ramos and MUTU-I were sensitive to monoclonal antibodies (mAb) recognizing the Fc region of surface IgM (anti-Fc?). Experiments using anti-Fc? mAb (single or non-crossblocking pairs), polyclonal anti-? Ab, and hyper-crosslinking with a secondary layer of Ab, showed that growth inhibition of B-cell lines was highly dependent on the extent of IgM crosslinking. This was confirmed by using Fab?, F(ab?)2and F(ab?)3derivatives from anti-Fc? mAb, where increasing valency caused corresponding increases in growth arrest and apoptosis, presumably as a result of more efficient BCR-crosslinking on the cell surface. The ability of a single mAb to induce growth arrest was highly dependent on epitope specificity, with mAb specific for the Fc region (C?2–C?4 domains) being much more effective than those recognizing the Fab region (anti-L chain, anti-Id and anti-Fd?, or C?1). Only when hyper-crosslinked with polyclonal anti-mouse IgG did the latter result in appreciable growth inhibition. Binding studies showed that these differences in function were not related to differences in the affinity, but probably related to intrinsic crosslinking capacity of mAb. © 1999 Cancer Research Campaign

Cragg, M S; Zhang, L; French, R R; Glennie, M J

1999-01-01

150

Severe cranial nerve involvement in a patient with monoclonal anti-MAG/SGPG IgM antibody and localized hard palate amyloidosis.  

PubMed

We report a patient with severe cranial polyneuropathy as well as sensory limb neuropathy. Biclonal serum IgM-kappa/IgM-lambda gammopathy was found and serum anti-myelin-associated glycoprotein (MAG)/sulfoglucuronyl paragloboside (SGPG) IgM antibody was also detected. Immunofluorescence analysis of a sural nerve biopsy specimen revealed binding of IgM and lambda-light chain on myelin sheaths. No amyloid deposition was detected in biopsied tissues except for the hard palate, suggesting that the amyloidosis was of the localized type and had no relation to the pathogenesis of cranial neuropathy. Our observations indicate that the anti-MAG/SGPG IgM antibody may be responsible for this patient's cranial polyneuropathy, which is a rare manifestation in anti-MAG/SGPG-associated neuropathy. PMID:16546215

Yoshida, Takuhiro; Yazaki, Masahide; Gono, Takahisa; Tazawa, Ko-ichi; Morita, Hiroshi; Matsuda, Masayuki; Funakoshi, Kei; Yuki, Nobuhiro; Ikeda, Shu-ichi

2006-05-15

151

Reduced IgG anti-small nuclear ribonucleoprotein autoantibody production in systemic lupus erythematosus patients with positive IgM anti-cytomegalovirus antibodies  

PubMed Central

Introduction Systemic lupus erythematosus is characterized by production of autoantibodies to RNA or DNA–protein complexes such as small nuclear ribonucleoproteins (snRNPs). A role of Epstein–Barr virus in the pathogenesis has been suggested. Similar to Epstein–Barr virus, cytomegalovirus (CMV) infects the majority of individuals at a young age and establishes latency with a potential for reactivation. Homology of CMV glycoprotein B (UL55) with the U1snRNP-70 kDa protein (U1–70 k) has been described; however, the role of CMV infection in production of anti-snRNPs is controversial. We investigated the association of CMV serology and autoantibodies in systemic lupus erythematosus. Methods Sixty-one Mexican patients with systemic lupus erythematosus were tested for CMV and Epstein–Barr virus serology (viral capsid antigen, IgG, IgM) and autoantibodies by immunoprecipitation and ELISA (IgG and IgM class, U1RNP/Sm, U1–70 k, P peptide, rheumatoid factor, dsDNA, ?2-glycoprotein I). Results IgG anti-CMV and IgM anti-CMV were positive in 95% (58/61) and 33% (20/61), respectively, and two cases were negative for both. Clinical manifestation and autoantibodies in the IgM anti-CMV(+) group (n = 20) versus the IgM anti-CMV(-)IgG (+) (n = 39) group were compared. Most (19/20) of the IgM anti-CMV(+) cases were IgG anti-CMV(+), consistent with reactivation or reinfection. IgM anti-CMV was unrelated to rheumatoid factor or IgM class autoantibodies and none was positive for IgM anti-Epstein–Barr virus–viral capsid antigen, indicating that this is not simply due to false positive results caused by rheumatoid factor or nonspecific binding by certain IgM. The IgM anti-CMV(+) group has significantly lower levels of IgG anti-U1RNP/Sm and IgG anti-U1–70 k (P = 0.0004 and P = 0.0046, respectively). This finding was also confirmed by immunoprecipitation. Among the IgM anti-CMV(-) subset, anti-Su was associated with anti-U1RNP and anti-Ro (P < 0.05). High levels of IgG anti-CMV were associated with production of lupus-related autoantibodies to RNA or DNA–protein complex (P = 0.0077). Conclusions Our findings suggest a potential role of CMV in regulation of autoantibodies to snRNPs and may provide a unique insight to understand the pathogenesis.

Palafox Sanchez, Claudia Azucena; Satoh, Minoru; Chan, Edward KL; Carcamo, Wendy C; Munoz Valle, Jose Francisco; Orozco Barocio, Gerardo; Oregon Romero, Edith; Navarro Hernandez, Rosa Elena; Salazar Paramo, Mario; Cabral Castaneda, Antonio; Vazquez del Mercado, Monica

2009-01-01

152

The Role of B-cells and IgM Antibodies in Parasitemia, Anemia, and VSG Switching in Trypanosoma brucei-Infected Mice  

PubMed Central

African trypanosomes are extracellular parasitic protozoa, predominantly transmitted by the bite of the haematophagic tsetse fly. The main mechanism considered to mediate parasitemia control in a mammalian host is the continuous interaction between antibodies and the parasite surface, covered by variant-specific surface glycoproteins. Early experimental studies have shown that B-cell responses can be strongly protective but are limited by their VSG-specificity. We have used B-cell (µMT) and IgM-deficient (IgM?/?) mice to investigate the role of B-cells and IgM antibodies in parasitemia control and the in vivo induction of trypanosomiasis-associated anemia. These infection studies revealed that that the initial setting of peak levels of parasitemia in Trypanosoma brucei–infected µMT and IgM?/? mice occurred independent of the presence of B-cells. However, B-cells helped to periodically reduce circulating parasites levels and were required for long term survival, while IgM antibodies played only a limited role in this process. Infection-associated anemia, hypothesized to be mediated by B-cell responses, was induced during infection in µMT mice as well as in IgM?/? mice, and as such occurred independently from the infection-induced host antibody response. Antigenic variation, the main immune evasion mechanism of African trypanosomes, occurred independently from host antibody responses against the parasite's ever-changing antigenic glycoprotein coat. Collectively, these results demonstrated that in murine experimental T. brucei trypanosomiasis, B-cells were crucial for periodic peak parasitemia clearance, whereas parasite-induced IgM antibodies played only a limited role in the outcome of the infection.

Magez, Stefan; Schwegmann, Anita; Atkinson, Robert; Claes, Filip; Drennan, Michael; De Baetselier, Patrick; Brombacher, Frank

2008-01-01

153

Reduced IgM levels and elevated IgG levels against oxidized low-density lipoproteins in HIV-1 infection  

PubMed Central

Background Chronic HIV infection is associated with increased risk of cardiovascular disease caused by atherosclerosis. Oxidized forms of low-density lipoprotein (LDL) are present in atherosclerotic lesions and constitute major epitopes for natural antibodies. IgM has been shown to be protective against atherosclerosis, whereas the role of corresponding IgG is less clear. The objective of this study was to determine if HIV?+?individuals have disturbed levels of IgM and IgG directed against oxidized forms of LDL as compared to HIV- individuals. Methods Ninety-one HIV?+?patients and 92 HIV- controls were included in this retrospective study. Circulating levels of IgG and IgM directed against two forms of oxidized LDL; copper oxidized (OxLDL) and malondialdehyde modified (MDA-LDL), total IgM and IgG, C-reactive protein (CRP), soluble CD14, and apolipoproteins A1 and B were determined. Results HIV?+?individuals had slightly lower levels of IgM against MDA-LDL and higher levels of IgG against MDA-LDL, OxLDL, and total IgG, than HIV- controls. Anti-MDA-LDL and Anti-OxLDL IgG displayed a positive correlation with viral load and a negative correlation with the CD4+ T-cell count. HIV?+?individuals also displayed elevated CRP and soluble CD14 levels compared to HIV- individuals, but there were no correlations between CRP or soluble CD14 and specific antibodies. Conclusions HIV infection is associated with higher levels of IgG including specific IgG against oxidized forms of LDL, and lower IgM against the same epitope. In addition to dyslipidemia, immune activation, HIV-replication and an accumulation of risk factors for atherosclerosis, this adverse antibody profile may be of major importance for the increased risk of cardiovascular disease in HIV?+?individuals.

2014-01-01

154

IgM AL amyloidosis due to B cell lymphoproliferative disorder: efficacy of high-dose melphalan followed by autologous stem cell transplantation.  

PubMed

This report concerns a patient with IgM AL amyloidosis due to a B cell lymphoproliferative disorder who was successfully treated with VAD and subsequent high-dose melphalan followed by autologous stem cell support. After this chemotherapeutic regimen, the patient showed complete hematological remission and improvement in nephrotic syndrome. These findings suggest that high-dose melphalan may also be effective for lymphoplasmacytoid cells producing monoclonal IgM which are phenotypically distinct from plasma cells. Myeloablative therapies, such as high-dose melphalan, should definitely be considered as a treatment option for AL amyloidosis, irrespective of the type of precursor immunoglobulin. PMID:15478470

Gono, Takahisa; Matsuda, Masayuki; Shimojima, Yasuhiro; Ishii, Wataru; Yamamoto, Kanji; Koyama, Jun; Sakashita, Kazuo; Koike, Kenichi; Itoh, Susumu; Isaka, Toshifumi; Ikeda, Shu-ichi

2004-06-01

155

Gold blot for detection of immunoglobulin M (IgM)- and IgG-specific antibodies for rapid serodiagnosis of melioidosis.  

PubMed Central

Gold blot tests for rapid serodiagnosis of melioidosis were developed and evaluated with sera from 40 melioidosis patients and 159 normal controls. The sensitivity and specificity were 87.5 and 88%, respectively, for the immunoglobulin M (IgM) test and 100 and 91%, respectively, for the protein A test for IgG. Combination of the IgM gold blot and protein A gold blot yielded 97.5% sensitivity and 94.3% specificity. The tests were rapid and simple.

Kunakorn, M; Petchclai, B; Khupulsup, K; Naigowit, P

1991-01-01

156

Clinicopathologic Characterization of Diffuse-Large-B-Cell Lymphoma with an Associated Serum Monoclonal IgM Component  

PubMed Central

Recently, diffuse-large-B-cell lymphoma (DLBCL) associated with serum IgM monoclonal component (MC) has been shown to be a very poor prognostic subset although, detailed pathological and molecular data are still lacking. In the present study, the clinicopathological features and survival of IgM-secreting DLBCL were analyzed and compared to non-secreting cases in a series of 151 conventional DLBCL treated with R-CHOP. IgM MC was detected in 19 (12.5%) out of 151 patients at disease onset. In 17 of these cases secretion was likely due to the neoplastic clone, as suggested by the expression of heavy chain IgM protein in the cytoplasm of tumor cells. In IgM-secreting cases immunoblastic features (p<.0001), non-GCB-type (p?=?.002) stage III-IV(p?=?.003), ?2 extra nodal sites (p<.0001), bone-marrow (p?=?.002), central-nervous-system (CNS) involvement at disease onset or relapse (p<.0001), IPI-score 3–5 (p?=?.009) and failure to achieve complete remission (p?=?.005), were significantly more frequent. FISH analyses for BCL2, BCL6 and MYC gene rearrangements detected only two cases harboring BCL2 gene translocation and in one case a concomitant BCL6 gene translocation was also observed. None of the IgM-secreting DLBCL was found to have L265P mutation of MYD88 gene. Thirty-six month event-free (11.8% vs 66.4% p<.0001), progression-free (23.5% vs 75.7%, p<.0001) and overall (47.1% vs 74.8%, p<.0001) survivals were significantly worse in the IgM-secreting group. In multivariate analysis IgM-secreting (p?=?.005, expB?=?0.339, CI?=?0.160-0.716) and IPI-score 3–5 (p?=?.010, expB?=?0.274, CI?=?0.102–0.737) were the only significant factors for progression-free-survival. Notably, four relapsed patients, who were treated with salvage immmunochemotherapy combined with bortezomib or lenalidomide, achieved lasting remission. Our data suggests that IgM-secreting cases are a distinct subset of DLBCL, originating from activated-B-cells with terminally differentiated features, prevalent extra nodal dissemination and at high risk of CNS involvement.

Scarpino, Stefania; Salerno, Gerardo; Tatarelli, Caterina; Talerico, Caterina; Lombardi, Mariangela; Monarca, Bruno; Amadori, Sergio; Ruco, Luigi

2014-01-01

157

Occurrence of mature B (IgM+, B220+) and T (CD3+) lymphocytes in scid mice.  

PubMed

Scid mice with and without detectable serum Ig (scid Ig+ and scid Ig- mice, respectively) were examined for the presence of mature "leaky" lymphocytes by flow microfluorimetry with the use of antibodies to B (IgM, B220) and T (CD3, CD4, CD8) lymphocyte surface Ag. The data showed that leaky scid mice are more frequent than is evident from serum Ig analysis and that the incidence of detectable B and T cells increases with age. IgM+ B220+ cells were not detectable in young adult mice (3 mo old), but in old mice (greater than or equal to 1 yr old) they were routinely present in the peritoneal cavity though not in the spleen. Striking differences in the representation of T cell subsets were seen in the thymus of these two age groups. Most young adult mice contained CD3- populations of CD4/CD8 double positive cells, and in some cases, CD4 or CD8 single positive cells as well. By contrast, identifiable T lineage cells in old mice were all CD3+ and predominantly single positive for CD4 or CD8. Detectable peripheral T cell populations numbered less than 10(5) cells, and the representation of T subset markers (CD4, CD8) varied widely among individual mice; further, Southern blot analysis of TCR gene rearrangements in the DNA of polyclonally stimulated lymphoid cultures from these mice showed very restricted heterogeneity relative to that of cultures from normal mice. We conclude that most leaky mice contain very few T cell clones. PMID:2473116

Carroll, A M; Hardy, R R; Bosma, M J

1989-08-15

158

Separation of different molecular forms of mouse IgA and IgM monoclonal antibodies by high-performance liquid chromatography on spherical hydroxyapatite beads.  

PubMed

High-performance liquid chromatography (HPLC) on newly developed spherical beads of hydroxyapatite (HAP) was applied to the separation of different molecular forms of mouse IgA and IgM monoclonal antibodies (mAbs). Monomeric, dimeric, trimeric and tetrameric forms of an IgA mAb were eluted from the column separately with appreciable differences in retention volume by a 20 ml (40 min) gradient of phosphate buffer (pH 6.8) of concentration from 10 to 400 mM. The volumes of respective forms were highly reproducible. In addition, a monomeric form was resolved successfully from a pentameric form of IgM mAbs by HPLC on HAP beads under the same conditions. All forms of IgA and IgM mAbs were eluted almost quantitatively from the column. The results indicate that HPLC on HAP beads is useful for isolation and characterization of different molecular forms of IgA and IgM mAbs. PMID:8391046

Aoyama, K; Chiba, J

1993-06-18

159

Polyclonal serum IgM level identifies a subgroup of multiple myeloma patients with low-risk clinicobiological features and superior survival.  

PubMed

Normal plasma cells (PCs) are either undetectable or outnumbered by the myelomatous PC compartment in bone marrow of multiple myeloma (MM). However, residual normal PCs have been detected in a minority of symptomatic MM patients with superior survival. The number of normal PCs is also an important factor to identify monoclonal gammopathy of undetermined significance (MGUS)-like MM. We speculate that the polyclonal serum IgM level in non-IgM myelomas may reflect the number of residual normal PCs. Here we investigated the prognostic relevance of polyclonal serum IgM level in a series of 485 newly diagnosed symptomatic MM (NDMM) patients. Our results showed that symptomatic MM patients with polyclonal IgM more than 0.5g/L displayed a favorable baseline clinical feature, together with a significantly lower frequency of high-risk cytogenetic abnormalities. This group of patients had a significantly prolonged progression-free survival (PFS) and overall survival (OS) regardless of thalidomide or bortezomib therapy. Furthermore, the superior outcome was independent of the depth of response. Our findings suggest that polyclonal IgM level is capable of identifying a group of symptomatic MM patients with distinct clinicobiological characteristics and favorable survival, similar with MGUS-like MM. PMID:24746293

An, Gang; Wang, Huijun; Qin, Xiaoqi; Shi, Lihui; Xu, Yan; Deng, Shuhui; Sui, Weiwei; Zhu, Guoqing; Yao, Hongjing; Yi, Shuhua; Qin, Yu; Li, Fei; Hao, Mu; Ru, Kun; Qi, Junyuan; Cheng, Tao; Wang, Jianxiang; Chang, Hong; Qiu, Lugui

2014-06-01

160

[Changes of IgA, IgG and IgM immunoglobulins and of 10 other plasma proteins in patients with duodenal ulcer treated with ranitidine].  

PubMed

In 25 patients with duodenal ulcer, before treatment and after three weeks, and another 30 days of treatment with ranitidine, plasma concentrations were determined of IgA, IgG, IgM immunoglobulins, and of 10 other proteins. In comparison to the control group of 20 persons, a statistically significant decrease was found in the concentration of alpha 2-M, prealbumins, and IgG, as well as a significant increase of alpha 1-AT, C4 complement component, and a non-significant increase of coeruloplasmin, haptoglobin and IgM. During the treatment a tendency was observed for an increase of IgG and IgM level, as well as a statistically significant decrease of alpha 1-AT, C4, and coeruloplasmin concentration. The treatment exerted no effect on the decreased level of alpha 2-M. It was accepted that the tendency for an increase of IgG and IgM level was due, most probably, to the immunostimulating action of ranitidine, and the changes of concentrations of other parameters induced by the treatment were related to the presence and healing of the ulceration. The observed decrease of alpha 2-M level was probably due to binding of alpha 2-M to pepsinogen whose blood level was increased during gastric ulcer. PMID:8249388

Przyby?owski, J; Bartelik, S; Szrajer, J; Kolus, D

1993-01-01

161

Measurement of murine IgG and IgM concentrations in the SCLC MAb panel; effects of concentration on sensitivity and specificity.  

PubMed

Sensitive, solid-phase enzyme immunoassays for detecting murine IgM and IgG were developed and used to quantitate immunoglobulin concentrations in the SCLC MAb panel. Among the IgM MAbs, most contained between 10-75 micrograms ml-1. At least three IgM MAbs, however, contained less than 2 micrograms ml-1 and six contained greater than 75 micrograms ml-1. Two of the three IgM's containing less than 2 micrograms ml-1 immunoglobulin were found to cluster with the negative controls. Among the IgG MAbs, the majority contained between 10-100 micrograms ml-1 Ig. At least five of the IgG MAbs contained greater than 100 micrograms ml-1; and six were less than 2 micrograms ml-1. Three of the MAbs containing less than 2 micrograms ml-1 IgG clustered with the negative controls. Many of the panel members containing greater than 50 micrograms ml-1 antibody were found to give nonspecific immunostaining on tissues and cell lines. Often this nonspecific immunostaining was eliminated when these MAbs were diluted. Although only a minority of the panel members contained very high or very low concentrations of antibody, the data highlight the inherent difficulties that may result, in part from this variable and suggest that efforts be made to normalise the Ig concentrations of panel members in future workshop panels. PMID:1645575

Manderino, G L

1991-06-01

162

Distribution of IgM and IgG antibodies to oxidized LDL in immune complexes isolated from patients with type 1 diabetes and its relationship with nephropathy  

PubMed Central

Modified lipoproteins are immunogenic and play a key pathogenic role in vascular disease. Antibodies to oxidized LDL (oxLDL) are mostly of the proinflammatory IgG1 and IgG3 isotypes. We measured IgG and IgM oxLDL antibodies in immune complexes (IC) isolated from 36 patients with type 1 diabetes using a nested case-control design. IgG antibodies predominated over IgM antibodies by an 8:1 ratio. IgG antibody concentrations were higher in the nephropathy cases compared to controls (p=0.09), but no significant difference was observed because of two patients included in the study who had end-stage renal disease (creatinine > 5mg/dl and glomerular filtration rate (GFR) less than 17 ml/min). After eliminating these patients from the analysis, significant positive associations of IgG antibody concentration with serum creatinine and albumin excretion rate were observed after eliminating two patients with significant renal impairment (serum creatinine > 5 mg/dl). Similarly, a negative correlation with estimated glomerular filtration rate was observed in this subsample of 34 patients. Differences in IgM antibody concentrations by nephropathy classification were not supported by the data. In conclusion, the predominance of pro-inflammatory IgG oxLDL antibodies is associated with existence of diabetic nephropathy, and a protective role of IgM antibodies could not be demonstrated.

Virella, Gabriel; Carter, Rickey E.; Saad, Antonio; Crosswell, Edward G.; Game, B. Andrew; Lopes-Virella, Maria F.

2008-01-01

163

Antibody-dependent cell-mediated cytotoxicity in the Moloney sarcoma virus system: differential activity of IgG and IgM with different subpopulations of lymphocytes  

PubMed Central

Antibody-dependent cell-mediated cytotoxicity in the Moloney sarcoma virus (MSV) system was evaluated in terms of the differential ability of IgG and IgM from MSV regressor animals to induce cytotoxicity by lymphocytes from lymph node, spleen, and thymus. The cell-mediated cytotoxicity induced by both IgM and IgG was specific for target possessing the appropriate virally determined cell surface antigen(s). IgM induced cytotoxicity by lymphocytes from all the organs tested. However, differences in magnitude and efficiency were revealed. Lymph node cells and thymocytes were most efficient against IgM-coated target cells. Against IgG-sensitized target cells, spleen and lymph node cells were about equally active, but thymocytes were inactive. Cortisone treatment of the donors of effector cells revealed that the cortisone resistant subpopulation of thymocytes, 2 days after cortisone injection, exhibited an increased cytotoxicity against target cells treated with unfractionated antiserum and its IgM fraction. This subpopulation of thymocytes was also cytotoxic against IgG-coated target cells. At 12 days after cortisone injection, the repopulated thymus showed little change in activity, compared to control thymus, against antibody-coated target cells.

1977-01-01

164

Effect of multiple freeze and thaw cycles on the sensitivity of IgG and IgM immunoglobulins in the sera of patients with syphilis.  

PubMed

We describe the effects of multiple freeze and thaw cycles on the sensitivity of the immunoglobulins IgG and IgM measured by enzyme-linked immunoassays in the sera of patients with syphilis. Stored frozen sera can withstand repeated freezing and thawing cycles with a minimal detrimental effect on the sensitivity of the sera. PMID:24113410

Castro, Arnold R; Jost, Heather A

2013-11-01

165

The enzyme-linked immunosorbent assay (ELISA) for determination of IgG and IgM antibodies after infection with mumps virus  

Microsoft Academic Search

Under routine laboratory conditions ELISA was tested for suitability for serological demonstration of specific antibodies of the immunoglobulin classes G and M against mumps virus. Sera from patients with known clinical and virological data were used. The results of ELISA were compared with those of CFT. 45 paired sera were tested in ELISA IgG, 87 first sera in ELISA IgM.

M. E. Nicolai-Scholten; R. Ziegelmaier; F. Behrens; W. Höpken

1980-01-01

166

Outcome of Patients With IgD and IgM Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplantation: A Retrospective CIBMTR Study  

PubMed Central

Introduction Immunoglobulin D (IgD) and IgM multiple myeloma represent uncommon immunoglobulin isotypes, accounting for 2% and 0.5% of cases, respectively. Limited information is available regarding the prognosis of these isotypes, but they have been considered to have a more aggressive course than the more common immunoglobulin G (IgG) and IgA isotypes. In particular, the outcome after autologous hematopoietic stem cell transplantation (auto-HCT) has not been well defined. Patients and Methods Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified 36 patients with IgD and 11 patients with IgM myeloma among 3578 myeloma patients who received intensive therapy and auto-HCT over a 10-year period. Results The progression-free and overall survival probabilities at 3 years were 38% (95% CI, 21%-56%) and 69% (95% CI, 51%-84%) for IgD myeloma, and 47% (95% CI, 17%-78%) and 68% (95% CI, 36%-93%), respectively, for IgM disease. Although formal statistical analysis was limited by the small sample size, these results were comparable to those for IgG and IgA patients autografted during the same time period. Transplantation-related mortality and disease relapse/progression of myeloma were also similar for all isotypes. Conclusion This analysis demonstrates comparable outcomes in all immunoglobulin isotypes. Therefore, auto-HCT should be offered to eligible patients with IgD and IgM myeloma.

Reece, Donna E.; Vesole, David H.; Shrestha, Smriti; Zhang, Mei-Jie; Perez, Waleska S.; Dispenzieri, Angela; Milone, Gustavo A.; Abidi, Muneer; Atkins, Harold; Bashey, Asad; Bredeson, Christopher N.; Boza, Willem Bujan; Freytes, Cesar O.; Gale, Robert Peter; Gajewski, James L.; Gibson, John; Hale, Gregory A.; Kumar, Shaji; Kyle, Robert A.; Lazarus, Hillard M.; McCarthy, Philip L.; Pavlovsky, Santiago; Roy, Vivek; Weisdorf, Daniel J.; Wiernik, Peter H.; Hari, Parameswaran N.

2012-01-01

167

Search for QSOS Suitable for Subsequent Observation of he II 304 Absorption Arising in the IGM, Ly-Alpha and ... PART3  

NASA Astrophysics Data System (ADS)

THIS IS PART Three OF PROPOSAL 3801. IT CONTAINS 40 TARGETS OF HIGH PRIORITY. EXCEPT FOR TARGETS, THIS PROPOSAL IS IDENTICAL TO 3801. Targets are in order of decreasing priority. Priority matters a lot. Best targets are listed first. Ultraviolet images will be obtained in snapshot mode of the 500 known high-redshift (z > 2.8) QSOs in order to identify the few (about 20) targets which have sufficient ultraviolet flux for subsequent FOC/FOS or GHRS observations of He II 304. The detection of absorption by the Helium II Lyman-alpha line at 304 A, one of the most exciting prospects of the HST, will provide the first direct detection of the diffuse intergalactic medium (IGM). The absence of Gunn-Peterson H I 1215 absorption shows that the IGM is hot and/or of very low density, thus He I 584 is not expected to be observable. He II 304--the most promising line--should be observable from three sources: the diffuse IGM, the discrete Ly-alpha clouds, and the much rarer metal line absorption systems. The Gunn-Peterson continuum optical depth is not well constrained by models (range 0.3-3000). The mere detection of only one QSO below 304 A would rule out many models, limiting the IGM density, temperature, and ionization mechanisms. Similarly the total absence of flux from several targets would rule out other models.

Tytler, David

1992-07-01

168

Search for QSOS Suitable for Subsequent Observation of he II 304 Absorption Arising in the IGM, Ly-Alpha and ... PART2  

NASA Astrophysics Data System (ADS)

THIS IS PART TWO OF PROPOSAL 3801, CONTAINING 55 TARGETS OF PRIORITY 7,8 AND 9. EXCEPT FOR TARGETS, THIS PROPOSAL IS IDENTICAL TO 3801, WHICH HAS 87 TARGETS OF PRIORITY 3,4,5 AND 6. Ultraviolet images will be obtained in snapshot mode of the 500 known high-redshift (z > 2.8) QSOs in order to identify the few (about 20) targets which have sufficient ultraviolet flux for subsequent FOC/FOS or GHRS observations of He II 304. The detection of absorption by the Helium II Lyman-alpha line at 304 A, one of the most exciting prospects of the HST, will provide the first direct detection of the diffuse intergalactic medium (IGM). The absence of Gunn-Peterson H I 1215 absorption shows that the IGM is hot and/or of very low density, thus He I 584 is not expected to be observable. He II 304--the most promising line--should be observable from three sources: the diffuse IGM, the discrete Ly-alpha clouds, and the much rarer metal line absorption systems. The Gunn-Peterson continuum optical depth is not well constrained by models (range 0.3-3000). The mere detection of only one QSO below 304 A would rule out many models, limiting the IGM density, temperature, and ionization mechanisms. Similarly the total absence of flux from several targets would rule out other models.

Tytler, David

1992-07-01

169

Low-affinity IgM antibodies lacking somatic hypermutations are produced in the secondary response of C57BL/6 mice to (4-hydroxy-3-nitrophenyl)acetyl hapten.  

PubMed

Class-switched memory B cells, which are generated through the processes of somatic hypermutation (SHM) and affinity-based selection in germinal centers, contribute to the production of affinity-matured IgG antibodies in the secondary immune response. However, changes in the affinity of IgM antibodies during the immune response have not yet been studied, although IgM(+) memory B cells have been shown to be generated. In order to understand the relationship between IgM affinity and the recall immune response, we prepared hybridomas producing anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) IgM antibodies from C57BL/6 mice and from activation-induced cytidine deaminase (AID)-deficient mice. Binding analysis by ELISA showed that mAbs obtained from the secondary immune response contained IgM mAbs with affinity lower than the affinity of mAbs obtained from the primary response. By analyzing sequences of the IgM genes of hybridomas and plasma cells, we found many unmutated VH genes. VH genes that had neither tyrosine nor glycine at position 95 were frequent. The repertoire change may correlate with the lower affinity of IgM antibodies in the secondary response. The sequence and affinity changes in IgM antibodies were shown to be independent of SHM by analyzing hybridomas from AID-deficient mice. A functional assay revealed a reciprocal relationship between affinity and complement-dependent hemolytic activity toward NP-conjugated sheep RBCs; IgM antibodies with lower affinities had higher hemolytic activity. These findings indicate that lower affinity IgM antibodies with enhanced complement activation function are produced in the secondary immune response. PMID:24285827

Murakami, Akikazu; Moriyama, Hayato; Osako-Kabasawa, Mina; Endo, Kanako; Nishimura, Miyuki; Udaka, Keiko; Muramatsu, Masamichi; Honjo, Tasuku; Azuma, Takachika; Shimizu, Takeyuki

2014-04-01

170

Activation of TLR9 by incorporated pDNA within PEG-coated lipoplex enhances anti-PEG IgM production.  

PubMed

Cationic liposome represents a promising alternative to viral vectors for the delivery of therapeutic genes. For in vivo use, surface modification of the liposome with polyethylene glycol (PEG) is frequently applied to achieve gene-expression in the targeted tissue. However, we have reported that PEG-coated liposomes have induced anti-PEG IgM, which has caused subsequent doses of PEG-coated liposome to be rapidly cleared from blood circulation, and the complexation of pDNA electrostatically associated with liposome surface has enhanced this antibody response. In this study, we investigated how a Toll-like receptor (TLR) might enhance anti-PEG IgM production. PEG-coated pDNA-lipoplex (PDCL) was injected into either wild type, MyD88 (all TLR adaptor protein, independent of TLR3) knock out (KO) or TLR9 KO mice, and the anti-PEG IgM production levels were detected. Attenuated anti-PEG IgM production following the injection of PDCL was observed in both MyD88 and TLR9 KO mice compared to wild type mice, probably due to the abolished induction of cytokines in both MyD88 and TLR9 KO mice. Our results suggest that TLR, exclusively TLR9, signaling plays a potential role in the enhanced anti-PEG IgM production following the injection of PDCL. This result may have important implications for the design and development of an efficient PEG-coated non-viral gene vector. PMID:24694537

Hashimoto, Y; Uehara, Y; Abu Lila, A S; Ishida, T; Kiwada, H

2014-06-01

171

Anti-alpha-galactosyl immunoglobulin A (IgA), IgG, and IgM in human secretions.  

PubMed Central

Anti-alpha-galactosyl (anti-Gal) is a natural human serum antibody that binds to the carbohydrate Gal alpha 1,3Gal beta 1,4GlcNAc-R (alpha-galactosyl epitope) and is synthesized by 1% of circulating B lymphocytes in response to immune stimulation by enteric bacteria. We were able to purify secretory anti-Gal from human colostrum and bile by affinity chromatography on silica-linked Gal alpha 1,3Gal beta 1,4GlcNAc. We found similar secretory anti-Gal antibodies in human milk, saliva, and vaginal washings. Secretory anti-Gal from milk and saliva was exclusively immunoglobulin A (IgA); that from colostrum and bile also contained IgG and IgM isotypes. Serum was also found to contain anti-Gal IgM and IgA in addition to the previously reported IgG. Anti-Gal IgA purified from colostrum and bile had both IgA1 and IgA2. Secretory anti-Gal from saliva, milk, colostrum, and bile agglutinated rabbit erythrocytes (RRBC) and bound to bovine thyroglobulin, both of which have abundant alpha-galactosyl epitopes. The RRBC-hemagglutinating capacity of human saliva, milk, bile, and serum was specifically adsorbed by immobilized Gal alpha 1,3Gal beta 1,4GlcNAc but not by Gal alpha 1,4Gal beta 1,4GlcNAc, Gal beta 1,3GalNAc, Gal beta 1,4GlcNAc, Gal beta 1,4GlcNAc alpha 1,2Man, or Fuc alpha 1,2Gal beta 1,4GlcNAc. No RRBC-hemagglutinating activity could be detected in rat milk, rat bile, cow milk, or rabbit bile, suggesting a restricted species distribution for secretory anti-Gal similar to that found for serum anti-Gal. Colostral anti-GaI IgA bound strongly to a sample of gram-negative bacteria isolated from the throats and stools of well children as well as to an Escherichia coli K-1 blood isolate. Colostral anti-GaI IgA inhibited the binding of a Neisseria meningitidis strain to human buccal epithelial cells, suggesting that this antibody may play a protective role at the mucosal surface.

Hamadeh, R M; Galili, U; Zhou, P; Griffiss, J M

1995-01-01

172

Chemically Self-assembled Antibody Nanorings (CSANs): Design and Characterization of an Anti-CD3 IgM Biomimetic  

PubMed Central

A number of clever recombinant methodologies have been developed that recapitulate the valencies of IgG’s (bivalent) and IgA’s (tetravalent). Although, higher synthetic valencies have been achieved by conjugation of either monoclonal antibodies or single-chain antibodies to nanoparticles and liposomes, a method for the preparation of recombinant antibodies with valencies similar to IgM’s (decavalent) but considerably less than what is generally found after antibody particle conjugation has yet to be devised. Recently, we have developed a methodology for the design of bivalent Chemically Self-Assembled Antibody Nanorings (CSANs). We now report the crystal structure of the nanoring subunit composed of the E. coli DHFR dimer and a methotrexate dimerizer (MTX2-C9) containing visible nine methylene linker and a protocol for the preparation of CSANs from this subunit with valencies similar to IgMs, ranging from 8–10 single chain antibodies (scFvs). The multivalent CSANs were reversibly assembled from a fusion protein dihydrofolate reductase (DHFR)-DHFR-antiCD3 scFv containing a single glycine linker between the two DHFR scaffolding proteins. We also demonstrate that, similar to the parental bivalent anti-CD3 monoclonal antibody (MAB), anti-CD3 CSANs selectively bind to CD3+ leukemia cells, and undergo rapid internalization through a caveolin-independent pathway that requires cholesterol, actin polymerization and protein tyrosine kinase activation. While treatment with the monoclonal antibody leads to T-cell activation and nearly complete loss (i.e. 90%) of surface displayed T-cell receptor (TCR), only 25–30% of the TCR down regulate and no significant T-cell proliferation is observed after treatment of peripheral blood mononuclear cells (PBMCs) with anti-CD3 CSANs. Consistent with the proliferation findings, 15–25 % less CD25 (IL-2 receptor) was found on the surface of PBMCs treated with either the polyvalent or bivalent anti-CD3 CSANs, respectively, than on PBMCs treated with the parental MAB. Comparative experiments with F(ab')2 derived from the MAB confirm that the activation of the T-cells by the MAB is dependent on the Fc domain, and thus interactions of the PBMC T-cells with accessory cells, such as macrophages. Taken together, our results demonstrate that anti-CD3 CSANs with valencies ranging from 2 to 8 could be employed for radionuclide, drug or potentially oligonucleotide delivery to T-cells without, as has been observed for other antibody conjugated nanoparticles, the deleterious affects of activation observed for MAB. Further the CSAN construct may be adapted for the preparation of other multivalent scFvs.

Li, Qing; So, Christopher R.; Fegan, Adrian; Cody, Vivian; Sarikaya, Mehmet; Vallera, Daniel A.; Wagner, Carston R.

2010-01-01

173

Kinetics of non-structural protein 1, IgM and IgG antibodies in dengue type 1 primary infection  

PubMed Central

Background Early and accurate diagnosis of dengue infection is essential for control of disease outbreaks. Recently, the dengue virus non-structural antigen 1 (NS1), a conserved and secreted glycoprotein, has been used as a marker for early diagnosis of dengue with convenience and cost-effectiveness. Serological tests of dengue IgM and IgG antibodies are still the most widely used for diagnosis of dengue. In order to assess combined diagnostic value of these tests, we study the kinetic profiles of circulating NS1, dengue IgM and IgG antibodies over the course of the disease by using an in-house dengue type 1 (DENV1) specific NS1 capture ELISA and the commercial Panbio Dengue IgM and IgG capture ELISAs. Results A panel of 313 acute-and early convalescent-phase serum specimens from 140 DENV1 primary infected patients during an outbreak of dengue in Guangzhou, China, in 2006 were studied. Dengue NS1 presented high levels in acute-phase serum samples. It was detectable as early as day 1 of illness, and up to 14 day after onset. The sensitivity of NS1 detection was ranged from 81.8% to 91.1% with samples taken during the first 7 days. Anti-dengue IgM antibody was detectable on the third day of onset with the positive rate of 42.9%, and rapidly increasing to 100% by day 8 of illness. Anti-dengue IgG antibody was detectable on the fifth day of onset with low level at the first week of onset, and slowly increasing to 100% by day 15 of illness. Combining the results of NS1 and IgM antibody detection allowed positive diagnosis in 96.9% -100% for samples taken after day 3 of onset. Conclusions Dengue NS1 detection might shorten the window period by first few days of illness. A combination of dengue NS1 antigen and IgM antibody testing facilitates enhanced diagnosis rates. The procedures should be suitable for developing countries where dengue is endemic.

2011-01-01

174

Characterization of RAG1 and IgM (mu chain) marking development of the immune system in red-spotted grouper (Epinephelus akaara).  

PubMed

In vertebrates, lymphoid-specific recombinase protein encoded by recombination-activating genes (RAG1/2) plays a key role in V(D)J recombination of the T-cell receptor and B-cell receptor. In this study, both RAG1 and the immunoglobulin M (IgM) mu chain were cloned to characterize their potential role in the immune defense at developmental stages of red-spotted grouper, Epinephelus akaara. The open reading frame (ORF) of E. akaara RAG1 included 2778 nucleotide residues encoding a putative protein of 925 amino acids, while the ORF of the IgM mu chain had 1734 nucleotide residues encoding 578 amino acids including variable (VH) and constant (CH1-CH2-CH3-CH4) regions. E. akaara RAG1 was composed of a zinc-binding dimerization domain (ZDD) with a RING finger and zinc finger A (ZFA) in the non-core region and a nonamer-binding region (NBR), with a zinc finger B (ZFB), the central and C-terminal domains in the core region. Tridimensional models of the ZDD and NBR of E. akaara RAG1 were constructed for the first time in fishes, while a 3D model of the E. akaara IgM mu chain was also clarified. The RAG1 mRNA was only detected in the thymus and kidney of 4-month and 1.5-year old groupers using qPCR, and the RAG1 protein was confirmed using western blotting and immunohistochemistry. The IgM mu mRNA was examined in most tissues except the gonad. RAG1 and IgM mu gene expression were observed at 15 dph (days post-hatching) and 23 dph respectively, and increased to a higher level at 37 dph. In addition, this was the first time that the morphology of the E. akaara thymus was characterized. The oval-shaped thymus of 4-month old fish was clearly seen and there were amounts of T lymphocytes present. The results suggested that the immune action of E. akaara was likely to start to develop around 15 dph to 29 dph. The transcript level of the RAG1 gene and the number of lymphocytes in the thymus between 4-month and 1.5-year old groupers indicated that age-related thymic atrophy also occurs in fishes. The similar functional structures of RAG1 and IgM protein between fish and mammals indicated that teleost species share a similar mechanism of V(D)J recombination with higher vertebrates. PMID:22796426

Mao, Ming-Guang; Lei, Ji-Lin; Alex, Perálvarez-Marín; Hong, Wan-Shu; Wang, Ke-Jian

2012-10-01

175

Zebrafish immunoglobulin IgD: unusual exon usage and quantitative expression profiles with IgM and IgZ/T heavy chain isotypes  

PubMed Central

The zebrafish is an emerging model for comparative immunology and biomedical research. In contrast to the five heavy chain isotype system of mice and human (IgD, IgM, IgA, IgG, IgE), zebrafish harbor gene segments for IgD, IgM, and novel heavy chain isotype called IgZ/T which appears restricted to bony fishes. The purpose of this study was to design and validate a suite of quantitative real time RT-PCR protocols to measure IgH expression in a vertebrate model which has considerable promise for modelling both pathogenic infection and chronic conditions leading to immune dysfunction. Specific primers were designed and following verification of their specificty, relative expression levels of IgD, IgM, and IgZ/T were measured in triplicate for zebrafish raised under standard laboratory conditions. During embryonic stages, low levels of each heavy chain isotype (IgH) were detected with each increasing steadily between 2 and 17 weeks post fertilization. Overall IgM>IgZ>IgD throughout zebrafish development with the copy number of IgM being several fold higher than that of IgD or IgZ/T. IgD exon usage was also characterized, as its extremely long size and presence of a stop codon in the second IgD exon in zebrafish, raised questions as to how this antibody might be expressed. Zebrafish IgD was found to be a chimeric immunoglobulin, with the third IgD exon spliced to the first IgM constant exon thereby circumventing the first and second IgD exons. Collectively, the qRT-PCR results represent the first comparative profile of IgD, IgM, IgZ/T expression over the lifespan of any fish species and the primers and assay parameters reported should prove useful in enabling researchers to rapidly quantify changes in IgH expression in zebrafish models of disease where altered IgH expression is manifested.

Zimmerman, Anastasia M.; Moustafa, Farah M.; Romanowski, Kryzstof E.; Steiner, Lisa A.

2011-01-01

176

Seeing the Lyman-Alpha Forest for the Trees: Constraints on the Thermal State of the IGM from SDSS-III/BOSS  

NASA Astrophysics Data System (ADS)

The Lyman-alpha (Lya) forest in the line-of-sight to distant quasars is an important probe of the intergalactic medium (IGM). The thermal properties of the IGM can provide insight the reionization history of the universe, as well as indirectly constraining energy sources in the universe such as galaxies and quasars. This thesis is concerned primarily with studying the IGM using moderate quality Lya forest data sets from large-scale spectroscopic surveys, such as the Sloan Digital Sky Survey (SDSS) and the Baryon Oscillations Spectroscopic Survey (BOSS). In Chapter 1, we study the potential of SDSS Lya forest data to study the IGM. Using simulated mock spectra, we show that the flux probability distribution function (PDF) of SDSS data can place interesting constraints on the spatially-averaged temperature-density relation (TDR) of the IGM. We also introduce the threshold probability functions, a one-dimensional two-point statistic adapted from material sciences that can be applied to SDSS data to detect ˜ 50 Mpc IGM thermal inhomogeneities arising from He II reionization. Chapter 2 discusses the effect of continuum biases in the TDR measured from high-resolution Lyalpha forest spectra in the context of recent evidence for an inverted (gamma < 1) TDR. We argue that forward modeling of continuum errors in mock spectra are necessary to make robust estimates of the TDR. Motivated by the importance of accurate continuum estimation in Lya forest analysis, Chapter 3 introduces the mean-flux regulated/principal component analysis (MF-PCA) continuum estimation technique. We show using mock spectra that this technique can achieve continuum accuracies of < 10% and < 4% in noisy spectra of S/N ˜ 2 and S/N ˜ 5, respectively. We have also publicly released ˜ 13,000 continua from SDSS Data Release 7. In Chapter 4, we measure the flux PDF from BOSS, drawing from an overall sample of ˜ 30,000 Lya forest sightlines. This uses a novel procedure for optimally combining the multiple BOSS exposures and estimating the spectral noise contribution. Comparing a high signal-to-noise subsample in BOSS with mock spectra generated from detailed hydrodynamical simulations, we find that the flux PDF from BOSS at 2 < z < 3 is consistent with an isothermal TDR, consistent with theoretical expectations from He II reionization.

Lee, Khee-Gan

177

Functionally responsive self-reactive B cells of low affinity express reduced levels of surface IgM.  

PubMed

Somatic gene rearrangement generates a diverse repertoire of B cells, many which have receptors possessing a range of affinities for self-Ag. Newly generated B cells express high and relatively uniform amounts of surface IgM (sIgM), while follicular (FO) B cells express sIgM at widely varying levels. It is plausible, therefore, that downmodulation of sIgM serves as a mechanism to maintain weakly self-reactive B cells in a responsive state by decreasing their avidity for self-Ag. We tested this hypothesis by performing comparative functional tests with FO IgM(hi) and IgM(lo) B cells from the unrestricted repertoire of WT C57BL/6 mice. We found that FO IgM(lo) B cells mobilized Ca(2+) equivalently to IgM(hi) B cells when the same number of sIgM molecules was engaged. In agreement, FO IgM(lo) B cells were functionally competent to produce an antibody response following adoptive transfer. The FO IgM(lo) cell population had elevated levels of Nur77 transcript, and was enriched with nuclear-reactive specificities. Hybridoma sampling revealed that these B-cell receptors were of low affinity. Collectively, these results suggest that sIgM downmodulation by low-affinity, self-reactive B cells preserves their immunocompetence and circumvents classical peripheral tolerance mechanisms that would otherwise reduce diversity within the B cell compartment. PMID:24375379

Kirchenbaum, Greg A; St Clair, James B; Detanico, Thiago; Aviszus, Katja; Wysocki, Lawrence J

2014-04-01

178

A novel immunosensor for detecting toxoplasma gondii-specific IgM based on goldmag nanoparticles and graphene sheets.  

PubMed

A novel electrochemical immunosensor for detecting toxoplasma gondii-specific IgM (Tg-IgM) was constructed based on goldmag (Au-Fe(3)O(4)) nanoparticles and graphene sheets (GS). Thionine (Thi), as a mediator, was first electropolymerized on a nafion-GS (Nf-GS) modified electrode. Subsequently, gold nanoparticles (AuNPs) were attached onto the poly-thionine film through ?-stacking interactions, and then were used to immobilize toxoplasma gondii antigen (Tg-Ag) for immunosensor fabrication. A sandwich-type immunoassay for Tg-IgM was performed using Au-Fe(3)O(4) labeled anti-IgM-horseradish peroxidase (HRP) as trace label. Electrochemical detection was carried out in the presence of H(2)O(2) as HRP substrate. Using Au-Fe(3)O(4) provided a simple, non-chemical damaging method for regeneration, and enhanced the HRP reduction ability toward H(2)O(2). The AuNPs/Thi/Nf-GS nanocomposite also had good conductivity and biocompatibility, which effectively improved the immunosensor sensitivity. Under optimal conditions, the immunosensor can detect Tg-IgM in two linear ranges from 0.0375 to 1.2 AU mL(-1) and from 2.0 to 18 AU mL(-1) with a detection limit of 0.016 AU mL(-1) (S/N=3). The immunosensor exhibited good reproducibility, stability, and selectivity as well. PMID:23010058

Jiang, Shuting; Hua, Erhui; Liang, Mo; Liu, Bei; Xie, Guoming

2013-01-01

179

Human IgM paraproteins demonstrate shared reactivity between Campylobacter jejuni lipopolysaccharides and human peripheral nerve disialylated gangliosides.  

PubMed

IgM paraproteins from patients with CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, M-protein, agglutination, anti-disialosyl antibodies) react with NeuAc(alpha 2-8)NeuAc epitopes on a wide range of gangliosides including GQ1b, GT1a, GD1b and GD3. The tissue distribution of reactive antigens in human peripheral nerve has not been addressed in detail. In addition, the origin of these antibodies is unknown. Here we report that purified anti-disialosyl paraproteins from two affected patients bind a wide array of human peripheral nerve structures including dorsal root ganglia, dorsal and ventral root axons, femoral and oculomotor nerves. We also show that these paraproteins bind lipopolysaccharides of Campylobacter jejuni isolates from 3/3 cases of Miller Fisher syndrome, and to a less frequent extent, from cases of Guillain-Barré syndrome and enteritis controls. In conjunction with our previous studies, these data provide a possible causal link between the origin and pathogenic effects of anti-disialosyl antibodies in human paraproteinaemic neuropathy. PMID:9413256

Jacobs, B C; O'Hanlon, G M; Breedland, E G; Veitch, J; van Doorn, P A; Willison, H J

1997-12-01

180

Motor-dominant polyneuropathy due to IgM monoclonal antibody against disialosyl gangliosides in a patient with mantle cell lymphoma.  

PubMed

A rapidly progressive motor-dominant neuropathy associated with IgM monoclonal antibody against gangliosides with disialosyl residues, GD3, GD1b, GT1b, and GQ1b, in a 60-year-old Japanese man with mantle cell lymphoma is reported. Plasma exchange and chemotherapy for mantle cell lymphoma were performed for the neuropathy and mantle cell lymphoma. After therapy, the motor neuropathy dramatically improved concurrently with substantial reduction of the antibody activities especially in reaction to GD1b. This is the first case report of neuropathy with anti-disialosyl IgM antibodies associated with mantle cell lymphoma, and plasma exchange and chemotherapy were effective. PMID:24315580

Mori, Akio; Ueno, Yuji; Kuroki, Takuma; Hoshino, Yasunobu; Shimura, Hideki; Sekiguchi, Yasunobu; Noguchi, Masaaki; Hamada, Yukihiro; Kusunoki, Susumu; Hattori, Nobutaka; Urabe, Takao

2014-02-15

181

Cold pressure test producing coronary spasm, coronary thrombosis and myocardial infarction in a patient with IgM antibodies against Coxsackie B virus.  

PubMed

Several lines of evidence have shown that viral infections are capable of causing coronary spasm and precipitating or mimicking clinical myocardial infarction. Here we report the case of a 41-year-old woman with recurrent angina who was admitted to our hospital because of ventricular tachycardia. Laboratory examination revealed positive IgM titers against Coxsackie B virus. Coronary angiography showed normal coronary arteries, but following a cold pressure test severe spasm of all coronaries with thrombotic occlusion of the second marginal branch of the circumflex artery occurred. We conclude that coronary spasm should be clinically suspected in patients with chest pain and ventricular arrhythmia in combination with IgM antibodies against Coxsackie B virus. In these patients, a cold pressure test should be avoided, and antithrombotic and antispastic therapy is recommended. PMID:10844390

Haberbosch, W; Roerich, N; Neuzner, J

1999-01-01

182

The relation between the two forms of COPT and levels of total IgG and IgM in acute and chronic schistosomiasis mansoni.  

PubMed

COPT was performed on 55 acute and 48 chronic male patients with schistosomiasis mansoni as well as on 20 control normal subject. The percentage of the segmented and the bleb reactions were determined. The total levels of IgG, IgM and IgA were measured. There was no distinct evidence that COPT shows only bleb precipitations in acute cases and only segmented reactions in chronic cases. The total levels of IgG were higher in patients who showed segmented that in those who showed bleb reactions especially in the segmented but not the bleb reactions especially in chronic cases. IgM may be responsible for the bleb reactions in acute cases. PMID:2496180

Seitz, H M; Khalil, H M; Makled, M K; el Missiry, A G; el Serougy, A O

1989-06-01

183

The TUBEX typhoid test based on particle-inhibition immunoassay detects IgM but not IgG anti-O9 antibodies.  

PubMed

A serological test kit (TUBEX, IDL Biotech, Sweden) developed recently for the diagnosis of typhoid fever detects antibodies to the Salmonella enterica serovar Typhi lipopolysaccharide (LPS) O9 antigen. The antibodies are detected by their ability to inhibit the interaction between two types of reagent particles: (a). indicator latex microspheres sensitized with an anti-O9 monoclonal antibody, and (b). magnetic microspheres sensitized with S. typhi LPS. Following rapid mixing of the serum with these reagents and sedimentation of the magnetic particles by magnetic force, the concentration of indicator particles left in suspension provides a measure of the inhibition. Whereas it was previously assumed that both IgM and IgG antibodies could inhibit in the system, the present study reveals, surprisingly, that only the IgM antibodies do. It is not clear why IgG anti-O9 antibodies, both of mouse and human origin, do not inhibit, although these can bind to the LPS-sensitized magnetic particles as efficiently as the IgM antibodies. In addition, they can also inhibit very well in another detection system (ELISA) which uses a similar assay format and the same antibody and antigen reagents. Increasing the size of the LPS-sensitized microspheres made no difference; microscopic analysis of the TUBEX reaction mixture revealed that while the indicator particles bound abundantly to the IgG-aggregated LPS-sensitized particles, forming large clumps, these only formed a very light decoration on the IgM-aggregated particles. Thus, the TUBEX system is ideally suited for use in the diagnosis of infections as it allows IgM antibodies to be detected easily and rapidly from whole sera. PMID:14604543

Tam, Frankie Chi Hang; Lim, Pak Leong

2003-11-01

184

Cold Pressure Test Producing Coronary Spasm, Coronary Thrombosis and Myocardial Infarction in a Patient with IgM Antibodies against Coxsackie B Virus  

Microsoft Academic Search

Several lines of evidence have shown that viral infections are capable of causing coronary spasm and precipitating or mimicking clinical myocardial infarction. Here we report the case of a 41-year-old woman with recurrent angina who was admitted to our hospital because of ventricular tachycardia. Laboratory examination revealed positive IgM titers against Coxsackie B virus. Coronary angiography showed normal coronary arteries,

Werner Haberbosch; Norbert Roerich; Joerg Neuzner

1999-01-01

185

Both IgM and IgG Anti-DNA Antibodies Are the Products of Clonally Selective B Cell Stimulation in (NZB x NZW)FI Mice  

Microsoft Academic Search

Summary Disease activity in systemic lupus erythematosus is closely associated with the appearance of immunoglobulin (Ig)G antibody to native DNA in both humans and mice. Like normal antibody responses, the anti-DNA autoantibody first appears as IgM and then switches to IgG. Structural studies of IgG anti-DNA suggest that these antibodies are the products of clonally selected, specifically stimulated B cells.

David M. Tillman; Nainn-Tsyr Jou; Robert J. HiU; Tony N. Marion

1992-01-01

186

A point-of-care test for measles diagnosis: detection of measles-specific IgM antibodies and viral nucleic acid  

PubMed Central

Abstract Objective To evaluate the performance of a newly developed point-of-care test (POCT) for the detection of measles-specific IgM antibodies in serum and oral fluid specimens and to assess if measles virus nucleic acid could be recovered from used POCT strips. Methods The POCT was used to test 170 serum specimens collected through measles surveillance or vaccination programmes in Ethiopia, Malaysia and the Russian Federation: 69 were positive for measles immunoglobulin M (IgM) antibodies, 74 were positive for rubella IgM antibodies and 7 were positive for both. Also tested were 282 oral fluid specimens from the measles, mumps and rubella (MMR) surveillance programme of the United Kingdom of Great Britain and Northern Ireland. The Microimmune measles IgM capture enzyme immunoassay was the gold standard for comparison. A panel of 24 oral fluids was used to investigate if measles virus haemagglutinin (H) and nucleocapsid (N) genes could be amplified by polymerase chain reaction directly from used POCT strips. Findings With serum POCT showed a sensitivity and specificity of 90.8% (69/76) and 93.6% (88/94), respectively; with oral fluids, sensitivity and specificity were 90.0% (63/70) and 96.2% (200/208), respectively. Both H and N genes were reliably detected in POCT strips and the N genes could be sequenced for genotyping. Measles virus genes could be recovered from POCT strips after storage for 5 weeks at 20–25 °C. Conclusion The POCT has the sensitivity and specificity required of a field-based test for measles diagnosis. However, its role in global measles control programmes requires further evaluation.

Slibinskas, Rimantas; Chua, Kaw Bing; Nigatu, Wondatir; Brown, Kevin E; Sasnauskas, Kestutis; Samuel, Dhanraj; Brown, David

2011-01-01

187

Avian glycan-specific IgM monoclonal antibodies for the detection and quantitation of type A and B haemagglutinins in egg-derived influenza vaccines  

Microsoft Academic Search

Two IgM monoclonal antibodies (MAbs), Y6F5 and Y13F9, were selected during a screening of clones obtained immunising BALB\\/c mice with purified envelop proteins of the A\\/Sydney\\/5\\/97 (H3N2) IVR108 influenza strain. These MAbs recognised avian glycans on the haemagglutinin (HA) of the virus. This broad recognition allowed these MAbs to be used as enzyme-labelled secondary antibody reagents in a strain specific

Isabelle Legastelois; Michel Chevalier; Marie-Clotilde Bernard; Aymeric de Montfort; Martine Fouque; Alexandra Pilloud; Christelle Serraille; Nicolas Devard; Olivier Engel; Régis Sodoyer; Catherine Moste

2011-01-01

188

Imbalanced distribution of IgM and IgG antibodies against Plasmodium falciparum antigens and merozoite surface protein-1 (MSP1) in pregnancy  

Microsoft Academic Search

In malaria endemic areas, pregnancy is assumed to be associated with a specific reduction in immunity to Plasmodium. falciparum malaria. To understand some of the mechanisms which underlie such a poor immunity, we have attempted to examine the frequency and distribution of IgM and IgG antibodies to a crude antigenic extract of parasitized erythrocytes and to the merozoite surface protein-1

Wilfrid S Nambei; Moctar Goumbala; André Spiegel; Alioune Dièye; Ronald Perraut; Olivier Garraud

1998-01-01

189

Evaluation of capture ELISA and rapid immunochromatographic test for the determination of IgM and IgG antibodies produced during dengue infection  

Microsoft Academic Search

Background: Rapid diagnosis of dengue infection is essential to patient management and disease control. The development of a rapid (5 min) immunochromatographic test and a 2 h commercial capture enzyme linked immunosorbent assay (ELISA) for anti-dengue IgM and IgG antibodies may lead to more rapid and accurate testing in peripheral health settings and diagnostic laboratories.Objectives: Evaluate two new commercial tests

S. K Lam; P. L Devine

1998-01-01

190

Detection of Lassa Virus Antinucleoprotein Immunoglobulin G (IgG) and IgM Antibodies by a Simple Recombinant Immunoblot Assay for Field Use  

Microsoft Academic Search

The nucleoprotein of Lassa virus, strain Josiah, was expressed in Escherichia coli as an N-terminally trun- cated, histidine-tagged recombinant protein. Following affinity purification the protein was completely dena- tured and spotted onto nitrocellulose membrane. A total of 1 mg of protein was applied for detection of Lassa virus antibodies (LVA) in a simple immunoblot assay. Specific anti-Lassa immunoglobulin M (IgM)

J. TER MEULEN; K. KOULEMOU; T. WITTEKINDT; K. WINDISCH; S. STRIGL; S. CONDE; H. SCHMITZ

1998-01-01

191

Use of Saccharomyces cerevisiae-Expressed Recombinant Nucleocapsid Protein To Detect Hantaan Virus-Specific Immunoglobulin G (IgG) and IgM in Oral Fluid  

Microsoft Academic Search

Hantaan virus is the causative agent of severe hemorrhagic fever with renal syndrome. Clinical surveillance for Hantaan virus infection is unreliable, and laboratory verification is essential. The detection of virus-specific immunoglobulin M (IgM) and IgG in serum is most commonly used for the diagnosis of hantavirus infection. Testing of oral fluid samples instead of serum offers many advantages for surveillance.

Rasa Petraityte; Li Jin; Rashpal Hunjan; A. Razanskiene; A. Zvirbliene; K. Sasnauskas

2007-01-01

192

Application of ELISA for IgM, IgA and antigen detection for rapid diagnosis of respiratory syncytial virus infections: a comparative study  

Microsoft Academic Search

Background: Infection with Respiratory Syncytial Virus (RSV) can be rapidly diagnosed by detection of viral antigen in nasopharyngeal secretions (NPS) or serologically by detecting IgM and IgA antibodies.Objectives: To evaluate the above methods for reliability and rapidity, and compare them with the complement fixation (CF) test and virus isolation.Study design: Viral antigen was tested in 145 NPS samples by ELISA

N. Varsano; R. Azar; M. Ben-Bassat; E. Mendelson

1995-01-01

193

Bovine IgM antibodies with exceptionally long complementarity-determining region 3 of the heavy chain share unique structural properties conferring restricted VH + V  pairings  

Microsoft Academic Search

Naturally occurring antibody repertoires of cattle (Bos taurus) include a group of IgMl antibodies with exceptionally long complementarity-determining region 3 of the heavy chain (CDR3H) segments, containing multiple Cys residues. These massive CDR3H segments will greatly influence the tertiary and quaternary structures of the bovine IgM combining sites. As an antibody's combining site is formed by both heavy and light

Surinder S. Saini; William Farrugia; Paul A. Ramsland; Azad K. Kaushik

2003-01-01

194

Development and partial validation of a recombinant E2-based indirect ELISA for detection of specific IgM antibody responses against classical swine fever virus.  

PubMed

Detecting classical swine fever virus specific antibody responses is critical for prevention and control of CSF. In this study, a ?E2-based indirect ELISA was developed to detect specific IgM antibodies against CSFV. The optimized conditions that were determined experimentally are: a ?E2 antigen concentration of 0.5 ?g/ml, a serum sample dilution of 1/100 incubated at 37°C for 1.5 h, and a HRP conjugated rabbit anti-pig IgM dilution of 1/50,000 incubated at 37°C for 1 h. Three hundred clinical sera were tested with ?E2-IgM-ELISA and IDEXX ELISA and the positive rates were 77.3% (232/300) and 71.7% (215/300), respectively. Concordance rate between them was 80.3% (241/300). The 59 inconsistent sera were tested further: among the 21 IDEXX ELISA +/?E2-IgM-ELISA - and 38 IDEXX ELISA +/?E2-IgM-ELISA - samples, 17 and 24 were determined positive by virus neutralization test; 15 and 25 were tested positive by ?E2-IgG-ELISA, respectively. In addition, the E2-specific IgM antibody response in 15 vaccinated piglets could be detected 2 weeks post-vaccination and earlier than specific IgG antibody. It increased regularly and reached high levels by 6 weeks post-vaccination. The ?E2-IgM-ELISA could be used for clinical detection and for exploring the kinetics of IgM antibody response. PMID:23500647

Li, Wenliang; Mao, Li; Yang, Leilei; Zhou, Bin; Jiang, Jieyuan

2013-07-01

195

IgM, IgG and IgA class enterobacterial antibodies in serum and synovial fluid in patients with ankylosing spondylitis and rheumatoid arthritis  

Microsoft Academic Search

SUMMARY IgM, IgG and IgA class antibodies against three Klebsiella pneumoniae capsular types, Escherichia coli and Proteus mirabilis, as well as total immunoglobulin concentrations, were measured by enzyme immunoassay and radial immunodiÄusion tech- nique, respectively, in paired serum and synovial fluid samples from eight patients with ankylosing spondylitis and 10 with rheumatoid arthritis. No clear evidence for intra-articular antibody production

O. MAKI-IKOLA; M. PENTTINEN; R. VON ESSEN; C. GRIPENBERG-LERCHE; H. ISOMAKI; K. GRANFORS

1997-01-01

196

I. Studies on pyridine dinucleotide transhydrogenase in rat liver mitochondria. II. Identification of the tissue and cellular sites of catabolism of IgM in the rat  

SciTech Connect

The orientation of the transmembrane enzyme, pyridine dinucleotide transhydrogenase, in the inner mitochondrial membrane of rat liver has been determined by evaluating effects of proteases on the integrity of the enzyme in mitoplasts and submitochondrial particles. Following treatment of these membranes with the non-specific protease, proteinase K, antigenic proteolytic products were detected by immunoblot analysis using polyclonal antibody prepared against purified bovine heart enzyme. Information from these proteolysis studies was used to construct a model of the orientation of transhydrogenase in the inner mitochondrial membrane. In this work, I have used the residualizing label, dilactitol-{sup 125}I-tyramine ({asterisk}I-DLT) to identify the tissue and cellular sites of catabolism of the immunoglobulin, IgM. Purified IgM was labeled conventionally with {sup 125}I or with the residualizing label, {asterisk}I-DLT. The circulating half-life of the protein, 2.7 {plus minus} 0.3 days, was the same when measured using either label, indicating that the residualizing label does not affect the kinetics of the protein's catabolism in vivo. At 2.4 or 5.1 days post injection, the liver contained the major fraction of catabolized protein compared to all the other organs in the body. Additionally, following collagenase digestion of the liver, the hepatocytes were shown to be 77% responsible for the catabolism of IgM by the liver. Autoradiography of the liver revealed that the remaining 23% of IgM catabolized by the liver was due to the Kupffer cells.

Weis, J.K.

1988-01-01

197

Detection of IgM and IgG against hepatitis E virus in serum and meat juice samples from pigs at slaughter in Bavaria, Germany.  

PubMed

Hepatitis E virus (HEV) is an emerging foodborne pathogen with domestic and wild pigs (and likely other species such as deer or rabbits) recognized as reservoir. Pathogenesis in pigs usually leads to an asymptomatic course of disease. Since there is no enzyme-linked immunosorbent assay (ELISA) kit for the detection of anti-HEV antibodies in pigs commercially available, the objective of this study was to assess the seroprevalence in fattening pigs at slaughter and at herd level using a newly developed ELISA based on genotype (GT) 1 and GT 3 in Bavaria, Germany. Based on 516 serum and 198 meat juice samples collected from different herds at four different Bavarian slaughterhouses, the overall seroprevalence of anti-HEV IgG in serum and meat juice samples was 68.6% and 67.6%, respectively. Analyzing the serum for the presence of anti-HEV IgM, 36/516 (7%) were positive for anti-HEV IgM. At herd level, most of the herds were seropositive for anti-HEV antibodies. The present study shows that HEV is widespread among the Bavarian pig population and that some pigs might test positive for anti-HEV IgM even at the age of slaughter. Also, meat juice serves as an equivalent matrix to serum to test for anti-HEV antibodies in pigs. PMID:22690762

Wacheck, Silke; Werres, Carolin; Mohn, Ulrich; Dorn, Silvia; Soutschek, Erwin; Fredriksson-Ahomaa, Maria; Märtlbauer, Erwin

2012-07-01

198

Biotin-avidin amplified enzyme-linked immunosorbent assay (ELISA) for the measurement of canine serum IgA, IgG and IgM.  

PubMed

An amplified capture enzyme-linked immunosorbent assay (ELISA) has been developed by the use of the biotin-avidin detection system, for the measurement of canine plasma immunoglobulins (Ig) A, G and M. Test responses of dilutions of both the Ig standards and test plasma samples were consistently linear (r > 0.987) for the three Ig classes. The within-assay variation was 3.53 per cent for IgG, 5.84 per cent for IgM and 6.34 per cent for IgA. The analytical recoveries were 95 per cent for IgA, 97 per cent for IgG and 98 per cent for IgM. The lower detection limits of the assay were 38.4 ng ml-1 for IgG, 20.3 ng ml-1 for IgM and 41.2 ng ml-1 for IgA. The results indicate that this ELISA has a much higher sensitivity than the single radial immunodiffusion assay or the non-amplified ELISA for measurements of canine Igs, but has a comparable specificity and precision. PMID:8685529

Ginel, P J; Margarito, J M; Molleda, J M; López, R; Novales, M; Bernadina, W E

1996-03-01

199

Preparation of positive control platelets for detection of canine platelet surface-associated IgG, IgM and complement (C3) by flow cytometry.  

PubMed

An assay for detection of platelet surface-associated (PSA-) IgG, IgM and/or complement (C3) in dogs was modified by preparation of artificial positive control platelets. Flow cytometry of fluorescein isothiocyanate (FITC)-conjugated anti-dog IgG, anti-dog IgM and anti-dog C3 antibodies was used to detect the PSA proteins. IgM single, IgM/C3 double and IgG/IgM/C3 triple positive platelets were prepared. FITC-conjugated anti-IgG antibody bound strongly only to the triple positive platelets. Binding of FITC-conjugated anti-IgM or anti-C3 antibody to the double and triple positive platelets was specifically blocked by preincubation with the respective non-FITC-conjugated same-origin antibodies. These results confirm that FITC-conjugated antibodies specifically detect PSA proteins and that the control platelets prepared in this study are appropriate positive controls for detection of PSA proteins by flow cytometry. PMID:20234115

Tsuchiya, Ryo; Komatsu, Takahiro; Ishikawa, Takefumi; Neo, Sakurako; McConnell, Mary F; Hisasue, Masaharu; Yamada, Takatsugu

2010-08-01

200

CD5-positive B-cell malignancies frequently express cross-reactive idiotypes associated with IgM autoantibodies.  

PubMed Central

Using monoclonal antibodies (MAb) specific for cross-reactive idiotypes (CRIs) associated with human monoclonal IgM autoantibodies, we examined 57 biopsy specimens that previously had been noted to have immunohistologic features of CD5-positive B-cell small lymphocytic (SL) non-Hodgkin's lymphoma (NHL). Twenty-five lymphoma specimens were noted to be from patients with chronic lymphocytic leukemia (CLL). Eight of thirty-four (24%) immunoglobulin (Ig) kappa light-chain expressing lymphomas reacted with 17.109, a MAb specific for a major CRI encoded by a conserved Ig kappa variable region gene (Vk gene) of the VkIIIb sub-subgroup. All 17.109-reactive tissues and two 17.109-negative specimens were recognized by another MAb specific for VkIIIb framework determinant(s). Seven of all fifty-six (13%) Ig-expressing tumors bound G6, a MAb specific for an autoantibody heavy-chain-associated CRI that is encoded by a conserved antibody heavy chain variable region gene(s) (VHgene) of the VH1 subgroup. All seven G6-positive lymphomas and two G6-negative tumors reacted with Cc1, another MAb specific for a rheumatoid factor heavy-chain-associated CRI. A third autoantibody-heavy-chain-associated CRI, termed Lc1, was expressed by seven (13%) other lymphomas. Finally, a fourth MAb specific for RF heavy-chain-associated CRI, named B6, detected two additional tumors. The expression frequencies of autoantibody-associated CRIs among SL NHL patients without peripheral lymphocytosis did not differ from those noted among patients with CLL but were significantly higher than those observed among patients with NHL of follicular center-cell origin. These data imply that the malignant B cells of patients with either CD5-positive B-cell SL NHL or CLL express a restricted set of Ig V genes that have not substantially diversified from the germline DNA. Images Figure 1

Kipps, T. J.; Robbins, B. A.; Tefferi, A.; Meisenholder, G.; Banks, P. M.; Carson, D. A.

1990-01-01

201

Molecular mechanisms and selective influences that shape the kappa gene repertoire of IgM+ B cells.  

PubMed Central

To analyze the human kappa chain repertoire and the influences that shape it, a single cell PCR technique was used that amplified Vkappa Jkappa rearrangements from genomic DNA of individual human B cells. More than 350 productive and 250 nonproductive Vkappa Jkappa rearrangements were sequenced. Nearly every functional Vkappa gene segment was used in rearrangements, although six Vkappa gene segments, A27, L2, L6, L12a, A17, and O12/O2 were used preferentially. Of these, A27, L2, L6, and L12a showed evidence of positive selection based on the variable region and not CDR3, whereas A17 was overrepresented because of a rearrangement bias based on molecular mechanisms. Utilization of Jkappa segments was also nonrandom, with Jkappa1 and Jkappa2 being overrepresented and Jkappa3 and Jkappa5 underrepresented in the nonproductive repertoire, implying a molecular basis for the bias. In B cells with two Vkappa Jkappa rearrangements, marked differences were noted in the Vkappa segments used for the initial and subsequent rearrangements, whereas Jkappa segments were used comparably. Junctional diversity was generated by n-nucleotide addition in 60% and by exonuclease trimming in 75% of the Vkappa Jkappa rearrangements analyzed. Despite this large degree of diversity, a strict CDR3 length was maintained in both productive and nonproductive rearrangements. More than 23% of the productive rearrangements, but only 7% of the nonproductive rearrangements contained somatic hypermutations. Mutations were significantly more frequent in Vkappa sequences derived from CD5- as compared with CD5+ B cells. These results document that the gene segment utilization within the Vkappa repertoire is biased by both intrinsic molecular processes as well as selection after light chain expression. Moreover, IgM+ memory cells with highly mutated kappa genes reside within the CD5- but not the CD5+ B cell compartment.

Foster, S J; Brezinschek, H P; Brezinschek, R I; Lipsky, P E

1997-01-01

202

Anergic responses characterize a large fraction of human autoreactive naive B cells expressing low levels of surface IgM.  

PubMed

B cell anergy represents an important mechanism of peripheral immunological tolerance for mature autoreactive B cells that escape central tolerance enforced by receptor editing and clonal deletion. Although well documented in mice, the extent of its participation in human B cell tolerance remains to be fully established. In this study, we characterize the functional behavior of strictly defined human naive B cells separated on the basis of their surface IgM (sIgM) expression levels. We demonstrate that cells with lower sIgM levels (IgM(lo)) are impaired in their ability to flux calcium in response to either anti-IgM or anti-IgD cross-linking and contain a significantly increased frequency of autoreactive cells compared with naive B cells with higher levels of sIgM. Phenotypically, in healthy subjects, IgM(lo) cells are characterized by the absence of activation markers, reduction of costimulatory molecules (CD19 and CD21), and increased levels of inhibitory CD22. Functionally, IgM(lo) cells display significantly weaker proliferation, impaired differentiation, and poor Ab production. In aggregate, the data indicate that hyporesponsiveness to BCR cross-linking associated with sIgM downregulation is present in a much larger fraction of all human naive B cells than previously reported and is likely to reflect a state of anergy induced by chronic autoantigen stimulation. Finally, our results indicate that in systemic lupus erythematosus patients, naive IgM(lo) cells display increased levels of CD95 and decreased levels of CD22, a phenotype consistent with enhanced activation of autoreactive naive B cells in this autoimmune disease. PMID:21398610

Quách, Tâm D; Manjarrez-Orduño, Nataly; Adlowitz, Diana G; Silver, Lin; Yang, Hongmei; Wei, Chungwen; Milner, Eric C B; Sanz, Iñaki

2011-04-15

203

High density of intraepithelial ?? lymphocytes and deposits of immunoglobulin (Ig)M anti-tissue transglutaminase antibodies in the jejunum of coeliac patients with IgA deficiency  

PubMed Central

The diagnosis of coeliac disease (CD) represents a special challenge in selective immunoglobulin (Ig)A deficiency (IgAD). A high density of T cell receptor (TCR)??+ intraepithelial lymphocytes (IELs) and intestinal IgA anti-tissue transglutaminase 2 (anti-TG2) antibody deposits are suggestive of CD. We analysed the density of TCR??+ IELs and the deposition of IgM anti-TG2 antibodies in the jejunal mucosa of IgAD patients with and without CD. Immunohistochemical analyses for the number of CD3+ and TCR??+ IELs and double immunofluorescence assay for IgM anti-TG2 antibody deposits were performed in biopsies from 25 children with IgAD (nine untreated CD, seven potential CD and nine without CD). Sixteen immunologically intact children without CD represented the controls. IgAD without CD had a higher number of CD3+ and TCR??+ IELs than controls (P < 0·05), but lower than IgAD with CD (P < 0·01). No significant differences were noted between IgAD subjects without CD and those with potential CD. Furthermore, IgAD patients without CD showed a higher TCR??+/CD3+ ratio than the control group (P < 0·05), while the ratio was similar to subjects with CD and potential CD. Intestinal IgM anti-TG2 antibody deposits were present in six of seven of the IgAD patients with untreated CD, one of seven with potential CD and none of those without CD. Most of the patients with IgAD show immune activation in the jejunal mucosa. IgM anti-TG2 antibody deposits are present only in CD. Intestinal IgM anti-TG2 and immunohistochemical markers do not discriminate between IgAD and potential CD with IgAD. Therefore, the serum IgG CD-associated autoantibodies remains very important for the diagnosis of CD in IgAD.

Borrelli, M; Maglio, M; Agnese, M; Paparo, F; Gentile, S; Colicchio, B; Tosco, A; Auricchio, R; Troncone, R

2010-01-01

204

Monoclonal IgM, IgG, and IgA human rheumatoid factors produced by synovial tissue-derived, EBV-transformed B cell lines.  

PubMed

In an effort to study disease-related autoantibodies in rheumatoid arthritis (RA), rheumatoid factor (RF)-producing B cell lines were developed from the heterogeneous B cell populations infiltrating the synovial tissue of patients with arthritis. Over 125 EBV-transformed B cell cultures were derived from three patients: one with early pre-erosive RA, one with advanced RA, and one with osteoarthritis (OA). IgM, IgG, and IgA RF-producing B cell lines were found in all three series but with several significant differences. In each of the two RA patients, 22% of the Ig-producing cell lines secreted RF compared to 7% in the OA patient. The isotypes of these RF were mostly IgM in the early RA (62%) and the OA patient (60%) as contrasted to predominantly IgA (75%) and, to a lesser extent, IgG (12.5%) in the advanced RA patient. Analyses of the light (L) chain composition of these RF revealed that 82% of the IgM RF used kappa L chains whereas only 31% of the non-IgM RF used kappa chains. Antigen-binding analyses of these RF revealed that all the synovial tissue-derived RF from the advanced RA patient exhibited antigen binding specificities restricted to a narrow range of gamma globulins. In contrast, the synovial RF of the other two patients were either reactive with a broader spectrum of gamma globulins or reactive with a variety of unrelated antigens. In every instance, the gamma globulin-specific RF were of all three major isotypes whereas the polyreactive RF were restricted to the IgM isotype. These data demonstrate that synovial B cells from both RA and OA patients can produce RF and that significant differences can exist among patients in the percentage of RF generated and their H and L chain isotype distribution. The reversal of the kappa:lambda ratio among the IgG and IgA RF and the more restricted antigen-binding specificities of the IgG and IgA vs IgM RF suggest that a non-stochastic, possibly antigen-driven selection process was involved in their generation. The relevance of these differences in RF precursor frequency, H and L chain distribution, and antigen specificity to these two diseases warrants further investigation. PMID:8382569

Kaplan, S; Hyman, K; Brooks, R; Wakai, M; Hashimoto, S; Furie, R; Chiorazzi, N

1993-01-01

205

Expansion of a B-lymphocyte clone producing IgM auto-antibodies encoded by a somatically mutated V H I gene in the spleen of an autoimmune patient  

Microsoft Academic Search

Seventy-six human B-cell hybridomas were obtained by fusing B lymphocytes from the spleen of a patient with chronic idiopathic thrombocytopenia (ITP). Two independent hybridoma clones producing IgM autoantibodies reacting with platelets and other antigens from both the internal and the external environments were established from this fusion experiment. The IgM autoantibodies produced by the two hybridoma clones were found to

S. Jahn; B. Niemann; T. Winkler; J. R. Kalden; R. Baehr

1994-01-01

206

Effect of some constituents of chicken egg yolk lipoprotein on the growth and IgM production of human-human hybridoma cells and other human-derived cells  

Microsoft Academic Search

Chicken egg yolk lipoprotein (YLP) was partially fractionated into some constituents, and the effect of constituents of YLP were examined on the growth and immunoglobulin (IgM and IgG) secretion of a HB4C5 human-human hybridoma cell line cultured in serum-free medium. Among the fractions, YP-1 and YP-2 fractions (LDL-rich fractions) were found to enhance the growth and IgM secretion of HB4C5

Kazuki Shinohara; Tatsunobu Fukushima; Michiko Suzuki; Masakazu Tsutsumi; Masuko Kobori; Zwe-Ling Kong

1993-01-01

207

B cell-intrinsic toll-like receptor 7 is responsible for the enhanced anti-PEG IgM production following injection of siRNA-containing PEGylated lipoplex in mice.  

PubMed

Recently, we reported that immunostimulatory siRNA-containing PEGylated lipoplex (PEGylated siRNA-lipoplex) activates the immune system, resulting in the enhanced production of anti-PEG IgM. However, the enhancing mechanism upon anti-PEG IgM production has not been fully elucidated. In this study, we employed toll-like receptor 7 knock out (TLR7 KO) mice, and showed how PEGylated siRNA-lipoplex activates the innate immune system through TLR7 and consequently enhances anti-PEG IgM production. In addition, we showed that SCID mice reconstituted with TLR7-deficient B cells failed to enhance anti-PEG IgM production following the injection of PEGylated siRNA-lipoplex, but that SCID mice reconstituted with wild type B cells did enhance anti-PEG IgM production. These results suggest that immune activation via B cell-intrinsic TLR7, but not other TLR7-expressing cells, contributes predominantly to an enhanced anti-PEG IgM production in response to the intravenous injection of PEGylated siRNA-lipoplexes. A strategy to evade B cell-intrinsic TLR7 activation by siRNA, such as chemical modification, may overcome immunological barriers to PEGylated liposome-based siRNA therapeutics. PMID:24727075

Hashimoto, Yosuke; Abu Lila, Amr S; Shimizu, Taro; Ishida, Tatsuhiro; Kiwada, Hiroshi

2014-06-28

208

Receptor-dependent inhibition by vasoactive intestinal peptide of phorbol ester-enhanced IgM secretion by a human B cell line  

SciTech Connect

Vasoactive intestinal peptide (VIP) is a 28 amino acid neuromediator, which is released into tissues during inflammatory reactions. To examine the mechanisms of VIP effects on lymphocyte functions, replicate 5 ml suspensions of 2{times}10{sup 6} cultured SKW 6.4 human B lymphocytes per ml of RPMI 1640 medium with 10% FCS were incubated with phorbol myristate acetate (PMA) at 37C. After 2 hr of exposure of SKW 6.4 cells to 100 ng/ml of PMA, the specific high-affinity binding of ({sup 125}I)VIP was decreased by 43{plus minus}7.8% and remained suppressed for up to 8 hr. Continued incubation of SKW 6.4 cells with PMA for 7 days increased the specific high-affinity binding of ({sup 125}I)VIP by 55{plus minus}16%. The secretion of IgM by SKW 6.4 cells, as quantified in an ELISA assay, was enhanced a mean of 3.6 fold by 100 ng/ml of PMA after 7 days. The concurrent addition of 10{sup {minus}12}M-10{sup {minus}6}M VIP to the SKW 6.4 cells inhibited the PMA-enhanced secretion of IgM in an concentration-dependent manner with maximal mean inhibition ({plus minus}S.D.) of 40{plus minus}2% by 10{sup {minus}10}M VIP at 7 days, without an effect on unstimulated levels of IgM. The potent inhibition of immunoglobulin production by VIP has apparent specificity for stimulated B cells with an increased number of VIP receptors.

Cheng, P.P.J.; Sreedharan, S.P.; Robichon, A.; Gronroos, E.; Goetzl, E.J. (Univ. of California, San Francisco (United States))

1991-03-15

209

Sulfated glucuronyl glycolipids reacting with anti-myelin-associated glycoprotein monoclonal antibodies including IgM paraproteins in neuropathy: species distribution and partial characterization of epitopes.  

PubMed

It was recently established that anti-myelin associated glycoprotein (MAG) IgM paraproteins associated with neuropathy and a substantial number of experimentally produced rat and mouse monoclonal antibodies that react with MAG (e.g. HNK-1) also bind to some sulfated glucuronic acid-containing sphingoglycolipids of human peripheral nerve. A species study revealed that these glycolipids could be detected readily by TLC overlay experiments in the acidic glycolipid fractions from human, monkey, bovine, cat and dog peripheral nerve. The glycolipids were also present in the nerves of rat, mouse, rabbit, guinea pig and chicken, but their concentration was about an order of magnitude lower. These antigenic glycolipids were present in the purified myelin fraction from cat nerve, but their level was not enriched over that in whole homogenate. Partial characterization of the epitopes in the glycolipids was accomplished by comparing binding of the human and experimental monoclonal antibodies to sulfated glucuronyl paragloboside (SGPG), to the desulfated lipid (GPG), and to the methyl ester of the desulfated lipid (MeGPG). All of the human, mouse and rat antibodies reacted with the intact SGPG, but none exhibited binding to MeGPG indicating that either the sulfate or the free carboxyl group on SGPG was required for reactivity. Five out of 11 human IgM paraproteins retained partial and variable reactivity with GPG showing that the sulfate was not absolutely required for binding, while the other 6 did not react with GPG. These results demonstrate idiotypic heterogeneity among the IgM paraproteins. Only 1 of 14 monoclonal antibodies produced experimentally in mice or rats retained reactivity with GPG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2429733

Ilyas, A A; Dalakas, M C; Brady, R O; Quarles, R H

1986-10-15

210

Expression of a new antigen, Tml on T cells after modulation by anti-T3 antibodies of IgM class  

SciTech Connect

During the modulation of the T3/Ti complex by anti-T3 antibody, 235, of IgM class, a new antigen, Tml was detected with an IgGl mAb produced against mAb 235 treated T cells. This antigen was inducible only on T cells modulated by IgM anti-T3 (mAb 235 and mAb 38.1) and not by anti-T3 of other isotypes. Tml was a 33Kd molecule which was detectable in a small percentage of T cells and B cells but not on granulocytes, platelets, erythrocytes and thymocytes. Significantly, monocytes displayed this antigen on their cell surfaces. While not detectable on leukemic T cells HPB-ALL and Jurkat, Tml was expressed when these cell lines were modulated with 235. T cells activated by PHA, Con A, TPA, PWM, PPD, and allo-antigens showed little increase in the expression of Tml. In contrast, B cells activated by S. aureus or goat anti-mu antibodies along with BCGF showed increased expression of this antigen. Attempts to precipitate Tml from activated B cells have not been successful. On T cells, Tml appeared after 30 minutes of T3 modulation, before the disappearance of T3 antigen. Cycloheximide, a protein synthesis inhibitor, did not block Tml expression, suggesting that the molecule was present before the modulation process. The expression of Tml is induced uniquely by IgM anti-T3 mAbs. Perturbation of the membrane by these mAbs may have allowed the emergence of an intracellular antigen, Tml, on the cell surface.

Jung, L.K.L.; Hara, T.; Fu, S.M.

1986-03-05

211

Enzyme-linked immunoassay for dengue virus IgM and IgG antibodies in serum and filter paper blood  

PubMed Central

Background The reproducibilty of dengue IgM and IgG ELISA was studied in serum and filter paper blood spots from Vietnamese febrile patients. Methods 781 pairs of acute (t0) and convalescent sera, obtained after three weeks (t3) and 161 corresponding pairs of filter paper blood spots were tested with ELISA for dengue IgG and IgM. 74 serum pairs were tested again in another laboratory with similar methods, after a mean of 252 days. Results Cases were classified as no dengue (10 %), past dengue (55%) acute primary (7%) or secondary (28%) dengue. Significant differences between the two laboratories' results were found leading to different diagnostic classification (kappa 0.46, p < 0.001). Filter paper results correlated poorly to serum values, being more variable and lower with a mean (95% CI) difference of 0.82 (0.36 to 1.28) for IgMt3, 0.94 (0.51 to 1.37) for IgGt0 and 0.26 (-0.20 to 0.71) for IgGt3. This also led to differences in diagnostic classification (kappa value 0.44, p < 0.001) The duration of storage of frozen serum and dried filter papers, sealed in nylon bags in an air-conditioned room, had no significant effect on the ELISA results. Conclusion Dengue virus IgG antibodies in serum and filter papers was not affected by duration of storage, but was subject to inter-laboratory variability. Dengue virus IgM antibodies measured in serum reconstituted from blood spots on filter papers were lower than in serum, in particular in the acute phase of disease. Therefore this method limits its value for diagnostic confirmation of individual patients with dengue virus infections. However the detection of dengue virus IgG antibodies eluted from filter paper can be used for sero-prevalence cross sectional studies.

Tran, Thanh Nga T; de Vries, Peter J; Hoang, Lan Phuong; Phan, Giao T; Le, Hung Q; Tran, Binh Q; Vo, Chi Mai T; Nguyen, Nam V; Kager, Piet A; Nagelkerke, Nico; Groen, Jan

2006-01-01

212

Detection of IgE, IgG, IgA and IgM antibodies against raw and processed food antigens  

PubMed Central

Background Despite the first documented case of food allergy to cooked food in 1921 by Prausnitz and Kustner, all commercial food antigens are prepared from raw food. Furthermore, all IgE and IgG antibodies against dietary proteins offered by many clinical laboratories are measured against raw food antigens. Methods We developed an enzyme-linked immunosorbent assay for the measurement of IgE, IgG, IgA and IgM antibodies against raw and processed food antigens. Sera with low or high reactivity to modified food antigens were subjected to myelin basic protein, oxidized low density lipoprotein, and advanced glycation end products (AGE) such as AGE-human serum albumin and AGE-hemoglobin. Results Compared to raw food antigens, IgE antibodies showed a 3–8-fold increase against processed food antigens in 31% of the patients. Similarly, IgG, IgA and IgM antibodies against modified food antigens overall were found at much higher levels than antibody reactions against raw food antigens. Almost every tested serum with high levels of antibodies against modified food antigens showed very high levels of antibodies against myelin basic protein, oxidized low density lipoprotein, AGE-human serum albumin and AGE-hemoglobin. Conclusion We conclude that the determination of food allergy, intolerance and sensitivity would be improved by testing IgE, IgG, IgA and IgM antibodies against both raw and processed food antigens. Antibodies against modified food antigens, by reacting with AGEs and tissue proteins, may cause perturbation in degenerative and autoimmune diseases such as diabetes, atherosclerosis, inflammation, autoimmunity, neurodegeneration and neuroautoimmunity.

Vojdani, Aristo

2009-01-01

213

Single or combined effects of Lactobacillus sakei and inulin on growth, non-specific immunity and IgM expression in leopard grouper (Mycteroperca rosacea).  

PubMed

The aim of this study was to evaluate the single or combined effects of Lactobacillus sakei with inulin suitable for immunological in vivo studies in farmed fish. By in vitro assays, L. sakei strain 5-4 showed antibacterial activities against all assayed fish pathogens (except the Vibrio harveyi strain CAIM-1793). L. sakei was able to survive at high fish bile concentrations. Fermentation of the agave inulin resulted in a large increase in number of lactobacilli. For the in vivo study, fish were fed for 8 weeks four practical diets: control diet (control), L. sakei 5-4 (10(7) CFU/g), inulin (1 % or 10 g/kg) and L. sakei + inulin (10(7) CFU/g + 10 g/kg). The weight gain showed clearly the synergistic effect of L. sakei 5-4 and inulin at 6 and 8 weeks of treatments. Leopard grouper fed with L. sakei alone or combined with inulin have significantly increased the assayed physiological and humoral immune parameters. By real-time PCR assays, the mRNA transcripts of immunoglobulin M (IgM) were found to be higher expressed in intestine, head kidney, mucus, gill, spleen and skin. Moreover, mRNA expression levels of IgM in head kidney and anterior intestine were measured by real-time PCR. L. sakei 5-4 and L. sakei + inulin supplemented diet up-regulated the expression of IgM at week 4 and 8 in intestine and head kidney, respectively. These results support the idea that the L. sakei 5-4 alone or combined with agave inulin improved growth performance and stimulates the immune system of leopard grouper. PMID:24464476

Reyes-Becerril, Martha; Ascencio, Felipe; Gracia-Lopez, Vicente; Macias, Ma Esther; Roa, Marcos Cadena; Esteban, María Angeles

2014-08-01

214

An Apoptosis-Associated Mammary Protein Deficiency Leads to Enhanced Production of IgM Antibodies against Multiple Damage-Associated Molecules  

PubMed Central

Milk fat globule epidermal growth factor 8 (MFG-E8) is a protein that binds to apoptotic cells by recognizing phosphatidylserine and enhances the engulfment of apoptotic cells by macrophages. Many apoptotic cells are left unengulfed in the germinal centers of the spleen in the MFG-E8-deficient (MFG-E8?/?) mice, and these mice develop an autoimmune disease resembling human systemic lupus erythematosus. We found that the MFG-E8 deficiency was accompanied by the increased production of immunoglobulins. Further Western blot and ELISA analyses validated the increase in the IgM levels in the MFG-E8?/? mice. It was also revealed that the sera from the MFG-E8?/? mice cross-reacted with oxidation-specific epitopes generated upon incubation of serum albumin with the peroxidized lipids. Among the modified proteins with several unsaturated aldehydes of chain lengths varying from three to nine carbons, the MFG-E8?/? mice sera exclusively cross-reacted with the protein-bound 4-oxo-2-nonenal (ONE), a highly reactive aldehyde originating from the peroxidation of ?6 polyunsaturated fatty acids. In addition, the IgM monoclonal antibodies (mAbs) that selectively cross-reacted with the ONE-modified proteins were generated from the MFG-E8?/? mice. A subset of the ONE-specific IgM mAbs significantly recognized the late apoptotic and necrotic cells and enhanced the phagocytosis by macrophages. These data demonstrate that the impairment of the phagocytic clearance of apoptotic cells through MFG-E8 can lead to the generation of natural antibodies, which may play a critical role in removing multiple damage-associated molecules, including oxidation-specific epitopes and late apoptotic/necrotic cells.

Shibata, Takahiro; Yasueda, Takehiko; Matsuda, Tsukasa; Uchida, Koji

2013-01-01

215

An apoptosis-associated mammary protein deficiency leads to enhanced production of IgM antibodies against multiple damage-associated molecules.  

PubMed

Milk fat globule epidermal growth factor 8 (MFG-E8) is a protein that binds to apoptotic cells by recognizing phosphatidylserine and enhances the engulfment of apoptotic cells by macrophages. Many apoptotic cells are left unengulfed in the germinal centers of the spleen in the MFG-E8-deficient (MFG-E8(-/-)) mice, and these mice develop an autoimmune disease resembling human systemic lupus erythematosus. We found that the MFG-E8 deficiency was accompanied by the increased production of immunoglobulins. Further Western blot and ELISA analyses validated the increase in the IgM levels in the MFG-E8(-/-) mice. It was also revealed that the sera from the MFG-E8(-/-) mice cross-reacted with oxidation-specific epitopes generated upon incubation of serum albumin with the peroxidized lipids. Among the modified proteins with several unsaturated aldehydes of chain lengths varying from three to nine carbons, the MFG-E8(-/-) mice sera exclusively cross-reacted with the protein-bound 4-oxo-2-nonenal (ONE), a highly reactive aldehyde originating from the peroxidation of ?6 polyunsaturated fatty acids. In addition, the IgM monoclonal antibodies (mAbs) that selectively cross-reacted with the ONE-modified proteins were generated from the MFG-E8(-/-) mice. A subset of the ONE-specific IgM mAbs significantly recognized the late apoptotic and necrotic cells and enhanced the phagocytosis by macrophages. These data demonstrate that the impairment of the phagocytic clearance of apoptotic cells through MFG-E8 can lead to the generation of natural antibodies, which may play a critical role in removing multiple damage-associated molecules, including oxidation-specific epitopes and late apoptotic/necrotic cells. PMID:23874637

Chikazawa, Miho; Otaki, Natsuki; Shibata, Takahiro; Yasueda, Takehiko; Matsuda, Tsukasa; Uchida, Koji

2013-01-01

216

Presence of Mycoplasma fermentans in the bloodstream of Mexican patients with rheumatoid arthritis and IgM and IgG antibodies against whole microorganism  

PubMed Central

Background Increasing evidence incriminates bacteria, especially Mycoplasma fermentans, as possible arthritogenic agents in humans. The purpose of this study was to investigate M. fermentans in the bloodstream of patients with rheumatoid arthritis. Methods Two hundred and nineteen blood samples from patients with rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, and healthy individuals were screened by bacterial culture and direct PCR in order to detect mycoplasmas; IgM and IgG against M. fermentans PG18 were also detected by ELISA and Immunoblotting assays in patients with rheumatoid arthritis and healthy individuals. Results Blood samples from patients with antiphospholipid syndrome and healthy individuals were negative for mycoplasma by culture or direct PCR. In blood samples from patients with systemic lupus erythematosus were detected by direct PCR M. fermentans in 2/50 (2%), M. hominis in 2/50 (2%) and U. urealyticum in 1/50 (0.5%). In patients with RA M. fermentans was detected by culture in 13/87 blood samples and in 13/87 by direct PCR, however, there was only concordance between culture and direct PCR in six samples, so M. fermentans was detected in 20/87(23%) of the blood samples from patients with RA by either culture or PCR. Antibody-specific ELISA assay to M. fermentans PG18 was done, IgM was detected in sera from 40/87 patients with RA and in sera of 7/67 control individuals, IgG was detected in sera from 48/87 RA patients and in sera from 7/67 healthy individuals. Antibody-specific immunoblotting to M. fermentans PG18 showed IgM in sera from 35/87 patients with RA and in sera from 4/67 healthy individuals, IgG was detected in sera from 34/87 patients and in sera from 5/67 healthy individuals. Conclusion Our findings show that only M. fermentans produce bacteremia in a high percentage of patients with RA. This finding is similar to those reported in the literature. IgM and IgG against M. fermentans PG18 were more frequent in patients with RA than healthy individuals.

Gil, Constantino; Rivera, Antonio; Banuelos, David; Salinas, Salvador; Garcia-Latorre, Ethel; Cedillo, Lilia

2009-01-01

217

Use of enzyme-linked-immunosorbent assay for detection of IgG and IgM antibodies to Fusobacterium necrophorum in cattle.  

PubMed

An enzyme-linked-immunosorbent assay (ELISA) with HCl heat-extracted antigen of Fusobacterium necrophorum was conducted to detect specific immunoglobulins G and M in infected cattle. The ELISA revealed an increase (> 0.40) in specific IgG in most of the animals with hepatic abscesses but not that in specific IgM. All the lesions were positive for F. necrophorum. These findings indicated that the ELISA for immunoglobulin G detection may prove to be a useful tool for predictive serodiagnosis of F. necrophorum infection in cattle. PMID:9082147

Kanoe, M; Hirabayashi, T; Matsuoka, Y; Inoue, M; Uraoka, Y; Taguchi, S; Motoyoshi, S

1996-01-01

218

[The importance and validity of anti-Toxoplasma gondii IgG, IgM, IgA antibodies and IgG avidity tests in the diagnosis of Toxoplasmosis infection during pregnancy.].  

PubMed

Detection of specific IgG, IgM and IgA antibodies by enzyme immunoassay (EIA) tests are not always sufficient in the diagnosis of early and late Toxoplasma gondii infection during pregnancy. For this reason, the specific IgG avidity test should be used to detect primary toxoplasmosis infection. In this study, an investigation was made of the serological status of pregnant women who were suspected of having primary or late toxoplasmosis as well as the importance and relationship of specific anti-Toxoplasma gondii IgG, IgM and IgA antibodies and specific IgG avidity in their sera. TORCH panels were also used for these patients. A total of 52 pregnant women who were admitted in the Dokuz Eylül University Gynecology and Obstetrics Clinic were included in this study. The sera were sent to the serology and immunology laboratory for investigation of the anti-Toxoplasma gondii IgG, IgM and IgA antibodies by the EIA (Cobas Core, Roche, Germany and ETI-TOXOK-A, DiaSorin, Germany) technique. The anti- Toxoplasma gondii IgG avidity test was performed on IgG as well as IgM and/or IgA in positive sera with the EIA (Toxoplasma IgG Avidity EIA Well- RADIM, Italia) technique. The anti-Toxoplasma gondii IgG avidity test was not performed on sera from 21 pregnant women negative for anti-Toxoplasma gondii IgG, IgM and IgA antibodies. Borderline and high IgM levels showed a good correlation with the IgG avidity results. The ratio for the IgM and IgA positivity was 32.3% and both the IgM positivity and IgA negativity were 29%. In conclusion, anti- Toxoplasma gondii IgG avidity and anti-Toxoplasma gondii IgM antibody tests should be used together. However, positivity or high avidity of IgA was limited in the diagnosis of active toxoplasmosis infection of pregnant women. PMID:17160829

Bahar, I Hakk?; Karaman, Meral; Kirdar, Sevin; Yilmaz, Ozlem; Cel?lo?lu, Murat; Mutlu, Derya

2005-01-01

219

Evaluation of Chlamydia immunoglobulin M (IgM), IgG, and IgA rELISAs Medac for diagnosis of Chlamydia pneumoniae infection.  

PubMed Central

Chlamydia pneumoniae is an important pathogen responsible for a variety of respiratory diseases in humans. Cell culture remains the most specific method for C. pneumoniae diagnosis, but it is labor-intensive and time-consuming. Thus, serology, particularly microimmunofluorescence (MIF) testing, is frequently utilized. However, the MIF test has a significant subjective component. We evaluated a new serological test: Chlamydia Immunoglobulin M (IgG, IgA, and IgM rELISAs Medac, based on a recombinant Chlamydia-specific lipopolysaccharide (LPS) fragment, for the diagnosis of C. pneumoniae infection. The results of this study demonstrated that the use of rELISAs Medac with single sera does not appear to be sensitive or specific for diagnosis of C. pneumoniae infection compared to culture. In children, sensitivities of the rELISAs compared to culture did not exceed 34.2%, and the specificities ranged from 68.4% (IgG) to 91.2% (IgA). In adults, the sensitivities of the rELISAs were slightly higher, up to 77.8% (IgA or IgG), but the specificities ranged from a very low 20.8% for IgA or IgG to 81.1% for IgM. When multiple sera were tested, the results of the rELISAs Medac correlated with culture results in five of eight (62.5%) patients. However, this offers only a retrospective diagnosis, which makes it difficult to manage these patients prospectively.

Kutlin, A; Tsumura, N; Emre, U; Roblin, P M; Hammerschlag, M R

1997-01-01

220

Detection of LipL32-specific IgM by ELISA in sera of patients with a clinical diagnosis of leptospirosis  

PubMed Central

Successful treatment of leptospirosis is heavily dependent on early diagnosis and prompt initiation of antibiotic therapy. An ELISA test to detect specific IgM antibodies against LipL32 for early diagnosis of leptospirosis is described and evaluated here. One thousand one hundred and eighty sera from clinically suspected leptospirosis cases were enrolled together with 109 healthy volunteers selected from an endemic area between October 2007 and January 2010. Patients were categorized based on their clinical signs and symptoms. Sera were screened for leptospiral antibodies by the microscopic agglutination test (MAT) using a panel of locally circulating serovars followed by enzyme-linked immunosorbent assay (ELISA) based on recombinant LipL32 from Leptospira interrogans serovar Autumnalis strain N2. The sensitivity and specificity of the ELISA test were determined to establish its diagnostic efficiency. The cut-off value was determined to be 0.205. Overall sensitivity and specificity compared to the MAT were found to be 96.4 and 90.4%, respectively. The LipL32-specific IgM ELISA had good sensitivity and acceptable specificity and may be a candidate for the early serodiagnosis of human leptospirosis.

Vedhagiri, Kumaresan; Velineni, Sridhar; Timoney, John F; Shanmughapriya, Santhanam; Vijayachari, Paluru; Narayanan, Ramasamy; Natarajaseenivasan, Kalimuthusamy

2013-01-01

221

Reference Intervals for Serum Immunoglobulins IgG, IgA, IgM and Complements C3 and C4 in Iranian Healthy Children  

PubMed Central

Background: Determination of reference ranges of each serum protein in normal population of each country is required for studies and clinical interpretation. The aim of this study was defining reference range values of immunoglobulins and complement components in Iranian healthy children. Methods: This study was conducted from June 2003 to June 2006 in Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences. Serum levels of IgG, IgM, IgA, C3 and C4 in 800 Iranian healthy children from newborn to 18 years of age in four population were measured by nephelometry. Kolmogrov-Smirnov tests and Pearson correlation tests were used for analysis. Results: Our results mainly agree with previous reports, except for some discrepancy that might be due to the ethnic and geographic variety. There was a significant difference between two sexes only with IgA in the group of 1–3 months old, which was higher in male group and IgM in groups of 3–5, 6–8 and 9–11 years old that were higher in female groups. Mean of other serum immunoglobulins and complements was not significantly different between male and female groups. Conclusion: These results can be considered as a local reference for use in laboratories, clinical interpretations, and research for Iranian children.

Kardar, GA; Oraei, M; Shahsavani, M; Namdar, Z; Kazemisefat, GE; Haghi Ashtiani, MT; Shams, S; Pourpak, Z; Moin, M

2012-01-01

222

Preparation of heavy chain specific antisera to bovine IgA, IgM, IgG1 and IgG2.  

PubMed

Goats, guinea pigs and rabbits were immunized with bovine IgM or with intact molecules, heavy chains, Fc portions or light chains of bovine IgG1 and IgG2. Rabbits and guinea pigs were immunized with bovine secretory IgA. Goats and guinea pigs produced heavy chain specific antisera to intact IgM whereas rabbits produced anti-light chain antibody and in one instance anti-alpha 2-macroglobulin antibody in addition to the anti-mu response. Goats and guinea pigs produced antisera to bovine IgG1 and IgG2 and their Fc portions that needed little absorption to render them monospecific for the heavy chain. In addition to antibody to the heavy chains, rabbits produced anti-light chain antibody when immunized with intact IgG1 or IgG2 molecules. These latter sera, and those produced by rabbits immunized with Fc portions of IgG1 or IgG2 required extensive absorption before they were monospecific for their respective heavy chains. Heavy chains were poor immunogens in all three species. Rabbits immunized with IgA produced both anti-alpha and anti-light chain antibodies while guinea pigs produced sera with antibody activity to the alpha chain only. PMID:3937323

Nielsen, K; Duncan, J R; Stemshorn, B

1985-08-01

223

New synthesis method for 4-MAPBA monomer and using for the recognition of IgM and mannose with MIP-based QCM sensors.  

PubMed

Quartz crystal microbalance (QCM) sensors coated with molecularly imprinted polymers (MIP) have been developed for the recognition of immunoglobulin M (IgM) and mannose. In this method, methacryloylamidophenylboronic acid (MAPBA) was used as a monomer and mannose was used as a template. For this purpose, initially, QCM electrodes were modified with 2-propene-1-thiol to form mannose-binding regions on the QCM sensor surface. In the second step, the methacryloylamidophenylboronic acid-mannose [MAPBA-mannose], pre-organized monomer system, was prepared using the MAPBA monomer. Then, a molecularly imprinted film was coated on to the QCM electrode surface under UV light using ethylene glycol dimethacrylate (EDMA), and azobisisobutyronitrile (AIBN) as a cross-linking agent and an initiator, respectively. The mannose can be simultaneously bound to MAPBA and fitted into the shape-selective cavities. The binding affinity of the mannose-imprinted sensors was investigated using the Langmuir isotherm. The mannose-imprinted QCM electrodes have shown homogeneous binding sites for mannose (K(a): 3.3 × 10(4) M(-1)) and heterogeneous binding sites for IgM (K(a1): 1.0 × 10(4) M(-1); K(a2): 3.3 × 10(3) M(-1)). PMID:23350065

Diltemiz, Sibel Emir; Hür, Deniz; Keçili, Rüstem; Ersöz, Arzu; Say, R?dvan

2013-03-01

224

A somatically mutated human antiganglioside IgM antibody that induces experimental neuropathy in mice is encoded by the variable region heavy chain gene, V1-18.  

PubMed Central

IgM paraproteins associated with autoimmune peripheral neuropathy and anti-Pr cold agglutinins react with sialic acid epitopes present on disialylated gangliosides including GD1b, GT1b, GQ1b, and GD3. A causal relationship between the paraprotein and the neuropathy has never been proven experimentally. From peripheral blood B cells of an affected patient, we have cloned a human hybridoma secreting an antidisialosyl IgM mAb, termed Ha1, that shows identical structural and functional characteristics to its serum counterpart. Variable region analysis shows Ha1 is encoded by the same VH1 family heavy chain gene, V1-18, as the only other known anti-Pr antibody sequence and is somatically mutated, suggesting that it [correction of is] arose in vivo in response to antigenic stimulation. In the rodent peripheral nervous system, Ha1 immunolocalizes to dorsal root ganglia, motor nerve terminals, muscle spindles, myelinated axons, and nodes of Ranvier. After intraperitoneal injection of affinity-purified antibody into mice for 10 d, electrophysiological recordings from the phrenic nerve-hemidiaphragm preparation demonstrated impairment of nerve excitability and a reduction in quantal release of neurotransmitter. These data unequivocally establish that an antidisialosyl antibody can exert pathophysiological effects on the peripheral nervous system and strongly support the view that the antibody contributes to the associated human disease.

Willison, H J; O'Hanlon, G M; Paterson, G; Veitch, J; Wilson, G; Roberts, M; Tang, T; Vincent, A

1996-01-01

225

Lenalidomide alone or lenalidomide plus dexamethasone significantly inhibit IgG and IgM in vitro... A possible explanation for their mechanism of action in treating multiple myeloma.  

PubMed

Lenalidomide (len) is an analog of thalidomide (thal), and both are used in the treatment of a diverse group of medical conditions. A common finding in this group is the detection of immunoglobulin in skin lesions, or high levels of immunoglobulin or myeloma protein in serum and urine. While their mechanism(s) of action is not known, the drugs are noted for their ability to modulate monocyte, lymphocyte, and natural killer cell functions; suppression of immunoglobulin synthesis could offer an explanation for their effectiveness in treating multiple myeloma (MM). Our objective was to determine if, on an equimolar basis, thal, len or dexamethasone (dex) could affect pokeweed (PWM)-induced synthesis of IgG, IgM and IL-2. When peripheral blood mononuclear cells were stimulated with PWM, len surpassed thal in suppressing IgM and IgG, and enhancing IL-2. Dex enhanced IgG, and suppressed IL-2. When the stimulated cells were treated with len (an effective promoter of IL-2 and suppressor of IgM and IgG) plus dex (an effective suppressor of IL-2 and enhancer of IgG), the net result was suppression of IgM and IgG. The synthesis of IgM and IgG by putative PWM-stimulated B cell blasts is significantly blocked by len. This suggest that the B-lymphocyte is a targeted cell for len, and that suppression of the synthesis of IgG and IgM could provide an explanation for the mechanism by which len effectively treats MM. PMID:22245427

Shannon, E; Sandoval, F; Greig, N; Stagg, P

2012-02-01

226

[Obtention of a heterohybridoma for production of type IgM monoclonal antibodies against the D antigen of the Rh system].  

PubMed

The objective was to obtain a heterohybridoma capable of producing a monoclonal antibody with IgM type anti-D specificity (Rh system), that could be used as a reactive for hemoclasification. Mononuclear cells (MNC) were extracted from a blood sample of a highly sensitized woman, five days after giving birth to an Rh positive child. These were then transformed with the culture supernatant (CSN) of B05.8 cells, rich in Epstein Barr virus (EBV). Once transformed and in exponential growth, they were fused with K6H6/B5 line cells using PEG 4.000 as a fusing agent in a 1:1 proportion. After fusion, they were seeded in culture plates in order to evaluate the formation of hybrids and the secretion of specific antibodies in the CSN of each well. The efficiency of the fusion was 1.8 x 10(-6), making it possible to obtain an anti-D IgM producing clone, which we named BMS-9. This clone could be maintained in constant culture for three months, producing antibodies in a concentration of 4 microg/mL in de CSN. It was also possible to obtain antibodies with an Artificial Capilar System (ACS) reaching a concentration of 24 microg/mL. Potency was determined using Ror cells. In CSN at immediate centrifugation (IC): 1 x 32, score 52; 15' from incubation at room temperature (RT): 1 x 1,024 score 105. With that ACS product at IC: 1 x 32 score 54; 15' from incubation at RT: 1 x 8.192 score 136; and a 37 degrees C: 1 x 8,192 score 136. Reactivity was detected with red cells D(IIIa), D(IV), D(Va), D(VI) type IV, D(VII), DFR, DNU, STEM+, DAR and DAU. There was no reactivity with red cells D(IIIc), DI(Va), D(V) type II, D(VI) types I, II y III, Ro(HAR), DOL and weak D type II. During field study, no false negative or false positive reactions were detected. A stable heterohybridoma was obtained, producer of IgM type anti-D, with enough qualities to be used in blood typing. Given the excellent qualities of the antibody, we are evaluating dilution media and the addition of type IgG antibodies in order to manufacture a reactive for use in hemoclassification. PMID:17432544

León-González, Graciela; Cruz, Carlos

2007-03-01

227

Low levels of IgM antibodies to oxidized cardiolipin increase and high levels decrease risk of cardiovascular disease among 60-year olds: a prospective study  

PubMed Central

Background Antibodies against cardiolipin (aCL) are associated with increased risk of cardiovascular disease (CVD). We here determine the role of antibodies against oxidized CL (aOxCL). Methods One third of sixty-year olds from the Stockholm County were screened (2039 men, 2193 women), where 211 incident CVD-cases and 633 age- and sex-matched controls were identified (5–7 year follow-up). Antibodies were determined by ELISA and uptake of oxLDL in macrophages by FACScan. Results IgM aOxCL was lower among CVD cases than controls (p=0.024). aOxCL-levels were divided in quartiles with the highest quartile set as the reference group. After adjustment for smoking, BMI, type II diabetes, hypercholesterolaemia and hypertension, an increased risk was determined in the lowest quartile of IgM aOxCL (OR: 1.80, CI: 1.12–2.91, p=0.0159); OR for men in the lowest quartile was 2.46 (CI 1.34–4.53, p=0.0037) for CVD and for stroke: 12.28 (CI: 1.48-101.77, p=0.02). IgG aOxCL levels did not differ between quartiles in CVD-risk. High levels of IgM aOxCL (reaching significance above 86th) and IgG aOxCL (above 95th percentile) were associated with decreased risk of CVD (OR: 0.485, CI: 0.283-0.829; p=0.0082 and OR: 0.23, CI: 0.07-0.69; p=0.0091). aCL were not associated with CVD. oxCL but not CL competed out uptake of OxLDL in macrophages, and aOxLDL recognized oxCL but not CL. In contrast to aCL, aOxCL was not dependent on co-factor Beta2-glycoprotein-I. Conclusions aOxCL is a novel risk/protection marker for CVD, with therapeutic implications. OxCL competes with oxLDL for uptake in macrophages and the possibility that aOxCL inhibits such uptake by interfering with same or similar epitopes in oxCL and oxLDL should be further studied.

2013-01-01

228

Morphological and histochemical analyses of two human T-cell subpopulations bearing receptors for IgM or IgG  

PubMed Central

Two subpopulation of circulating human T cells forming rosettes with neuraminidase-treated sheep erythrocytes were purified on the basis of the presence of receptors for IgG (TG cells) or for IgM (TM cells), and were shown to have distinguishing morphological and histochemical characteristics. TM cells had the general features of typical small- or medium-sized lymphocytes; most were easily identifiable by distinctive cytoplasmic accumulations, usually one and sometimes two large spots, of nonspecific acid esterase activity. The release of the vesicular contents on short-term culture of TG cells was inhibited by cytochalasin B. Definition of these distinguishing characteristics of TM and TG cells provides a basis for practical enumeration of these functionally distinct subpopulations of human T cells. Some of the TG cells were capable of endocytosis of IgG antibody-coated erythrocytes.

1978-01-01

229

Molecular cloning of a new immunomodulatory protein from Anoectochilus formosanus which induces B cell IgM secretion through a T-independent mechanism.  

PubMed

An immunomodulatory protein (IPAF) was purified and cloned from Anoectochilus formosanus, an Orchidaceae herbal plant in Asia. The major targeting immune cells of IPAF and its modulating effects toward B lymphocytes were investigated. Rapid amplification of cDNA ends (RACE) was conducted to clone the IPAF gene, and the obtained sequence was BLAST compared on the NCBI database. MACS-purified mouse T and B lymphocytes were stimulated with IPAF and the cell proliferation, activation, and Igs production were examined. IPAF comprised a 25 amino acids signal peptide and a 138 amino acids protein which was homologous to the lectins from Orchidaceae plant. IPAF selectively induced the cell proliferation in mouse splenic B lymphocytes but not T lymphocytes. The IPAF-induced B cells exhibited increased CD69 and MHC class II expression, and a dose- and time-dependent enhancement in IgM production. These results suggested potential benefits of IPAF to strengthen the humoral immunity. PMID:21698210

Kuan, Yen-Chou; Wu, Tsai-Jen; Kuo, Che-Yu; Hsu, Ju-Chun; Chang, Wen-Ying; Sheu, Fuu

2011-01-01

230

Natural IgM mediates complement-dependent uptake of Francisella tularensis by human neutrophils via complement receptors 1 and 3 in nonimmune serum.  

PubMed

A fundamental step in the life cycle of Francisella tularensis is bacterial entry into host cells. F. tularensis activates complement, and recent data suggest that the classical pathway is required for complement factor C3 deposition on the bacterial surface. Nevertheless, C3 deposition is inefficient and neither the specific serum components necessary for classical pathway activation by F. tularensis in nonimmune human serum nor the receptors that mediate infection of neutrophils have been defined. In this study, human neutrophil uptake of GFP-expressing F. tularensis strains live vaccine strain and Schu S4 was quantified with high efficiency by flow cytometry. Using depleted sera and purified complement components, we demonstrated first that C1q and C3 were essential for F. tularensis phagocytosis, whereas C5 was not. Second, we used purification and immunodepletion approaches to identify a critical role for natural IgM in this process, and then used a wbtA2 mutant to identify LPS O-Ag and capsule as prominent targets of these Abs on the bacterial surface. Finally, we demonstrate using receptor-blocking Abs that CR1 (CD35) and CR3 (CD11b/CD18) acted in concert for phagocytosis of opsonized F. tularensis by human neutrophils, whereas CR3 and CR4 (CD11c/CD18) mediated infection of human monocyte-derived macrophages. Altogether, our data provide fundamental insight into mechanisms of F. tularensis phagocytosis and support a model whereby natural IgM binds to surface capsular and O-Ag polysaccharides of F. tularensis and initiates the classical complement cascade via C1q to promote C3 opsonization of the bacterium and phagocytosis via CR3 and either CR1 or CR4 in a phagocyte-specific manner. PMID:22888138

Schwartz, Justin T; Barker, Jason H; Long, Matthew E; Kaufman, Justin; McCracken, Jenna; Allen, Lee-Ann H

2012-09-15

231

Long term recovery of IgG and IgM production during HIV infection in a patient with common variable immunodeficiency (CVID)  

PubMed Central

Aims—Common variable immunodeficiency (CVID) is the most common serious primary immunodeficiency. This paper describes the immunological consequences of human immunodeficiency virus (HIV) infection in a patient with familial CVID subsequently treated with highly active antiretroviral therapy (HAART). Methods—Serial measurements over 11 years of serum immunoglobulins, specific antibodies to tetanus toxoid and pneumococcal polysaccharides, lymphocyte phenotypes, and HIV viral load were made. Results—The patient recovered total serum IgG and IgM, but not IgA production, with adequate concentrations of specific antibodies, allowing withdrawal of intravenous immunoglobulin without an increase in infections. T cell numbers gradually declined and the patient developed a high grade B cell lymphoma. After successful chemotherapy, HAART was commenced, viral load fell from 472 000 to < 50 copies/ml, and CD4+ T cell numbers increased from 13 to 661 x 106/litre. Antibody production was maintained after suppression of viral load. Conclusions—This is the first definitive report of reversal of IgG and IgM deficiency in familial CVID after HIV infection. Failure to normalise IgA supports the concept of separate predisposing genetic factors for selective IgA deficiency, which when combined with others lead to CVID. Furthermore, a persistently high viraemia is not required to maintain the recovery of immunoglobulin values, suggesting this depends either on a transitory effect of a high viral load, or a persistence of low amounts of virus. Key Words: common variable immunodeficiency • human immunodeficiency virus • seroconversion • highly active antiretroviral therapy

Jolles, S; Tyrer, M; Johnson, M; Webster, D

2001-01-01

232

Correlation of plasma viral loads and presence of Chikungunya IgM antibodies with cytokine/chemokine levels during acute Chikungunya virus infection.  

PubMed

Chikungunya (CHIKV) is an emerging arboviral infection of public health concern in India contributing to widespread morbidity. The precise molecular events occurring early in the infection have not been well understood. Cytokines/chemokines are suspected to play a key role in its pathogenesis. Very few studies have correlated the plasma levels of cytokines/chemokines with diagnostic markers such as viral loads and presence of CHIKV IgM antibodies. Understanding these dynamics in the early phase of CHIKV infection is likely to provide an insight into the evolution of the immune response, identify biomarkers for assessing severity, and for development of newer therapeutic strategies. This study was therefore undertaken to estimate the levels of various cytokines/chemokines in plasma samples of patients infected with CHIKV and correlate to viral load and CHIKV IgM antibodies. Cytokine/chemokine levels and viral loads in plasma were measured using cytometric bead array and TaqMan real time PCR assay, respectively. The findings revealed that acute phase of CHIKV infection is characterized by predominant inflammatory responses mediated by IL-6, IL-8, IP-10, MCP-1, and MIG (P?

Reddy, Vijayalakshmi; Mani, Reeta Subramaniam; Desai, Anita; Ravi, Vasanthapuram

2014-08-01

233

Avian glycan-specific IgM monoclonal antibodies for the detection and quantitation of type A and B haemagglutinins in egg-derived influenza vaccines.  

PubMed

Two IgM monoclonal antibodies (MAbs), Y6F5 and Y13F9, were selected during a screening of clones obtained immunising BALB/c mice with purified envelop proteins of the A/Sydney/5/97 (H3N2) IVR108 influenza strain. These MAbs recognised avian glycans on the haemagglutinin (HA) of the virus. This broad recognition allowed these MAbs to be used as enzyme-labelled secondary antibody reagents in a strain specific enzyme-linked immunosorbent assay (ELISA) in combination with a capture MAb that recognised and allowed the quantitation of the strain specific HA protein present in an egg-produced influenza vaccine. Advantage was taken of these MAbs to develop a universal ELISA in which the MAbs were used both as capture antibody and as enzyme-labelled secondary antibody to detect and quantify the HA protein of any egg-derived influenza vaccine. These avian-glycan specific IgM MAbs may prove to be particularly useful for determining the HA concentration in monovalent egg-derived pandemic influenza vaccines, in which the HA concentration may be lower than 5?g/ml. The HA detection limit in the ELISA assays developed in this study was 1.9?g/ml, as opposed to the 5?g/ml quantitation limit generally accepted for the standard single-radial-immunodiffusion (SRID) assay, the approved technique for quantifying HA content in influenza vaccines. These ELISAs can also be used to quantify influenza HA formulated with emulsion-based or mineral salt adjuvants that could interfere with HA measurement by the SRID assay. PMID:21907241

Legastelois, Isabelle; Chevalier, Michel; Bernard, Marie-Clotilde; de Montfort, Aymeric; Fouque, Martine; Pilloud, Alexandra; Serraille, Christelle; Devard, Nicolas; Engel, Olivier; Sodoyer, Régis; Moste, Catherine

2011-12-01

234

Advanced glycation end-product (AGE)-damaged IgG and IgM autoantibodies to IgG-AGE in patients with early synovitis  

PubMed Central

Advanced glycation end-product (AGE)-damaged IgG occurs as a result of hyperglycemia and/or oxidative stress. Autoantibodies to IgG-AGE were previously demonstrated in patients with severe, longstanding rheumatoid arthritis (RA). We investigated whether IgG-AGE and anti-IgG-AGE antibodies were present early in the course of RA and other inflammatory arthropathies. We prospectively followed a cohort of 238 patients with inflammatory arthritis of duration less than 1 year. Patients were evaluated clinically and serologically, and radiographs were obtained at initial and 1-year visits. Sera were assayed for IgG-AGE and anti-IgG-AGE antibodies by enzyme-linked immunosorbent assay (ELISA). Rheumatoid factor (RF) was determined by nephelometry and ELISA. Of all patients, 29% had RF-positive RA, 15% had RF-negative RA, 18% had spondyloarthropathy, and 38% had undifferentiated arthritis. IgG-AGE was present in 19% of patients, and was similar in amount and frequency in all groups. Patients with elevated IgG-AGE levels had significantly higher levels of the inflammatory markers C-reactive protein and erythrocyte sedimentation rate, but there was no correlation with blood glucose levels. Overall, 27% of the patients had IgM anti-IgG-AGE antibodies. These antibodies were highly significantly associated with RFs (P < 0.0001) and with swollen joint count (P < 0.01). In early onset arthritis, IgG damaged by AGE was detected in all patient groups. The ability to make IgM anti-IgG-AGE antibodies, however, was restricted to a subset of RF-positive RA patients with more active disease. The persistence of the anti-IgG-AGE response was more specific to RA, and was transient in the patients with spondyloarthropathy and with undifferentiated arthritis who were initially found to be positive for anti-IgG-AGE antibodies.

Newkirk, Marianna M; Goldbach-Mansky, Raphaela; Lee, Jennifer; Hoxworth, Joseph; McCoy, Angie; Yarboro, Cheryl; Klippel, John; El-Gabalawy, Hani S

2003-01-01

235

IgG and IgM isotypes of anti-cardiolipin and anti-beta2-glycoprotein i antibodies reflect different forms of recent thrombo-embolic events.  

PubMed

We correlated the distribution and levels of serum anti-cardiolipin (aCL) and anti-beta(2)-glycoprotein-1 antibodies (anti-beta(2)-GPI) of the IgG and IgM isotypes to the clinical spectrum of recent (<6 months) thrombo-embolic events in a cohort of 162 patients. Clinical information was obtained by questionnaires from the referring physicians. Cerebro-vascular infarction (CVI) had taken place in 82 patients, deep venous thrombosis (DVT) in 34, pulmonary embolism (PE) in 14, myocardial infarction (MI) in four, and other thromboses in 28 patients. SLE was the most commonly associated rheumatic disease and accounted for 20 (12%) patients. In 124 (77%) patients no underlying rheumatic disease was identified. Isolated IgG aCL was found in 31 of 48 patients with DVT/PE (65%), but in only 21 of 82 patients with CVI (26%); p<0.0001. IgG anti-beta(2)-GPI were detected in 23 (48%) DVT/PE patients, but in only 13 (16%) CVI patients; p<0.001. The IgG class anti-beta(2)-GPI positive patients had significantly higher levels of IgG aCL (mean 65 units) compared to IgG anti-beta(2)-GPI negative patients (mean 29 units); p<0.0001. In contrast, isolated IgM aCL was found in nine (19%) patients with DVT/PE, but in 46 (56%) CVI patients; p<0.0001. Only ten patients had IgM anti-beta(2)-GPI. The present study shows that the IgG and IgM aCL isotypes seem to define different clinical subsets of patients with thrombo-embolic events with IgG aCL being most prevalent in the group having DVT/PE, IgM aCL being found primarily among CVI patients. PMID:16177835

Locht, Henning; Wiik, Allan

2006-03-01

236

Fractionation of Membrane Components from Tachyzoite Forms of Toxoplasma gondii: Differential Recognition by Immunoglobulin M (IgM) and IgG Present in Sera from Patients with Acute or Chronic Toxoplasmosis  

PubMed Central

Tachyzoite forms of Toxoplasma gondii were subjected to a sequential organic solvent extraction, which allows fractionation of membrane components according to their degrees of hydrophobicity, yielding three fractions named F1 (most hydrophobic) to F3 (least hydrophobic). Fractions F2 (80.85% specificity and 86.95% sensitivity) and F3 (89.36% specificity and 93.61% sensitivity) gave the best results, being preferentially recognized by immunoglobulin M (IgM) and IgG in sera from patients with acute and chronic toxoplasmosis, respectively. Improved scores of specificity (100%) and sensitivity (100%) were achieved when a secondary antibody against human IgG1 instead of total IgG was employed to measure the reactivity of IgG antibodies with the F3 fraction. To purify tachyzoite antigens recognized by human IgM or IgG antibodies, the F2 or F3 fraction was loaded onto an octyl-Sepharose column and eluted with a propan-1-ol gradient. The main antigen(s) recognized by IgM or IgG eluted in a single peak from the octyl-Sepharose resin loaded with either F2 (30 to 50% propan-1-ol) or F3 (15 to 35% propan-1-ol), respectively. These semipurified fractions gave improved scores when used to detect T. gondii-specific IgM (95.7% specificity and 81.8% sensitivity) or IgG (100% specificity and 93.75% sensitivity) in an enzyme-linked immunosorbent assay. Further biochemical and immunological analyses of antigens partially purified from F2 and F3 indicate that glycoinositolphospholipids are preferentially recognized by IgM, whereas proteins of approximately 30 to 40 kDa are recognized by IgG, elicited during T. gondii infection in humans.

Giraldo, Monica; Cannizzaro, Helia; Ferguson, Michael A. J.; Almeida, Igor C.; Gazzinelli, Ricardo T.

2000-01-01

237

Quantitative immunohistochemical assessment of IgA, IgM, IgG and antigen-specific immunoglobulin secreting plasma cells in pig small intestinal lamina propria.  

PubMed

Intestinal immune response plays an important defensive role for pathogens, particularly for those transmitted by the oro-faecal route or for foecal shedding modulation. This work examined three parts of intestine from twelve gilts experimentally infected with PCV2-spiked semen, six vaccinated (V group) and six unvaccinated (NV group) against PCV2, 29 and 53 days post infection (DPI). An immunohistochemical investigation for IgA-, IgG- and IgM-antibody bearing plasma cells (PCs) was run on intestinal samples coupled with a sandwich immunohistochemical method to reveal anti-PCV2 antibody-secreting PCs. Plasma cell density was compared in the two groups of animals at 29 and 53 DPI. The IgA, IgG and IgM PC density did not differ between groups but displayed an increase from the upper (villus) to the lower part of the crypts while a decreasing trend in PC density was identified from duodenum to ileum. In the NV group, no increase in anti-PCV2 PC density was demonstrable in the two sampling moment: the amounts of lamina propria PCV2-specific antibody-producing PCs remained constant, 10.55±4.24 and 10.06±5.01 at 29 DPI and 53 DPI, respectively. In the V group a significant increase in PCV2-specific antibody-producing PCs was observed over time. The amounts of PCV2-specific antibody-producing PCs increased from 9.37±13.36 at 29 DPI to 18.76±15.83 at 53 DPI. The data on IgA, IgM and IgG PC counts can be considered reference values in a population of adult pigs. The sandwich method can be proposed as a technique able to identify specific antibody-secreting PCs in formalin-fixed paraffin-embedded tissues. A practical application of the sandwich method is the demonstration of a "booster-like" response of the lamina propria in vaccinated compared to unvaccinated animals. After virus challenge, vaccination induced an increase in the number of PCs containing specific anti-PCV2 antibodies at the level of intestinal mucosa. PMID:24961900

Bianco, C; Felice, V; Panarese, S; Marrocco, R; Ostanello, F; Brunetti, B; Muscatello, L V; Leotti, G; Vila, T; Joisel, F; Sarli, G

2014-08-15

238

Immunoglobulin (Ig)M antibodies against oxidized cardiolipin but not native cardiolipin are novel biomarkers in haemodialysis patients, associated negatively with mortality.  

PubMed

The risk of premature death is high in haemodialysis (HD) patients. Antibodies against cardiolipin (anti-CL) are thrombogenic in diseases such as systemic lupus erythematosus (SLE). CL is easily oxidized (Ox) and plays a role in apoptosis. In this work we studied immunoglobulin (Ig)M anti-CL and anti-OxCL in HD-patients. We conducted an observational study with a prospective follow-up examining the relationship between anti-CL, anti-OxCL and mortality risk in a well-characterized cohort of 221 prevalent HD patients [56% men, median age 66 (interquartile range 51-74) years, vintage time 29 (15-58) months] with a mean follow-up period of 41 (20-48 months). According to the receiver operator characteristic (ROC) analysis, anti-OxCL [area under the curve (AUC) 0·62, P?IgM is ?2-glycoprotein 1 (GPI)-independent and a novel biomarker; low levels are associated with death among HD patients (and high levels with decreased risk). Combination with anti-PC increases this association. Putative therapeutic implications warrant further investigation. PMID:23879320

Frostegård, A G; Hua, X; Su, J; Carrero, J J; Heimbürger, O; Bárány, P; Stenvinkel, P; Frostegård, J

2013-12-01

239

Protein-bound polysaccharide-K (PSK) directly enhanced IgM production in the human B cell line BALL-1.  

PubMed

Protein-bound polysaccharide-K (PSK) prepared from the basidiomycete Coriolus versicolor has been used as a biological response modifier for the treatment of cancer patients. Many studies describing the immunomodulatory effects and direct anti-cancer effects of PSK have been reported. Most of studies describing the immunomodulatory effects focused on cellular immunity, although there were several studies which focused on humoral immunity where PSK was shown to be able to induce antibody production in vivo. However, even in these humoral immunity studies, it is thought that the enhancement of antibody production was due to the activation of cellular immunity. In this study, we investigated the direct effect of PSK on B cells and discovered that PSK was able to enhance IgM production in the human B cell line BALL-1. Furthermore, BALL-1 was shown to have the characteristic features of B-1a cells, which are independently involved in the primary immune response. These results show that there is a possibility that PSK directly acts on B cells and simultaneously enhances both humoral immunity and cellular immunity. PMID:18848763

Maruyama, Shinjiro; Akasaka, Taiki; Yamada, Koji; Tachibana, Hirofumi

2009-07-01

240

The significance of blood levels of IgM, IgA, IgG and IgG subclasses in Sudanese visceral leishmaniasis patients.  

PubMed Central

We developed an ELISA test using leishmania antigenic extracts to detect antigen-specific antibody responses, including subclass and isotype analysis, in visceral leishmaniasis (VL) patients from the Sudan. A total of 92 parasitologically proven patients were compared with cutaneous leishmaniasis, schistosomiasis, malaria, onchocerciasis and tuberculosis patients, as well as with healthy endemic and non-endemic controls. Some VL patients were examined before and after chemotherapy. VL patients showed significantly higher IgG responses compared with all other groups (93.4% sensitivity, 93.7% specificity), and higher (but not significantly) IgM responses. All groups showed low IgA levels. All IgG subclasses, IgG1, 2, 3, and 4, showed higher levels in patients than all other groups, with IgG1 and IgG3 levels being significantly reduced following treatment. The rank order for specificity and sensitivity for IgG subclasses was IgG3 > IgG1 > IgG2 > IgG4.

Elassad, A M; Younis, S A; Siddig, M; Grayson, J; Petersen, E; Ghalib, H W

1994-01-01

241

B-cell activation by crosslinking of surface IgM or ligation of CD40 involves alternative signal pathways and results in different B-cell phenotypes.  

PubMed Central

Treatment of small resting B cells with soluble F(ab')2 fragments of anti-IgM, an analogue of T-independent type 2 antigens, induced activation characterized by proliferation and the expression of surface CD5. In contrast, B cells induced to proliferate in response to thymus-dependent inductive signals provided by either fixed activated T-helper 2 cells or soluble CD40 ligand-CD8 (CD40L) recombinant protein displayed elevated levels of CD23 (Fc epsilon II receptor) and no surface CD5. Treatment with anti-IgM and CD40L induced higher levels of proliferation and generated a single population of B cells coexpressing minimal amounts of CD5 and only a slight elevation of CD23. Anti-IgM- but not CD40L-mediated activation was highly sensitive to inhibition by cyclosporin A and FK520. Sp-cAMPS, an analogue of cAMP, augmented CD40L and suppressed surface IgM-mediated activation. Taken together these results are interpreted to mean that there is a single population of small resting B cells that can respond to either T-independent type 2 (surface IgM)- or T-dependent (CD40)-mediated activation. In response to different intracellular signals these cells are induced to enter alternative differentiation pathways.

Wortis, H H; Teutsch, M; Higer, M; Zheng, J; Parker, D C

1995-01-01

242

B-cell activation by crosslinking of surface IgM or ligation of CD40 involves alternative signal pathways and results in different B-cell phenotypes.  

PubMed

Treatment of small resting B cells with soluble F(ab')2 fragments of anti-IgM, an analogue of T-independent type 2 antigens, induced activation characterized by proliferation and the expression of surface CD5. In contrast, B cells induced to proliferate in response to thymus-dependent inductive signals provided by either fixed activated T-helper 2 cells or soluble CD40 ligand-CD8 (CD40L) recombinant protein displayed elevated levels of CD23 (Fc epsilon II receptor) and no surface CD5. Treatment with anti-IgM and CD40L induced higher levels of proliferation and generated a single population of B cells coexpressing minimal amounts of CD5 and only a slight elevation of CD23. Anti-IgM- but not CD40L-mediated activation was highly sensitive to inhibition by cyclosporin A and FK520. Sp-cAMPS, an analogue of cAMP, augmented CD40L and suppressed surface IgM-mediated activation. Taken together these results are interpreted to mean that there is a single population of small resting B cells that can respond to either T-independent type 2 (surface IgM)- or T-dependent (CD40)-mediated activation. In response to different intracellular signals these cells are induced to enter alternative differentiation pathways. PMID:7536930

Wortis, H H; Teutsch, M; Higer, M; Zheng, J; Parker, D C

1995-04-11

243

Defective expression of the CD40 ligand in X chromosome-linked immunoglobulin deficiency with normal or elevated IgM.  

PubMed

B lymphocytes from patients with X chromosome-linked immunoglobulin deficiency with normal or elevated serum IgM are unable to switch from the synthesis of IgM/IgD to that of other immunoglobulin isotypes. Isotype switch recombination was evaluated in three affected males by examining interleukin 4-driven IgE synthesis. T-cell-dependent IgE synthesis was completely absent in the B lymphocytes of the patients. In contrast, CD40 mAb plus interleukin 4 induced the patients' B cells to synthesize IgE and to undergo deletional switch recombination. Because interaction between CD40 and its ligand on activated T cells is critical for T-cell-driven isotype switching, we examined CD40 ligand expression. In contrast to normal T cells, lymphocytes from the patients expressed no detectable CD40 ligand on their surface after stimulation with phorbol 12-myristate 13-acetate and ionomycin, although the mRNA of the ligand was expressed normally. These results suggest that defective expression of the CD40 ligand underlies the failure of isotype switching in this disease. PMID:7681587

Fuleihan, R; Ramesh, N; Loh, R; Jabara, H; Rosen, R S; Chatila, T; Fu, S M; Stamenkovic, I; Geha, R S

1993-03-15

244

The natural human IgM antibody PAT-SM6 induces apoptosis in primary human multiple myeloma cells by targeting heat shock protein GRP78.  

PubMed

In contrast to other haematological malignancies, targeted immunotherapy has not entered standard treatment regimens for de novo or relapsed multiple myeloma (MM) yet. While a number of IgG-formatted monoclonal antibodies are currently being evaluated in clinical trials in MM, our study aimed to investigate whether the fully human IgM monoclonal antibody PAT-SM6 that targets a tumour-specific variant of the heat shock protein GRP78 might be an attractive candidate for future immunotherapeutic approaches. We here show that GRP78 is stably and consistently expressed on the surface on tumour cells from patients with de novo, but also relapsed MM and that binding of PAT-SM6 to MM cells can specifically exert cytotoxic effects on malignant plasma cells, whereas non-malignant cells are not targeted. We demonstrate that the induction of apoptosis and, to a lesser extent, complement dependent cytotoxicity is the main mode of action of PAT-SM6, whereas antibody dependent cellular cytotoxicity does not appear to contribute to the cytotoxic properties of this antibody. Given the favourable safety profile of PAT-SM6 in monkeys, but also in a recent phase I trial in patients with malignant melanoma, our results form the basis for a planned phase I study in patients with relapsed MM. PMID:23667612

Rasche, Leo; Duell, Johannes; Morgner, Charlotte; Chatterjee, Manik; Hensel, Frank; Rosenwald, Andreas; Einsele, Hermann; Topp, Max S; Brändlein, Stephanie

2013-01-01

245

The Natural Human IgM Antibody PAT-SM6 Induces Apoptosis in Primary Human Multiple Myeloma Cells by Targeting Heat Shock Protein GRP78  

PubMed Central

In contrast to other haematological malignancies, targeted immunotherapy has not entered standard treatment regimens for de novo or relapsed multiple myeloma (MM) yet. While a number of IgG-formatted monoclonal antibodies are currently being evaluated in clinical trials in MM, our study aimed to investigate whether the fully human IgM monoclonal antibody PAT-SM6 that targets a tumour-specific variant of the heat shock protein GRP78 might be an attractive candidate for future immunotherapeutic approaches. We here show that GRP78 is stably and consistently expressed on the surface on tumour cells from patients with de novo, but also relapsed MM and that binding of PAT-SM6 to MM cells can specifically exert cytotoxic effects on malignant plasma cells, whereas non-malignant cells are not targeted. We demonstrate that the induction of apoptosis and, to a lesser extent, complement dependent cytotoxicity is the main mode of action of PAT-SM6, whereas antibody dependent cellular cytotoxicity does not appear to contribute to the cytotoxic properties of this antibody. Given the favourable safety profile of PAT-SM6 in monkeys, but also in a recent phase I trial in patients with malignant melanoma, our results form the basis for a planned phase I study in patients with relapsed MM.

Rasche, Leo; Duell, Johannes; Morgner, Charlotte; Chatterjee, Manik; Hensel, Frank; Rosenwald, Andreas; Einsele, Hermann

2013-01-01

246

Evaluation of serological diagnostic indices for mucocutaneous leishmaniasis: immunofluorescence tests and enzyme-linked immunoassays for IgG, IgM and IgA antibodies.  

PubMed Central

The sensitivity, specificity, positive predictive value, negative predictive value, and efficiency of immunofluorescence (IF) and enzyme-linked immunoassays (ELISA) for IgG, IgM and IgA antibodies were assessed on sera from mucocutaneous leishmaniasis patients and controls. The sensitivity of the IgG-ELISA test was 93.3% with 95% confidence interval higher than what could be due to a random test not associated with the disease. The specificity of all tests, except the IgM-ELISA, gave indices that could not have been due to chance. The IgG-ELISA and IgG-IF had the highest positive predictive value and the kappa statistic showed that the strength of agreement between the disease and the test was strongest for IgG-ELISA. The IgG-ELISA had a negative predictive value with 95% confidence limits that were not due to chance alone. Efficiency was highest for IgG-ELISA and IgG-IF. These results were obtained using sera from patients with severe or long-standing disease and from controls in whom the disease was ruled out by a negative Montenegro skin test. In field surveys where the differences between cases and controls are less easy to define the diagnostic indices of these tests may vary with the disease prevalence.

Guimaraes, M. C.; Celeste, B. J.; Franco, E. L.; Cuce, L. C.; Belda, W.

1989-01-01

247

Prevalence of IgM and IgG antibodies to West Nile virus among blood donors in an affected area of north-eastern Italy, summer 2009.  

PubMed

Following reports of West Nile neuroinvasive disease in the north-eastern area of Italy in 2009, all blood donations dating from the period between 1 August and 31 October 2009 in the Rovigo province of the Veneto region were routinely checked to exclude those with a positive nucleic acid test for West Nile virus (WNV). Only one of 5,726 blood donations was positive (17.5 per 100,000 donations; 95% confidence interval (CI): 0.4–97.3). In addition, a selection of 2,507 blood donations collected during the period from 20 July to 15 November 2009 were screened by ELISA for IgG and IgM antibodies against WNV. A positive result was received for 94 of them. The positive sera were further evaluated using immunofluorescence and plaque reduction neutralisation test (PRNT), in which only 17 sera were confirmed positive. This corresponds to a prevalence of 6.8 per 1,000 sera (95% CI: 4.0–10.9). In a case-control study that matched each of the 17 PRNT-positive sera with four negative sera with the same date of donation and same donation centre, we did not find a significant association with age and sex of the donor; donors who worked mainly outdoors were significantly more at risk to have a positive PRNT for WNV. PMID:21435323

Pezzotti, P; Piovesan, C; Barzon, L; Cusinato, R; Cattai, M; Pacenti, M; Piazza, A; Franchin, E; Pagni, S; Bressan, S; Martello, T; Potenza, R; Scipioni, C; Ammendola, R; Breda, A; Palu, G; Russo, F; Rezza, G

2011-01-01

248

Synthetic blood group antigens for anti-A removal device and their interaction with monoclonal anti-A IgM  

PubMed Central

Removal of blood group antibodies against the donor organ prior to ABO-incompatible transplantation can prevent episodes of hyperacute rejection. We are developing a specific antibody filter (SAF) device consisting of immobilized synthetic Atrisaccharide antigens conjugated to polyacrylamide (Atri-PAA) to selectively remove anti-A antibodies directly from whole blood. In this study, we evaluated eight anti-A IgM monoclonal antibodies (mAbs) using Enzyme-Linked Immunosorbent Assay (ELISA) to determine their specificity for binding to Atri-PAA. Five of the eight mAbs met our criteria for specificity by binding to Atri-PAA with at least five times greater affinity compared to the negative controls. These selected mAbs will be studied for their binding characteristics to Atri-PAA which will aid in the development of the SAF. The study of kinetics of antibody removal and quantification of antibody removal will be used in our mathematical model to maximize the antibody removal rate and binding capacity of the SAF.

Solovan, Jennifer C.; Oh, Heung-Il; Alikhani, Azadeh; Gautam, Shalini; Vlasova, Katherine; Korchagina, Elena Y.; Bovin, Nicolai V.; Federspiel, William J.

2007-01-01

249

Predictive nature of IgM anti-?-glucose serum biomarker for relapse activity and EDSS progression in CIS patients: a BENEFIT study analysis  

PubMed Central

Background: Higher serum levels of at least one of a panel of four ?-glucose IgM antibodies (gMS-Classifier1) in clinically isolated syndrome (CIS) patients are associated with imminent early relapse within 2 years. Objective: The objective of this study was to determine the prognostic value of gMS-Classifier1 in a large study cohort of CIS patients. Methods: The BEtaseron® in Newly Emerging multiple sclerosis For Initial Treatment (BENEFIT) 5-year study was designed to evaluate the impact of early versus delayed interferon-?-1b (IFN?-1b; Betaseron®) treatment in patients with a first event suggestive of multiple sclerosis (MS). Patients (n = 258, 61% of total) with a minimum of 2 ml baseline serum were eligible for the biomarker study. gMS-Classifier1 antibodies’ panel (anti-GAGA2, anti-GAGA3, anti-GAGA4 and anti-GAGA6) levels were measured blinded to clinical data. Subjects were classified as either ‘positive’ or ‘negative’ according to a classification rule. Results: gMS-Classifier1 was not predictive for the time to clinically definite MS or time to MS according to the revised McDonald’s criteria, but did significantly predict an increased risk for confirmed disability progression (log-rank test: p = 0.012). Conclusions: We could not confirm previous results that gMS-Classifier1 can predict early conversion to MS in CIS. However, raised titres of these antibodies may predict early disability progression in this patient population.

Metzig, C; Kappos, L; Polman, CH; Edan, G; Hartung, H-P; Miller, DH; Montalban, X; Yarden, J; Spector, L; Fire, E; Dotan, N; Schwenke, S; Lanius, V; Sandbrink, R; Pohl, C

2012-01-01

250

Plasmodium falciparum-specific immunoglobulin G (IgG), IgM, and IgE antibodies in paired maternal-cord sera from east Sepik Province, Papua New Guinea.  

PubMed Central

Enzyme-linked immunosorbent assay (ELISA) and Western blot (immunoblot) serological analyses for immunoglobulin G (IgG), IgM, and IgE antibodies to Plasmodium falciparum were made from 46 maternal-cord serum pairs obtained from parturient East Sepik (Papua New Guinea) women and their newborn. Concurrent study of these women had shown that placental parasitemia rates were related to parity with the highest rate (41%) in the primiparous group and the lowest rate (3%) in the women who had given birth more than three times (> 3 parity group). Overall ELISA positivity rates for antimalarial IgG, IgM, and IgE antibodies in the maternal sera were 54.3, 28.2, and 8.3%, respectively, while those for the cord sera were 36.9, 0, and 16.6% respectively. Seropositivity rates were not related to maternal parity group, except for maternal IgE, in which there was a higher rate, of borderline significance, in the > 3 parity group than in the primiparous group. Cord IgE positivity was largely independent of maternal positivity and vice versa. Cord and maternal IgG immunoblot pairs showed near homology. IgG antibodies to the P. falciparum antigens of sizes < 36 kDa were either weak or absent in parity group 1 and 2 maternal-cord serum pairs. Neither ELISA or immunoblot revealed IgM antibody in the cord serum samples. Maternal IgM antibodies showed a heterogeneity of responses both between paired IgG immunoblots and between different serum samples. The IgE immunoblots exhibited a similar diversity, albeit of less complexity. The presence of P. falciparum-specific IgE in the cord sera would indicate that prenatal immune hypersensitization of the fetus to malaria had occurred. Images

Desowitz, R S; Elm, J; Alpers, M P

1993-01-01

251

[Responsiveness of a new parvovirus B19 antigen produced in baculovirus expression system to B19-specific IgG and IgM antibodies in every epidemic, 1968, 1980, 1987 and 1992 in Japan].  

PubMed

A new recombinant parvovirus B19 antigen was tested whether it was responsive to human serum antibodies in every epidemic year of erythema infectiosum for 25 years, because wild strains of B19 parvovirus were changeable genetically. The antigen was empty particles of both B19-VP1 and VP2 produced in baculovirus expression system. Specimens were 21 sera in 1968, 19 in 1980, 44 in 1987 and 33 in 1992, derived from 67 patients with erythema infectiosum, fever and/or non-specific exanthem and aplastic crisis in persons with hereditary spherocytosis. Each patient had been confirmed of B19 parvovirus infection by other methods as radio immunoassay and/or enzyme-linked immunosolvent assay for B19-IgG and IgM using other antigens and by detection of B19-genome DNA using the polymerase chain reaction. Days of the illness of every serum were confirmed including before infection to 216 days after onset. Sera from 23 patients with measles, Kawasaki disease and rubella were selected for controls, and those patients who had not been infected with B19 parvovirus. Tests were carried out by enzyme immunoassay, indirect method for IgG and IgM capture method. In a total of 103 specimens after onset of symptoms B19-IgG was positive in yearly specimens, and B19-IgM was also positive in all acute phase sera. B19-IgG in most of all sera was kept in peak level up to 216 days after onset. B19-IgM increased rapidly in acute phase and seemed to disappear within one to 5 months after onset. Thirty-seven specimens including 14 obtained at state before infection and 23 controls were completely negative for both B19-IgG and IgM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7602188

Nunoue, T

1995-05-01

252

Studies on the Induction of IgG-Fc Receptors and Synthesis of IgM in Primary and Chronically-Infected Lymphoid (Raji) Cells by Herpes Simplex Virus  

Microsoft Academic Search

SUMMARY The present paper reports on the induction of two cell surface markers on human lymphoid cells following herpes simplex virus (HSV) infection. While both primary and chronic infections of human lymphoid cells led to the induction of receptors for the Fc region of 7S IgG, chronic HSV infection was also charac- terized by the induction of surface-bound IgM. Surface

ANGELO E. BOURKAS; J. Menezes

1979-01-01

253

Apoptosis or plasma cell differentiation of CD38-positive B-chronic lymphocytic leukemia cells induced by cross-linking of surface IgM or IgD  

Microsoft Academic Search

Previously, we demonstrated that B- chronic lymphocytic leukemia (B-CLL) cells could be divided into 2 groups depending on the expression of CD38 by the malignant cells. The 2 groups differed in their signal-transducing capacities ini- tiated by cross-linking of surface IgM; only in CD38-positive cells was an effi- cient signal delivered, invariably result- ing in cell apoptosis. In this study,

Simona Zupo; Rosanna Massara; Mariella Dono; Edoardo Rossi; Fabio Malavasi; Elisabetta Cosulich; Manlio Ferrarini

2000-01-01

254

Comparative Evaluation of Capsular Polysaccharide-Specific IgM and IgG Antibodies and F(ab¶)2 and Fab Fragments as Delivery Vehicles for Radioimmunotherapy of Fungal Infection  

Microsoft Academic Search

Purpose: The applicability ofradioimmunotherapy with organism-specif ic monoclonal anti- bodies to treatment ofinf ectious disease in experimental models has been recently shown f or fungal, bacterial, and viral infections. To identify the best delivery vehicle for radioimmunotherapy ofhuman pathogenic f ungus Cryptococcus neoformans (CN), we have done comparative evaluation ofcapsular polysaccharide-specif ic antibodies with IgG1 and IgM isotypes and F(ab¶)2

Ekaterina Dadachova; Ruth A. Bryan; Xianchun Huang; Geraldina Ortiz; Tiffany Moadel; Arturo Casadevall

2007-01-01

255

Changes in DNA Methylation and Gene Expression during 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Induced Suppression of the Lipopolysaccharide-Stimulated IgM Response in Splenocytes  

PubMed Central

Lipopolysaccharide (LPS) is a bacterial endotoxin and a potent B-cell activator capable of inducing a humoral immune response. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a well-established immunotoxicant that can suppress humoral immune responses, including those initiated by LPS stimulation. In murine models, TCDD-induced suppression of the LPS-activated primary immunoglobulin M (IgM) response is observed both in vivo and in vitro and is typically evaluated as a decrease in the number of IgM antibody–forming cells. The TCDD-induced suppression of the primary humoral immune response occurs, at least in part, upstream of IgM production. The current study was designed as an initial test of our hypothesis that altered DNA methylation, an epigenetic event, is involved in the LPS-induced IgM response by splenocytes as is the suppression of this response by TCDD. Splenocyte-derived DNA from mice treated in vivo with sesame oil + PBS, LPS, TCDD, or LPS + TCDD was used for the current investigation. DNA methylation was evaluated using a technique that permits assessment of the methylation status of multiple genomic regions simultaneously in an unbiased fashion (no specific genes or genomic regions are preselected). Additionally, the expression of selected genes was determined. Our results indicate that treatment with LPS or TCDD can alter DNA methylation and, importantly, combined TCDD + LPS results in altered DNA methylation that was not simply the addition of the changes discerned in the individual treatment groups. Thus, we have identified cross talk between LPS and TCDD at the level of DNA methylation and gene expression.

McClure, Emily A.; North, Colin M.; Kaminski, Norbert E.; Goodman, Jay I.

2011-01-01

256

Skin Injuries Reduce Survival and Modulate Corticosterone, C-Reactive Protein, Complement Component 3, IgM, and Prostaglandin E2 after Whole-Body Reactor-Produced Mixed Field (n + ?-Photons) Irradiation  

PubMed Central

Skin injuries such as wounds or burns following whole-body ?-irradiation (radiation combined injury (RCI)) increase mortality more than whole-body ?-irradiation alone. Wound-induced decreases in survival after irradiation are triggered by sustained activation of inducible nitric oxide synthase pathways, persistent alteration of cytokine homeostasis, and increased susceptibility to systemic bacterial infection. Among these factors, radiation-induced increases in interleukin-6 (IL-6) concentrations in serum were amplified by skin wound trauma. Herein, the IL-6-induced stress proteins including C-reactive protein (CRP), complement 3 (C3), immunoglobulin M (IgM), and prostaglandin E2 (PGE2) were evaluated after skin injuries given following a mixed radiation environment that might be found after a nuclear incident. In this report, mice received 3?Gy of reactor-produced mixed field (n + ?-photons) radiations at 0.38?Gy/min followed by nonlethal skin wounding or burning. Both wounds and burns reduced survival and increased CRP, C3, and PGE2 in serum after radiation. Decreased IgM production along with an early rise in corticosterone followed by a subsequent decrease was noted for each RCI situation. These results suggest that RCI-induced alterations of corticosterone, CRP, C3, IgM, and PGE2 cause homeostatic imbalance and may contribute to reduced survival. Agents inhibiting these responses may prove to be therapeutic for RCI and improve related survival.

Kiang, Juliann G.; Ledney, G. David

2013-01-01

257

Clinical virology of Ebola hemorrhagic fever (EHF): virus, virus antigen, and IgG and IgM antibody findings among EHF patients in Kikwit, Democratic Republic of the Congo, 1995.  

PubMed

Ebola hemorrhagic fever (EHF) patients treated at Kikwit General Hospital during the 1995 outbreak were tested for viral antigen, IgG and IgM antibody, and infectious virus. Viral antigen could be detected in virtually all patients during the acute phase of illness, while antibody was not always detectable before death. Virus was also isolated from patients during the course of their febrile illness, but attempts to quantify virus in Vero E6 cells by standard plaque assay were often unsuccessful. IgG and IgM antibody appeared at approximately the same time after disease onset (8-10 days), but IgM persisted for a much shorter period among the surviving convalescent patients. IgG antibody was detectable in surviving patients through about 2 years after onset, the latest time that samples were obtained. Detection of Ebola virus antigens or virus isolation appears to be the most reliable means of diagnosis for patients with suspected acute EHF, since patients with this often-fatal disease (80% mortality) may not develop detectable antibodies before death. PMID:9988182

Ksiazek, T G; Rollin, P E; Williams, A J; Bressler, D S; Martin, M L; Swanepoel, R; Burt, F J; Leman, P A; Khan, A S; Rowe, A K; Mukunu, R; Sanchez, A; Peters, C J

1999-02-01

258

Semiquantitative measurement of IgG subclasses and IgM of platelet-specific antibodies in a glycoprotein-specific platelet-antigen capture assay.  

PubMed

The detection of platelet-specific antibodies is of high clinical interest in diseases with immune thrombocytopenia. The glycoprotein-specific platelet-antigen capture (PAC)-assay developed in this study is especially suited to the differentiation of platelet-specific immunoglobulin (Ig) G subclasses and the determination of platelet-specific IgM in serum or on platelets. The problems with unspecific signals or low sensitivity usually seen with the detector antibodies available are effectively overcome, as unbound detector antibodies are removed at an early stage in the assay. We investigated 14 maternal alloantisera from cases of neonatal alloimmune thrombocytopenia (NAITP) and six sera from patients with autoimmune thrombocytopenic purpura (AITP). In NAITP sera, we found IgG1 alone in 57%, IgG1 + IgG3 in 21% and IgG1 + IgG2 in 14% of cases. One serum contained IgG1 + IgG2 + IgG3. In AITP, three out of the six sera contained IgG1 alone. One serum contained IgG1 + IgG2. One patient, with highly refractory AITP, had platelet-specific IgG1 + IgG2 + IgG3 in his serum. A patient with AITP in remission and normal platelet counts only showed platelet-bound IgG2. The detection of platelet-specific 'whole IgG' is possible too. However, at this time the commonly used monoclonal antibody-specific immobilization of platelet antigens (MAIPA) method should not be replaced for this purpose, as it is well standardized and used with similar results in many laboratories. The PAC assay sensitively detects the subclasses of platelet-specific IgG and human leucocyte antigen (HLA)-antibodies independently. It is easy to perform and takes less time than other platelet glycoprotein-specific methods. PMID:11918546

Kelsch, Reinhard; Hutt, Kerstin; Cassens, Uwe; Sibrowski, Walter

2002-04-01

259

Simultaneous binding of the anti-cancer IgM monoclonal antibody PAT-SM6 to low density lipoproteins and GRP78.  

PubMed

The tumour-derived monoclonal IgM antibody PAT-SM6 specifically kills malignant cells by an apoptotic mechanism linked to the excessive uptake of plasma lipids. The mechanism is postulated to occur via the multi-point attachment of PAT-SM6 to the unfolded protein response regulator GRP78, located on the surface of tumour cells, coupled to the simultaneous binding of plasma low density lipoprotein (LDL). We prepared and characterised LDL and oxidized LDL using sedimentation velocity and small-angle X-ray scattering (SAXS) analysis. Enzyme-linked immunosorbent (ELISA) techniques indicated apparent dissociation constants of approximately 20 nM for the binding of LDL or oxidized LDL to PAT-SM6. ELISA experiments showed cross competition with LDL inhibiting PAT-SM6 binding to immobilised GRP78, while, in the reverse experiment, GRP78 inhibited PAT-SM6 binding to immobilized LDL. In contrast to the results of the ELISA experiments, sedimentation velocity experiments indicated relatively weak interactions between LDL and PAT-SM6, suggesting immunoabsorbance to the microtiter plate is driven by an avidity-based binding mechanism. The importance of avidity and the multipoint attachment of antigens to PAT-SM6 was further investigated using antigen-coated polystyrene beads. Absorption of GRP78 or LDL to polystyrene microspheres led to an increase in the inhibition of PAT-SM6 binding to microtiter plates coated with GRP78 or LDL, respectively. These results support the hypothesis that the biological action of PAT-SM6 in tumour cell apoptosis depends on the multivalent nature of PAT-SM6 and the ability to interact simultaneously with LDL and multiple GRP78 molecules clustered on the tumour cell surface. PMID:23620733

Rosenes, Zachary; Mok, Yee-Foong; Yang, Shuo; Griffin, Michael D W; Mulhern, Terrence D; Hatters, Danny M; Hensel, Frank; Howlett, Geoffrey J

2013-01-01

260

Hyperphosphorylated paratarg-7: a new molecularly defined risk factor for monoclonal gammopathy of undetermined significance of the IgM type and Waldenstrom macroglobulinemia.  

PubMed

We recently described paratarg-7 (P-7), a protein of unknown function, as the target of 15% of immunoglobulin A (IgA) and IgG paraproteins in monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma. To determine the frequency of P-7 as a paraprotein target in IgM-MGUS and Waldenström macroglobulinemia (WM), sera from patients with IgM-MGUS/WM were tested for reactivity with recombinant P-7 by enzyme-linked immunoabsorbent assay. The specificity of the paraprotein-mediated reaction was shown by absorption studies and cloning of the respective B-cell receptor. The paraproteins of 18 (9 WM and 9 IgM-MGUS) of 161 patients (11%) reacted with P-7. Isoelectric focusing and phosphatase treatment showed that P-7 was hyperphosphorylated (pP-7) in all patients with an anti-P-7-specific IgM paraprotein tested. Because only 4 of 200 healthy controls (2%) were carriers of pP-7, pP-7 carrier state is associated with a significantly increased risk (odds ratio = 6.2; P = .001) for developing IgM-MGUS/MW. Family analyses showed that the pP-7 carrier state is inherited as a dominant trait. After IgA/IgG-MGUS and multiple myeloma, IgM-MGUS/WM is the second neoplasia associated with pP-7 carrier state. The dominant inheritance of pP-7 explains cases of familial IgM-MGUS/WM and enables the identification of family members at increased risk. PMID:21220746

Grass, Sandra; Preuss, Klaus-Dieter; Wikowicz, Alexandra; Terpos, Evangelos; Ziepert, Marita; Nikolaus, Diana; Yang, Yin; Fadle, Natalie; Regitz, Evi; Dimopoulos, Meletios A; Treon, Steven P; Hunter, Zachary R; Pfreundschuh, Michael

2011-03-10

261

High density of intraepithelial gammadelta lymphocytes and deposits of immunoglobulin (Ig)M anti-tissue transglutaminase antibodies in the jejunum of coeliac patients with IgA deficiency.  

PubMed

The diagnosis of coeliac disease (CD) represents a special challenge in selective immunoglobulin (Ig)A deficiency (IgAD). A high density of T cell receptor (TCR)gammadelta(+) intraepithelial lymphocytes (IELs) and intestinal IgA anti-tissue transglutaminase 2 (anti-TG2) antibody deposits are suggestive of CD. We analysed the density of TCRgammadelta(+) IELs and the deposition of IgM anti-TG2 antibodies in the jejunal mucosa of IgAD patients with and without CD. Immunohistochemical analyses for the number of CD3+ and TCRgammadelta(+) IELs and double immunofluorescence assay for IgM anti-TG2 antibody deposits were performed in biopsies from 25 children with IgAD (nine untreated CD, seven potential CD and nine without CD). Sixteen immunologically intact children without CD represented the controls. IgAD without CD had a higher number of CD3+ and TCRgammadelta(+) IELs than controls (P < 0.05), but lower than IgAD with CD (P < 0.01). No significant differences were noted between IgAD subjects without CD and those with potential CD. Furthermore, IgAD patients without CD showed a higher TCRgammadelta(+)/CD3+ ratio than the control group (P < 0.05), while the ratio was similar to subjects with CD and potential CD. Intestinal IgM anti-TG2 antibody deposits were present in six of seven of the IgAD patients with untreated CD, one of seven with potential CD and none of those without CD. Most of the patients with IgAD show immune activation in the jejunal mucosa. IgM anti-TG2 antibody deposits are present only in CD. Intestinal IgM anti-TG2 and immunohistochemical markers do not discriminate between IgAD and potential CD with IgAD. Therefore, the serum IgG CD-associated autoantibodies remains very important for the diagnosis of CD in IgAD. PMID:20030673

Borrelli, M; Maglio, M; Agnese, M; Paparo, F; Gentile, S; Colicchio, B; Tosco, A; Auricchio, R; Troncone, R

2010-05-01

262

Evaluation of human (genotype 1) and swine (genotype 4)-ORF2-based ELISAs for anti-HEV IgM and IgG detection in an endemic country and search for type 4 human HEV infections.  

PubMed

Open reading frame 2 proteins (ORF2) from swine (genotype 4, S-ORF2) and human (genotype 1, H-ORF2) hepatitis E virus (HEV) having 91.4% identity at amino acid level were expressed using baculovirus expression system. Comparison of ELISAs based on the two proteins yielded identical results when sequential serum samples from monkeys and pigs experimentally infected with genotypes 1 and 4 HEV, respectively, were tested. Samples from patients (n = 258) suffering from non-A, non-B hepatitis during outbreaks of the disease and 180 sera from apparently healthy children were screened by H-ORF2-, S-ORF2-based ELISAs and Genelabs ELISA, a widely used commercial test for HEV diagnosis. Specificity of all three tests in detecting IgM and IgG antibodies in healthy children was comparable. Excellent correlation was noted in detecting both IgM (98.7% concordance) and IgG (97.7% concordance) anti-HEV antibodies when H-ORF2 and S-ORF2 ELISAs were compared. When compared with Genelabs ELISA, both H-ORF2 and S-ORF2 ELISAs identified 34 and 18 additional positives, respectively, in IgM and IgG anti-HEV tests showing comparatively less sensitivity of the commercial assay. The concordance of Genelabs ELISA in IgM detection was 86.4% and 85.6%, respectively, with H-ORF2 and S-ORF2 ELISAs. The concordance between Genelabs ELISA and H-ORF2 decreased further to 73.6% when 129 human samples from recent HEV epidemics (2002-2004) were tested for IgM. Similar results were obtained when sequential samples from 11 hepatitis E patients were examined. Screening of serum samples from 137 sporadic non-A, non-B hepatitis cases further confirmed the superiority of the H-ORF2 and S-ORF2 ELISAs. All 36/137 HEV-RNA-positive samples from sporadic cases belonged to genotype 1 confirming absence/rarity of type 4 human infections. H-ORF2 and S-ORF2 antigens were swappable in ELISAs for detecting both genotypes 1 and 4 HEV infections. PMID:17501765

Arankalle, V A; Lole, K S; Deshmukh, T M; Chobe, L P; Gandhe, S S

2007-06-01

263

Production and characterization of a murine monoclonal IgM antibody to human C1q receptor (C1qR)  

SciTech Connect

A hybridoma cell line that produces a monoclonal antibody (MAb) to cell surface C1q receptor (C1qr) has been produced by fusion of the P3 x 63-Ag8.653 mouse myeloma cell line with the spleen cells of a CD-1 mouse that had been hyperimmunized with viable Raji cell suspensions (5 x 10/sup 7/ cells/inoculum). This MAb, designated II1/D1, is an IgM antibody with lambda-light chain specificity. Radiolabeled or unlabeled, highly purified II1/D1 was used to determine that: a) this antibody competes for C1q binding sites on C1qR-bearing cells; b) the molecule recognized by this MAb is the C1qR; and c) cells that are known to bind C1q also bind II1/D1 in a specific manner. Western blot analysis of solubilized Raji, or U937 cell membranes, showed that the /sup 125/I-MAb detected a major protein band of approximately 85000 m.w. in its unreduced state, indicating that the C1qR is similar, if not identical, in both types of cells. Analyses of /sup 125/I-II/D1 binding experiments revealed that the antibody bound to Raji cells or u937 cells in a specific manner. Uptake of the antibody was saturable, with equilibrium virtually attained within 35 min. Scatchard analysis of the binding data using the intact MAb suggests that the affinity constant K/sub D/ is 2.9 x 10/sup -10/ M, and at apparent saturation, 24.6 ng of the antibody were bound per 2 x 10/sup 6/ cells, giving an estimated 7.8 x 10/sup 3/ antibody molecules bound per cell. That the II1/D1 antibody is specifically directed to the C1q was further evidenced by an ELISA in which the ability of C1qR-bearing cells to bind the MAb was abrogated by c-C1q in a specific dose-dependent manner.

Ghebrehiwet, B.

1986-07-15

264

Preferential expression of IgG1 antibodies specific for the L2C leukaemia IgM idiotypic determinants in tumour-protected strain 2 guinea-pigs  

PubMed Central

Immunization of strain 2 guinea-pigs with 107 syngeneic Ia+ L2C leukaemia cells in adjuvant leads to L2C tumour protection. After subsequent challenges with L2C tumour cells, the sera of twelve out of seventy protected guinea-pigs had detectable L2C reactivity as determined by a [125I]-protein A binding assay. The antibodies bound equally well to Ia+ and Ia- L2C tumour cells, but did not bind to L1 and L10 guinea-pig hepatocarcinoma cells or normal guinea-pig B and T lymphocytes. The binding was blocked appreciably by F(ab')2 reagents specific for the L2C IgM idiotype but not by those specific for Ia or B.1 alloantigens or ?2 microglobulin. These results lead to provisional identification of anti-idiotype among the syngeneic antibody population. After ion-exchange chromatography, the L2C reactivity in eleven of the twelve immune sera analysed was exclusively in the IgG1 fraction. The syngeneic anti-idiotypic antibodies precipitated only IgM molecules from the NP-40 extracts of L2C tumour cells and were dissociated from the L2C leukaemia cells more readily than the xenogeneic anti-idiotypic antibodies at pH 6.5 and 6.0. These results suggest that the L2C IgM idiotype may function as a tumour-associated antigen or is near the antigenic complex recognized by the low affinity L2C antibodies. The preferential expression of IgG1 antibodies suggests that humoral immunity effects a minimum level of protection because this isotype, in the guinea-pig, has a restricted capacity to mediate tumour rejection by secondary immune mechanisms.

Ricardo, M. J.; Grimm, D. T.

1983-01-01

265

Anti-type II collagen antibodies, anti-CCP, IgA RF and IgM RF are associated with joint damage, assessed eight years after onset of juvenile idiopathic arthritis (JIA)  

PubMed Central

Background Early appearance of antibodies specific for native human type II collagen (anti-CII) characterizes an early inflammatory and destructive phenotype in adults with rheumatoid arthritis (RA). The objective of this study was to investigate the occurrence of anti-CII, IgM RF, IgA RF and anti-CCP in serum samples obtained early after diagnosis, and to relate the occurrence of autoantibodies to outcome after eight years of disease in children with juvenile idiopathic arthritis (JIA). Methods The Nordic JIA database prospectively included JIA patients followed for eight years with data on remission and joint damage. From this database, serum samples collected from 192 patients, at a median of four months after disease onset, were analysed for IgG anti-CII, IgM RF, IgA RF and IgG anti-CCP. Joint damage was assessed based on Juvenile Arthritis Damage Index for Articular damage (JADI-A), a validated clinical instrument for joint damage. Results Elevated serum levels of anti-CII occurred in 3.1%, IgM RF in 3.6%, IgA RF in 3.1% and anti-CCP in 2.6% of the patients. Occurrence of RF and anti-CCP did to some extent overlap, but rarely with anti-CII. The polyarticular and oligoarticular extended categories were overrepresented in patients with two or more autoantibodies. Anti-CII occurred in younger children, usually without overlap with the other autoantibodies and was associated with high levels of C-reactive protein (CRP) early in the disease course. All four autoantibodies were significantly associated with joint damage, but not with active disease at the eight-year follow up. Conclusions Anti-CII, anti-CCP, IgA RF and IgM RF detected early in the disease course predicted joint damage when assessed after eight years of disease. The role of anti-CII in JIA should be further studied.

2014-01-01

266

Low incidence of positive smooth muscle antibody and high incidence of isolated IgM elevation in Chinese patients with autoimmune hepatitis and primary biliary cirrhosis overlap syndrome: a retrospective study  

PubMed Central

Background Up to now, few data are available regarding the clinical characteristics of autoimmune hepatitis and primary biliary cirrhosis overlap syndrome. The study was to investigate and analyze the prevalent and clinical features of Chinese patients with this disease. Methods Clinical data on patients diagnosed as autoimmune hepatitis and primary biliary cirrhosis overlap syndrome in our hospital from January 2001 to December 2006 were collected and analyzed. Results Overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis accounted for 10.33% of patients with autoimmune liver diseases during the past six years. For these patients with overlap syndrome, xanthochromia, lethargy and anorexia were the predominant complaints; a low incidence (14/146) of smooth muscle antibody positivity and a high incidence (37/89) of isolated IgM elevation were the main serological characteristics. Conclusions Overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis was not rare in Chinese patients with clinical manifests of autoimmune liver diseases. Overlap of the diseases should not be disregarded when isolated IgM elevation was exhibited, and smooth muscle antibody might have little diagnostic significance in the overlap syndrome. If it was difficult to make a definite diagnosis, liver biopsy was necessary.

2012-01-01

267

[Serum levels of acid alpha 1-glycoprotein, haptoglobin, C 3c component of the complement and immunoglobulins IgG, IgA and IgM in liver damage in patients with chronic renal failure treated by repeated hemodialysis].  

PubMed

Thirty-five patients with chronic renal failure treated with repeated haemodialyses were divided into 3 groups: without evidence of hepatocellular damage (n = 11), with HBs-negative hepatocellular damage (n = 13), with HBS-positive, HBe-positive hepatocellular damage (n = 10). The concentrations of acid alpha 1-glycoprotein, haptoglobin, C3c complement component, IgG, IgA, IgM were determined in the serum before haemodialysis. The serum concentration of acid alpha 1-glycoprotein was statistically significantly higher in the patients in comparison with the healthy subjects. The concentrations of haptoglobin and C3c complement component in the serum were not statistically significantly different form those in healthy controls. The serum levels of IgG, IgA and IgM in patients with hepatocellular damage HBs-positive and HBe-positive were statistically significantly higher in relation to healthy subjects, the serum IgG level in this group was statistically significantly higher than in the group without hepatocellular damage and the group with HBs-negative hepatocellular damage. PMID:2629317

Bartelik, S; Starzyk, J

1989-04-30

268

[Sero-diagnosis for human parvovirus B19 infection by IgM and IgG antibody capture method of enzyme-linked immunosorbent assay--study on an epidemic case of erythema infectiosum].  

PubMed

The IgM and IgG antibody capture methods of the enzyme-linked immunosorbent assay (ELISA) for human parvovirus B19 were performed using Horseradish peroxidase (HRPO)-labeled anti B19 monoclonal antibody. Serially obtained serum samples from one erythema infectiosum (E.I.) patient were examined at once by this methods. The dOD values of the IgM and IgG antibodies decreased on the typical curves according to the course of recovery. In the epidemic case of E.I. among students of one nurse school, 1) The first patients was estimated by comparing the change of dOD values of sera obtained at end of the epidemic and 1.5 months later. 2) In the pre-existing antibody positive persons, the dOD values of IgG antibody did not changed during the epidemic. 3) After the E.I. epidemic, and approximately 30% of the students were remained uninfected. PMID:1624835

Matsunaga, Y; Yamazaki, S; Moritsugu, Y; Kuwabara, Y; Nishigaki, M

1992-04-01

269

Comparisons of the ability of human IgG3 hinge mutants, IgM, IgE, and IgA2, to form small immune complexes: a role for flexibility and geometry.  

PubMed

Various native and hinge-modified forms of Ig with identical Ids were reacted with an anti-Id mAb, and the resultant immune complexes were analyzed by negative stain immunoelectron microscopy. Complexes were scored for their geometry (linear versus ring complexes) and size (dimer, trimer, etc.). Ring dimers are the thermodynamically most favorable configuration, unless inhibited by steric and/or flexibility constraints. We found ring dimerization to correlate with the length of the upper, but not middle or lower, hinge. In contrast, the geometry and size of complexes of those molecules lacking formal hinges were unpredictable. A hingeless IgG mutant and native IgE readily formed ring dimers. Remarkably, monomeric IgM formed more ring dimers than any of the other Igs tested, including IgG3. We also tagged the Fab arms and measured the mean Fab-Fab angles and the degree of angular variation for each type of Ig. Surprisingly, IgM proved the most flexible by this assay. In hinged Igs, there was a correlation between length of the upper hinge and Fab-Fab flexibility. In contrast, we found no correlation between the mean Fab-Fab angle in uncomplexed Igs and their ability to dimerize with anti-Id mAb. These data suggest that the physicochemical methods typically used to evaluate molecular flexibility are often of low predictive value when tested in a functional assay. PMID:9780179

Roux, K H; Strelets, L; Brekke, O H; Sandlie, I; Michaelsen, T E

1998-10-15

270

Anti-N-methyl-D-aspartate receptor encephalitis with serum anti-thyroid antibodies and IgM antibodies against Epstein-Barr virus viral capsid antigen: a case report and one year follow-up  

PubMed Central

Background Anti-N-methyl-D-aspartate receptor encephalitis is an increasingly common autoimmune disorder mediated by antibodies to certain subunit of the N-methyl-D-aspartate receptor. Recent literatures have described anti-thyroid and infectious serology in this encephalitis but without follow-up. Case presentation A 17-year-old Chinese female patient presented with psychiatric symptoms, memory deficits, behavioral problems and seizures. She then progressed through unresponsiveness, dyskinesias, autonomic instability and central hypoventilation during treatment. Her conventional blood work on admission showed high titers of IgG antibodies to thyroglobulin, thyroid peroxidase and IgM antibodies to Epstein-Barr virus viral capsid antigen. An immature ovarian teratoma was found and removal of the tumor resulted in a full recovery. The final diagnosis of anti-N-methyl-D-aspartate receptor encephalitis was made by the identification of anti-N-methyl-D-aspartate receptor antibodies in her cerebral spinal fluid. Pathology studies of the teratoma revealed N-methyl-D-aspartate receptor subunit 1 positive ectopic immature nervous tissue and Epstein-Barr virus latent infection. She was discharged with symptoms free, but titers of anti-thyroid peroxidase and anti-thyroglobulin antibodies remained elevated. One year after discharge, her serum remained positive for anti-thyroid peroxidase and anti-N-methyl-D-aspartate receptor antibodies, but negative for anti-thyroglobulin antibodies and IgM against Epstein-Barr virus viral capsid antigen. Conclusions Persistent high titers of anti-thyroid peroxidase antibodies from admission to discharge and until one year later in this patient may suggest a propensity to autoimmunity in anti- N-methyl-D-aspartate receptor encephalitis and support the idea that neuronal and thyroid autoimmunities represent a pathogenic spectrum. Enduring anti-N-methyl-D-aspartate receptor antibodies from admission to one year follow-up but seroreversion of Epstein-Barr virus viral capsid antigen IgM may raise the important issue of elucidating the triggers and boosters of anti- N-methyl-D-aspartate receptor encephalitis.

2011-01-01

271

Two years' performance of an in-house ELISA for diagnosis of Legionnaires' disease: detection of specific IgM and IgG antibodies against Legionella pneumophila serogroup 1, 3 and 6 in human serum.  

PubMed

The aim of this study was to evaluate the performance of an in-house ELISA for the diagnosis of Legionnaires' disease (LD) by detection of IgM and IgG antibodies against Legionella (L.) pneumophila serogroups (sg) 1, 3 and 6. The evaluation was done throughout a two-year period in a diagnostic routine laboratory. Furthermore, the sensitivity of four different methods, the in-house L. pneumophila antibody test (ELISA), the urinary antigen test (Binax® EIA), an in-house PCR and culture, both alone and in combination was evaluated. From 2008 to 2010, 12,158 serum samples from 10,503 patients were analysed. During the same period, 361 cases of laboratory-confirmed LD cases were recorded in Denmark, but of these only 113 had a serum sample examined. The positive predictive value of the in-house ELISA was calculated to be 12.8 and the negative predictive value was 99.6, using only the confirmed LD cases as true positives. The sensitivity of the in-house ELISA for the detection of IgM and IgG antibodies in the confirmed LD cases was 61% and 36%, respectively. By combining the two ELISA assays the sensitivity increased to 66%. The sensitivity of the Legionella urinary antigen test (Binax® EIA) was 63%, of the in-house PCR 87% and of culture 69%. When all the different methods were combined, a higher sensitivity was calculated--for in-house ELISA (IgM+IgG) and Binax® EIA 91%, in-house ELISA (IgM+IgG) and in-house PCR 93%, in-house ELISA (IgM+IgG) and culture 93%, Binax® EIA and in-house PCR 79%, Binax® EIA and culture 68% and in-house PCR and culture 94%. This study confirms that the detection of IgG and IgM antibodies by ELISA is an important diagnostic tool, also during the initial phase of the disease. Furthermore, we showed that LD in Denmark with or without serum samples collected exhibits the same age and sex distribution and epidemiology, as in the rest of Europe, i.e., mostly men are infected, infections are mostly community acquired, followed by infection from travelling abroad. Apart from patients with notified LD, the patients investigated by serology were evenly distributed in all age groups; there was only a slightly higher ratio of men tested for "atypical pneumonia" in the serology laboratory. PMID:23657054

Elverdal, P L; Jørgensen, C S; Krogfelt, K A; Uldum, S A

2013-08-01

272

Antivirus and immune enhancement activities of sulfated polysaccharide from Angelica sinensis.  

PubMed

This study is to synthesize sulfated Angelica polysaccharides (APSs) and investigate the activity of one of the sulfated derivatives APS-1 on murine leukemia virus in vivo. Six sulfated derivatives with degree of sulfation ranging from 0.68 to 1.91 were obtained. And the virus replication was inhibited by APS-1 at the dose of 10 and 30 mg/kg (26% and 30% inhibition respectively). Furthermore, both the percentage of CD4(+) cells and CD4(+)/CD8(+) ratio in peripheral blood cells were significantly enhanced by APS-1 at 3-30 mg/kg. In addition, the reduced thymus/body weight index by murine leukemia virus infection was increased by ASP-1 in a dose dependent manner. These results suggest that APS-1 could not only inhibit virus replication, but also improve the immune function. APS-1 may be a potential new and better antiviral drug. PMID:22155400

Yang, Tiehong; Jia, Min; Zhou, Siyuan; Pan, Feng; Mei, Qibing

2012-04-01

273

Budding of Enveloped Viruses: Interferon-Induced ISG15--Antivirus Mechanisms Targeting the Release Process  

PubMed Central

Pathogenic strains of viruses that infect humans are encapsulated in membranes derived from the host cell in which they infect. After replication, these viruses are released by a budding process that requires cell/viral membrane scission. As such, this represents a natural target for innate immunity mechanisms to interdict enveloped virus spread and recent advances in this field will be the subject of this paper.

Seo, Eun Joo; Leis, Jonathan

2012-01-01

274

F(ab')2 fragment of a gp41 NHR-trimer-induced IgM monoclonal antibody neutralizes HIV-1 infection and blocks viral fusion by targeting the conserved gp41 pocket.  

PubMed

Using a recombinant protein N46FdFc that mimics the HIV-1 gp41 N-helix trimer to immunize mice, we identified the first IgM monoclonal antibody 18D3 that specifically bound to the conserved gp41 pocket. Its F(ab')2 fragment potently inhibited HIV-1 Env-mediated cell-cell fusion and neutralized infection by laboratory-adapted and primary HIV-1 isolates with different subtypes and tropism, including the T20-resistant variants. This F(ab')2 fragment can be used to develop a bispecific broad neutralizing monoclonal antibody or HIV-1 inactivator as a novel immunotherapeutic for treatment and prevention of HIV-1 infection. PMID:24141089

Lu, Lu; Wei, Meili; Chen, Yanxia; Xiong, Weiliang; Yu, Fei; Qi, Zhi; Jiang, Shibo; Pan, Chungen

2013-11-01

275

Decreased IgA+ B cells population and IgA, IgG, IgM contents of the cecal tonsil induced by dietary high fluorine in broilers.  

PubMed

Fluoride is an environmental and industrial pollutant that affects various organs in humans and animals. The cecal tonsil is an important component of the mucosal immune system and performs important and unique immune functions. In the present study, we investigated the effects of dietary high fluorine on the quantities of IgA+ B cells in the cecal tonsil by immunohistochemistry, and the immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM) contents in the cecal tonsil by ELISA. A total of 280 one-day-old avian broilers were divided into four groups and fed on a corn-soybean basal diet as control diet (fluorine 22.6 mg/kg) or the same diet supplemented with 400, 800 and 1,200 mg/kg fluorine (high fluorine groups I, II and III) in the form of sodium fluoride, respectively, throughout a 42-day experimental period. The results showed that the quantities of IgA+ B cells were lower (p < 0.05 or p < 0.01) and the IgA, IgG, and IgM contents were decreased (p < 0.05 or p < 0.01) in high fluorine groups II and III in comparison with those of control group. It was concluded that dietary fluorine, in the 800-1,200 mg/kg range, could reduce the numbers of the IgA+ B cells and immunoglobulin contents in the cecal tonsil, implying the local mucosal immune function was ultimately impacted in broilers. PMID:23644827

Liu, Juan; Cui, Hengmin; Peng, Xi; Fang, Jing; Zuo, Zhicai; Deng, Junliang; Wang, Hesong; Wu, Bangyuan; Deng, Yuanxin; Wang, Kangping

2013-05-01

276

Evaluation of the Architect Epstein-Barr Virus (EBV) Viral Capsid Antigen (VCA) IgG, VCA IgM, and EBV Nuclear Antigen 1 IgG Chemiluminescent Immunoassays for Detection of EBV Antibodies and Categorization of EBV Infection Status Using Immunofluorescence Assays as the Reference Method.  

PubMed

Commercial immunoassays for detecting IgG and IgM antibodies against Epstein-Barr virus (EBV), viral capsid antigens (VCA), and IgGs toward EBV nuclear antigen-1 (EBNA-1) are routinely used in combination to categorize EBV infection status. In this study, we evaluated the performances of the Architect EBV VCA IgG, VCA IgM, and EBNA-1 IgG chemiluminescent microparticle assays (CMIAs) in EBV serological analyses using indirect immunofluorescence assays and anticomplement immunofluorescence assays as the reference methods for VCA IgG, VCA IgM, and EBNA-1 IgG antibody detection, respectively. A total of 365 serum samples representing different EBV serological profiles were included in this study. The ? values (concordances between the results) obtained in the Architect CMIA and those in the reference assays were 0.905 (P < 0.0001) for VCA IgM, 0.889 (P < 0.0001) for VCA IgG, and 0.961 (P < 0.0001) for EBNA-1 IgG. The sensitivities and specificities were, respectively, 91.08% and 99.48% for VCA IgM, 99.23% and 86.27% for VCA IgG, and 96.77% and 99.16% for EBNA-1 IgG. The sensitivities and specificities of the Architect CMIA panel were, respectively, 99.15% and 98.6% for diagnosing a primary infection, 97.62% and 93.39% for diagnosing a past EBV infection, and 92.42% and 97.82% for diagnosing the absence of an EBV infection. In summary, we demonstrated that the Architect EBV antibody panel performs very well for EBV antibody detection and correctly categorizes clinically relevant EBV infection states. PMID:24623623

Corrales, Isabel; Giménez, Estela; Navarro, David

2014-05-01

277

Immunization with N-propionyl polysialic acid-KLH conjugate in patients with small cell lung cancer is safe and induces IgM antibodies reactive with SCLC cells and bactericidal against group B meningococci  

PubMed Central

Purpose Polysialic acid (polySA) is a polymer side chain bound to the neural cell adhesion molecule that is extensively expressed on the surface of small cell lung cancer (SCLC) cells. In our previous study, a robust antibody response was noted in patients with SCLC after vaccination with 30 ?g of keyhole limpet hemocyanin (KLH)-conjugated N-propionylated (NP-) polySA, but peripheral neuropathy and ataxia were detected in several vaccinated patients. The objectives of the current trial were to establish the lowest optimal dose and to confirm the safety of the induction of antibodies against polySA with the NP-polySA vaccine. Experimental design Patients with SCLC who completed initial treatment and had no evidence of disease progression were injected with either 10 or 3 ?g of NP-polySA conjugated to KLH and mixed with 100 ?g of immunologic adjuvant (QS-21) at weeks 1, 2, 3, 4, 8, and 16. Results Nine patients were enrolled at each of the two dose levels. Prior to vaccination, one patient in each group had low-titer antibodies against polysialic acid. All patients at the 10 ?g vaccine dose level responded to vaccination with IgM antibody titers against polysialic acid (median titer 1/1,280 by ELISA), and all but one patient made IgM and IgG antibodies against the artificial vaccine immunogen, NP-polysialic acid (median titer 1/10,240). The antibody responses at the 3 ?g vaccine dose level were lower; six of nine patients developed antibodies against polysialic acid (median titer 1/160). Post-vaccination sera from 6/9 and 3/9 patients in the 10 and 3 ?g groups reacted strongly with human SCLC cells by fluorescent-activated cell sorting (FACS). Sera from all patients in the 10 ?g dose group also had bactericidal activity against group B meningococci with rabbit complement. Self-limited grade 3 ataxia of unclear etiology was seen in 1 of 18 patients. Conclusions Vaccination with NP-polySA–KLH resulted in consistent high-titer antibody responses, with the 10 ?g dose significantly more immunogenic than the 3 ?g dose. This study establishes the lowest optimally immunogenic dose of NP-polysialic acid in this NP-polysialic acid–KLH conjugate vaccine to be at least 10 ?g, and it establishes the vaccine’s safety. We plan to incorporate NP-polySA into a polyvalent vaccine against SCLC with four glycolipid antigens also widely expressed in SCLC–GD2, GD3, fucosylated GM1, and globo H.

Krug, Lee M.; Ragupathi, Govind; Hood, Chandra; George, Constantine; Hong, Feng; Shen, Ronglai; Abrey, Lauren; Jennings, Harold J.; Kris, Mark G.; Livingston, Philip O.

2013-01-01

278

De novo 13q12.3-q14.11 deletion involving BRCA2 gene in a patient with developmental delay, elevated IgM levels, transient ataxia, and cerebellar hypoplasia, mimicking an A-T like phenotype.  

PubMed

We report on a child with a de novo deletion of approximately 12 Mb detected through array comparative genomic hybridization (CGH). The deletion involved chromosome bands 13q12.3-13q14.11 and determined the loss of ?50 genes. A second deletion on chromosome 12p11.3p11.22 of 43-167 kb, including about 12 genes, was unlikely of clinical relevance because inherited from the asymptomatic father. The child had developmental delay, dysmorphisms, and many features reminiscent of ataxia-telangiectasia (A-T), as cerebellar ataxia, oculocutaneus telangiectasia, and recurrent upper airway infections. Atraumatic fractures of the metatarsus were noted. Moreover, this is a rare case of 13q deletion syndrome associated with peripheral blood white cells radiosensitivity to bleomycin, reminiscent of what previously reported on X-ray hypersensitivity of fibroblasts from patients with alterations of this chromosome. The immunological evaluation revealed increased IgM serum levels and a low proliferative response to mitogens, PHA, and CD3 cross-linking (CD3 XL). After 12 years of age only a mild dysmetria persisted, while the proliferative response to mitogens became normal by 9 years of age. PMID:22903806

Cirillo, Emilia; Romano, Rosa; Romano, Alfonso; Giardino, Giuliana; Durandy, Anne; Nitsch, Lucio; Genesio, Rita; Di Gregorio, Eleonora; Cavalieri, Simona; Abate, Giovanna; Del Vecchio, Luigi; Brusco, Alfredo; Pignata, Claudio

2012-10-01

279

Viral nervous necrosis virus persistently replicates in the central nervous system of asymptomatic gilthead seabream and promotes a transient inflammatory response followed by the infiltration of IgM+ B lymphocytes.  

PubMed

The viral nervous necrosis virus (VNNV) is the causal agent of viral encephalopathy and retinopathy (VER), a worldwide fish disease that is responsible for high mortality in both marine and freshwater species. Infected fish suffer from encephalitis, which leads to abnormal swimming behavior and extensive cellular vacuolation and neuronal degeneration in the central nervous system (CNS) and retina. The marine fish gilthead seabream (Sparus aurata) does not develop VER but it is an asymptomatic carrier of VNNV. In this study, we report that VNNV was able to replicate and persist for up to 3 months in the CNS of the gilthead seabream without causing any neural damage. In addition, we found an early inflammatory response in the CNS that was characterized by the induction of genes encoding pro-inflammatory cytokines, a delayed but persistent induction of anti-inflammatory cytokines, and the infiltration of IgM(+) B lymphocytes, suggesting that local adaptive immunity played a major role in the control of VNNV in the CNS of this species. PMID:22402274

López-Muñoz, Azucena; Sepulcre, María P; García-Moreno, Diana; Fuentes, Inmaculada; Béjar, Julia; Manchado, Manuel; Álvarez, M Carmen; Meseguer, José; Mulero, Victoriano

2012-07-01

280

Marsupial immunoglobulins: the distribution and evolution of macropod IgG2, IgG1, IgM and light chain antigenic markers within the sub-class Metatheria.  

PubMed Central

The distribution within Australian and American marsupials of the heavy and light chain antigenic markers identified by antisera to purified quokka (Setonix brachyurus) immunoglobulins is described. Markers for IgM and IgG2 constant region determinants as well as for light chains were widely distributed in Australian species and were also detected in Didelphis, the American opossum, thus indicating a long-term structural conservatism of some immunoglobulins within the marsupials. More detailed analysis of the distribution of quokka IgG2 determinants by quantitative precipitation and sequential absorption procedures suggested that there had been a gradual and cumulative acquisition of these markers with time. The presence of IgG2 markers in species separated for 130 million years (quokka and opossum) suggested that IgG2 was the ancestral IgG present before the divergence of these separate lines. The origin of IgG1 remains obscure as it appears to be limited to a small group of closely related diprotodont marsupials suggesting a recent origin. Images Figure 1

Bell, R G

1977-01-01

281

Cannabinoid Receptor 2 (CB2) Plays a Role in the Generation of Germinal Center and Memory B Cells, but Not in the Production of Antigen-Specific IgG and IgM, in Response to T-dependent Antigens  

PubMed Central

The cannabinoid receptor 2 (CB2) has been reported to modulate B cell functions including migration, proliferation and isotype class switching. Since these processes are required for the generation of the germinal center (GC) and antigen-specific plasma and memory cells following immunization with a T-dependent antigen, CB2 has the capacity to alter the quality and magnitude of T-dependent immune responses. To address this question, we immunized WT and CB2?/? mice with the T-dependent antigen 4-hydroxy-3-nitrophenylacetyl (NP)-chicken-gamma-globulin (CGG) and measured GC B cell formation and the generation of antigen-specific B cells and serum immunoglobulin (Ig). While there was a significant reduction in the number of splenic GC B cells in CB2?/? mice early in the response there was no detectable difference in the number of NP-specific IgM and IgG1 plasma cells. There was also no difference in NP-specific IgM and class switched IgG1 in the serum. In addition, we found no defect in the homing of plasma cells to the bone marrow (BM) and affinity maturation, although memory B cell cells in the spleen were reduced in CB2?/? mice. CB2-deficient mice also generated similar levels of antigen-specific IgM and IgG in the serum as WT following immunization with sheep red blood cells (sRBC). This study demonstrates that although CB2 plays a role in promoting GC and memory B cell formation/maintenance in the spleen, it is dispensable on all immune cell types required for the generation of antigen-specific IgM and IgG in T-dependent immune responses.

Dittel, Bonnie N.

2013-01-01

282

Intrathecally produced IgG and IgM antibodies to recombinant VlsE, VlsE peptide, recombinant OspC and whole cell extracts in the diagnosis of Lyme neuroborreliosis.  

PubMed

Detection of intrathecally produced specific antibodies (AI) is essential in the diagnosis of Lyme neuroborreliosis (LNB); however, the performance of various newer AI detection methods has not been systematically assessed. Here we assessed and compared advanced test systems for detecting borrelia IgG-AI and IgM-AI. Serum and cerebrospinal fluid (CSF) samples from well-defined LNB and tick-borne encephalitis (TBE) patients, 25 each, were tested with three antibody detection systems, one based on chemiluminescence (CLA) and two based on enzyme-linked immunosorbent assays (ELISA), employing different antigens for detection of IgG and IgM antibodies. In samples from patients with LNB, IgG-AI was detected in 20 samples by CLA, 19 by ELISA1, and 22 by ELISA2, and IgM-AI was detected in 16 samples by CLA, six by ELISA1, and 11 by ELISA2. In samples from TBE patients, IgG-AI was positive in one case by CLA and ELISA2, and in 7 cases by ELISA1, whereas IgM-AI was positive in one case by CLA and in none by ELISA. IgG-AI and IgM-AI were not detected within the first week of disease. Duration of disease correlated with IgG-AI while IgM-AI results were heterogeneous for each test assay. Moreover, the levels of IgG-AI, but not IgM-AI, correlated with protein concentration in CSF. IgG is the relevant immunoglobulin isotype for detecting intrathecal synthesis of borrelia antibodies. The highest sensitivity and specificity were achieved by the antibody detection assay using VlsE IR6 peptide. Detection of IgM-AI yielded heterogenous results and did not support the laboratory diagnosis of LNB. PMID:24363169

Stanek, Gerold; Lusa, Lara; Ogrinc, Katarina; Markowicz, Mateusz; Strle, Franc

2014-04-01

283

Thalidomide inhibited the synthesis of IgM and IgG whereas Thalidomide+Dexamethasone and Dexamethasone alone acted as co-stimulants with pokeweed and enhanced their synthesis.  

PubMed

Thalidomide (Thal) provides effective treatment for erythema nodosum leprosum (ENL). In combination with Dexamethasome (Dex) it is an effective treatment for multiple myeloma (MM) and Waldenström's macroglobulinemia (WM). Thal's mechanism(s) of action in the treatment of these diverse medical conditions is not known, but it could be suppression of immunoglobulin (Ig) synthesis. Mononuclear cells were stimulated with pokeweed (PWM), and treated with Thal, Thal+Dex or Dex. The cultures were assayed for IgM and IgG. The maximum synthesis was expected to occur in cultures stimulated with PWM at 0.5, 5.0 or 10 microg/ml. The test agents at 15 microM each were expected to alter the response. Compared to cultures stimulated with PWM alone, there was significantly less Ig in the cultures containing Thal+PWM, and significantly more Ig in the cultures containing Thal+Dex+PWM or Dex+PWM (Wilcoxon). The median % of maximum was 57 for cultures treated with Thal+PWM; 184 for cultures treated with Thal+Dex+PWM, and 139 for cultures treated with Dex+PWM. Thal also acted as a co-stimulant with PWM and enhanced the synthesis of IL-2, IL-6 and DNA; whereas, Thal+Dex or Dex enhanced Ig synthesis, but suppressed IL-2, IL-6 and cell proliferation. Thal's ability to suppress Ig may explain its activity in ENL, MM and WM. The enhancement of Ig by Dex does not help to explain a role for Dex alone or in combination with Thal for the treatment of MM and WM. PMID:20123041

Shannon, E J; Sandoval, F

2010-04-01

284

Crystal structure of a human autoimmune complex between IgM rheumatoid factor RF61 and IgG1 Fc reveals a novel epitope and evidence for affinity maturation.  

PubMed

Rheumatoid factors (RF) are autoantibodies that recognize epitopes in the Fc region of immunoglobulin (Ig) G and that correlate with the clinical severity of rheumatoid arthritis (RA). Here we report the X-ray crystallographic structure, at 3 A resolution, of a complex between the Fc region of human IgG1 and the Fab fragment of a monoclonal IgM RF (RF61), derived from an RA patient and with a relatively high affinity for IgG Fc. In the complex, two Fab fragments bind to each Fc at epitopes close to the C terminus, and each epitope comprises residues from both Cgamma3 domains. A central role in the unusually hydrophilic epitope is played by the side-chain of Arg355, accounting for the subclass specificity of RF61, which recognizes IgG1,-2, and -3 in preference to IgG4, in which the corresponding residue is Gln355. Compared with a previously determined complex of a lower affinity RF (RF-AN) bound to IgG4 Fc, in which only residues at the very edge of the antibody combining site were involved in binding, the epitope bound by RF61 is centered in classic fashion on the axis of the V(H):V(L) beta-barrel. The complementarity determining region-H3 loop plays a key role, forming a pocket in which Arg355 is bound by two salt-bridges. The antibody contacts also involve two somatically mutated V(H) residues, reinforcing the suggestion of a process of antigen-driven maturation and selection for IgG Fc during the generation of this RF autoantibody. PMID:17395205

Duquerroy, Stephane; Stura, Enrico A; Bressanelli, Stéphane; Fabiane, Stella M; Vaney, Marie C; Beale, Dennis; Hamon, Maureen; Casali, Paolo; Rey, Felix A; Sutton, Brian J; Taussig, Michael J

2007-05-18

285

A facile one-step hydrothermal synthesis of rhombohedral CuFeO2 crystals with antivirus property.  

PubMed

The rhombohedral-like CuFeO(2) crystals are synthesized via a facile hydrothermal route by using propionaldehyde as a reducing agent. The obtained CuFeO(2) crystals show promising efficiency in the inactivation of bacteriophage Q?. PMID:22711005

Qiu, Xiaoqing; Liu, Min; Sunada, Kayano; Miyauchi, Masahiro; Hashimoto, Kazuhito

2012-07-28

286

Cincuentenario del descubrimiento de la estructura química de los anticuerpos  

Microsoft Academic Search

The identification of the antitoxic property of serum in 1890 by Emil von Behring and the introduction of the term “Antikörper” by Paul Ehrlich in 1891 referring to one of the most relevant mechanisms of defense of the adaptive immune system, i.e., the humoral immune response mediators, mark the beginning of modern immunology. The “Y” structure was described 50 years

Dolores Ramos-Bello; Luis Llorente

2009-01-01

287

Evaluation of exposure index (IgM) in orthopaedic radiography.  

PubMed

The exposure index (lgM) obtained from a radiographic image may be a useful feedback indicator to the radiographer about the appropriate exposure level in routine clinical practice. This study aims to evaluate lgM in orthopaedic radiography performed in the standard clinical environment. We analysed the lgM of 267 exposures performed with an AGFA CR system. The mean value of lgM in our sample is 2.14. A significant difference (P = 0.000 < or =0.05) from 1.96 lgM reference is shown. Data show that 72% of exposures are above the 1.96 lgM and 42% are above the limit of 2.26. Median values of lgM are above 1.96 and below 2.26 for Speed class (SC) 200 (2.16) and SC400 (2.13). The interquartile range is lower in SC400 than in SC200. Data seem to indicate that lgM values are above the manufacturer's reference of 1.96. Departmental exposure charts should be optimised to reduce the dose given to patients. PMID:18430719

Lança, L; Silva, A

2008-01-01

288

Large Scale Simulations of the Jet-Igm Interaction  

NASA Astrophysics Data System (ADS)

In a parameter study extending to jet densities of 10-5 times the ambient one, I have recently shown that light large-scale jets start their lives in a spherical bow shock phase. This allows an easy description of the sideways bow shock propagation in that phase. Here, I present new, bipolar, simulations of very light jets in 2.5D and 3D, reaching the observationally relevant scale of > 200 jet radii. Deviations from the early bow shock propagation law are expected because of various effects. The net effect is, however, shown to remain small. I calculate the X-ray appearance of the shocked cluster gas and compare it with Cygnus A and 3C 317. Rings, bright spots and enhancements inside the radio cocoon may be explained.

Krause, Martin G. H.

2004-09-01

289

Treatment Failure Related to Intrathecal Immunoglobulin M (IgM) Synthesis, Cerebrospinal Fluid IgM, and Interleukin10 in Patients with Hemolymphatic-Stage Sleeping Sickness  

Microsoft Academic Search

Human African trypanosomiasis treatment is stage dependent, but the tests used for staging are contro- versial. Central nervous system involvement and its relationship with suramin treatment failure were assessed in 60 patients with parasitologically confirmed hemolymphatic-stage Trypanosoma brucei gambiense infection (white blood cell count of <5\\/l and no trypanosomes in the cerebrospinal fluid (CSF)). The prognostic value of CSF interleukin-10,

Veerle Lejon; Jo Robays; Francois Xavier N'Siesi; D. Mumba; A. Hoogstoel; S. Bisser; H. Reiber; M. Boelaert; P. Buscher

2007-01-01

290

A randomised controlled trial of intravenous immunoglobulin in IgM paraprotein associated demyelinating neuropathy  

Microsoft Academic Search

.   This multicentre randomised double blind crossover trial tested the short term efficacy of intravenous immunoglobulin (IVIg)\\u000a 2.0 g\\/kg given over 24 or 48 hours in patients with paraproteinaemic demyelinating neuropathy (PDN). Twenty-two patients were\\u000a randomised and completed the trial. After 2 weeks, the overall disability grade decreased during both IVIg treatment and placebo\\u000a but neither change was significant nor

Giancarlo Comi; Luisa Roveri; Antony Swan; Hugh Willison; Martin Bojar; Isabel Illa; Clementine Karageorgiou; Eduardo Nobile-Orazio; Peter van den Bergh; Tony Swan; Richard Hughes

2002-01-01

291

Accelerated Clearance of Polyethylene Glycol-Modified Proteins by Anti-Polyethylene Glycol IgM  

Microsoft Academic Search

Tumor therapy by the preferential activation of a prodrug at tumor cells targeted with an antibody- enzyme conjugate may allow improved treatment efficacy with reduced side effects. We examined antibody-mediated clearance of poly(ethylene glycol)-modified ‚-glucuronidase (‚G-sPEG) as a method to reduce serum concentrations of enzyme and minimize systemic prodrug activation. Enzyme-linked immunosorbent assay and immunoblot analysis of two monoclonal antibodies

Tian-Lu Cheng; Pin-Yi Wu; Ming-Fang Wu; Ji-Wang Chern; Steve R. Roffler

1999-01-01

292

[Presence of IgM antibodies for Leptospira interrogans in wild animals from Tocantins State, 2002].  

PubMed

Four hundred and twenty-seven serum samples of wild animals were tested against 18 serovars of Leptospira interrogans. Of 286 samples of Cebus apella, 46 (16.1%) were positive for the serovars pomona, brasiliensis, mini, swajizak, grippotyphosa, sarmin, fluminense, autumnalis, hebdomadis, guaratuba, javanica and icterohaemorrhagiae. Of 82 samples of Alouatta caraya, 2 (2.4%) were positive for the serovars mangus and fluminense. Of 31 samples of Nasua nasua, 4 (12.9%) were positive for the serovars fluminense and javanica, and of 10 samples of Cerdocyon thous, 2 (20 %) were positive for the serovars fluminense and brasiliensis. Seven samples of Dasyprocta sp, 6 of Tamandua tetradactyla and 5 of Euphractus sexcintus did not present reactivity. PMID:16906258

de Souza Júnior, Milton Formiga; Lobato, Zélia Inês Portela; Lobato, Francisco Carlos Faria; Moreira, Elvio Carlos; de Oliveira, Rogério Rodrigues; Leite, Geysa Goulart; Freitas, Theonys Diógenes; de Assis, Ronnie Antunes

2006-01-01

293

Successful treatment of multi-agent chemotherapy with rituximab for IgM plasma cell leukemia  

Microsoft Academic Search

A 67-year-old woman presented with impaired general performance, suffering from fatigue, dyspnea on exertion, and paresthesia of the finger tips. The laboratory findings showed increased white blood cells at 11.37×103cells\\/?l with 26.5% abnormal cells, low haemoglobin and, elevated creatinine, although serum lactate dehydrogenase and calcium levels were normal. Serum immunofixation was positive for monoclonal IgM-kappa paraprotein. Total serum protein and

Satoko Oka; Taiji Yokote; Toshikazu Akioka; Satoshi Hara; Takeshi Yamano; Motomu Tsuji; Toshiaki Hanafusa

2006-01-01

294

Peripheral neuropathy associated with monoclonal IgM anti-Pr2 cold agglutinins.  

PubMed Central

A patient with a chronic, large fibre sensory neuropathy had an immunoglobulin M lambda monoclonal paraprotein reactive at titres in excess of 1/10(5) with NeuNAc(alpha 2-8)NeuNAc(alpha 2-3)Gal configured disialosyl groups present on the gangliosides GD1b, GT1b, GQ1b, and GD3. The paraprotein showed weaker reactivity with GD1a, GM3, and LM1 but no reactivity with GM2, GM1, or asialo-GM1. In addition, the paraprotein had cold agglutinating activity with anti-Pr2 specificity, Pr2 being an antigenic determinant on membrane glycoproteins or glycolipids in erythrocytes or both. A large fibre sensory neuropathy with monoclonal anti-disialosyl antibodies is an increasingly recognised form of paraproteinaemic neuropathy. Images

Willison, H J; Paterson, G; Veitch, J; Inglis, G; Barnett, S C

1993-01-01

295

In Pursuit of the Thermal State of the IGM at Redshift 20: Radio Foreground Characterization  

NASA Astrophysics Data System (ADS)

One of the great challenges of cosmology today is tracing the thermal history of the Universe from global reionization back to recombination. The Large Aperture Experiment to Detect the Dark Age (LEDA) will set direct constraints on sky-averaged spectral-line absorption of the Cosmic Microwave Background by neutral Hydrogen in the intergalactic medium at redshift ~ 20. Line intensity, breadth, and center frequency enable hypothesis testing for models of heating during the preceding Dark Age and the epoch at which sustained star formation began. LEDA has begun science observations at the Long Wavelength Array in Owens Valley. I will report initial characterizations of the foreground sky, effectiveness of subtraction, and assessment of how difficult or easy it may be to take the next step: measurement of the angular power spectrum of HI fluctuations just after the end of the Dark Age.

Greenhill, Lincoln J.; LEDA Collaboration

2014-01-01

296

A Critical Role for Induced IgM in the Protection against West Nile Virus Infection  

Microsoft Academic Search

In humans, the elderly and immunocompromised are at greatest risk for disseminated West Nile virus (WNV) infection, yet the immunologic basis for this remains unclear. We demon- strated previously that B cells and IgG contributed to the defense against disseminated WNV infection (Diamond, M.S., B. Shrestha, A. Marri, D. Mahan, and M. Engle. 2003. J. Virol. 77: 2578-2586). In this

Michael S. Diamond; Elizabeth M. Sitati; Lindzy D. Friend; Stephen Higgs; Bimmi Shrestha; Michael Engle

297

A critical role for induced IgM in the protection against West Nile virus infection  

Microsoft Academic Search

In humans, the elderly and immunocompromised are at greatest risk for disseminated West Nile virus (WNV) infection, yet the immunologic basis for this remains unclear. We demon- strated previously that B cells and IgG contributed to the defense against disseminated WNV infection (Diamond, M.S., B. Shrestha, A. Marri, D. Mahan, and M. Engle. 2003. J. Virol. 77: 2578-2586). In this

Michael S. Diamond; Elizabeth M. Sitati; Lindzy D. Friend; Stephen Higgs; Bimmi Shrestha; Michael Engle

2003-01-01

298

Balancing the baryon budget: the fraction of the IGM due to galaxy mergers  

NASA Astrophysics Data System (ADS)

Observations indicate that roughly 60 per cent of the baryons may exist in a warm-hot intergalactic medium (WHIM) at low redshifts. Following up on previous results showing that gas is released through galaxy mergers, we use a semi-analytic technique to estimate the fraction of gas mass lost from haloes solely due to mergers. We find that up to ~25 per cent of the gas in a halo can unbind over the course of galaxy assembly. This process does not act preferentially on smaller mass haloes; bigger haloes always release larger amounts of gas in a given volume of the Universe. However, if we include multiphase gas accretion on to haloes, we find that only a few per cent is unbound. We conclude that either non-gravitational processes may be in play to heat up the gas in the galaxies prior to unbinding by mergers or most of the baryons in the WHIM have never fallen into virialized dark matter haloes. We present a budget for stocking the WHIM compiled from recent work.

Sinha, Manodeep; Holley-Bockelmann, Kelly

2010-06-01

299

Lower and upper bounds on CSL parameters from latent image formation and IGM heating  

Microsoft Academic Search

We study lower and upper bounds on the parameters for stochastic state vector reduction, focusing on the mass-proportional continuous spontaneous localization (CSL) model. We show that the assumption that the state vector is reduced when a latent image is formed, in photography or etched track detection, requires a CSL reduction rate parameter ? that is larger than conventionally assumed by

Stephen L. Adler

2007-01-01

300

Lower and Upper Bounds on CSL Parameters from Latent Image Formation and IGM Heating  

Microsoft Academic Search

We study lower and upper bounds on the parameters for stochastic state vector\\u000areduction, focusing on the mass-proportional continuous spontaneous\\u000alocalization (CSL) model. We show that the assumption that the state vector is\\u000areduced whan a latent image is formed, in photography or etched track\\u000adetection, requires a CSL rate parameter $\\\\lambda$ that is larger than\\u000aconventionally assumed by a

Stephen L. Adler

2006-01-01

301

ZAP-70 enhances IgM signaling independent of its kinase activity in chronic lymphocytic leukemia.  

PubMed

We transduced chronic lymphocytic leukemia (CLL) cells lacking ZAP-70 with vectors encoding ZAP-70 or various mutant forms of ZAP-70 and monitored the response of transduced CLL cells to treatment with F(ab)(2) anti-IgM (anti-mu). CLL cells made to express ZAP-70, a kinase-defective ZAP-70 (ZAP-70-KA(369)), or a ZAP-70 unable to bind c-Cbl (ZAP-YF(292)) experienced greater intracellular calcium flux and had greater increases in the levels of phosphorylated p72(Syk), B-cell linker protein (BLNK), and phospholipase C-gamma, and greater activation of the Ig accessory molecule CD79b in response to treatment with anti-mu than did mock-transfected CLL cells lacking ZAP-70. Transfection of CLL cells with vectors encoding truncated forms of ZAP-70 revealed that the SH2 domain, but not the SH1 domain, was necessary to enhance intracellular calcium flux in response to treatment with anti-mu. We conclude that ZAP-70 most likely acts as an adapter protein that facilitates B-cell receptor (BCR) signaling in CLL cells independent of its tyrosine kinase activity or its ability to interact with c-Cbl. PMID:18048647

Chen, Liguang; Huynh, Lang; Apgar, John; Tang, Li; Rassenti, Laura; Weiss, Arthur; Kipps, Thomas J

2008-03-01

302

ZAP-70 enhances IgM signaling independent of its kinase activity in chronic lymphocytic leukemia  

PubMed Central

We transduced chronic lymphocytic leukemia (CLL) cells lacking ZAP-70 with vectors encoding ZAP-70 or various mutant forms of ZAP-70 and monitored the response of transduced CLL cells to treatment with F(ab)2 anti-IgM (anti-?). CLL cells made to express ZAP-70, a kinase-defective ZAP-70 (ZAP-70-KA369), or a ZAP-70 unable to bind c-Cbl (ZAP-YF292) experienced greater intracellular calcium flux and had greater increases in the levels of phosphorylated p72Syk, B-cell linker protein (BLNK), and phospholipase C-?, and greater activation of the Ig accessory molecule CD79b in response to treatment with anti-? than did mock-transfected CLL cells lacking ZAP-70. Transfection of CLL cells with vectors encoding truncated forms of ZAP-70 revealed that the SH2 domain, but not the SH1 domain, was necessary to enhance intracellular calcium flux in response to treatment with anti-?. We conclude that ZAP-70 most likely acts as an adapter protein that facilitates B-cell receptor (BCR) signaling in CLL cells independent of its tyrosine kinase activity or its ability to interact with c-Cbl.

Chen, Liguang; Huynh, Lang; Apgar, John; Tang, Li; Rassenti, Laura; Weiss, Arthur

2008-01-01

303

Long Term Maintenance of Polysaccharide-specific Antibodies by IgM Secreting Cells1  

PubMed Central

Many bacteria-associated polysaccharides induce long-lived antibody responses that protect against pathogenic microorganisms. The maintenance of polysaccharide-specific antibody titers may be due to long-lived plasma cells or ongoing antigen-driven B cell activation due to polysaccharide persistence. BALB/c and VHJ558.3 transgenic (TG) mice respond to ? 1?3-dextran (DEX) by generating a peak anti-DEX response at 7 days, followed by maintenance of serum antibody levels for up to 150 days. Analysis of the cellular response to DEX identified a population of short-lived, cyclophosphamide sensitive DEX-specific plasmablasts in the spleen, and a quiescent, cyclophosphamide resistant DEX-specific antibody-secreting population in the bone marrow. BrdU pulse-chase experiments demonstrated the longevity of the DEX-specific antibody-secreting population in the bone marrow. Splenic DEX-specific plasmablasts were located in the red pulp with persisting DEX-associated CD11c+ dendritic cells 90 days after immunization, whereas DEX was not detected in the bone marrow after 28 days. Selective depletion of short-lived DEX-specific plasmablasts and memory B1b B cells using cyclophosphamide and anti-CD20 treatment had a minimal impact on the maintenance of serum anti-DEX antibodies. Collectively, these findings demonstrate that the maintenance of serum polysaccharide-specific antibodies is the result of continuous antigen-driven formation of short-lived plasmablasts in the spleen and a quiescent population of antibody-secreting cells maintained in the bone marrow for a long duration.

Foote, Jeremy B.; Mahmoud, Tamer I.; Vale, Andre M.; Kearney, John F.

2011-01-01

304

Identificación de péptidos miméticos al epítopo reconocido por el anticuerpo monoclonal específico por el EGF, CB-EGF1  

Microsoft Academic Search

Identification of peptide mimics of the epitope recognized by CB-EGF1, a monoclonal antibody EGF specific. As part of an integral structure and function study, we characterized the natural epitope on the EGF recognized by the CB-EGF1 monoclonal antibody, by using peptides displayed on the coat protein of filamentous bacteriophages. Data analyzed demonstrated that the CB-EGF1 monoclonal antibody recognizes a conformational

Yaquelin Puchades; Ariana G Ojalvo; Yanet García; Glay Chinea; Haydée Gerónimo; Nelson S Vispo

305

Anti Listeria monocytogenes immunity in ?-suppressed mice: a comparison of treatment with conventional hyperimmune rabbit anti-mouse IgM and affinity-purified, monoclonal rat anti-mouse IgM  

Microsoft Academic Search

The capacity of anti-IgM treated, B-cell-depleted mice to control infection by Listeria monocytogenes was evaluated. Suppression was achieved with a hyperimmune rabbit anti-mouse-IgM antiserum (IRS), with affinity-purified IRS (IRP), or with an affinity-purified, monoclonal, rat anti-mouse-IgM antibody (LO-MM-9). B-cell depletion in specifically treated mice was judged to be complete by the following criteria: absence of significant response to a B-cell

A. Cerny; A. W. Hiigin; H. Bazin; S. Sutter; H. Hengartner; R. M. Zinkernagel

1988-01-01

306

Evaluation of the Abbott AxSYM Cytomegalovirus (CMV) Immunoglobulin M (IgM) Assay in Conjunction with Other CMV IgM Tests and a CMV IgG Avidity Assay  

Microsoft Academic Search

The measurement of the avidity of cytomegalovirus (CMV) immunoglobulin G (IgG) antibodies has been shown by several investigators to be useful in identifying and excluding primary CMV infections in pregnant women. In this work, we examined the diagnostic utility of reflex testing of CMV IgM-positive specimens from pregnant women by using a CMV IgG avidity assay. The utility of this

T. Lazzarotto; C. Galli; R. Pulvirenti; R. Rescaldani; R. Vezzo; A. La Gioia; C. Martinelli; S. La Rocca; G. Agresti; L. Grillner; M. Nordin; M. van Ranst; B. Combs; G. T. Maine; M. P. Landini

2001-01-01

307

Elevated levels of IgM and IgA antibodies to Proteus mirabilis and IgM antibodies to Escherichia coli are associated with early rheumatoid factor (RF)-positive rheumatoid arthritis  

Microsoft Academic Search

Objective. Antibodies to Proteus mirabilis were previously detected in patients with established rheumatoid arthritis (RA). We examined the prevalence of antibodies to P. mirabilis and their associations with RA in early synovitis patients. Methods. Two hundred and forty-six patients with inflammatory arthritis for less than 1 yr were prospectively evaluated for 1 yr. Of these patients, 30% had rheumatoid factor

M. M. Newkirk; R. Goldbach-Mansky; B. W. Senior; J. Klippel; H. R. Schumacher Jr; H. S. El-Gabalawy

2005-01-01

308

B Cell-dependent T Cell Responses: IgM Antibodies Are Required to Elicit Contact Sensitivity  

Microsoft Academic Search

Contact sensitivity (CS) is a classic example of in vivo T cell immunity in which skin sensiti- zation with reactive hapten leads to immunized T cells, which are then recruited locally to mediate antigen-specific inflammation after subsequent skin challenge. We have previously shown that T cell recruitment in CS is triggered by local activation of complement, which generates C5a that

Ryohei F. Tsuji; Marian Szczepanik; Ivana Kawikova; Vipin Paliwal; Regis A. Campos; Atsuko Itakura; Moe Akahira-Azuma; Nicole Baumgarth; Leonore A. Herzenberg; Philip W. Askenase

2002-01-01

309

Analysis of Functional Epitopes on the Dengue 2 Envelope (E) Protein using Monoclonal IgM Antibodies.  

National Technical Information Service (NTIS)

Forty-two hybridomas secreting lgM antibody against dengue virus were derived from spleen cells of dengue 2 infected mice. Antibody from 27 of these recognised the E protein of this virus. Of the 22 antibodies which neutralised dengue 2, only two cross-re...

Z. Jianmin M. L. Linn R. Bulich M. K. Gentry J. G. Aaskov

1995-01-01

310

Comparative Specificities of Serum and Synovial Cell 19S IgM Rheumatoid Factors in Rheumatoid Arthritis.  

National Technical Information Service (NTIS)

Rheumatoid factor (RF) may play a key role in sustaining the inflammatory events and tissue damage in rheumatoid arthritis (RA). However, many serum RF have greater specificity for rabbit IgG than for human IgG, thus raising questions about RF pathogenici...

D. L. Robbins R. Wistar

1985-01-01

311

Pivotal Advance: Eosinophils mediate early alum adjuvant-elicited B cell priming and IgM production  

Microsoft Academic Search

Alum, aluminum-hydroxide-containing compounds, long used as adjuvants in human vac- cinations, functions by ill-defined, immunostimula- tory mechanisms. Antigen-free alum has been shown to act via a previously unidentified, splenic Gr1, IL-4-expressing myeloid cell population to stimulate early B cell priming. We demonstrate that the alum-elicited and -activated splenic my- eloid cells are IL-4-expressing eosinophils that function to prime B cell

Hai-Bin Wang; Peter F. Weller

2008-01-01

312

Viremia, Fecal Shedding, and IgM and IgG Responses in Patients with Hepatitis E.  

National Technical Information Service (NTIS)

Viremia, fecal shedding and antibody responses to hepatitis E virus (HEV) infections are poorly understood. To better characterize HEV infections, these responses were examined in 67 patients with acute markers for hepatitis E who were admitted to the Inf...

E. T. Clayson K. S. Myint R. Snitbhan D. W. Vaughn B. L. Innis

1995-01-01

313

Obtencion de anticuerpos anti-prolactina a partir de prolactina humana de produccion nacional. (Obtention of antibodies anti prolactin from human prolactin of national production).  

National Technical Information Service (NTIS)

In this work was studied the use of the the Prolactin hormone as immuno gen, which is obtained in Cuba by the pharmaceutical institute Mario Munoz, to produce the antibody antiprolactin. Was made the validation of obtained antibody (tritatium, specificity...

R. Caso M. Mosquera E. Perez C. Amanz

1996-01-01

314

[The anti-adenovirus activity of larifan in a cell culture].  

PubMed

Larifan, belonging to the number of highly active interferon inducers with a broad antivirus spectrum of action, did not manifest any antivirus effect in vitro in respect to human adenovirus of serotype 2 when it was used to treat the cells before and after the infection. PMID:9785803

Nosach, L N; Diachenko, N S; Zhovnovataia, V L; Butenko, S I

1998-01-01

315

Computer Virus Strategies and Detection Methods  

Microsoft Academic Search

The typical antivirus approach consists of waiting for a number of computers to be infected, detecting the virus, designing a solution, and delivering and deploying the solution, in such situation, it is very difficult to prevent every machine from being compromised by virus. This paper shows that to develop new reliable antivirus software some problems must be solved such as:

Essam Al Daoud; Iqbal H. Jebril; Belal Zaqaibeh

2008-01-01

316

Performance Evaluation of Defense Strategies against Computer Virus  

Microsoft Academic Search

We evaluate performance of anti-virus strategies by using stochastic processes. The typical installations of anti- virus software is either at client PCs or the network gateway. By installing gateway anti-virus, many internet service providers and cooperate LANs are offering the screening service of emails to protect their users from the menace of computer viruses. At the same time, we are

Hiroshi Toyoizumi

317

Field Evaluation and Impact on Clinical Management of a Rapid Diagnostic Kit That Detects Dengue NS1, IgM and IgG  

PubMed Central

Background Dengue diagnosis is complex and until recently only specialized laboratories were able to definitively confirm dengue infection. Rapid tests are now available commercially making biological diagnosis possible in the field. The aim of this study was to evaluate a combined dengue rapid test for the detection of NS1 and IgM/IgG antibodies. The evaluation was made prospectively in the field conditions and included the study of the impact of its use as a point-of-care test for case management as well as retrospectively against a panel of well-characterized samples in a reference laboratory. Methodology/Principal Findings During the prospective study, 157 patients hospitalized for a suspicion of dengue were enrolled. In the hospital laboratories, the overall sensitivity, specificity, PPV and NPV of the NS1/IgM/IgG combination tests were 85.7%, 83.9%, 95.6% and 59.1% respectively, whereas they were 94,4%, 90.0%, 97.5% and 77.1% respectively in the national reference laboratory at Institut Pasteur in Cambodia. These results demonstrate that optimal performances require adequate training and quality assurance. The retrospective study showed that the sensitivity of the combined kit did not vary significantly between the serotypes and was not affected by the immune status or by the interval of time between onset of fever and sample collection. The analysis of the medical records indicates that the physicians did not take into consideration the results obtained with the rapid test including for care management and use of antibiotic therapy. Conclusions In the context of our prospective field study, we demonstrated that if the SD Bioline Dengue Duo kit is correctly used, a positive result highly suggests a dengue case but a negative result doesn't rule out a dengue infection. Nevertheless, Cambodian pediatricians in their daily practice relied on their clinical diagnosis and thus the false negative results obtained did not directly impact on the clinical management.

Andries, Anne-Claire; Duong, Veasna; Ngan, Chantha; Ong, Sivuth; Huy, Rekol; Sroin, Kim Kim; Te, Vantha; Y, Bunthin; Try, Patrich Lorn; Buchy, Philippe

2012-01-01

318

Glycosphingolipid Antigens in Cultured Microvascular Bovine Brain Endothelial Cells: Sulfoglucuronosyl Paragloboside as a Target of Monoclonal IgM in Demyelinative Neuropathy  

Microsoft Academic Search

Since a number of anti-glycosphingolipid (GSL) antibody activities have been demonstrated in patients with various neurological disorders, the pres- ence of common antigens between brain microvascular endothelial cells (BMECs) and the nervous tissues presents a potential mechanism for the penetration of macromolecules from the circulation to the nervous system parenchyma. We first investigated GSL compo- sition of cultured bovine BMECs.

Takashi Kanda; Hiide Yoshino; Toshio Ariga; Masanaga Yamawaki; Robert K. Yu

1994-01-01

319

Determination of IgG, IgM, and IgA antibodies to Mycoplasma pneumoniae by an indirect staphylococcal radioimmunoassay  

Microsoft Academic Search

An indirect staphylococcal radioimmunoassay (SRIA) has been developed for determination ofM. pneumoniae antibodies. This test allows the detection of antibodies in various immunoglobulin (Ig) classes similar to the previously described radioimmunoprecipitation test (RIP). SRIA has two advantages over RIP: first, it uses 100-fold less anti-Ig reagents than RIP; second, bound can be separated from unbound antigen more easily by the

Helmut Brunner; Werner Schaeg; Ursula Briick; Ulrich Schummer; Dorothea Sziegoleit; Hans-Gerd Schiefer

1978-01-01

320

Injection of PEGylated liposomes in rats elicits PEG-specific IgM, which is responsible for rapid elimination of a second dose of PEGylated liposomes  

Microsoft Academic Search

Steric stabilization of the surface of liposomes by a PEG conjugated lipid results in reduced recognition of the liposomes by the cells of the mononuclear phagocyte system and consequently extended their circulation times (t1\\/2?20h in rat). Recently, we reported on the “accelerated blood clearance phenomenon”, causing ‘invisible’ PEGylated liposomes to be cleared very rapidly from the circulation upon repeated injection.

Tatsuhiro Ishida; Masako Ichihara; XinYu Wang; Kenji Yamamoto; Junji Kimura; Eiji Majima; Hiroshi Kiwada

2006-01-01

321

Antibodies of IgG, IgA and IgM isotypes against cyclic citrullinated peptide precede the development of rheumatoid arthritis  

Microsoft Academic Search

INTRODUCTION: We and others have previously shown that antibodies against cyclic citrullinated proteins (anti-CCP) precede the development of rheumatoid arthritis (RA) and in a more recent study we reported that individuals who subsequently developed RA had increased concentrations of several cytokines and chemokines years before the onset of symptoms of joint disease. Here we aimed to evaluate the prevalence and

Heidi Kokkonen; Mohammed Mullazehi; Ewa Berglin; Göran Hallmans; Göran Wadell; Johan Rönnelid; Solbritt Rantapää-Dahlqvist

2011-01-01

322

Detection of IgE, IgG, IgA and IgM antibodies against raw and processed food antigens  

Microsoft Academic Search

BACKGROUND: Despite the first documented case of food allergy to cooked food in 1921 by Prausnitz and Kustner, all commercial food antigens are prepared from raw food. Furthermore, all IgE and IgG antibodies against dietary proteins offered by many clinical laboratories are measured against raw food antigens. METHODS: We developed an enzyme-linked immunosorbent assay for the measurement of IgE, IgG,

Aristo Vojdani

2009-01-01

323

Evaluation of the MRL Diagnostics Dengue Fever Virus IgM Capture ELISA and the PanBio Rapid Immunochromatographic Test for Diagnosis of Dengue Fever in Jamaica  

Microsoft Academic Search

Dengue fever (DF) is an acute febrile illness caused by a mosquito-borne flavivirus. The more severe form of DF, known as dengue hemorrhagic fever (DHF)-dengue shock syndrome (DSS), can prove fatal, especially among young children, who account for the majority of the 5% annual case-fatality rate in countries where DF is endemic (4). The most challenging problem associated with patient

CAROL J. PALMER; S. DOROTHY KING; RAUL R. CUADRADO; EDDY PEREZ; MARIANA BAUM; ARBA L. AGER

1999-01-01

324

COMPARISON OF A SLIDE AGGLUTINATION TEST, LEPTOTEK DRI-DOT, AND IGM-ELISA WITH MICROSCOPIC AGGLUTINATION TEST FOR LEPTOSPIRA ANTIBODY DETECTION  

Microsoft Academic Search

A slide agglutination test (SAT), LeptoTek Dri-Dot and IgM-ELISA were compared with a microscopic agglutination test (MAT) for the detection of Leptospira antibodies. Paired sera from 10 patients whose leptospirosis was clinically suspected and diagnosed by MAT, were evaluated in this study. Our data, especially from acute samples, demonstrate the SAT and Dri-Dot were more sensitive as initial screening tests

Chintana Chirathaworn; Yada Kaewopas; Yong Poovorawan

325

Development of an IgM capture assay for the diagnosis of B19 parvovirus infection using recombinant baculoviruses expressing VP1 or VP2 antigens  

Microsoft Academic Search

Background: The clinical manifestations of human parvovirus B19 infection are often similar to those induced as the result of infection by other infectious agents such as rubella and some bacteria. Although diagnosis of B19 infection is feasible by detection of specific antibodies, the tests require viraemic serum as a source of antigen. This inevitably leads to problems of reproducibility and

H. J. O'Neill; K. Venugopal; P. V. Coyle; E. A. Gould

1995-01-01

326

Development of a measles specific IgM ELISA for use with serum and oral fluid samples using recombinant measles nucleoprotein produced in Saccharomyces cerevisiae  

Microsoft Academic Search

In order to develop sensitive assays for detecting measles antibodies in oral fluid specimens, we have produced recombinant measles virus nucleoprotein (rMVN) in a yeast expression system and prepared monoclonal antibodies to the protein. Measles nucleoprotein gene from the Schwarz vaccine strain was cloned into a yeast expression vector, pFX7 under the control of the hybrid GAL10-PYK1 promoter. High levels

Dhanraj Samuel; Kestutis Sasnauskas; Li Jin; Alma Gedvilaite; Rimas Slibinskas; Stuart Beard; Aurelija Zvirbliene; Solange Artimos Oliveira; Juozas Staniulis; Bernard Cohen; David Brown

2003-01-01

327

IgM RNA switch from membrane to secretory form is prevented by adding antireceptor antibody to bacterial lipopolysaccharide-stimulated murine primary B-cell cultures.  

PubMed Central

Bacterial lipopolysaccharide (LPS) induces proliferation of resting primary murine B lymphocytes and their differentiation into Ig-secreting cells. This is accompanied by an increase in the rate of Ig gene transcription and the accumulation of mu heavy chain secretory mRNA. Specific antiantigen receptor antibody (anti-mu) induces resting B cells to proliferation but not differentiation. Upon addition of both LPS and anti-mu to cultures, resting B cells again proliferate but do not differentiate. RNA transfer blots of the Ig mRNA 2 days after induction with LPS/anti-mu show a specific deficiency of the 2.4-kilobase (kb) mu secretory mRNA, whereas the levels of the 2.7-kb mu membrane and 1.2-kb kappa light chain mRNAs are as high as in cells treated with LPS alone. Between days 3 and 4 after treatment with both reagents, reductions of mu membrane and, to a smaller extent, kappa mRNA become apparent. As measured by nuclear run-on transcription experiments at day 2, the transcription rates of Ig mu and the Ig kappa transcription units are equal in both induction experiments. Only at later stages do the LPS/anti-mu-treated cells transcribe Ig genes at a lower rate. Thus, the anti-mu treatment, drastically reducing the mu secretory mRNA production at early stages, represents a negative regulation occurring primarily at the posttranscriptional level. Images

Chen-Bettecken, U; Wecker, E; Schimpl, A

1985-01-01

328

Molecular Cloning of a New Immunomodulatory Protein from Anoectochilus formosanus which Induces B Cell IgM Secretion through a T-Independent Mechanism  

Microsoft Academic Search

An immunomodulatory protein (IPAF) was purified and cloned from Anoectochilus formosanus, an Orchidaceae herbal plant in Asia. The major targeting immune cells of IPAF and its modulating effects toward B lymphocytes were investigated. Rapid amplification of cDNA ends (RACE) was conducted to clone the IPAF gene, and the obtained sequence was BLAST compared on the NCBI database. MACS-purified mouse T

Yen-Chou Kuan; Tsai-Jen Wu; Che-Yu Kuo; Ju-Chun Hsu; Wen-Ying Chang; Fuu Sheu

2011-01-01

329

Comparative studies on monotypic IgM lambda and IgG kappa from an individual patient. IV. Immunofluorescent evidence for a common clonal synthesis.  

PubMed

Previous studies have presented evidence of shared idiotypic antigenic determinants located within the variable (VH) region of the heavy chains of monotypic IgMlambda and IgGkappa isolated from the serum of an individual patient, Bro, with Waldenström macroglobulinemia. Comparative N-terminal VH sequence analyses have demonstrated that the respective micron and gamma chains belong to separate VH subgroups. The entire VH sequence of the Bro micron chain has been reported, but the VH sequence of the Bro gamma chain still awaits completion. We report the results of an immunofluorescent analysis of cytoplasmic Ig of lymphoid cells isolated from the patient's peripheral blood and bone marrow. Between 6% and 9% of the cytoplasmic Ig-positive lymphoid cells exhibited fluorescent evidence for the dual presence of kappa and lambda chains are well as micron and gamma chains. These results strongly suggest that the idiotypically related Bro IgMlambda and IgGkappa paraproteins are derived from a common clonal origin. Moreover, these findings extend the results of a previous study that has demonstrated the dual presence of IgGkappa and IgGlambda paraproteins within individual myeloma plasma cells. Collectively, these studies suggest that a single neoplastic lymphoid clone may not necessarily be restricted to the synthesis of Ig proteins of the identical light chain class. These findings may have a broad implication for the understanding of surface and cytoplasmic Ig markers of neoplastic lymphoid cells in certain other lymphoproliferative disorders. PMID:405992

Hopper, J E

1977-08-01

330

Characterization of Nine Novel Mutations in the CD40 Ligand Gene in Patients with X-Linked Hyper IgM Syndrome of Various Ancestry  

PubMed Central

X-linked immunodeficiency with hyper-IgM (HIGMX-1) is a rare disorder caused by defective expression of the CD40 ligand (CD40L) by activated T lymphocytes, resulting in inefficient T-B cell cooperation and failure of B cells to undergo immunoglobulin isotype switch. In the present work, we describe nine patients of various ancestry who bear different mutations in the X chromosome–specific CD40L gene. Two of the mutations were nonsense mutations, one each resulting in premature stop codons at amino acid residues 39 and 140. Three patients had single point missense mutations, one each at codons 126, 140, and 144. Another patient had a 4-bp genomic deletion in exon 2, resulting in a frameshift and premature termination. Three patients showed insertions, one each of 1, 2, and 4 nt, probably because of polymerase slippage, resulting in frameshift mutation and premature termination. Overall, these observations confirm the heterogeneity of mutations in HIGMX-1. However, the identification of two patients whose mutation involves codon 140 (previously shown to be altered in two other unrelated subjects) suggests that this may be a hotspot of mutation in HIGMX-1. In two additional patients with clinical and immunological features indistinguishable from canonical HIGMX-1, no mutation was detected in the coding sequence, in the 5' flanking region, or in the 3' UTR. ImagesFigure 3Figure 4Figure 5

Macchi, Paolo; Villa, Anna; Strina, Dario; Sacco, Maria Grazia; Morali, Federica; Brugnoni, Duilio; Giliani, Silvia; Mantuano, Elide; Fasth, Anders; Andersson, Bengt; Zegers, Ben J. M.; Cavagni, Giovanni; Reznick, Igor; Levy, Jacov; Zan-Bar, Israel; Porat, Yael; Airo, Paolo; Plebani, Alessandro; Vezzoni, Paolo; Notarangelo, Luigi D.

1995-01-01

331

An Alternative Form of IL18 in Human Blood Plasma: Complex Formation with IgM Defined by Monoclonal Antibodies1  

Microsoft Academic Search

Monoclonal Abs 21 and 132 were raised against human functionally inactive rIL-18, and plasma IL-18 levels were determined by the sandwich ELISA established with these mAbs. Plasma IL-18, designated type 2, was detected by this ELISA, and the levels found were not consistent with those obtained with the commercially available kit for determination of functionally active IL-18 (type 1). Type

Kyoko Shida; Ikuo Shiratori; Misak Matsumoto; Yasuo Fukumori; Akio Matsuhisa; Satomi Kikkawa; Shoutaro Tsuji; Haruki Okamura; Kumao Toyoshima; Tsukasa Seya

332

48 CFR 352.239-70 - Standard for security configurations.  

Code of Federal Regulations, 2013 CFR

...The Contractor shall configure its computers that contain HHS data with the applicable...index.cfm ) and ensure that its computers have and maintain the latest operating system patch level and anti-virus software level. Note:...

2013-10-01

333

Classification of packed executables for accurate computer virus detection  

Microsoft Academic Search

Executable packing is the most common technique used by computer virus writers to obfuscate malicious code and evade detection by anti-virus software. Universal unpackers have been proposed that can detect and extract encrypted code from packed executables, therefore potentially revealing hidden viruses that can then be detected by traditional signature-based anti-virus software. However, universal unpackers are computationally expensive and scanning

Roberto Perdisci; Andrea Lanzi; Wenke Lee

2008-01-01

334

Obtencion de anticuerpos anti-globulinas de conejo en carnero para su utilizacion en los radioinmunoanalisis de LH, FSH, y prolactina. (Production of anti-IgG antibodies in sheep for using in the radioimmunoassays of LH, FSH and prolactin).  

National Technical Information Service (NTIS)

In this work described the production of second antibodies in sheep against rabbit IgG for being used in radioimmunoassays for determination LH, FSH and Prolactin. There was made the comparison between the results obtained using the Kits-RIA produced by u...

R. Caso E. Perez M. Mosquera C. Arranz

1996-01-01

335

Evaluation of the Diagnostic Accuracy of a Typhoid IgM Flow Assay for the Diagnosis of Typhoid Fever in Cambodian Children Using a Bayesian Latent Class Model Assuming an Imperfect Gold Standard  

PubMed Central

Rapid diagnostic tests are needed for typhoid fever (TF) diagnosis in febrile children in endemic areas. Five hundred children admitted to the hospital in Cambodia between 2009 and 2010 with documented fever (? 38°C) were investigated using blood cultures (BCs), Salmonella Typhi/Paratyphi A real-time polymerase chain reactions (PCRs), and a Typhoid immunoglobulin M flow assay (IgMFA). Test performance was determined by conventional methods and Bayesian latent class modeling. There were 32 cases of TF (10 BC- and PCR-positive cases, 14 BC-positive and PCR-negative cases, and 8 BC-negative and PCR-positive cases). IgMFA sensitivity was 59.4% (95% confidence interval = 41–76), and specificity was 97.8% (95% confidence interval = 96–99). The model estimate sensitivity for BC was 81.0% (95% credible interval = 54–99). The model estimate sensitivity for PCR was 37.8% (95% credible interval = 26–55), with a specificity of 98.2% (95% credible interval = 97–99). The model estimate sensitivity for IgMFA (? 2+) was 77.9% (95% credible interval = 58–90), with a specificity of 97.5% (95% credible interval = 95–100). The model estimates of IgMFA sensitivity and specificity were comparable with BCs and better than estimates using conventional analysis.

Moore, Catrin E.; Pan-Ngum, Wirichada; Wijedoru, Lalith P. M.; Sona, Soeng; Nga, Tran Vu Thieu; Duy, Pham Thanh; Vinh, Phat Voong; Chheng, Kheng; Kumar, Varun; Emary, Kate; Carter, Michael; White, Lisa; Baker, Stephen; Day, Nicholas P. J.; Parry, Christopher M.

2014-01-01

336

Evaluation of the diagnostic accuracy of a typhoid IgM flow assay for the diagnosis of typhoid fever in Cambodian children using a Bayesian latent class model assuming an imperfect gold standard.  

PubMed

Rapid diagnostic tests are needed for typhoid fever (TF) diagnosis in febrile children in endemic areas. Five hundred children admitted to the hospital in Cambodia between 2009 and 2010 with documented fever (? 38°C) were investigated using blood cultures (BCs), Salmonella Typhi/Paratyphi A real-time polymerase chain reactions (PCRs), and a Typhoid immunoglobulin M flow assay (IgMFA). Test performance was determined by conventional methods and Bayesian latent class modeling. There were 32 cases of TF (10 BC- and PCR-positive cases, 14 BC-positive and PCR-negative cases, and 8 BC-negative and PCR-positive cases). IgMFA sensitivity was 59.4% (95% confidence interval = 41-76), and specificity was 97.8% (95% confidence interval = 96-99). The model estimate sensitivity for BC was 81.0% (95% credible interval = 54-99). The model estimate sensitivity for PCR was 37.8% (95% credible interval = 26-55), with a specificity of 98.2% (95% credible interval = 97-99). The model estimate sensitivity for IgMFA (? 2+) was 77.9% (95% credible interval = 58-90), with a specificity of 97.5% (95% credible interval = 95-100). The model estimates of IgMFA sensitivity and specificity were comparable with BCs and better than estimates using conventional analysis. PMID:24218407

Moore, Catrin E; Pan-Ngum, Wirichada; Wijedoru, Lalith P M; Sona, Soeng; Nga, Tran Vu Thieu; Duy, Pham Thanh; Vinh, Phat Voong; Chheng, Kheng; Kumar, Varun; Emary, Kate; Carter, Michael; White, Lisa; Baker, Stephen; Day, Nicholas P J; Parry, Christopher M

2014-01-01

337

A LONGITUDINAL INVESTIGATION OF IgG AND IgM ANTIBODY RESPONSES TO THE MEROZOITE SURFACE PROTEIN1 19-KILODALTON DOMAIN OF PLASMODIUM FALCIPARUMIN PREGNANT WOMEN AND INFANTS: ASSOCIATIONS WITH FEBRILE ILLNESS, PARASITEMIA, AND ANEMIA  

Microsoft Academic Search

This study was aimed at delineating characteristics of naturally acquired immunity against the merozoite surface antigen-1 (MSP-1) of Plasmodium falciparum,a candidate malaria vaccine antigen. A case\\/control study was performed on 75 case\\/control pairs of infants with febrile illness at the time of the first detected infection indicating a clinical case. The presence and level of antibodies at one month prior

ORALEE H. BRANCH; VENKATACHALAM UDHAYAKUMAR; ALLEN W. HIGHTOWER; AGGREY J. OLOO; WILLIAM A. HAWLEY; BERNARD L. NAHLEN; PETER B. BLOLAND; DAVID C. KASLOW; ALTAF A. LAL

338

Automated reading and processing of quantitative IgG, IgM, IgA, and IgE isotypic agglutination results in microplates Development and application in parasitology-mycology  

Microsoft Academic Search

Microplate agglutination techniques represent a simple and commonly used approach for the quantitative or qualitative isotypic analysis of specific antibodies. However, they require optical reading by the investigator and are thus prone to an important degree of variability. In order to solve some of the problems associated with the variability of optical readings, we have used an automatic reader scanning

D. Aubert; F. Foudrinier; M. L. Kaltenbach; D. Guyot-Walser; C. Marx-Chemla; R. Geers; H. Lepan; J. M. Pinon

1995-01-01

339

Early Neonatal Diagnosis of Congenital Toxoplasmosis: Value of Comparative Enzyme-Linked Immunofiltration Assay Immunological Profiles and Anti-Toxoplasma gondiiImmunoglobulin M (IgM) or IgA Immunocapture and Implications for Postnatal Therapeutic Strategies  

Microsoft Academic Search

Diagnostic strategies for congenital toxoplasmosis have changed profoundly in recent years. Immunological diagnosticmethods,longconsidereddisappointing,cannowbeusedataveryearlystage.Overa3-yearperiod, 1,050 infants at risk of congenital toxoplasmosis (born to 1,048 mothers infected during pregnancy) were monitored for a minimum of 12 months and a maximum of 7 years. More than 6,000 serum specimens were analyzed by comparative mother-infant immunological profiles (CIPs) based on an enzyme-linked immuno- filtrationassay(ELIFA)andanimmunocapturemethodforthedetectionofspecificimmunoglobulinM(IgM)

J. M. PINON; C. CHEMLA; I. VILLENA; F. FOUDRINIER; D. AUBERT; D. PUYGAUTHIER-TOUBAS; B. LEROUX; D. DUPOUY; C. QUEREUX; M. TALMUD; T. TRENQUE; G. POTRON; M. PLUOT; G. REMY; Robert Debre ´

340

Idiopathic granulomatous mastitis associated with risperidone-induced hyperprolactinemia.  

PubMed

Idiopathic granulomatous mastitis (IGM) is a rare inflammatory breast disease. The etiology and treatment options of IGM remain controversial. Previous case reports have suggested that hyperprolactinemia may be associated with IGM. In the present report, we describe the first case of IGM associated with risperidone-induced hyperprolactinemia. PMID:22221904

Lin, Chih-Hsun; Hsu, Chih-Wei; Tsao, Tang-Yi; Chou, Jason

2012-01-01

341

Managing software security risks  

Microsoft Academic Search

Most organizations manage computer security risk reactively by investing in technologies designed to protect against known system vulnerabilities and monitor intrusions as they occur. However, firewalls, cryptography, and antivirus protection address the symptoms, not the root cause, of most security problems. Buying and maintaining a firewall, for example, is ineffective if external users can access remotely exploitable Internet-enabled applications through

G. McGraw

2002-01-01

342

Biologically Inspired Defenses Against Computer Viruses  

Microsoft Academic Search

Today's anti-virus technology, based largely on analysis of existing viruses by human experts, is just barely able to keep pace with the more than three new computer viruses that are writ­ ten daily. In a few years, intelligent agents nav­ igating through highly connected networks are likely to form an extremely fertile medium for a new breed of viruses. At

Jeffrey O. Kephart; Gregory B. Sorkin; William C. Arnold; David M. Chess; Gerald Tesauro; Steve R. White

1995-01-01

343

Wireless security patch management system  

Microsoft Academic Search

Wireless access on college campuses facilitates the spread of computer viruses and worms due to laptops that do not have current software patches and\\/or antivirus protection connecting to the network. Wireless local area networks provide a luxury of mobility to clients so that they may roam about without the restriction of wires, room, and\\/or buildings. At the same time, wireless

Charles Higby; Michael Bailey

2004-01-01

344

Science and Technology Resources on the Internet: Computer Security.  

ERIC Educational Resources Information Center

Discusses issues related to computer security, including confidentiality, integrity, and authentication or availability; and presents a selected list of Web sites that cover the basic issues of computer security under subject headings that include ethics, privacy, kids, antivirus, policies, cryptography, operating system security, and biometrics.…

Kinkus, Jane F.

2002-01-01

345

Extraction of Phenolic Compounds from Fruits of Bitter Melon (Momordica charantia ) with Subcritical Water Extraction and Antioxidant Activities of These  

Microsoft Academic Search

Bitter melon (Momordica charantia) is traditionally known for its medicinal properties such as antidiabetic, anticancer, anti-inflammation, antivirus, and cholesterol lowering effects. It contains many phenolic compounds that may have the potential as antioxidant and antimutagen. Although the value of bitter melon is realized, scientific information on phenolic composition of bitter melon and antioxidant and antimutagenic activities of its extracts from

Extracts Parichat Budrat; Artiwan Shotipruk

346

Bioactive metabolites from marine microorganisms  

Microsoft Academic Search

Diverse arrays of new bioactive secondary metabolites have been isolated from marine microorganisms; and the number of publications in this area has greatly increased in recent years. In this review, the emphasis is placed on new compounds with antitumor, enzyme inhibitors, antivirus, and other bioactive metabolites from fungi, bacteria, actinomycetes, and cyanobacteria reported between 2000 and 2005. Supply is a

Xiaohong Liu; Fang Xu; Changlun Shao; Zhigang She; Yongcheng Lin; Wing Lai Chan

2008-01-01

347

Using API Sequence and Bayes Algorithm to Detect Suspicious Behavior  

Microsoft Academic Search

Computer viruses have become the main threat of the safety and security of industry. Unfortunately, no mature products of anti-virus can protect computers effectively. This paper presents an approach of virus detection which is based on analysis and distilling of representative behavior characteristic and systemic description of the suspicious behaviors indicated by the sequences of APIs which called under Windows.

Cheng Wang; Jianmin Pang; Rongcai Zhao; Xiaoxian Liu

2009-01-01

348

Framework for Zombie Detection Using Neural Networks  

Microsoft Academic Search

One of the most important threats to personal and corporate Internet security is the proliferation of zombie PCs operating as an organized network. Zombie detection is currently performed at the host level and\\/or network level, but these options have some important drawbacks: antivirus, anti-spyware and personal firewalls are ineffective in the detection of hosts that are compromised via new or

Paulo Salvador; Ant ´ onio Nogueira; U. Franca; R. Valadas

2009-01-01

349

Malicious Webpage Detection by Semantics-Aware Reasoning  

Microsoft Academic Search

The evolutional development of dynamic HTML techniques empowers attackers a new and powerful tool to compromise machines. A malicious DHTML code disguises itself as a normal Webpage. The malicious Webpage infects the victim when a user browses it. Furthermore, such DHTML code can disguise easily through obfuscation or transformation, which makes detection even harder. Anti-virus software packages commonly use signature-based

Shih-fen Lin; Yung-tsung Hou; Chia-mei Chen; Bingchiang Jeng; Chi-sung Laih

2008-01-01

350

Malware Detection in Cloud Computing  

Microsoft Academic Search

Detecting malicious software is a complex problem. The vast, ever-increasing ecosystem of malicious software and tools presents a daunting challenge for network operators and IT administrators. Antivirus software is one of the most widely used tools for detecting and stopping malicious and unwanted software. However, the elevating sophistication of modern malicious software means that it is increased challenging for any

Safaa Salam Hatem; Mahmoud M. El-Khouly

2014-01-01

351

Open Problems in Computer Virus Research  

Microsoft Academic Search

Over a decade of work on the computer virus problem has resulted in a number of useful scientific and technological achievements. The study of biological epidemiology has been extended to help us understand when and why computer viruses spread. Techniques have been developed to help us estimate the safety and effectiveness of anti-virus technology before it is deployed. Technology for

Steve R. White

1998-01-01

352

Biological activities and corresponding SARs of andrographolide and its derivatives.  

PubMed

In recent years, pharmaceutical chemists have synthesized large numbers of andrographolide derivatives, which bear important biological activities such as anti-inflammatory, antibacterial, antivirus, antitumor, antidiabetic, and antifeedant. Consequently, corresponding SARs were increasingly obvious. This paper aimed to review all the available literature in this field, highlighting the significant achievements on the structural modification and SARs of andrographolide and its derivatives. PMID:23438057

Zhou, Bin; Zhang, Dayong; Wu, Xiaoming

2013-02-01

353

A Mission-Impact-Based Approach to INFOSEC Alarm Correlation  

Microsoft Academic Search

We describe a mission-impact-based approach to the analysis of security alerts produced by spatially distributed heterogeneous information security (INFOSEC) devices, such as firewalls, intrusion detection systems, authentication services, and antivirus software. The intent of this work is to deliver an automated capa- bility to reduce the time and cost of managing multiple INFOSEC devices through a strategy of topology analysis,

Phillip A. Porras; Martin W. Fong; Alfonso Valdes

2002-01-01

354

Safe Computing: An Overview of Viruses.  

ERIC Educational Resources Information Center

A computer virus is a program that replicates itself, in conjunction with an additional program that can harm a computer system. Common viruses include boot-sector, macro, companion, overwriting, and multipartite. Viruses can be fast, slow, stealthy, and polymorphic. Anti-virus products are described. (MLH)

Wodarz, Nan

2001-01-01

355

An artificial immune system architecture for computer security applications  

Microsoft Academic Search

With increased global interconnectivity, reliance on e-commerce, network services, and Internet communication, computer security has become a necessity. Organizations must protect their systems from intrusion and computer-virus attacks. Such protection must detect anomalous patterns by exploiting known signatures while monitoring normal computer programs and network usage for abnormalities. Current antivirus and net- work intrusion detection (ID) solutions can become overwhelmed

Paul K. Harmer; Paul D. Williams; Gregg H. Gunsch; Gary B. Lamont

2002-01-01

356

Proteochemometric Modeling of the Bioactivity Spectra of HIV1 Protease Inhibitors by Introducing Protein-Ligand Interaction Fingerprint  

Microsoft Academic Search

HIV-1 protease is one of the main therapeutic targets in HIV. However, a major problem in treatment of HIV is the rapid emergence of drug-resistant strains. It should be particularly helpful to clinical therapy of AIDS if one method can be used to predict antivirus capability of compounds for different variants. In our study, proteochemometric (PCM) models were created to

Qi Huang; Haixiao Jin; Qi Liu; Qiong Wu; Hong Kang; Zhiwei Cao; Ruixin Zhu

2012-01-01

357

Recent Advances on Triterpenes from Ganoderma Mushroom  

Microsoft Academic Search

This review addresses the most recent research advances on Ganoderma triterpenes in the past five years, including three major topics of structural characteristics, physiological activities, and production. Thirty-two newly found triterpenes are summarized and more triterpenes, which were found to exhibit anticancer, antivirus, antioxidation, hepatoprotection, and cholesterol synthesis inhibition bioactivities, are reported in this article. Furthermore, new physiological activities including

Yueqin Zhou; Xiaotong Yang; Qingyao Yang

2006-01-01

358

Saving Face — The Facts About Website Vandalism  

Microsoft Academic Search

It is known that developments in the IT world occur rapidly and regularly. Unlike any other industry, routine precautions that needed to be taken a couple of years ago, no longer need to be carried out. Technical developments mean the precautions do not need the same human intervention. Anti-Virus (AV) protection is a prime example. Do you see anyone scour

Iain Franklin

2001-01-01

359

How To: Protect against a Zero-Hour Attack  

ERIC Educational Resources Information Center

In the last year, a series of viruses and worms that caused damage across the Internet in record time has made very clear how vulnerable computer systems are. The MS Blaster, Slammer, Sasser, and Korgo.W worms have shown that signature-based antivirus software and traditional firewalls are not enough to protect networks. Everyone is worried about…

McCarthy, Rob

2005-01-01

360

A Distributed Approach to Computer Virus Detection and Neutralization by Autonomous and Heterogeneous Agents  

Microsoft Academic Search

Recent expansion of the computer network opened a possibility of explosive spread of computer viruses. We propose a distributed approach against computer virus using also the computer network that allows distributed and agent-based approach. Our anti-virus system consists of several heterogeneous agents similarly to the immune system. Among these agents, antibody agents use the information of “self” (files of host

Takeshi Okamoto; Yoshiteru Ishida

1999-01-01

361

Research on the Variation of the Computer Virus Based on Random Function  

Microsoft Academic Search

Studying the variation principle of the computer virus can deeply understand and grasp the variation laws and trends of the computer virus; offer the theoretical foundation for technical research of the anti-virus. In the foundation of summarizing the principle and the development of the virus technology, we introduced the idea of joining the random function in the trigger module of

Xie Hui; Zhang Zhi-gang; Wu Rui; Nie Feng

2009-01-01

362

Virus Alert: Ten Steps to Safe Computing.  

ERIC Educational Resources Information Center

Discusses computer viruses and explains how to detect them; discusses virus protection and the need to update antivirus software; and offers 10 safe computing tips, including scanning floppy disks and commercial software, how to safely download files from the Internet, avoiding pirated software copies, and backing up files. (LRW)

Gunter, Glenda A.

1997-01-01

363

Computer Viruses: Pathology and Detection.  

ERIC Educational Resources Information Center

Explains how computer viruses were originally created, how a computer can become infected by a virus, how viruses operate, symptoms that indicate a computer is infected, how to detect and remove viruses, and how to prevent a reinfection. A sidebar lists eight antivirus resources. (four references) (LRW)

Maxwell, John R.; Lamon, William E.

1992-01-01

364

The Computer Virus Threat and What You Can Do about It.  

ERIC Educational Resources Information Center

Discussion of computer viruses describes two types of viruses and how they work; suggests ways to prevent or minimize virus risk; and explains how to recognize a virus and limit damage once a virus attacks. A sidebar lists several antivirus software products. (two references) (NRP)

Lateulere, John

1992-01-01

365

Help for the Help Desk: School District Technology Managers Learn to Do with Less.  

ERIC Educational Resources Information Center

Although the E-Rate has been a catalyst for school technology purchases, there are no subsidies for hiring qualified technology support staff. District technology coordinators are relying on technology support systems and shoestring survival strategies, employing standardized equipment and hard-drive configurations, desktop lockdowns, anti-virus

Kongshem, Lars

2001-01-01

366

Marginal zone B cells transport and deposit IgM-containing immune complexes onto follicular dendritic cells  

Microsoft Academic Search

Secreted IgM and complement are important mediators in the optimal initiation of primary T-dependent humoral immune responses. Secreted IgM serves as a natural adjuvant by enhancing the immunogenicity of protein antigens, perhaps as a result of IgM's ability to facilitate antigen deposition onto follicular dendritic cells (FDCs) and promote rapid germinal center (GC) formation. To understand how IgM enhances adaptive

Andrew R. Ferguson; Michele E. Youd; Ronald B. Corley

2004-01-01

367

IDENTIFICATION OF SUBPOPULATIONS OF MONONUCLEAR CELLS IN CUTANEOUS INFILTRATES I. DIFFERENTIATION BETWEEN B CELLS, T CELLS, AND HISTIOCYTES  

Microsoft Academic Search

Differentiation between bone marrow-derived lymphocytes (B cells), thymus-derived lymphocytes (T cells), and histiocytes has been achieved in tissue sections through utilization of known differences in cell membrane receptors.Sheep erythrocytes (E) were coated with either IgG or IgM antibody (A) to form IgG or IgM EA. IgM EA was incubated with mouse complement (C) to form IgM EAC. Cryosections were layered

Richard L. Edelson; Richard W. Smith; Michael M. Frank; Ira Green

1973-01-01

368

Idiopathic granulomatous mastitis associated with risperidone-induced hyperprolactinemia  

PubMed Central

Idiopathic granulomatous mastitis (IGM) is a rare inflammatory breast disease. The etiology and treatment options of IGM remain controversial. Previous case reports have suggested that hyperprolactinemia may be associated with IGM. In the present report, we describe the first case of IGM associated with risperidone-induced hyperprolactinemia. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8120093785928228

2012-01-01

369

Idiopathic Granulomatous Mastitis Associated with Corynebacterium Sp. Infection  

PubMed Central

Idiopathic granulomatous mastitis (IGM) is a rare inflammatory condition of the breast. The etiology and treatments options of IGM remain controversial. Previous case reports have suggested that Corynebacterium sp., a gram-positive bacillus endogenous to the skin, may be associated with IGM. In the present report, we describe the first case of IGM with a positive culture for Corynebacterium sp. reported in the United States.

Lee, Yun Sun; Balfour, John

2011-01-01

370

Idiopathic granulomatous mastitis associated with corynebacterium sp. Infection.  

PubMed

Idiopathic granulomatous mastitis (IGM) is a rare inflammatory condition of the breast. The etiology and treatments options of IGM remain controversial. Previous case reports have suggested that Corynebacterium sp., a gram-positive bacillus endogenous to the skin, may be associated with IGM. In the present report, we describe the first case of IGM with a positive culture for Corynebacterium sp. reported in the United States. PMID:21857740

Stary, Creed Michael; Lee, Yun Sun; Balfour, John

2011-05-01

371

Good Performance of Immunoglobulin M Assays in Diagnosing Genotype 3 Hepatitis E Virus Infections?  

PubMed Central

We have evaluated three anti-hepatitis E virus (anti-HEV) immunoglobulin M (IgM) assays, the EIAgen HEV IgM assay (Adaltis), the HEV IgM enzyme-linked immunosorbent assay 3.0, and the Assure HEV IgM rapid test (MP Diagnostics), for the routine detection of acute genotype 3 HEV. Their sensitivities were fairly good (90%, 88%, and 82%), and their specificities were excellent (100%, 99.5%, and 100%).

Legrand-Abravanel, Florence; Thevenet, Isabelle; Mansuy, Jean-Michel; Saune, Karine; Vischi, Francoise; Peron, Jean-Marie; Kamar, Nassim; Rostaing, Lionel; Izopet, Jacques

2009-01-01

372

Spontaneous Production of Immunoglobulin M in Human Epithelial Cancer Cells  

PubMed Central

It is well known that B-1 B cells are the main cell type that is responsible for the production of natural immunoglobulin M (IgM) and can respond to infection by increasing IgM secretion. However, we unexpectedly found that some epithelial cells also can express rearranged IgM transcript that has natural IgM characteristics, such as germline-encoded and restricted rearrangement patterns. Here we studied IgM expression in human non-B cells and found that IgM was frequently expressed by many human epithelial cancer cells as well as non-cancer epithelial cells. Moreover, CD79A and CD79B, two molecules that are physically linked to membranous IgM on the surface of B cells to form the B cell antigen receptor complex, were also expressed on the cell surface of epithelial cancer cells and co-located with IgM. Like the natural IgM, the epithelial cancer cell-derived IgM recognized a series of microbial antigens, such as single-stranded DNA, double-stranded DNA, lipopolysaccharide, and the HEp-2 cell antigen. More important, stimulation of the toll-like receptor 9 (TLR9), which mimics bacterial infection, substantially increased the secretion of IgM in human epithelial cancer cells. These findings indicate that human epithelial cancer cells as well as non-cancer epithelial cells can spontaneously produce IgM with natural antibody activity.

Hu, Fanlei; Zhang, Li; Zheng, Jie; Zhao, Ling; Huang, Jing; Shao, Wenwei; Liao, Qinyuan; Ma, Teng; Geng, Li; Yin, C. Cameron; Qiu, Xiaoyan

2012-01-01

373

Investigations of the structural function of the J chain in human immunoglobulin M  

PubMed Central

Human IgM molecules were treated with Na2SO3 or mercaptoethylamine in concentrations ranging from 2 to 14mm or 2 to 22mm respectively. The dissociation of IgM to IgMs varied from 0% to 100%. At the intermediate concentrations of either reagent the amount of freed J chains was less than expected. In an attempt to find an explanation for this, IgM was partially dissociated to IgMs with mercaptoethylamine. The IgMs isolated by gel filtration was divided according to the ascending and descending portions of the elution curve. These portions were treated with 24mm-mercaptoethylamine and analysed for the presence of J chains. Only the ascending portion contained free J chains. Thus, after mild reduction where not all the IgM molecules are dissociated to IgMs, some J chains remain covalently attached to some IgMs molecules although most of the J chains are freed. It was concluded that the J chain could serve as a `hitch' for IgMs molecules forming intact IgM. ImagesPLATE 1PLATE 2(a) AND (b)PLATE 2(c) AND (d)

Ricardo, Manuel J.; Inman, Franklin P.

1973-01-01

374

The incorporation of J chain into reassembled human immunoglobulin M  

PubMed Central

Human IgM (immunoglobulin M) was reduced with 24mm-mercaptoethylamine. This atreatment resulted in complete dissociation to IgMs subunits and free J chain. Intr-subunit interchain disulphide bonds remained intact. The mixture then was encouraged to reoxidize. The schlieren pattern of the reoxidized mixture showed the presence of a considerable quantity of IgM in addition to residual IgMs. The isolated reassembled IgM did not dissociate in 5m-guanidinium hydrochloride. It apparently contained the same amount of covalently attached J chain as did native IgM. The J chain was a part of the high-molecular-weight Fc fragment obtained from the reassembled IgM. ImagesFig. 1.Fig. 2.PLATE 2Fig. 3.PLATE 1

Ricardo, Manuel J.; Inman, Franklin P.

1974-01-01

375

Distributive immunization of networks against viruses using the `honey-pot' architecture  

NASA Astrophysics Data System (ADS)

Although computer viruses cause tremendous economic loss, defence mechanisms fail to adapt to their rapid evolution. Previous immunization strategies have been characterized as being static and centralized, which has made virus containment difficult or even impossible. We suggest, instead, to propagate the immunization agent as an epidemic. The main problem with epidemic vaccine propagation is that it is bound to lag behind the virus. We suggest giving the vaccine an advantage over the virus by allowing it to leapfrog through a separate, overlapping, partially correlated network. This enables the antivirus to contain the epidemic efficiently. We systemize this concept with a `honey-pot' architecture that achieves both early virus discovery and rapid antivirus dissemination. We present analytic, as well as simulation, results for a set of realistic topologies that illustrate the effectiveness of this approach.

Goldenberg, Jacob; Shavitt, Yuval; Shir, Eran; Solomon, Sorin

2005-12-01

376

The WildList Organization International  

NSDL National Science Digital Library

The WildList is a free list of all known computer viruses that are spreading in the world, as compiled by volunteer antivirus experts of the WildList Organization International. It is updated monthly and, as one can imagine, is quite lengthy. The site has many other interesting features besides the list. For example, a somewhat humorous article by the WildList's founder describes his views on "how scientific naming works" for computer viruses. Several other papers are also offered that deal with virus issues. Some links to sites that test products or describe viruses are given as well. This site takes a very objective approach to releasing information and, therefore, does not endorse any particular antivirus software.

1999-01-01

377

Chicken recombinant antibodies against infectious bursal disease virus are able to form antibody–virus immune complex  

Microsoft Academic Search

Virus particles exposed to specific anti-virus antibodies result in the formation of immune complexes (Icx). Recent vaccination strategies have employed this feature, and an infectious bursal disease virus (IBDV) vaccine based on Icx has been released and is expected to replace conventional IBDV vaccines. We evaluated whether chicken recombinant antibodies (rAb) specific for IBDV, rather than conventional chicken anti-IBDV sera,

J. Ignjatovic; G. Gould; L. Trinidad; S. Sapats

2006-01-01

378

In GFP with high risk HPV18E6 fusion protein expressed 293T and MCF7 cells, the endogenous wild-type p53 could be transiently phosphorylated at multiple sites  

Microsoft Academic Search

BACKGROUND: Infected cells recognize viral replication as a DNA damage stress and elicit the host surveillance mechanism to anti-virus infection. Modulation of the activity of tumor suppressor p53 is a key event in the replication of many viruses. They could manipulate p53 function through phosphorylation modification for their own purpose. But there is rarely research about p53 phosphorylation status in

Lina Sun; Ge Zhang; Zongfang Li; Tusheng Song; Chen Huang; Lusheng Si

2008-01-01

379

Malicious Code Detection Using Active Learning  

Microsoft Academic Search

The recent growth in network usage has motivated the creation of new malicious code for various purposes, including economic\\u000a and other malicious purposes. Currently, dozens of new malicious codes are created every day and this number is expected to\\u000a increase in the coming years. Today’s signature-based anti-viruses and heuristic-based methods are accurate, but cannot detect\\u000a new malicious code. Recently, classification

Robert Moskovitch; Nir Nissim; Yuval Elovici

2008-01-01

380

Design and Implementation of a Secure Modbus Protocol  

Microsoft Academic Search

The interconnectivity of modern and legacy supervisory control and data acquisition (SCADA) systems with corporate networks\\u000a and the Internet has significantly increased the threats to critical infrastructure assets. Meanwhile, traditional IT security\\u000a solutions such as firewalls, intrusion detection systems and antivirus software are relatively ineffective against attacks\\u000a that specifically target vulnerabilities in SCADA protocols. This paper describes a secure version

Igor Nai Fovino; Andrea Carcano; Marcelo Masera; Alberto Trombetta

2009-01-01

381

N-gram analysis for computer virus detection  

Microsoft Academic Search

Generic computer virus detection is the need of the hour as most commercial antivirus software fail to detect unknown and new viruses. Motivated by the success of datamining\\/machine learning techniques in intrusion detection systems, recent research in detecting malicious executables is directed towards devising efficient non-signature-based techniques that can profile the program characteristics from a set of training examples. Byte

D. Krishna Sandeep Reddy; Arun K. Pujari

2006-01-01

382

Biological Activities and Corresponding Sar Analysis of Andrographolide and its Derivatives.  

PubMed

In recent years pharmaceutical chemists have synthesized large numbers of andrographolide derivatives, which bear important biological activities such as anti-inflammatory, antibacterial, antivirus, antitumor, antidiabetic, and antifeedant. Consequently, the corresponding SAR presents more and more pronounced. This paper aimed to review all the available literature on this field, which highlighted the significant achievements on the structural modification and SAR of andrographolide and its derivatives. PMID:22512591

Zhou, Bin; Zhang, Dayong; Wu, Xiaoming

2012-04-17

383

Kinetics of circulating immunoglobulin M in sepsis: relationship with final outcome  

PubMed Central

Introduction The aim of this study was to investigate the kinetics of immunoglobulin M (IgM) during the different stages of sepsis. Methods In this prospective multicenter study, blood sampling for IgM measurement was done within the first 24 hours from diagnosis in 332 critically ill patients; in 83 patients this was repeated upon progression to more severe stages. Among these 83 patients, 30 patients with severe sepsis progressed into shock and IgM was monitored daily for seven consecutive days. Peripheral blood mononuclear cells (PBMCs) were isolated from 55 patients and stimulated for IgM production. Results Serum IgM was decreased in septic shock compared to patients with systemic inflammatory response syndrome (SIRS) and patients with severe sepsis. Paired comparisons at distinct time points of the sepsis course showed that IgM was decreased only when patients deteriorated from severe sepsis to septic shock. Serial measurements in these patients, beginning from the early start of vasopressors, showed that the distribution of IgM over time was significantly greater for survivors than for non-survivors. Production of IgM by PBMCs was significantly lower at all stages of sepsis compared with healthy controls. Conclusions Specific changes of circulating IgM occur when patients with severe sepsis progress into septic shock. The distribution of IgM is lower among non-survivors.

2013-01-01

384

An unusual case of bilateral granulomatous mastitis.  

PubMed

Idiopathic granulomatous mastitis (IGM) is an uncommon benign disorder of the breast. At clinical examination, IGM is characterized by an inflammatory process of the breast, usually unilateral. Possible clinical findings are palpable mass with erythematous skin, pain, sterile abscesses, fistula and nipple retraction. Mammography and ultrasound findings are not specific for IGM. Magnetic resonance imaging (MRI) is a useful tool for the differential diagnosis; it is also necessary to delineate the exact extension of the disease and to plan the correct treatment. Final diagnosis is histological. We described an unusual case of IGM with bilateral involvement in a patient with history of pacemaker implantation and IGM typical clinical symptoms. Mammography, ultrasound, and MRI examinations were performed to identify the inflammatory disorder and to plan the correct therapy. Imaging features were correlated with final histological diagnosis of IGM. PMID:23781373

Pistolese, C A; Di Trapano, R; Girardi, V; Costanzo, E; Di Poce, I; Simonetti, G

2013-01-01

385

An Unusual Case of Bilateral Granulomatous Mastitis  

PubMed Central

Idiopathic granulomatous mastitis (IGM) is an uncommon benign disorder of the breast. At clinical examination, IGM is characterized by an inflammatory process of the breast, usually unilateral. Possible clinical findings are palpable mass with erythematous skin, pain, sterile abscesses, fistula and nipple retraction. Mammography and ultrasound findings are not specific for IGM. Magnetic resonance imaging (MRI) is a useful tool for the differential diagnosis; it is also necessary to delineate the exact extension of the disease and to plan the correct treatment. Final diagnosis is histological. We described an unusual case of IGM with bilateral involvement in a patient with history of pacemaker implantation and IGM typical clinical symptoms. Mammography, ultrasound, and MRI examinations were performed to identify the inflammatory disorder and to plan the correct therapy. Imaging features were correlated with final histological diagnosis of IGM.

Pistolese, C. A.; Di Trapano, R.; Girardi, V.; Costanzo, E.; Di Poce, I.; Simonetti, G.

2013-01-01

386

IgM-antibody response to the hepatitis B core antigen in acute and chronic hepatitis B.  

PubMed Central

A solid phase M-antibody capture radioimmunoassay (MACRIA) and a serum fractionation method were used to quantitate the IgM response to the hepatitis B core antigen (IgM anti-HBc) in acute and chronic hepatitis B infections. Antibody to the core antigen was predominantly of the IgM class during the acute phase of hepatitis B. Resolving acute infections remained positive by MACRIA, but at decreasing levels, for as long as 6 months. IgM anti-HBc persisted in HBsAg carriers but at levels very much lower than seen in acute infections. There was no correlation of IgM anti-HBc with severity of chronic liver disease in carriers. Measurement of IgM anti-HBc by MACRIA enabled accurate identification of acute hepatitis B on single serum specimens.

Tedder, R. S.; Wilson-Croome, R.

1981-01-01

387

Immunobullous dermatosis associated with Waldenström macroglobulinaemia treated with rituximab.  

PubMed

Waldenström macroglobulinaemia (WM) is a chronic lymphoproliferative disorder characterized by the presence of a monoclonal IgM paraprotein. Specific cutaneous features of WM include neoplastic cell infiltrates, IgM storage papules and IgM bullous dermatosis. We report a patient with subepidermal bullous disease associated with WM. Immunofluorescence identified IgM deposition along the basement membrane zone (BMZ) with circulating anti-BMZ IgM antibodies reacting with the dermal side of salt-split skin. The autoantibodies did not react with type VII collagen or laminin 332. Following failed treatment with doxycycline, prednisolone, intravenous immunoglobulin and dapsone, the patient was successfully treated with a modified RCVP regimen (rituximab, cyclophosphamide and prednisolone). To our knowledge, this is the first reported case of IgM bullous disease of WM treated with rituximab. PMID:23782150

Chattopadhyay, M; Rytina, E; Dada, M; Bhogal, B S; Groves, R; Handfield-Jones, S

2013-12-01

388

NCI Funded Research Portfolio - ZIA CP005804 08244 Detail  

Cancer.gov

Waldenstrom macroglobulinemia (WM) is a distinctive subtype of non-Hodgkin lymphoma featuring overproduction of immunoglobulin M (IgM) and has a clear familial component. No susceptibility genes have been identified. We performed a genome-wide linkage analysis in eleven high-risk WM families having 122 individuals with DNA samples, including 34 WM cases and 10 cases of IgM monoclonal gammopathy of undetermined significance (IgM MGUS) which is a potential precursor to WM.

389

NCI Funded Research Portfolio - ZIA CP005804-08244 Detail  

Cancer.gov

Waldenstrom macroglobulinemia (WM) is a distinctive subtype of non-Hodgkin lymphoma featuring overproduction of immunoglobulin M (IgM) and has a clear familial component. No susceptibility genes have been identified. We performed a genome-wide linkage analysis in eleven high-risk WM families having 122 individuals with DNA samples, including 34 WM cases and 10 cases of IgM monoclonal gammopathy of undetermined significance (IgM MGUS) which is a potential precursor to WM.

390

Enzyme-linked immunosorbent assay for detection of Mycoplasma pneumoniae specific immunoglobulin M  

Microsoft Academic Search

An ELISA was developed for the detection of IgM antibodies toMycoplasma pneumoniae in human sera, using microtiter plates coated with rabbit antiserum to human IgM selecting for IgM antibodies in the first reaction step. The specific antibodies were detected using enzyme-labelled, detergent-solubilized antigen. The complement fixation test was used as reference method. In a prospective study of 59 patients with

L. Hirschberg I; A. Krook; C.-A. Pettersson; T. Vikerfors

1988-01-01

391

Idiopathic ganulomatous mastitis.  

PubMed

Idiopathic granulomatous mastitis (IGM) is a rare chronic benign disease of the breast. Histologically, the disease presents as an inflammatory reaction with non-caseating granulomas considered characteristic for IGM. IGM is often confused with breast cancer or mastitis with abcedations, and is treated with surgery which involves mutilation of the breast. Although no consensus exists on the best treatment modality, the use of low-dose oral and topical steroids has proven efficacy. PMID:23188836

Casteren, Christelle Van; Jacquemyn, Yves; Himpe, Ellen; Verslegers, Inge

2012-01-01

392

Differential Diagnosis in Idiopathic Granulomatous Mastitis and Tuberculous Mastitis  

PubMed Central

Purpose Idiopathic granulomatous mastitis (IGM) is a rare chronic inflammatory disease of unknown etiology. The diagnosis of IGM requires that other granulomatous lesions in the breast be excluded. Tuberculous mastitis (TM) is also an uncommon disease that is often difficult to differentiate from IGM. The purpose of this study is to develop a new algorithm for the differential diagnosis and treatment of IGM and TM. Methods Medical records of 68 patients (58 with IGM and 10 with TM) between July 1999 and February 2009 were retrospectively reviewed. Results The mean age of the patients was 33.5 (IGM) and 40 (TM) years (p=0.018). The median follow-up was 84 months. Of the total 10 patients with TM, 5 patients had a history of pulmonary tuberculosis. The most common symptoms of the diseases were breast lump and pain. However, axillary lymphadenopathy was more seen in TM (50%) compared to IGM (20.6%) (p=0.048). TM showed more cancer-mimicking findings on radiologic study (p=0.028). In IGM, 48 patients (82.7%) underwent surgical wide excision and 21 patients (36.2%) were managed with corticosteroid therapy and antibiotics. All of the TM patients received anti-tuberculosis medications and 9 patients (90%) underwent wide excision. The mean treatment duration was 2.8 months in IGM and 8.4 months in TM. Recurrence developed in 5 patients (8.6%) in IGM and 1 patient (10%) in TM. Conclusion This study shows different characteristics between IGM and TM. The IGM patients were younger and had more mastalgia symptoms than the TM patients. Axillary lymphadenopathy was seen more often in TM patients. Half of the TM patients had pulmonary tuberculosis or tuberculosis lymphadenitis. Surgical wide excision might be both therapeutic and useful for providing an exact diagnosis.

Seo, Hee Ri Na; Na, Kuk Young; Yim, Hyun Ee; Kim, Tae Hee; Kang, Doo Kyoung; Oh, Ki Keun; Kang, Seok Yun; An, Young-Sil; Chun, Mison; Kim, Woojae; Park, Rae Woong; Jung, Yong Sik

2012-01-01

393

Specific immunoglobulin M response to hepatitis A virus determined by solid-phase radioimmunoassay.  

PubMed Central

Immunoglobulin M antibody to hepatitis A virus (IgM anti-HAV) is found in most patients with acute type A hepatitis. To determine the duration of this IgM response as well as to confirm that IgM anti-HAV is a specific marker for acute infection, we developed a solid-phase radioimmunoassay for IgM anti-HAV. This new assay is 25-fold more sensitive than a conventional blocking radioimmunoassay for anti-HAV, and interference due to rheumatoid factor was eliminated by simultaneously testing sera against virus-free control antigen. Maximum IgM anti-HAV titers (1:6,400 to greater than or equal to 1:51,200) were detected during the first 30 days after the onset of illness. Although the IgM anti-HAV titer subsequently declined 64-fold over the ensuing 90 days, low-titer IgM anti-HAV (1:100 to 1:400) persisted in many sera for 90 to 150 days. Acute sera having an IgM anti-HAV titer of greater than or equal to 1:25,600 possessed a significantly higher mean IgM concentration (492 mg/dl) than acute sera with an IgM anti-HAV titer of less than or equal to 1:12,800 (344 mg/dl; P < 0.05). IgM anti-HAV titers did not correlate with other clinical or laboratory measures of disease severity. Detection of IgM anti-HAV proved to be both a highly specific (>99%) and a sensitive (>99%) method for the diagnosis of type A hepatitis.

Lemon, S M; Brown, C D; Brooks, D S; Simms, T E; Bancroft, W H

1980-01-01

394

Accuracy of immunoglobulin M immunoassay for diagnosis of chlamydial infections in infants and adults.  

PubMed Central

An improved solid-phase enzyme immunoassay (EIA) with Chlamydia trachomatis L2 434/Bu elementary bodies was developed for the measurement of immunoglobulin M (IgM) antibody to C. trachomatis in serum. Comparison of EIA and microimmunofluorescence IgM antibody titers of 156 serum samples revealed an EIA sensitivity and specificity of 100% for infants, but reduced sensitivity (85%) and specificity (76%) for sera from adults. Sera containing IgM class rheumatoid factor produced false-positive IgM results which could easily be eliminated by pretreatment of the sera with anti-human IgG. Analysis of sera from infants with chlamydial infections revealed that 17 of 17 infants with C. trachomatis pneumonia had high IgM antibody titers (geometric mean titer, 1:64,812), whereas two infants with conjunctivitis only lacked detectable IgM antibody. EIA detected IgM antibody to several serovar groups in serum, including serovars B, BDE, FG, and J. IgM antibody to C. trachomatis in serum was detected as early as 5 days after the infection that was acquired at delivery and persisted for 3 months. The availability of an EIA possessing good sensitivity and specificity for the detection of IgM antibody to C. trachomatis may permit more laboratories to diagnose perinatal chlamydial infections.

Mahony, J B; Chernesky, M A; Bromberg, K; Schachter, J

1986-01-01

395

Stimulation of proliferation and immunoglobulin M production by lactoferrin in human-human and mouse-mouse hybridomas cultures in serum-free conditions.  

PubMed

The effects of growth factors, such as insulin, transferrin, lactoferrin, ethanolamine, and selenium, on proliferation and IgM production of human-human hybridomas HB4C5 cells in a serum-free enriched RDF (eRDF) medium were studied. Among them, lactoferrin markedly stimulated proliferation and IgM production of the cells. Another iron-binding protein, transferrin, stimulated proliferation of HB4C5 cells as well as lactoferrin, but its stimulatory effect on IgM production was negligible. The proliferation and IgM production of HB4C5 cells gave some detectable delays in conventional ITES-eRDF medium at low cell densities, but the delays were avoided by the addition of lactoferrin. However, eRDF medium supplemented with lactoferrin could not support proliferation and IgM production of the cells at high cell densities. For proliferation and IgM production of HB4C5 cells, eRDF medium supplemented with 25 micrograms/ml lactoferrin, 10 microM ethanolamine, 35 micrograms/ml transferrin, and 2.5 nM selenium (LETS-eRDF) gave the best result. Lactoferrin stimulated proliferation of human-human and mouse-mouse hybridomas producing IgG or IgM, but stimulation of Ig production was detected only in IgM producers. These results suggest that cell proliferation, IgM production, and IgG production of hybridomas are regulated by different mechanisms. PMID:1366591

Yamada, K; Ikeda, I; Sugahara, T; Hashizume, S; Shirahata, S; Murakami, H

1990-03-01

396

Evaluation of a New Commercially Available Immunoglobulin M Capture Enzyme-Linked Immunosorbent Assay for Diagnosis of Dengue Virus Infection  

PubMed Central

We evaluated the FDA-cleared InBios dengue virus (DENV) IgM capture enzyme-linked immunosorbent assay (ELISA) for qualitative detection of anti-DENV IgM antibodies from 79 serum samples obtained from dengue virus-infected patients or suspected dengue cases. The agreement, sensitivity, and specificity of the InBios assay compared to the gold standard in-house DENV IgM capture ELISA were 94, 92, and 94%, respectively. We conclude that the InBios DENV IgM capture ELISA can be effectively used for rapid diagnosis of acute or recent DENV infection.

Namekar, Madhuri; Ellis, Esther M.; O'Connell, Maile; Elm, Joe; Gurary, Alexandra; Park, Sarah Y.; Imrie, Allison

2013-01-01

397

Idiopathic granulomatous mastitis: case reports and review of literature.  

PubMed

Idiopathic granulomatous mastitis (IGM) is an uncommon benign disorder of the breast that can mimic two frequent breast disorders, breast carcinoma and breast abscess. In this report, we present two patients seen in a community teaching hospital over a period of one year, diagnosed with IGM after histological evaluation. One patient responded well to immunosuppressive therapy, but the second patient required bilateral mastectomy due to the severe and recurrent nature of the disease. IGM is a disorder that should be considered in the evaluation of women who present with painful breast disease. We discuss the diagnosis, clinical presentation and management of IGM. PMID:20013067

Patel, Rakshitkumar A; Strickland, Pamela; Sankara, Ishwara R; Pinkston, Glen; Many, Wickliffe; Rodriguez, Martin

2010-03-01

398

Idiopathic granulomatous mastitis: a case report of breast abscess.  

PubMed

Idiopathic granulomatous mastitis (IGM) is an uncommon breast disease often mistaken for breast infection or abscess. We present a case of IGM diagnosed after prolonged ineffective treatment of presumed infectious mastitis with abscess. Once the diagnosis was made with biopsy and further evaluation to exclude other causes of granulomatous disease, sinus tract debridement and closure by secondary intent resulted in resolution of symptoms in our patient. Many cases of IGM require immunosuppression with steroids, methotrexate or extensive surgery. To prevent morbidity, IGM should be considered in the differential diagnosis when presumed infectious mastitis with breast abscess does not respond to usual treatment. PMID:22687677

Olsen, Molly L; Dilaveri, Christina A

2011-01-01

399

A monoclonal macroglobulin with antinuclear activity.  

PubMed Central

Serum containing a monoclonal IgM protein from a patient with Waldenstroms' macroglobulinaemia gave intense immunofluorescent staining of kidney nuclei. The Fab mu fragments of this immunoglobulin were obtained. The IgM and Fab fragments reacted in vitro with kidney nuclei using unfixed cryostat sections of rat or mouse kidney. After treatment of the patient with chemotherapy, the monoclonal IgM disappeared, and no more antinuclear activity could be detected in the serum. The results strongly suggest that this IgM protein had antinuclear activity. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5

Intrator, L; Andre, C; Chenal, C; Sultan, C

1979-01-01

400

Rapid active assay for the detection of antibodies to West Nile virus in chickens.  

PubMed

To reduce the assay time for detecting virus-specific antibodies in serum, we developed microarray-based active immunoassay techniques for detecting West Nile virus (WNV)-specific IgM molecules in chicken blood. The assay uses electrophoretic concentration of IgM molecules onto WNV antigens arrayed on a dialysis membrane followed by detection of bound IgM molecules with functionalized magnetic beads as active labels. This assay takes only 15 minutes and has the same sensitivity as a commercially available human WNV IgM antibody-capture enzyme-linked immunosorbent assay (commonly called a MAC-ELISA) modified for use with chicken sera. PMID:18187786

Groves, Stephanie S; Turell, Michael J; Bailey, Charles L; Morozov, Victor N

2008-01-01

401

Photoionization of intergalactic gas and cooling flows in clusters of galaxies  

Microsoft Academic Search

We examine the environmental impact of quasars on the intergalactic medium (IGM) and derive analytic and numerical results for ionization-front expansion as a function of redshift z in an expanding Friedmann cosmology. We find that in order for the IGM to be ionized by quasars, the closure parameter of intergalactic gas, omegaI is less than .03. We present new photoionization

Megan Elizabeth Donahue

1990-01-01

402

Laboratory diagnosis of primary and secondary dengue infection  

Microsoft Academic Search

Background: Dengue fever is routinely detected in many laboratories using commercial tests for the specific detection of dengue IgM antibodies. Objectives: We have studied the sensitivity of IgM antibody detection in paired serum samples of 43 patients with either with primary dengue (PD) or secondary dengue (SD). Study design: Two consecutive samples were drawn from 23 Vietnamese and 20 German

Stefan Schilling; Diana Ludolfs; Le Van An; Herbert Schmitz

2004-01-01

403

Characterization and Classification of the Light Chain Composition of a Macromolecular Cryoprecipitating Factor.  

National Technical Information Service (NTIS)

Several patients were reported to have a form of cryoglobulinemia in which the IgM protein precipitated in the complex with the IgG protein. In certain instances, the light chains of the IgM were of both kappa and lambda types. In one previous instance, t...

R. A. Gams J. J. Costanzi C. A. Coltman

1967-01-01

404

Diagnosis of Natural and Induced Diseases of Military Importance. Phase 1.  

National Technical Information Service (NTIS)

The purpose of this research project was to demonstrate the feasibility of the Optical Biossay (OBA) system for the quantitation of circulating serum IgG and IgM antibodies against Hantaan virus. Reference ELISA assays were set up to measure IgG and IgM a...

D. E. Charlton

1990-01-01

405

77 FR 35690 - Medical Devices; Availability of Safety and Effectiveness Summaries for Premarket Approval...  

Federal Register 2010, 2011, 2012, 2013

...P110031, FDA-2012-M-0024.......... Roche Diagnostics Elecsys Anti-HBc IgM January 3, 2012. Corp. Immunoassay and Elecsys PreciControl Anti- HBc IgM. P040043.S040, FDA-2012-M-0056..... W.L. Gore & Gore TAG...

2012-06-14

406

Acute Sporadic Hepatitis E in Children Living in Cairo, Egypt. (Reannouncement with New Availability Information).  

National Technical Information Service (NTIS)

Seventy-three pediatric patients with acute hepatitis and 19 control patients without liver disease living in Cairo, Egypt, were evaluated with a newly developed Western blot assay for IgM antibody to hepatitis E virus (IgM anti-HEV). The mean age of acut...

K. C. Hyams M. C. McCarthy M. Kaur M. A. Purdy D. W. Bradley

1992-01-01

407

Persistence of immunoglobulin G and immunoglobulin M antibodies after postnatal rubella infection determined by solid-phase radioimmunoassay.  

PubMed Central

The appearance and persistence of immunoglobulin M (IgM) and IgG antibodies in postnatal rubella infections were studied by employing a solid-phase radioimmunoassay test. Altogether, 222 serial serum specimens from 51 patients with acute rubella infection were tested. Both IgG and IgM antibodies developed rapidly and appeared in all patients within 4 days after the onset of rash. In some patients, the IgM antibodies clearly preceded the IgG antibodies; however, the reverse situation was also noticed in a few cases. The IgG antibodies showed only minor changes after 8 to 10 days from the onset of rash. The IgM titers also reached a maximum level at approximately 8 to 10 days after the onset of rash, after which time a rapid decrease was normally seen. The mean half-life of IgM antibodies after 15 days from the onset of rash was 4.5 days, giving for IgM antibodies persistence times from 43 to approximately 80 days. Two patients with a prolonged IgM antibody response were detected. One of these patients had bilateral arthritis of the knee as a complication, whereas in the other patient no complication caused by rubella virus was detected. The IgM antibody response and its value in diagnosis are discussed.

Meurman, O H

1978-01-01

408

Association of Leucogenenol with Specific Proteins in Serum.  

National Technical Information Service (NTIS)

Determination of the concentration of leucogenenol in the IgM, IgG, albumin, and low molecular weight protein fractions of serum demonstrated that leucogenenol is found only in protein fractions of molecular weights in the range of IgM and IgG. Determinat...

F. A. H. Rice B. R. Griffin P. D. Dass

1974-01-01

409

Incidence, clinical spectrum, and outcome of intrauterine infections in neonates.  

PubMed

A prospective study was undertaken on the incidence of intrauterine infections by screening 1302 cord blood samples for total IgM by radial immunodiffusion. Specific IgM against cytomegalovirus (CMV), rubella and Toxoplasma were estimated in cord blood samples found to contain total IgM > 20 mg/dl. All these neonates were examined at birth and at discharge. Cord blood samples with total IgM > 20 mg/dl were further screened for specific IgM against rubella, CMV and Toxoplasma. Neonates found to have positive specific IgM were followed-up for hearing, opthalmological and developmental assessment. Raised cord blood (IgM > 20 mg/dl) was found in 270/1302 (20.6 per cent). Mean birth weight was comparable in babies with raised (> 20 mg/dl) or low (< 20 mg/dl) cord blood total IgM. Incidence of prematurity and low birth weight were not statistically different in babies with raised cord blood IgM when compared to those with low cord blood IgM levels. Similarly, incidence of intrauterine growth retardation (IUGR) idiopathic was similar in two groups. Specific IgM for rubella was found to be positive in eight (0.6 per cent). Of these, three had symptomatic rubella infection. Two mothers of these symptomatic babies had exanthematous viral illness during first trimester. Specific IgM for CMV was found to be positive in 23 (1.8 per cent) while two infants had symptomatic CMV disease. None of the babies was found to have specific IgM against Toxoplasma. One baby with symptomatic CMV disease and one with rubella died. Another baby with symptomatic CMV disease developed neonatal hepatitis which improved on follow-up but the infant went on to develop sensorineural deafness. All other asymptomatic babies with specific IgM positive against rubella and CMV were found to have normal vision, hearing and development on follow-up. PMID:10893916

Deorari, A K; Broor, S; Maitreyi, R S; Agarwal, D; Kumar, H; Paul, V K; Singh, M

2000-06-01

410

The DNA-binding and bioactivity of rare earth metal complexes.  

PubMed

Recently more and more attention is paid to the rare earth metal complexes, because the properties of the rare earth metals are similar to those of the transition metals such as the similar atomic and the ionic radius. A large number of rare metal complexes were synthesized, and their bioactivities were also studied. This review highlights recent researches on the interaction of some rare earth metal complexes with DNA, analyzes how the configuration of the complexes influences the binding affinity, and focuses on the pharmacological activities of the complexes, such as anticancer, antibacterial, antioxidant, anti-inflammatory and anti-virus. PMID:24568297

Yang, Li; Wang, Bochu; Tan, Jun; Zhu, Liancai

2013-08-01

411

High cell density perfusion culture of mouse-human hybridomas  

Microsoft Academic Search

Five mouse-human hybridomas, H2, H3, V1, V2 and V6 cells secreting anti-virus human monoclonal immunoglobulin G (IgG) were cultured in serum-free media at high density in a settling perfusion culture vessel with an inner cell sedimentation zone. The H2, H3 and V6 cells reached a density of 107 cells\\/ml in 0.5% (w\\/v) BSA-ITES-eRDF (see Materials and methods). The H2 cells

Yoshiharu Takazawa; Michiyuki Tokashiki

1989-01-01

412

Interferon ?-induced sarcoidosis to a patient with polycythemia vera  

PubMed Central

Treatment with interferon (IFN) can precipitate a variety of inflammatory conditions, including sarcoidosis. Although many other systems can be affected, the clinical picture in this case mostly includes cutaneous and pulmonary symptoms. The prognosis is better than the idiopathic form of the disease, and the most effective treatment is considered the discontinuation of antivirus therapy alone or in combination with corticosteroid administration. The authors present the case of a 36-year-old man who developed sarcoidosis stage I after 2 years of IFN? therapy for polycythemia vera.

Sionidou, M; Spyratos, D; Chloros, D; Sichletidis, L

2011-01-01

413

Evaluation of Tools for Protection of Interest against Hacking and Cracking  

NASA Astrophysics Data System (ADS)

The internet considered a tool that effectively ensures communication globally has been hindered by hackers and crackers continuously. In so doing, a multitude of network facilitated tools such as firewalls, virtual private networks (VPN) and a variety of antivirus software packages has been enabled for dealing with such predicaments. However, more often than not these facilitated tools are marketed as perfect solutions to the ever culminating problems such as loss of data and privacy in networked and world wide intercommunications. We provide a forum for addressing these perceived problems in this paper.

Jahankhani, Hossein; Antonijevic, Branko; Walcott, Terry

414

MicroRNA Roles in the NF-?B Signaling Pathway during Viral Infections  

PubMed Central

NF-?B signaling network is a crucial component of innate immunity. miRNAs are a subtype of small noncoding RNAs, involved in regulation of gene expression at the posttranscriptional level. Increasing evidence has emerged that miRNAs play an important role in regulation of NF-?B signaling pathway during viral infections. Both host and viral miRNAs are attributed to modulation of NF-?B activity, thus affecting viral infection and clearance. Understandings of the mechanisms of these miRNAs will open a direction for development of novel antivirus drugs.

Dou, Yongxi; Chen, Yixia

2014-01-01

415

[Inhibition of adenovirus reproduction in cell culture by specific antibodies].  

PubMed

The capacity of specific antibodies to inhibit the reproduction of homo- and heterologous adenoviruses in Hela cell added to culture medium after virus adsorption was studied. The inhibiting effect of polyclonal antivirus and monospecific antihexone antibodies to homo- and heterologous adenoviruses was shown. The effect was more expressed when using antibodies to homologous antibodies. The intensity of inhibition depended on antibodies concentration in the medium and infecting dose of the virus. Essential reduction of the quantity of infected cells and a decrease of the titer of adenovirus synthesized in the presence of homo- and heterologous antibodies was shown but adenovirus reproduction was not inhibited completely. PMID:19663330

Povnytsia, O Iu; Nosach, L M; Zhovnovata, V L; Zahorodnia, S D; Vantsak, N P; Tokarchuk, L V; Polishchuk, O M; Diachenko, N S

2009-01-01