The present invention discloses the use of bacterial IgA1 proteases to treat IgA1 deposition in tissue and organs. Bacterial IgA1 proteases specifically cleave IgA1 molecules and thus provide a means to ...

Immunoglobulin A1 (IgA1) proteases from Haemophilus influenzae are extracellular proteases that specifically cleave the hinge region of human IgA1, the predominant class of immunoglobulin present on mucosal membranes. The IgA1 proteases may have the ...

Indirect evidence suggests that immunoglobulin A1 (IgA1) proteases may be factors in the pathogenesis of certain infectious diseases, including meningitis, gonorrhoea, and destructive periodontitis. Bacterial IgA1 proteases are therefore potential candidates as vaccines. In ...

To understand more about the factors influencing the cleavage of immunoglobulin A1 (IgA1) by microbial IgA1 proteases, a recombinant human IgA2/IgA1 hybrid molecule was generated. In the hybrid, termed ...

By comparing the initial colonization of cleaned teeth in immunoglobulin A (IgA)-deficient, IgM-compensating individuals with that in normal individuals, no significant difference in the proportion of IgA1 protease-producing streptococci was found. Thus, as one of several bacterial means of immune evasion, the ability to cleave secretory ...

Immunoglobulin A1 (IgA1) protease, an enzyme that selectively cleaves human IgA1, may be a virulence factor for pathogenic organisms such as Neisseria gonorrhoeae. Host protection from the effects of IgA1 protease includes antibody-mediated inhibition ...

The immunoglobulin A1 (IgA1) proteases of Neisseria gonorrhoeae have been defined as having human IgA1 as their single permissive substrate. However, in recent years there have been reports of other proteins which are susceptible to the proteolytic activity of these ...

Attention has recently been focused on bacterial proteases with the capacity to cleave immunoglobulin A (IgA proteases) as possible pathogenic factors in bacterial meningitis, gonorrhoea, and destructive periodontal disease. Here, we describe a method for the rapid purification of a specific IgA1 protease from Bacteroides ...

Respiratory pathogens, such as Neisseria meningitidis, secrete site-specific proteases able to cleave human immunoglobulin A1 (IgA1), the first line of defense at mucosal membranes. Bacterial isolates show wide variability in IgA1 protease activity, and those isolated from patients with ...

The purpose of this study was to determine the occurrence and nature of immunoglobulin A1 (IgA1) protease activity in members of the genus Gemella and related taxa. Among a total of 22 Gemella strains belonging to the four species Gemella haemolysans, Gemella morbillorum, Gemella sanguinis, and Gemella bergeriae ...

Proteus mirabilis strains associated with human urinary tract infections have previously been shown to secrete an extracellular metalloproteinase which cleaves serum immunoglobulin A (IgA). The enzyme has now been purified to apparent homogeneity from culture supernatants of P. mirabilis 64676. The protease activity is associated with a 50-kilodalton (kDa) protein. Unlike that ...

Immunoglobulin A (IgA) proteases are extracellular enzymes elaborated by Neisseria gonorrhoeae, N. meningitidis, and Streptococcus sanguis. These enzymes each cleave human IgA1 at a critically situated prolyl-threonly peptide bond to yield Factor B Alpha ...

Using a panel of 143 strains classified according to a novel taxonomic system for oral viridans-type streptococci, we reexamined the ability of oral streptococci to attack human immunoglobulin A1 (IgA1) molecules with IgA1 protease or glycosidases. IgA1 protease production ...

Using a panel of 143 strains classified according to a novel taxonomic system for oral viridans-type streptococci, we reexamined the ability of oral streptococci to attack human immunoglobulin A1 (IgA1) molecules with IgA1 protease or glycosidases. IgA1 protease production ...

Attention has recently been focused on immunoglobulin A1 (IgA1) protease production as a possible virulence factor of bacteria implicated in meningitis and gonorrhea. This report demonstrates that suspected principal etiological agents in destructive periodontal disease include bacteria capable of degrading ...

Attention has recently been focused on immunoglobulin A1 (IgA1) protease production as a possible virulence factor of bacteria implicated in meningitis and gonorrhea. This report demonstrates that suspected principal etiological agents in destructive periodontal disease include bacteria capable of degrading ...

Bacteroides and Capnocytophaga species have been implicated as periodontal pathogens. Some of these species possess immunoglobulin A1 (IgA1) proteases that are capable of cleaving the human IgA1 molecule in the hinge region, leaving intact Fc alpha and ...

IgA, the major class of Ig in secretions, classically functions by interfering with microbial attachment to host tissues. Many mucosal pathogens, including Streptococcus pneumoniae, express an IgA1 protease that may circumvent the protective effects of this Ig subclass. Because these proteases are specific for human IgA1, we generated human mAbs to the ...

IgA nephropathy (IgAN) is the most common glomerular disease and it is characterized by deposition of IgA1 molecules in mesangium. Recent studies had demonstrated that serum and mesangial IgA1 in IgAN were deglycosylated and IgA1 could bind to human mesangial cells (HMC) through a novel receptor. The aim of the current study is to investigate and compare ...

BackgroundThe IgA1 protease of Streptococcus pneumoniae is a proteolytic enzyme that specifically cleaves the hinge regions of human IgA1, which dominates most mucosal surfaces and is the major IgA isotype in serum. This protease is expressed in all of the known pneumococcal strains and plays a ...

IgA nephropathy (IgAN), the most common glomerulonephritis, is characterized by mesangial IgA1-containing immunodeposits, proliferation of mesangial cells, and matrix expansion. Clinical onset is frequently heralded by synpharyngitic hematuria, macroscopic hematuria during an upper-respiratory tract infection. Clinical and laboratory data support a ...

Because immunoglobulin A (IgA) is the predominant immunoglobulin at mucosal surfaces, IgA proteases produced by pathogenic bacteria are considered potential virulence factors for organisms that cause disease or gain entry at mucous membranes. To determine the role of IgA protease in the pathogenicity of mycoplasmal disease, a variety of human and animal mycoplasma and ureaplasma species were ...

This study was performed to isolate and investigate the IgA1 that could accumulate in glomeruli (glomerulophilic IgA1). IgA1 was fractionated by the electric charge and the reactivity to Jacalin. Serum IgA1 of IgA nephropathy patients was separated and fractionated using a ...

In IgA nephropathy (IgAN), serum IgA1 with abnormal O-glycosylation deposits in the glomerular mesangium. The underlying mechanism of this IgA1 O-glycosylation abnormality is poorly understood, but recent evidence argues against a generic defect in B cell glycosyltransferases, suggesting that only a subpopulation of IgA1-committed B cells are affected. For ...

Many bacteria which establish infections after invasion at human mucosal surfaces produce enzymes which cleave immunoglobulin A (IgA), the primary immunoglobulin involved with protection at these sites. Bacterial species such as Haemophilus influenzae which produce IgA1 proteases secrete this enzyme into their environment. However, ...

In celiac disease, gluten ingestion provokes small-bowel mucosal injury and production of IgA autoantibodies against transglutaminase 2 (TG2). It has been suggested that in celiac patients IgA could mediate the transepithelial passage of gluten peptides in a mechanism involving the transferrin receptor. As IgA1 with galactose-deficient O-linked glycans has elevated affinity for the transferrin ...

Haemophilus parasuis, the bacterium responsible for Gl�sser's disease, is a pathogen of significant concern in modern high-health swine production systems but there is little information regarding the identity or function of its virulence factors. Several important human mucosal pathogens, including the closely related bacterium Haemophilus influenzae, utilize IgA proteases to aid in defeating ...

This paper describes an IgA related protein Vla which occurred in the serum and urine of a patient with multiple myeloma. The protein was isolated from urine; it had a molecular mass of 70,000 daltons. It was shown to be a two chain IgA half molecule, consisting of a deleted alpha heavy chain, with a molecular mass of 42,000 daltons, which was disulphide linked to a normal kappa type light chain. ...

In the present study we have investigated whether bovine erythrocytes (Eb) specifically sensitized with human polyclonal IgA1 (Eb-IgA1) are able to bind to resident adherent rat peritoneal cells (PM phi). Rat PM phi formed rosettes with Eb-IgA1 at room temperature and at 37 degrees. The formation of these rosettes ...

In the present study we have investigated whether bovine erythrocytes (Eb) specifically sensitized with human polyclonal IgA1 (Eb-IgA1) are able to bind to resident adherent rat peritoneal cells (PM phi). Rat PM phi formed rosettes with Eb-IgA1 at room temperature and at 37 degrees. The formation of these rosettes ...

Human isolates of Streptococcus pneumoniae tested by traditional immunochemical methods produce a protease that cleaves human immunoglobulin A1 (IgA1) into Fab and Fc fragments. The protease may be an important virulence factor, but studies of its pathogenetic significance have been hampered by ...

The pneumococcus expresses a protease that hydrolyzes human immunoglobulin A1 (IgA1). A gene for IgA1 protease was identified from a plasmid library of pneumococcal DNA because of the effect of its overexpression on the colony morphology of Streptococcus pneumoniae. The deduced 1,964-amino-acid sequence is highly ...

SummaryBackground and objectives We assessed the activation of the oxidative stress pathway in patients with IgA nephropathy (IgAN), while evaluating the classic marker of the disease (galactose-deficient serum IgA1). Design, setting, participants, & measurements Sera from 292 patients and 69 healthy controls from Italy and the United States were ...

Human immunoglobulin (Ig)A exists in blood as two isotypes, IgA1 and IgA2, with IgA2 present as three allotypes: IgA2m(1), IgA2m(2), and IgA2m(n). We now demonstrate that recombinant, chimeric IgA1 and IgA2 differ in their pharmacokinetic properties. The major pathway for the clearance of all IgA2 allotypes is the ...

Aberrant glycosylation of IgA1 plays an essential role in the pathogenesis of IgA nephropathy. This abnormality is manifested by a deficiency of galactose in the hinge-region O-linked glycans of IgA1. Biosynthesis of these glycans occurs in a stepwise fashion beginning with the addition of N-acetylgalactosamine by the enzyme N-acetylgalactosaminyltransferase 2 and continuing with the addition of ...

Heat or chemically aggregated IgA or IgG stimulated degranulation of neutrophils with comparable efficiency. The same aggregates induced a neutrophil respiratory burst which could be measured by lucigenin-enhanced chemiluminescence. Serum IgA1 or IgA2 coated onto microtitre plates were both capable of inducing a respiratory burst in neutrophils, as was ...

Differential deglycosylation was introduced as an effective technique to characterize glycosylation in glycoprotein containing both N-linked and O-linked glycans at both protein and peptide levels. Human IgA1 was used as a model glycoprotein to demonstrate this technique. The glycans attached to Human IgA1 were ...

Predominant or codominant immunoglobulin (Ig) A deposition in the glomerular mesangium characterizes IgA nephropathy (IgAN). Accumulated glomerular IgA is limited to the IgA1 subclass and usually galactose-deficient. This underglycosylated IgA may play an important role in the pathogenesis of IgAN. Recently, antibodies against galactose-deficient IgA1 were ...

New data from Kiryluk et al. show the importance of genetic factors in determining the profile of serum IgA1 O-glycoforms in IgA nephropathy and Henoch-Sch�nlein purpura nephritis. Elevated serum levels of poorly galactosylated IgA1 O-glycoforms do not, however, appear sufficient in themselves to cause nephritis ...

In contrast to antigen-antibody complexes containing native human IgA, solid-phase-deposited IgA activates the alternative complement pathway and binds C3b. To investigate the role of carbohydrate chains in this, various human IgA preparations were treated with neuraminidase alone or together with N-glycanase or O-glycanase, or with mixed glycosidases from the oral bacterium, Streptococcus mitis. ...

The biological functions of immunoglobulin (Ig)A antibodies depend primarily on their interaction with cell surface receptors. Four IgA receptors are presently characterized. The Fc?RI (CD89) expressed by myeloid cells selectively binds IgA1 and IgA2 antibodies, whereas the poly-IgR, Fc?/?R, and asialoglycoprotein receptors bind other ligands in addition ...

The IgA isotype of human antibodies triggers inflammatory responses via the IgA-specific receptor Fc?RI (CD89). Structural studies have suggested that IgA1 N-glycans could modulate the interaction with Fc?RI. We have carried out detailed biophysical analyses of three IgA1 samples purified from human serum and recombinant ...

Although secretory IgA is the most abundantly produced Ig isotype, the mechanisms underlying the differential distribution of IgA subclasses in various body fluids remain unclear. To explore these mechanisms, we examined the distribution of IgA subclasses, the influence of the nature and sites of encounters with antigens, and the correlation between IgA subclass distribution and homing potentials ...

Although secretory IgA is the most abundantly produced Ig isotype, the mechanisms underlying the differential distribution of IgA subclasses in various body fluids remain unclear. To explore these mechanisms, we examined the distribution of IgA subclasses, the influence of the nature and sites of encounters with antigens, and the correlation between IgA subclass distribution and homing potentials ...

Abnormalities of IgA arise in alcoholic cirrhosis, including mesangial IgA deposits with possible development of secondary IgA nephropathy (IgAN). Since little is known about circulating immune complexes in cases of secondary IgAN, we analyzed IgA-associated parameters in the serum of 32 patients with compensated or advanced alcoholic cirrhosis. Galactose deficiency and decreased sialylation of ...

Ureaplasma urealyticum strains of all serotypes express a specific human immunoglobulin A1 protease that cleaves immunoglobulin A1 to produce intact Fab and Fc fragments. The use of a variety of inhibitors suggests that the enzyme is a serine protease. N-terminal sequencing of the Fc digestion ...

Serum and nasal wash specimens from 13 human volunteers undergoing experimental secondary infection with influenza A/Peking/2/79 (H3N2) wild-type virus were examined for the molecular form and subclass distribution of immunoglobulin A (IgA) antibodies to the viral hemagglutinin (HA). Nasal IgA antibodies were polymeric and did not bind radiolabeled secretory component, indicating that they were ...

BACKGROUND: Circulating immune complexes (CIC) containing galactose (Gal)-deficient IgA1 from adults with IgA nephropathy (IgAN) induce proliferation of cultured mesangial cells, but activities of CIC from pediatric patients with the disease have not been studied. METHODS: CIC of different sizes were isolated from sera of pediatric and adult IgAN patients ...

Fc receptor for human IgA was detected on rabbit, sheep and human ORh- red blood cells. This Fc alpha receptor was able to bind human secretory or myeloma IgA, IgA1 or IgA2 and alpha chains. The ligand binding was detected by complement mediated lysis and agglutination with specific anti-IgA serum. Blocking experiments showed the inability of Fab(IgA) ...

S � IgE M NB M S � IgA W NB W S M IgA1 W NB W S M IgA2 W NB W S M Fab W W W S M ScFv W NB W S M Mouse, and five IgG-binding sites are included, resulting in a mass of 44.6 kDa.Some researchers believe weakly to Fab fragments.1 Native Protein G contains two immunoglobulin-binding sites, as well as albumin

The ability of specific secretory immunoglobulin A (S-IgA) antibodies to inhibit bacterial colonization of mucosal surfaces may be neutralized by the activity of bacterial IgA1 proteases. Because of the resistance of the IgA2 subclass to these enzymes, the biological effect of IgA1 proteases in vivo may depend on the subclass distribution of the ...

Lectins are proteins with specificity of binding to certain monosaccharides or oligosaccharides. They can detect abnormal glycosylation patterns on immunoglobulins in patients with various chronic inflammatory diseases, including rheumatoid arthritis and IgA nephropathy (IgAN). However, lectins exhibit binding heterogeneity, depending on their source and methods of isolation. To characterize ...

Lectins are proteins with specificity of binding to certain monosaccharides or oligosaccharides. They can detect abnormal glycosylation patterns on immunoglobulins in patients with various chronic inflammatory diseases, including rheumatoid arthritis and IgA nephropathy (IgAN). However, lectins exhibit binding heterogeneity, depending on their source and methods of isolation. To characterize ...

Since its first description more than 40 years ago, IgA nephropathy has become the most common pattern of primary glomerulonephritis identified in all areas of the world where renal biopsy is routinely performed. This review discusses advances in our understanding of the pathogenesis of IgA nephropathy, principally focusing on work published in the past 5 years. It has been recognized for some ...

The subclass distribution of IgA producing cells was determined by paired immunofluorescence staining in colonic specimens from 10 patients with ulcerative colitis and eight with Crohn's disease. Compared with normal colonic mucosa, the percentage of IgA1 immunocytes showed a striking increase in both disorders. The proportion of mucosal IgA1 cells was ...

A study was made of the gliadin antibodies containing secretory piece (SP) found in 73 sera samples obtained from 38 children with coeliac disease (CD); simultaneously an intestinal biopsy was carried out. In 32 cases the mucosa was flat and the remaining 41, following a gluten-free diet, had a normal intestinal histology. Thirty chronic non-coeliac gastrointestinal patients and 22 normal children ...

To trace the emergence of modern IgA isotypes during vertebrate evolution we have studied the immunoglobulin repertoire of a model monotreme, the platypus. Two highly divergent IgA-like isotypes (IgA1 and IgA2) were identified and their primary structures were determined from full-length cDNAs. A comparative analysis of the amino acid sequences for IgA ...

Serum galactose-deficient immunoglobulin A1 (Gd-IgA1) is an inherited risk factor for adult IgA nephropathy (IgAN). In this paper, we determined the heritability of serum Gd-IgA1 levels in children with IgAN and Henoch-Sch�nlein purpura nephritis (HSPN), two disorders ...

The effect of human secretory immunoglobulin A (S-IgA) and serum antibodies to surface protein antigen (Ag) I/II on the adherence of Ag I/II-bearing Streptococcus mutans and of free Ag I/II to saliva-coated hydroxyapatite (SHA) was investigated. The inhibition by S-IgA of binding of both S. mutans and free Ag I/II to SHA was dependent on antibody to Ag I/II. Essentially no difference was found ...

IgA deposition in glomerular mesangium and the interaction with mesangial cells may well be the final common pathway to IgA nephropathy (IgAN). Altered hinge-region O-glycosylation of IgA1 from patients with IgAN may predispose to mesangial deposition and activation of the mesangial cell (MC) by IgA1, via a novel IgA1 receptor, and may be a key event in ...

A receptor which binds secretory IgA (sIgA) is expressed on human T cells from patients with systemic lupus erythematosus, rheumatoid arthritis, Behcet's syndrome and IgA nephropathy and on normal T cells following phytohaemagglutinin (PHA) stimulation. The specificity of this receptor was initially probed with a panel of normal serum immunoglobulins in competitive inhibition assays with sIgA ...

As the initial phase of the determination of the complete covalent structure of a human immunoglobulin A, 52 chymotryptic peptides, ranging in length from 2 to 37 residues, were isolated and characterized from the reduced and carboxymethylated alpha1 heavy chain of the myeloma IgA protein Bur. The peptides were subjected to sequence analysis by the dansylation technique, manual and automatic Edman ...

All of 14 serotype standards and 34 of 35 wild-type strains of Ureaplasma urealyticum isolated from humans demonstrated an immunoglobulin A (IgA) protease activity. This activity degraded radiolabeled human IgA including IgA1 but not IgG or azocasein. The IgA fragments were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by ...

Streptococcus suis (S. suis) is a major swine pathogen and emerging zoonotic agent. However, the current understanding of the S. suis pathogenesis of infection remains limited. In the present study, the contribution to the pathogenesis of S. suis was evaluated on IgA1 protease (or iga gene), which has been regarded as a virulence factor of gram-negative pathogenic bacteria and of certain ...

The mechanisms by which immunoglobulin A1 (IgA1) protease activity may enable bacteria to evade the effect of specific secretory IgA (S-IgA) antibodies are not clear. A possibility which has received indirect experimental support is that bacteria, as a consequence of the protease activity, become coated with ...

BackgroundMucosal antibodies have been suggested to have a role in defence against pneumococcal infections. We investigated here the ability of a seven-valent pneumococcal conjugate vaccine, PncOMPC, to induce mucosal immune response.MethodsHealthy Finnish children (n = 111), a subcohort of the Finnish Otitis Media Vaccine Trial, were recruited and 56 of them were immunised with the PncOMPC at the ...

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease in which the colonic mucosa is infiltrated with plasma cells producing IgG autoantibodies. It is not known whether this represents a local mucosal response which has switched to IgG or a peripheral response which may have been initiated by peripheral antigen which homed to the colonic mucosa. The clonal distribution of IgG ...

SUMMARYObjectiveThe purpose of the study was to explore the physiological and antigenic diversity of a large number of S. mitis biovar 1 isolates in order to begin to determine whether these properties contribute to species persistence.DesignS. mitis biovar 1 was collected from four infants from birth to one year of age. At each of 8�9 visits 60 isolates each were obtained from the cheeks, ...

Background. Henoch-Sch�nlein purpura (HSP) and IgA nephropathy (IgAN) are characterized by mesangial deposition of polyclonal IgA eventually showing aberrant glycosylation, affinity for mesangial cells and/or co-precipitation with antigen, bacterial peptides, autoantibodies or soluble receptors. IgA were also suggested to be negatively charged and predominantly of ? type but rarely in a ...

IgA is the most abundantly produced Ab isotype in humans, but its potential as immunotherapeutic reagent has hardly been explored. In this study, we describe anti-tumor mechanisms of mouse/human chimeric IgA Abs against the epidermal growth factor receptor (EGF-R). EGF-R Abs of IgG isotype are currently approved for the treatment of colon or head and neck cancers. As expected, the human IgG1, ...

In order to determine the glycosylation pattern for IgD, and to examine whether there are changes in the pattern of IgD and IgA1 O-glycosylation in patients with hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) during acute febrile attacks and during periods of quiescence, serum was obtained from 20 patients with HIDS and 20 control subjects. In the HIDS group, serum was obtained ...

Abs have been shown to be protective in passive immunotherapy of tuberculous infection using mouse experimental models. In this study, we report on the properties of a novel human IgA1, constructed using a single-chain variable fragment clone (2E9), selected from an Ab phage library. The purified Ab monomer revealed high binding affinities for the ...

Secretory IgA (SIgA) is the most prevalent human antibody and is central to mucosal immunity. It exists as two subclasses, SIgA1 and SIgA2, where SIgA2 has a shorter hinge joining the Fab and Fc regions. Both forms of SIgA are predominantly dimeric and contain an additional protein called the secretory component (SC) that is attached during the secretory ...

The primary structures of the N-linked oligosaccharides from normal human serum IgA1 were determined by a combination of sequential exoglycosidase digestion, Bio-Gel P-4 chromatography, anion-exchange chromatography and one-dimensional n.m.r. spectroscopy. Three major N-linked disialylated biantennary-complex-type structures were found (55%). The remaining ...

Henoch-Sch�nlein purpura (HSP) is a systemic disorder characterized by leukocytoclastic vasculitis involving the capillaries and the deposition of IgA immune complexes. Renal involvement is the principal cause of morbidity and mortality in children with HSP. Thus, it is important to clarify the onset mechanism of Henoch-Sch�nlein purpura nephritis (HSPN) and to identify the most appropriate ...

The IgG and IgA subclass distribution of specific antibodies as well as the distribution of total and specific IgE in 15 patients with schistosomiasis was determined in consecutive samples before and after initiation of treatment. An adult worm antigen preparation and a soluble egg antigen preparation were used as antigens in the ELISA assays. After initiation of treatment a rise was noted in ...

Secreted proteins of pathogenic bacteria are often essential virulence factors. They are involved, for example, in the adherence of the bacteria to host cells or required to suppress the host's defence mechanisms. Until recently, only IgA1 protease had been studied in detail in the NeisseriaceaeNeisseria meningitidis and Neisseria gonorrhoeae. The ...

Although impaired immune regulation along the mucosa-bone marrow axis has been postulated to play an important role, the pathogenesis of IgA nephropathy (IgAN) is unknown; thus, no disease-specific therapy for this disease exists. The therapeutic efficacy of tonsillectomy or tonsillectomy in combination with steroid pulse therapy for IgAN has been discussed. Although randomized control trials for ...

Experimental infection of male volunteers with Neisseria gonorrhoeae is safe and reproduces the clinical features of naturally acquired gonococcal urethritis. Human inoculation studies have helped define the natural history of experimental infection with two well-characterized strains of N. gonorrhoeae, FA1090 and MS11mkC. The human model has proved useful for testing the importance of putative ...

The two clinical phenotypes of gluten enteropathy, coeliac disease (CD) and dermatitis herpetiformis (DH), were characterized for numbers and homing profiles of circulating final effector B cells, plasmablasts, identified as immunoglobulin (Ig)-secreting cells (ISC). In CD, the numbers of ISC were approximately 50% lower than in DH or controls. ISC expressed peripheral lymph node homing receptor ...

The two clinical phenotypes of gluten enteropathy, coeliac disease (CD) and dermatitis herpetiformis (DH), were characterized for numbers and homing profiles of circulating final effector B cells, plasmablasts, identified as immunoglobulin (Ig)-secreting cells (ISC). In CD, the numbers of ISC were ?50% lower than in DH or controls. ISC expressed peripheral lymph node homing receptor (HR), ...

Immunoglobulin A (IgA), the predominant immunoglobulin class in mucosal secretions, has been found in the cerebrospinal fluid of patients with multiple sclerosis (MS). In this study we examined the infiltration of clonally expanded IgA plasma cells in lesions of MS brains. Sequences of complementarity-determining region 3 of IgA variable heavy chain (V(H)) genes demonstrated the clonal expansion ...

Comparative studies of the N-linked carbohydrate chains of human myeloma proteins of the IgA1 and IgA2 subclasses were performed. The N-linked carbohydrate chains were released by hydrazinolysis from the polypeptide backbone, converted to radioactive oligosaccharides by sodium borotritide reduction after N-acetylation and separated into one neutral and two acidic fractions by paper ...

The serine protease, furin, is involved in the activation of a number of proteins most notably epithelial sodium channels (ENaC). The urea transporter UT-A1, located in the kidney inner medullary collecting duct (IMCD), is important for urine concentrating ability. UT-A1's amino acid sequence has a consensus furin ...

It has been reported that glomerulosclerosis with IgA deposition is likely to be complicated with alcoholic liver cirrhosis. On the other hand, it is said that complications of nephrotic syndrome or rapidly progressive glomerulonephritis (RPGN) are relatively rare. We experienced two patients with alcoholic liver cirrhosis complicated with RPGN syndrome who had obtained favorable outcomes through ...

The emergence of cells that produce IgG and IgA subclass antibodies to Bacteroides gingivalis (Porphyromonas gingivalis) fimbriae and lipopolysaccharide (LPS) antigens was examined in mononuclear cells isolated from inflamed gingiva of different stages (slight, moderate or advanced) of adult periodontitis (AP). Antigen-specific IgM, IgG (including IgG1, IgG2, IgG3 and IgG4) and IgA (including ...

... METALLOGRAPHIC OBSERVATION OF CLEAVED GRAINS IN POLYCRYSTALLINE ... RECENT STUDIES OF CLEAVED GRAIN DENSITIES ...

Human polymorphonuclear leukocytes adhesion to endothelial cells during the early stage of inflammation leads to cell surface externalization of Annexin A1 (AnxA1), an effector of endogenous anti-inflammation. The antiadhesive properties of AnxA1 become operative to finely tune polymorphonuclear leukocytes ...

The hinge region of human immunoglobulin A1 (IgA1), connecting the Fab and Fc regions, is mostly composed of Ser, Thr, and Pro (VPSTPPTPSPSTPPTPSPS); hinge peptide (HP). O-Glycans are naturally attached on only particular five Ser/Thr residues in this region. NMR was employed for analysis of the structural changes ...

Recently published taxonomic studies of viridans streptococci have resulted in several changes in the nomenclature and definition of oral streptococcal species. With this background, the ecology of streptococci in the oropharyngeal cavities was reinvestigated. The results based on the examination of 1426 streptococcal isolates confirmed and extended earlier findings. Apart from mature ...

Using modified ELISA and spot-ELISA, which permit the parallel determination of heavy chain subclass and the presence of covalently linked J chain, we analysed IgA found in cell culture supernatants or secreted by individual cells from peripheral blood, spleen, bone marrow, gingiva and synovial tissue, with respect to its polymeric or monomeric IgA form (pIgA, mIgA) and IgA1 or IgA2 subclass. The ...

Collagenase (matrix metalloproteinase 1) cleaves type I, II, and III collagen helices at a specific site between Gly-Ile or Gly-Leu bonds (residues 775 and 776, P1-P1'). To understand the mechanism of collagen processing, mutations around the cleavage site have been introduced into the cloned murine pro alpha 1(I) collagen (Col1a1) ...

We investigated Toll-like receptors (TLR-3, -4 and -7) expression in circulating mononuclear cells of patients with immunoglobulin A nephropathy (IgAN), a disease with debated relationships with mucosal immunity. TLR-4 expression (detected by fluorescence activated cell sorter) and mRNA transcriptional levels (Taqman) were significantly higher in patients with IgAN than in healthy controls (P = ...

Expression of receptors for IgA (Fc alpha Rs) was investigated on a panel of 35 human B cell lines by labelling with human secretory IgA (0.5 mg/ml) and flow cytometry analysis after staining with fluoresceinated goat anti-human secretory component and/or anti-alpha chain F(ab')2 fragments. Receptors for IgA could be demonstrated on one out of nine Burkitt's lymphoma cell lines, three out of five ...

The binding of 125I-labeled human myeloma immunoglobulin A (IgA) to four type II strains and one nontypable strain of group B streptococci was measured after streptococcal chains were broken by brief sonication. Some IgA binding was observed with all strains, but specific binding (binding that was inhibited by excess unlabeled IgA, was dose dependent, and was saturable) occurred only with those ...

The binding of 125I-labeled human myeloma immunoglobulin A (IgA) to four type II strains and one nontypable strain of group B streptococci was measured after streptococcal chains were broken by brief sonication. Some IgA binding was observed with all strains, but specific binding (binding that was inhibited by excess unlabeled IgA, was dose dependent, and was saturable) occurred only with those ...

The effect of nedocromil sodium (NES) on human immunoglobulin (Ig) isotypes, IgG subclasses and IgA subclasses was studied. NES inhibited IgM and IgA1 production from human lymphoblastoid B-cell lines CBL and GM-1056, respectively, in a dose-dependent fashion. This inhibition was not due to decreased cell growth as cell proliferation was not affected by NES and cell viability was always greater ...

Inflammatory myofibroblastic tumor (IMT) of the lung is a rare condition. Radiological properties and clinical presentation of this disease can mimic malignant process. We present a case of IMT of the lung in a 58year old female patient with a single lung nodule. Tumor was unencapsulated, firm, and well circumscribed. Microscopically tumor had multinodular structure with single or multiple small ...

IgA nephropathy (IgAN) is generally thought to be mediated by the glomerular deposition of circulating immune complexes containing IgA as the major antibody component. Upper respiratory infections and tonsillitis often precede IgAN, and in some cases tonsillectomy is effective for the treatment of IgAN. Thus, the tonsil seems to be a unique organ causing initial and/or progressive events to ...

The discovery of jacalin, a group of lectins from jackfruit seeds (Artocarpus heterophyllus), has attracted considerable attention due to its numerous interesting immunological properties as well as its usefulness in the isolation of various serum proteins. We have further identified a similar lectin from the seeds of Champedak (Artocarpus integer) which we refer to as lectin-C and performed ...

The scarcity of monoclonal human IgE antibodies with specificity for defined allergens is a bottleneck for the molecular characterisation of allergens and their epitopes. Insights into the characteristics of such antibodies may allow for analyses of the molecular basis underlying allergenicity and cross-reactivity, standardisation of allergens as well as improvement of allergy diagnostics and ...

The mechanism of IgA deposition in the kidneys in IgA nephropathy is unknown. Mesangial IgA is of the IgA1 subclass, and since no consistent antigenic target for the IgA1 has been described, we have investigated the glycosylation of the molecule, as a potential non-immunological abnormality which may contribute to its deposition. IgA1 is rich in ...

Serum and stool samples were collected from 128 individuals: 96 diarrhea patients and 32 apparently healthy controls. Stool specimens were cultured for enteric bacterial pathogens, while sera were screened by enzyme-linked immunosorbent assay for Campylobacter jejuni-reactive antibodies. Of 28 diarrhea patients who demonstrated C. jejuni-reactive antibodies (titers, > 100), 14 were culture ...

Porphyromonas gingivalis has been implicated as a causative pathogen in periodontitis. Immunotherapeutic approaches have recently been suggested to aid in the clearance of P. gingivalis from disease sites. Because antibody-Fc receptor (FcR) interactions play a role in the effector functions of polymorphonuclear neutrophils (PMN), we evaluated which FcR on PMN from gingival crevicular fluid (GCF) ...

Presently, several pneumococcal proteins are being evaluated as potential vaccine candidates. Here, we gather novel insights in the immunogenicity of PLY, PsaA, PspA, PspC, NanA, Hyl, PpmA, SlrA, Eno, IgA1-protease, PdBD, BVH-3, SP1003, SP1633, SP1651, SP0189 and SP0376. We developed a multiplex bead-based immunoassay (xMAP(�) Technology, Luminex ...

In this paper, the authors report the use of liquid-liquid partition chromatography (LLPC) in an aqueous polyethylene glycol (PEG)/dextran two-phase system to compare the surface properties (partition properties) of human antibodies and fragments thereof. The surface properties of all the monoclonal antibodies of different classes and subclasses investigated were within the same broad range as ...

In the present study the in vitro binding, internalization and degradation of IgA immune complexes (IC) by phagocytes was studied. As a model for IgA IC, heat-aggregated human secretory IgA (AsIgA) was prepared and resident rat peritoneal macrophages (PM phi) were used as a source of phagocytes. First, binding of 125I-AsIgA to rat PM phi was investigated. Binding of 125I-AsIgA to PM phi at 4 ...

In our previous report [Iwase et al., J. Biochem., 120 (1996) 393], the number of O-linked oligosaccharide chains on the hinge region of IgA1 was estimated by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOFMS). In this experiment, the number of non-substituted N-acetylgalactosamines and Galbeta1,3GalNAc residues, as the core O-linked oligosaccharide ...

Cyanogen bromide cleavage of the deleted heavy (alpha) chain of mouse IgA 47A yielded five peptides, CNBr 1-5, consisting of 34, 50, 28, 70, and 160 residues. A 217-residue NH2-terminal sequence, which comprises the variable region and the first domain of the constant region (CH1), and a 19-residue COOH-terminal sequence of the chain were obtained from the sequences of CNBr 1-4 and the ...

Most patients with common variable immunodeficiency (CVI) have normal numbers of circulating B cells but low concentrations of serum Ig. To determine if the hypogammaglobulinemia is caused by an intrinsic B cell defect, we studied B cell function of 22 CVI patients. Cultured B cells from all CVI patients underwent normal proliferation and synthesized normal quantities of IgE in the presence of ...

A human monoclonal IgA1-IgA2 lambda hybrid molecule was detected in a myeloma patient homozygous for the A2m(1) allotype during a systematic study of monoclonal IgA with subclass-specific monoclonal antibodies (mAb) and the lectin jacalin. This monoclonal immunoglobulin (GAU) reacted with both, although not with all, anti-alpha 1 and anti-alpha 2 mAb. Its ...

Resveratrol (3,4',5-trihydroxy-trans-stilbene), one of secondary metabolites of low molecular weight present in plant, has various important biological effects. It can induce apoptosis in human leukemia cell types in vitro, although the mechanism is not fully understood. In the present study, we demonstrated reduced viability and DNA synthesis, as well as increased proportion of the subdiploid ...

Botulinum toxins (BoNT) are zinc proteases (serotypes A-G) which cause flaccid paralysis through the cleavage of SNARE proteins within motor neurons. BoNT/A was originally organized into two subtypes: BoNT/A1 and BoNT/A2, which are ~ 95 % homologous and possess similar catalytic activities. Subsequently, two additional subtypes were identified; BoNT/A3 ...

Autophagy is associated with luteal cells death during regression of the corpus luteum (CL) in some species. However, the involvement of autophagy or the association between autophagy and apoptosis in CL regression are largely unknown. Therefore, we investigated the role of autophagy in CL regression and its association with apoptosis. Ovaries were obtained from pseudopregnant rats at Days 2 ...

The synthetic Liver X receptor (LXR) activator T0901317 has been reported to exert neuroprotective effect in Alzheimer's disease, but the relationship between LXR activation and beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1) remains uncertain. This study investigated the effect of T0901317 on membrane cholesterol levels, BACE1 expression and activity. We found ...

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Atopy is a persistent, aberrant humoral response to certain classes of proteins (allergens) characterized by the presence of allergen-specific IgE. Yet, in both atopic and non-atopic individuals, allergen-specific responses involving the IgA and IgG subclasses have been observed, which evidence does not support models suggesting inherited differences in sensitivity to certain protein classes. ...

PurposeDeposition of polymeric IgA1 in the kidney mesangium is the hallmark of IgA nephropathy, but the molecular mechanisms of IgA-mediated mesangial responses and inflammatory injuries remain poorly understood. We hypothesize that Toll-like receptor 4 (TLR4) is involved in IgA-induced mesangial cell activation.Materials and MethodsMouse mesangial cells ...

The mucosae and exocrine glands harbour the largest activated B-cell system of the body, amounting to some 80-90% of all immunoglobulin (Ig)-producing cells. The major product of these immunocytes is polymeric (p)IgA (mainly dimers) with associated J chain. Both pIgA and pentameric IgM contain a binding site for the polymeric Ig receptor (pIgR), or secretory component (SC), which is a requirement ...

BackgroundGenital mucosae play a key role in protection from STD and HIV infection, due to their involvement in both horizontal and vertical disease transmission. High variability of published observations concerning IgA isolation and quantification underlies the strong requirement of specific methods able to maximize investigation on HIV-specific IgA.MethodologyGenital fluids from 109 subjects, ...

Allergen immunotherapy (IT) has long-term efficacy in IgE-mediated allergic rhinitis and asthma. IT has been shown to modify lymphocyte responses to allergen, inducing IL-10 production and IgG Abs. In contrast, a putative role for IgA and local TGF-beta-producing cells remains to be determined. In 44 patients with seasonal rhinitis/asthma, serum IgA1, ...

A high prevalence of systemic infections caused by enterobacteria such as Escherichia coli is observed during the neonatal period. Lipopolysaccharide (LPS) is one of the major factors responsible for septic shock caused by these Gram-negative bacteria. We have recently demonstrated the presence of anti-LPS immunoglobulin (Ig)G antibodies in cord blood with a repertoire identical to that found in ...

... Materials that cleave under normal circumstances have been observed to cleave in the same manner during shock comminution. ...

... Accession Number : AD0629482. Title : DISLOCATION STRUCTURES IN CLEAVED MAGNESIUM OXIDE. Descriptive Note : Technical rept.,. ...

The metabolic fate of azimilide in man is unusual as it undergoes a cleavage in vivo resulting in the formation of two classes of structurally distinct metabolites. During a metabolite profiling study conducted in human volunteers to assess the contribution of all pathways to the clearance of (14)C-azimilide, greater than 82% of radioactivity was recovered in urine (49%-58%) and feces (33%). ...

Mitochondrial cytochrome P450 11A1 (CYP11A1 or P450 11A1) is the only known enzyme that cleaves the side chain of cholesterol, yielding pregnenolone, the precursor of all steroid hormones. Pregnenolone is formed via three sequential monooxygenation ...

A technique has been developed for cleaving the mirrors of AlGaAs lasers without cleaving the substrate. Micro-cleaving involves cleaving a suspended heterostructure cantilever by ultrasonic vibrations. Lasers with microcleaved mirrors have threshold currents and quantum efficiencies identical to those of similar ...

alpha 1-Antitrypsin is the best-characterized member of the serpin (serine-proteinase inhibitor) superfamily. Its solution structure was studied by high-flux neutron-scattering and synchrotron X-ray-scattering. Neutron data show that its absorption coefficient A1% 280,1cm is 5.4. The neutron radius of gyration RG at infinite contrast for native alpha ...

A disintegrin and metalloprotease with a thrombospondin type 1 motifs 13 (ADAMTS-13) regulates hemostasis by cleaving the folded A2 domain of von Willebrand factor (VWF). The cleavage is regulated by forces as it occurs in flowing blood. We tested the hypothesis that force-induced A2 domain unfolding facilitates cleavage using atomic force microscopy to pull single VWF ...

The aim of this study was to determine age-related degradation of betaA3/A1-crystallin in human lenses. The betaA3/A1-crystallin fragments were identified by Western blot analysis using two site-specific anti-betaA3/A1-crystallin antibodies. The first antibody was raised against a N-terminal region (residues 35-66), and the second to the C-terminal ...

We have investigated whether the proteolysis of members of the cGMP binding phosphodiesterases (PDE6, PDE5A1, and PDE10A2) by caspase-3 is modulated by the gamma inhibitor subunit of PDE6. We show here that purified caspase-3 proteolyses PDE6, an enzyme composed of two nonidentical catalytic subunits (termed alpha and beta) with molecular mass of 88 and 84 ...

Enterovirus 71 (EV71) infections continue to remain an important public health problem around the world, especially in the Asia-Pacific region. There is a significant mortality rate following such infections, and there is neither any proven therapy nor a vaccine for EV71. This has spurred much fundamental research into the replication of the virus. In this review, we discuss recent work ...

Artesunate (ART), a semi-synthetic derivative of the sesquiterpene artemisinin extracted from the Chinese herb Artemisia annua, exerts a broad spectrum of clinical activity against human cancers. Artemisinin-derivative combination chemotherapy is recommended by WHO since it acts rapidly and is well tolerated and particularly effective. In present investigation, we used CKK-8 assay to assess the ...

Etv5 is a member of the Etv4 subfamily of Ets transcription factors. In female mice, Etv5 was previously shown to be expressed in the mouse ovary. In this work, we show that Etv5-/- female mice are infertile due to a complex reproductive phenotype. Defects in the ovarian tissue architecture were noted as early as 2 weeks of age in Etv5-/- mice. Adult Etv5-/- female mice show decreased ovulation ...

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