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Sample records for bullous pemphigoid antigen

  1. Bullous pemphigoid after radiation therapy

    SciTech Connect

    Duschet, P.; Schwarz, T.; Gschnait, F.

    1988-02-01

    Electron beam therapy applied to a lymph node metastasis from a squamous cell carcinoma was followed by the development of histologically and immunologically typical bullous pemphigoid, the lesions being initially strictly confined to the irradiation area. This observation suggests that the bullous pemphigoid antigen may be altered or unmasked by electron beam radiotherapy, leading subsequently to the production of autoantibodies. The disease in this case effectively responded to the administration of tetracycline and niacinamide, a therapeutic regimen described recently.

  2. Mechanisms of Disease: Pemphigus and Bullous Pemphigoid.

    PubMed

    Hammers, Christoph M; Stanley, John R

    2016-05-23

    Pemphigus and bullous pemphigoid are autoantibody-mediated blistering skin diseases. In pemphigus, keratinocytes in epidermis and mucous membranes lose cell-cell adhesion, and in pemphigoid, the basal keratinocytes lose adhesion to the basement membrane. Pemphigus lesions are mediated directly by the autoantibodies, whereas the autoantibodies in pemphigoid fix complement and mediate inflammation. In both diseases, the autoantigens have been cloned and characterized; pemphigus antigens are desmogleins (cell adhesion molecules in desmosomes), and pemphigoid antigens are found in hemidesmosomes (which mediate adhesion to the basement membrane). This knowledge has enabled diagnostic testing for these diseases by enzyme-linked immunosorbent assays and dissection of various pathophysiological mechanisms, including direct inhibition of cell adhesion, antibody-induced internalization of antigen, and cell signaling. Understanding these mechanisms of disease has led to rational targeted therapeutic strategies. PMID:26907530

  3. Bullous pemphigoid induced by vildagliptin: a report of three cases.

    PubMed

    Béné, Johana; Jacobsoone, Aurélie; Coupe, Patrick; Auffret, Marine; Babai, Samy; Hillaire-Buys, Dominique; Jean-Pastor, Marie-Josèphe; Vonarx, Marlène; Vermersch, Annie; Tronquoy, Anne-Fleur; Gautier, Sophie

    2015-02-01

    To report three cases of bullous pemphigoid in patients treated with vildagliptin. Case 1: An 86-year-old woman presented with bullous pemphigoid after 1 month of treatment with vildagliptin and metformin. After introduction of clobetasol, the symptoms resolved although vildagliptin was continued. However, the skin lesions reappeared 3 months later. Sustained remission was achieved only after definitive withdrawal of vildagliptin. Case 2: A 79-year-old man presented with bullous pemphigoid after 37-month treatment with gliclazide, vildagliptin and metformin. The disease at first responded to clobetasol but 3 months later the lesions reappeared. They finally regressed when the gliptin was discontinued. Case 3: A 77-year-old woman, treated with gliclazide and vildagliptin for 26 months, presented with bullous pemphigoid, which responded well to discontinuation of the gliptin and topical clobetasol. Gliptins are new molecules for treatment of type 2 diabetes mellitus, which have been suspected of implication in bullous pemphigoid. Such cases have been described in the literature (seven with vildagliptin and three with sitagliptin). In nine of these cases, the gliptin was associated with metformin, but the latter had never been considered responsible. The mechanism implicated in the development of bullous pemphigoid has not yet been clearly identified, but may involve a modified immune response or alteration of the antigenic properties of the epidermal basement membrane. These reports support the risk of bullous pemphigoid in patients exposed to gliptins. PMID:24861252

  4. Coexistence of psoriasis with bullous pemphigoid

    PubMed Central

    Rao, Raghavendra; Gupta, Akash; Yunis, Fousiya; Handettu, Sripathi; Chandrashekar, Balachandran

    2012-01-01

    Psoriasis vulgaris and bullous pemphigoid (BP) represent two clinically well-characterized, chronic, inflammatory skin conditions. The concomitant occurrence of these two entities in a patient is rare. Here we report a 57-year-old male suffering from psoriasis vulgaris for 15 years on irregular medication who noticed eruption of blisters all over the body. We believe that this is the first case report of psoriasis vulgaris coexistent with bullous pemphigoid in Indian literature. Please check where you want bullous pemphigoid and where you want psoriasis pemphigoides. PMID:23130285

  5. Advances in understanding and managing bullous pemphigoid

    PubMed Central

    Zhao, Cathy Y.; Murrell, Dedee F.

    2015-01-01

    Bullous pemphigoid (BP) is the commonest subtype of autoimmune blistering disease in most countries of the world. It occurs most frequently in elderly patients and is characterised clinically by large, tense blisters in the skin preceded by urticarial plaques and pruritus. Immunopathologically, it is characterised by autoantibodies directed against the 180 kD antigen (BP180) and the 230 kD antigen (BP230). New knowledge regarding BP is being continually uncovered. This article reviews the recent advances in BP, including newer diagnostic tests, standardised outcome measures and emerging therapeutic options, as well as the evidence supporting their use. PMID:26918143

  6. Frequency of IgA antibodies in pemphigus, bullous pemphigoid and mucous membrane pemphigoid.

    PubMed

    Cozzani, Emanuele; Drosera, Massimo; Parodi, Aurora; Carrozzo, Marco; Gandolfo, Sergio; Rebora, Alfredo

    2004-01-01

    Circulating and bound IgA antibodies can be found in the autoimmune blistering diseases, but their prevalence, clinical relevance and target antigens remain unknown. Thirty-two patients with pemphigus, 73 with bullous pemphigoid and 28 with mucous membrane pemphigoid were studied retrospectively. Direct immunofluorescence (DIF) analysis of IgG, IgA, IgM and C3 was carried out for all cases. Sera were studied by standard indirect immunofluorescence, indirect immunofluorescence on salt-split skin, immunoblotting for bullous pemphigoid and mucous membrane pemphigoid and ELISA for pemphigus. With DIF, we found IgA autoantibodies in 22 of all 133 cases. Circulating IgA antibodies to skin were detected in 2 of 3 IgA-DIF-positive patients with pemphigus, in 3 of 6 with bullous pemphigoid, and in 6 of 13 with mucous membrane pemphigoid. We confirm that the IgA reactivity is more frequently associated with mucous membrane involvement, especially in cases without critical involvement (5/8). The role of IgA and its antigenic specificity in these diseases remain unclear. PMID:15370705

  7. Bullous pemphigoid in infant post vaccination: Myth or reality?

    PubMed

    Neri, Iria; Greco, Antonella; Bassi, Andrea; Orgaz-Molina, Jacinto; Balestri, Riccardo; Oranges, Teresa; Patrizi, Annalisa; de Martino, Maurizio

    2016-06-01

    Bullous pemphigoid is rare in children and even rarer in infants. By presenting two cases of bullous pemphigoid related by their temporal proximity with a previous episode of vaccination, it will be carefully discussed if a relationship is or is not possible. Our final conclusion is that the association is mostly a myth rather than a reality and bullous pemphigoid is not a contraindication to continue with the normal vaccination schedule of infants. It is important to know about this clinical entity in order to perform adequate treatment that avoids any worsening or future relapse of this disease. PMID:26684642

  8. Metronidazole-Induced Bullous Pemphigoid: A Case Report

    PubMed Central

    Moitra, Saibal; Banerjee, Indranil; Sikder, Ayan; Das, Prasanta

    2015-01-01

    Bullous pemphigoid is an autoimmune cutaneous blistering disorder, the exact pathogenesis of which is still not fully elucidated. Drug-induced bullous pemphigoid eruptions are rare but have been reported earlier with the use of frusemide, psoralens, ibuprofen, galantamine hydrobromide, ACE inhibitors like captopril, spironolactone, penicillin, ampicillin, levofloxacin, penicillamine. We hereby report a case of metronidazole induced bullous pemphigoid (BP) in a 52-year-old male patient suffering from liver abscess following 4 days of drug administration. The skin biopsy findings obtained from the patient were consistent with the diagnosis of bullous pemphigoid (BP). Metronidazole was discontinued and symptomatic treatment was offered to the patient. Following withdrawal of metronidazole, the bullae subsided in the next 7-10 days without any significant residual scarring. The causality assessment performed as per the Naranjo algorithm revealed the case to be probable (Naranjo score 7). PMID:26816913

  9. [Infantile bullous pemphigoid developing after hexavalent, meningococcal and pneumococcal vaccinations].

    PubMed

    Valdivielso-Ramos, M; Velázquez, D; Tortoledo, A; Hernanz, J M

    2011-09-01

    Bullous pemphigoid is an acquired autoimmune blistering disorder extremely uncommon in children, characterized by circulating IgG antibodies to antigens of the epidermal basement membrane zone. In general, the clinical course of this condition is good and relapses are rare. The early diagnosis and treatment are fundamental. We present a 3-month-old girl with a blistering eruption on her palms and soles, and urticarial plaques on trunk, and face, 3 weeks after vaccine at two months (hepatitis B, diphtheria, tetanus, pertussis, polio, Haemophilus influenzae B, meningococcal C, pneumococcus). The clinical course worsened with vaccinations at 4 and 6 months. The control of lesions was achieved with oral deflazacort 1 mg/kg/day, with a gradual decrease until 3 months of therapy. The patient is still in remission after 8 months of follow-up. Bullous pemphigoid has been connected with some drugs and vaccinations, 1 day to 4 weeks after receiving immunization. Although the exact mechanism of induction is unclear, this case report has a visible relationship with vaccinations. PMID:21676664

  10. Mutations in the 180-kD bullous pemphigoid antigen (BPAG2), a hemidesmosomal transmembrane collagen (COL17A1), in generalized atrophic benign epidermolysis bullosa.

    PubMed

    McGrath, J A; Gatalica, B; Christiano, A M; Li, K; Owaribe, K; McMillan, J R; Eady, R A; Uitto, J

    1995-09-01

    Junctional epidermolysis bullosa (JEB) is a heterogeneous autosomal recessively inherited blistering skin disorder associated with fragility at the dermal-epidermal junction. Characteristic ultrastructural findings in JEB are abnormalities in the hemidesmosome-anchoring filament complexes. These focal attachment structures, which extend from the intracellular compartment of the basal keratinocytes to the underlying basement membrane, have been shown to be hypoplastic or rudimentary in different forms of JEB. Previously, in different JEB phenotypes, mutations have been found in the three genes for the anchoring filament component laminin 5 (LAMA3, LAMB3, and LAMC2) and in the gene for the hemidesmosome-associated integrin beta 4 subunit. Here, we describe the first mutations in the gene encoding the 180-kD bullous pemphigoid antigen (BPAG2), a transmembranous hemidesmosomal collagen, also known as type XVII collagen (COL17A1). The patient is affected with generalized atrophic benign epidermolysis bullosa (GABEB), a rare variant of JEB, and is a compound heterozygote for premature termination codons on both alleles. These novel findings emphasize the molecular heterogeneity of this group of genodermatoses, and attest to the importance of BPAG2 in maintaining adhesion between the epidermis and the dermis. PMID:7550320

  11. Elevated expression and release of tissue-type, but not urokinase-type, plasminogen activator after binding of autoantibodies to bullous pemphigoid antigen 180 in cultured human keratinocytes

    PubMed Central

    SCHMIDT, E; WEHR, B; TABENGWA, E M; REIMER, S; BRÖCKER, E-B; ZILLIKENS, D

    2004-01-01

    In bullous pemphigoid (BP), the binding of BP180-specific antibodies to their hemidesmosomal target antigen is not sufficient for blister formation, but must be accompanied by the release of proteases. Using plasminogen activator (PA) knock-out mice, the PA system has previously been shown to be a prerequisite for blister formation in experimental murine BP. Here, we found elevated levels of plasmin and tPA, but not of uPA, in blister fluid from BP patients (n = 7) compared to blisters from patients with toxic epidermal necrolysis (n = 4) and suction blisters in healthy controls (n = 7). Subsequently, we addressed the question whether keratinocytes release PA in response to the binding of anti-BP180 antibodies. Treatment of cultured normal human keratinocytes with BP IgG, but not with control IgG, led to both increased protein and mRNA levels of tPA, but not of uPA, as determined by ELISA and RT-PCR, respectively. The specificity of this finding was confirmed using BP180-deficient keratinocytes from a patient with generalized atrophic benign epidermolysis bullosa, where no tPA release was observed after stimulation with BP IgG. Our results show the elevated expression and release of tPA from normal human keratinocytes upon stimulation with antibodies to human BP180. Keratinocytes, by secreting tPA, may thus play an active role in blister formation of BP. PMID:15008985

  12. Diagnosis and classification of pemphigus and bullous pemphigoid.

    PubMed

    Kershenovich, Ruben; Hodak, Emmilia; Mimouni, Daniel

    2014-01-01

    Pemphigus and bullous pemphigoid represent the two major groups of autoimmune blistering diseases. Pemphigus has three major variants: pemphigus vulgaris, pemphigus foliaceus and paraneoplastic pemphigus and is characterized by autoantibodies directed against the cell surface of keratinocytes, producing acantholysis that in turn leads to intraepithelial blisters in the skin and/or mucous membranes. In bullous pemphigoid, the autoantibodies are present at the dermo-epidermal junction and attack the hemidesmosomes, causing subepidermal blister formation. The classification of the major variants of both the pemphigus group and bullous pemphigoid can be based on the combination of clinical, histopathological and immunopathological criteria. Many tools are available for the diagnosis of these entities including biopsy, direct and indirect immunofluorescence, immunoprecipitation, immunoblotting and ELISA. However, currently there are no generally accepted criteria for the diagnosis of these disorders. The present review provides a proposal for diagnostic criteria. PMID:24424192

  13. Diagnosis and clinical severity markers of bullous pemphigoid

    PubMed Central

    Zillikens, Detlef

    2009-01-01

    The use of a broad spectrum of novel detection systems for autoantibodies to the basement membrane proteins BP180 and BP230 has greatly facilitated the diagnosis of bullous pemphigoid, which most likely explains its increasing incidence in central Europe. Because the pathogenic relevance of antibodies to human BP180 has been convincingly shown both in vitro and in vivo, repeated testing for these antibodies appears to be helpful in guiding treatment decisions during the course of the disease. PMID:20948767

  14. Development of bullous pemphigoid after change of dialysis membrane.

    PubMed

    Sodemoto, Kinuyo; Yamahana, Junya; Echigo, Takeshi; Nishijima, Chihiro; Shimada, Yuka; Inaoki, Makoto

    2014-04-01

    A 75-year-old Japanese man presented with pruritic blisters and macules on his trunk and extremities. He had been on hemodialysis for 4 years because of chronic renal failure, and in recent months, a polymethylmethacrylate membrane had been used for dialysis. After a change in dialysis membrane to a cellulose triacetate membrane, pruritic tense blisters developed on the extremities in combination with marked blood eosinophilia. Physical examination showed erythematous macules and tense blisters on the trunk and extremities. A biopsy specimen of an erythematous macule showed subepidermal vesicles and eosinophils that attached to the dermal-epidermal junction. Serum level of eosinophilic cationic protein was elevated. From clinical, histological, and immunological findings, a diagnosis of bullous pemphigoid was made. New blisters continued to erupt during the period in which the patient used the cellulose triacetate membrane dialyzer, and even after the use of clobetasol propionate. It resolved only after the patient came back to the use of a synthetic membrane dialyzer. We discontinued the use of clobetasol propionate, and neither bullous eruptions nor blood eosinophilia recurred. These observations suggest that cellulose membrane may be involved in the development of bullous pemphigoid through activation of eosinophils in the blood and the skin lesion, as in the present case. PMID:24165026

  15. Bullous Pemphigoid With a Dual Pattern of Glomerular Immune Complex Disease.

    PubMed

    Hoorn, Ewout J; Taams, Noor E; Hurskainen, Tiina; Salih, Mahdi; Weening, Jan J; Jonkman, Marcel F; Pas, Hendri H; Schreurs, Marco W J

    2016-02-01

    A 75-year-old man presented with a blistering skin disease and nephrotic syndrome. Bullous pemphigoid was diagnosed by linear immunoglobulin G (IgG) and C3 staining along the basement membrane zone of a skin biopsy specimen and by the presence of circulating IgG recognizing the 180-kDa bullous pemphigoid antigen (BP180; type XVII collagen). A kidney biopsy specimen showed endocapillary inflammation without crescents. Direct immunofluorescence showed strong IgG and C3 staining in a combined granular and linear pattern along the glomerular basement membrane. Electron microscopy showed subepithelial deposits. In serum, no antibodies against the Goodpasture antigen (type IV collagen) or phospholipase A2 receptor were detected. Indirect immunofluorescence studies using the patient's serum showed a strikingly linear but not granular IgG pattern along the epithelial basement membranes of monkey esophagus and kidney. Although type XVII collagen was recently identified in the glomerulus, the patient's serum did not produce a 180-kDa band on immunoblot of kidney tissue and still stained glomeruli of BP180 knockout mice by indirect immunofluorescence. The patient was treated with prednisone and azathioprine, which resulted in complete remission of skin and kidney manifestations. Although bullous pemphigoid has been reported previously in association with anti-glomerular basement membrane disease or membranous nephropathy, this case demonstrates both elements in 1 patient. This concurrence and the linear pattern on indirect immunofluorescence support the possibility of cross-reactive or parallel autoantibodies to basement membranes with a secondary membranous component. PMID:26616334

  16. Bullous pemphigoid. Occurrence in a patient with mycosis fungoides receiving PUVA and topical nitrogen mustard therapy

    SciTech Connect

    Patterson, J.W.; Ali, M.; Murray, J.C.; Hazra, T.A.

    1985-04-01

    A 57-year-old woman with mycosis fungoides developed blisters within cutaneous plaques while receiving PUVA therapy and topical nitrogen mustard. Direct and indirect immunofluorescence studies showed the findings of bullous pemphigoid. Her bullous disease was controlled after cessation of these therapies and institution of prednisone and methotrexate. During the 5 months following completion of a course of electron-beam therapy, she has been free of the cutaneous manifestations of both diseases. Previous instances of PUVA-related pemphigoid have occurred in psoriatics. The role of ultraviolet light in the induction of pemphigoid is discussed, particularly with regard to its possible interaction with the altered skin of psoriasis or mycosis fungoides. Some of the rare cases of bullous mycosis fungoides might actually have represented ultraviolet-unmasked bullous pemphigoid.

  17. Bullous pemphigoid after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Kato, Keisuke; Koike, Kazutoshi; Kobayashi, Chie; Iijima, Shigeruko; Hashimoto, Takashi; Tsuchida, Masahiro

    2015-06-01

    Bullous pemphigoid (BP) is an autoimmune skin disorder characterized by subepidermal blisters due to deposit of autoantibody against dermal basement membrane protein. It has been reported that BP can occur after allogeneic hematopoietic stem cell transplantation (HSCT). We describe a patient with BP having autoantibody against BP180 after unrelated-donor HSCT against T lymphoblastic leukemia. The patient was treated with steroid leading to complete resolution of BP, but T lymphoblastic leukemia progressed rapidly after steroid hormone treatment. Given that immunosuppressant may reduce graft-versus-tumor effect, immunomodulatory agents such as nicotinamide and tetracycline, erythromycin, and immunoglobulin may be appropriate as soon as typical blister lesions are seen after HSCT. PMID:26113316

  18. A case of paraneoplastic bullous pemphigoid in association with squamous cell carcinoma of lung

    PubMed Central

    Das, A; Das, S; Das, SK; Basuthakur, S

    2015-01-01

    Bullous pemphigoid is a chronic, autoimmune, acquired subepidermal blistering disorder. It is idiopathic in origin, and mainly seen in elderly individuals. Association between bullous pemphigoid and internal malignancies is reported in the literature, but the exact causal relation is not established. Paraneoplastic bullous pemphigoid is rarely reported in lung cancers, especially in squamous cell variety. So their presence should raise the suspicion of various internal malignancies including lung cancer. It is presented mainly with tense, large blisters over the erythematous base or over normal skin. Subepidermal blisters with tissue eosinophilia are characteristic histopathological features of bullous pemphigoid. Direct immunofluorescence shows linear deposits of IgG — complement complex along the dermoepidermal junction. Conventional treatment of bullous pemphigoid along with treatment of lung cancer (surgery, chemotherapy, radiotherapy) may result in successful resolution of skin lesions. Here, we report a rare association of paraneoplastic bullous phemphigoid and squamous cell carcinoma of lung in a 76-year-old male to increase the awareness among the clinicians regarding this variety of cutaneous paraneoplastic manifestation of lung cancer. PMID:26119440

  19. Bullous pemphigoid-like skin blistering disease in a rhesus macaque (Macaca mulatta).

    PubMed

    Kim, Jong-Min; Kim, Hyun-Je; Min, Byoung-Hoon; Shin, Jun-Seop; Jeong, Won Young; Lee, Ga Eul; Kim, Min Sun; Kim, Ju Eun; Park, Chung-Gyu

    2016-08-01

    Autoimmune bullous disease is very uncommon in non-human primates. We observed a bullous skin disease in a male rhesus monkey while conducting porcine islet xenotransplantation. Fifty days after the transplantation, multiple bullous skin lesions were observed. There was no mucosal involvement. Skin biopsy results demonstrated a subepidermal blister with no necrotic keratinocytes. Immunofluorescent staining showed linear IgG deposition at the roof of the blister. These skin lesions spontaneously disappeared. Considering these results, this monkey was diagnosed with bullous pemphigoid (BP). As far as we know, this is the first report of BP in non-human primates. PMID:27373989

  20. Evaluation of Recombinant Antigen-Based Assays for Diagnosis of Bullous Autoimmune Diseases

    PubMed Central

    D'Agosto, G.; Latini, A.; Carducci, M.; Mastroianni, A.; Vento, A.; Fei, P. Cordiali

    2004-01-01

    The diagnosis of autoimmune bullous diseases is based on clinical observation and on the presence of autoantibodies directed to molecules involved in the adhesion systems of the skin. Immunofluorescence assays are the currently accepted method for detection of autoantibodies; such assays depend greatly on the skill of operators and are difficult to standardize. Recombinant desmoglein-1 (Dsg1), Dsg3, and BP180 peptides, the main autoantigens in pemphigus or bullous pemphigoid, have been used to develop new quantitative enzyme immunoassays (EIA) for the detection of specific antibodies. The present study was undertaken to evaluate the sensitivity and specificity of these immunoassays and to determine the correlation between the results and the clinical aspects of diseases. Serum samples from patients with pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, or mucous membrane pemphigoid, from healthy individuals, and from patients with unrelated autoimmune conditions were tested. Anti-desmoglein reactivity was detected in all the patients with pemphigus and in none of the controls. Patients with the more benign form of cutaneous disease had anti-Dsg1 antibodies, while patients with deeper cutaneous lesions or with mucosal involvement had anti-Dsg3 reactivity also, or exclusively. The BP180-based assay was positive for 66.6% of patients with bullous pemphigoid and for none of the patients with mucous membrane pemphigoid, and no reactivity was detected in the control sera. In conclusion, the anti-Dsg1 and anti-Dsg3 assays are useful in the diagnosis of pemphigus and provide information on the clinical phenotype of the disease. However, the sensitivity of EIA for detection of autoantibodies in bullous pemphigoid should be improved by the use of additional antigens or epitopes. PMID:15242953

  1. A Case of Orf Disease Complicated with Erythema Multiforme and Bullous Pemphigoid-Like Eruptions

    PubMed Central

    Alian, Shahriar; Ahangarkani, Fatemeh; Arabsheybani, Sara

    2015-01-01

    Parapoxvirus infection in sheep and goats is usually referred to as contagious pustular dermatitis/ecthyma, or orf, and the corresponding human infection is referred to as orf. In humans, after a brief incubation period of 3 to 5 days, lesions begin as pruritic erythematous macules and then rise to form papules, often with a target appearance. Lesions become nodular or vesicular, and orf lesions often ulcerate after 14 to 21 days. Erythema multiforme and bullous pemphigoid have been associated with parapoxvirus infections and they are rare complications of orf disease. In this case report, we presented a 36-year-old woman with history of contact with sheep, developing a typical orf lesion that is complicated with erythema multiforme and bullous pemphigoid-like eruptions. PMID:26294986

  2. A Case of Orf Disease Complicated with Erythema Multiforme and Bullous Pemphigoid-Like Eruptions.

    PubMed

    Alian, Shahriar; Ahangarkani, Fatemeh; Arabsheybani, Sara

    2015-01-01

    Parapoxvirus infection in sheep and goats is usually referred to as contagious pustular dermatitis/ecthyma, or orf, and the corresponding human infection is referred to as orf. In humans, after a brief incubation period of 3 to 5 days, lesions begin as pruritic erythematous macules and then rise to form papules, often with a target appearance. Lesions become nodular or vesicular, and orf lesions often ulcerate after 14 to 21 days. Erythema multiforme and bullous pemphigoid have been associated with parapoxvirus infections and they are rare complications of orf disease. In this case report, we presented a 36-year-old woman with history of contact with sheep, developing a typical orf lesion that is complicated with erythema multiforme and bullous pemphigoid-like eruptions. PMID:26294986

  3. Tissue Factor in Dermatitis Herpetiformis and Bullous Pemphigoid: Link between Immune and Coagulation System in Subepidermal Autoimmune Bullous Diseases

    PubMed Central

    Zebrowska, Agnieszka; Wagrowska-Danilewicz, Malgorzata; Danilewicz, Marian; Wieczfinska, Joanna; Pniewska, Ewa; Zebrowski, Michal; Waszczykowska, Elzbieta; Wozniacka, Anna; Eusebio, Makandjou-Ola; Pietruczuk, Miroslawa; Pawliczak, Rafal

    2015-01-01

    Dermatitis herpetiformis (DH) and bullous pemphigoid (BP) are skin diseases associated with eosinophilic and neutrophilic infiltrations. Although chemokines are critical for the selective accumulation and activation of various leukocyte subsets in the inflammatory process, there are few findings concerning inflammatory cells and production of coagulation factors in blistering diseases. Skin biopsies were taken from 14 patients with DH, 27 with BP, and 20 control subjects. The localization and expression of tissue factor (TF) in skin lesions and perilesional skin were studied by immunohistochemistry and confirmed by Western Blot. Moreover the plasma concentrations of TF were measured by immunoassays. D dimers, fibrinogen, and selected coagulation parameters were measured by routine methods. Expression of TF in the epidermis and in inflammatory influxed cells in dermis was detected in skin biopsies from BP patients. Examined TF expression was detected in perilesional skin of all BP patients too. The expression of TF was not observed in biopsies from healthy people and DH patients. The findings of the study show an increased expression of tissue factor in the lesional and perilesional skin of patients with bullous pemphigoid. The difference in chemokine pattern expression and variations in the cellular infiltration in BP and DH cause variable expression of TF. PMID:27057091

  4. Definitions and outcome measures for bullous pemphigoid: Recommendations by an international panel of experts

    PubMed Central

    Murrell, Dedee F.; Daniel, Benjamin S.; Joly, Pascal; Borradori, Luca; Amagai, Masayuki; Hashimoto, Takashi; Caux, Frédéric; Marinovic, Branka; Sinha, Animesh A.; Hertl, Michael; Bernard, Philippe; Sirois, David; Cianchini, Giuseppe; Fairley, Janet A.; Jonkman, Marcel F.; Pandya, Amit G.; Rubenstein, David; Zillikens, Detlef; Payne, Aimee S.; Woodley, David; Zambruno, Giovanna; Aoki, Valeria; Pincelli, Carlo; Diaz, Luis; Hall, Russell P.; Meurer, Michael; Mascaro, Jose M.; Schmidt, Enno; Shimizu, Hiroshi; Zone, John; Swerlick, Robert; Mimouni, Daniel; Culton, Donna; Lipozencic, Jasna; Bince, Benjamin; Grando, Sergei A.; Bystryn, Jean-Claude; Werth, Victoria P.

    2011-01-01

    Our scientific knowledge of bullous pemphigoid (BP) has dramatically progressed in recent years. However, despite the availability of various therapeutic options for the treatment of inflammatory diseases, only a few multicenter controlled trials have helped to define effective therapies in BP. A major obstacle in sharing multicenter-based evidences for therapeutic efforts is the lack of generally accepted definitions for the clinical evaluation of patients with BP. Common terms and end points of BP are needed so that experts in the field can accurately measure and assess disease extent, activity, severity, and therapeutic response, and thus facilitate and advance clinical trials. These recommendations from the International Pemphigoid Committee represent 2 years of collaborative efforts to attain mutually acceptable common definitions for BP and proposes a disease extent score, the BP Disease Area Index. These items should assist in the development of consistent reporting of outcomes in future BP reports and studies. PMID:22056920

  5. Immunoadsorber for specific apheresis of autoantibodies in the treatment of bullous pemphigoid.

    PubMed

    Mersmann, Michael; Dworschak, Jenny; Ebermann, Kristin; Komorowski, Lars; Schlumberger, Wolfgang; Stöcker, Winfried; Zillikens, Detlef; Probst, Christian; Schmidt, Enno

    2016-01-01

    Bullous pemphigoid (BP) is an autoimmune blistering skin disease associated with autoantibodies against two hemidesmosomal proteins, BP180 (type XVII collagen) and BP230. As the pathogenic relevance of antibodies against the immunodominant NC16A domain of BP180 has been clearly demonstrated, specific removal of these antibodies should be a rational therapeutic approach. Here, we evaluated three recombinant forms of bacterially produced BP180 NC16A, a monomer, trimer, and tetramer, together with different matrices for their efficacy to specifically adsorb autoantibodies from BP plasma samples. An adsorber consisting of NC16A-trimer coupled to NHS-activated Sepharose 4 Fast Flow revealed satisfying adsorption rates and a high specificity. The NC16A-trimer adsorber was regenerable and autoclavable. It has the potential to be used for specific immunoadsorption to treat severe and refractory BP and other pemphigoid diseases associated with BP180 NC16A reactivity. PMID:26498290

  6. [Characterization of lymphocytic infiltrate cells in bullous pemphigoid and pemphigus vulgaris].

    PubMed

    Schaller, J; Niedecken, H W; Biwer, E; Stefan, J A; Kreysel, H W; Haustein, U F

    1990-01-01

    By means of monoclonal antibodies (mab) and alkaline phosphatase anti-alkaline-phosphatase (APAAP) technique, the distribution and characteristics of lymphocytic infiltrates were studied in biopsies from 15 patients with bullous pemphigoid (b.P.) and 5 patients with pemphigus vulgaris (P.v.). The biopsies were obtained from freshly developed blisters along with perilesional tissue. The lymphocytic infiltrates in b.P. as well as in P.v. were located in the area of the fresh lesions and consisted almost exclusively of T cells (CD3 positive lymphocytes). In b.P., the discrepancy between a decreased number of CD2 positive lymphocytes (10-20%) and markedly higher number of CD3 staining cells (50-60% of all infiltrate cells) was striking. The characterization of the T cell subpopulations in both dermatoses showed mainly T helper cell infiltrates (CD4), while only up to 10% of T suppressor cells (CD8) were detected. CD45R positive (CD4+/CD45R+: suppression inducing) as well as CD29-positive (CD4+CD29+: cells which provide help for antibody production) T-cell subpopulations were detected in both dermatoses particularly adjacent to blister in up to 10% of the cell infiltrates. Epidermal staining with CD29 mab in b.P. up to the stratum spinosum and in P.v. within intraepidermal blisters was detected. By means of CD19 and CD21 mab B lymphocytes were minimal. Perivascular individual cell staining occurred with CD7 CD16, CD56 and CD57 mab (K/NK cells) in b.P. as well as in P.v. patients. The predominance in T cell infiltrates, particularly T helper cells, suggests the role of cellular immune mechanism in the pathogenesis of these diseases, in b.P. the CD2 antigen (SE receptor) appears to be of particular importance. PMID:2083606

  7. Immunohistochemical study of toll-like receptors 2, 4, and 9 expressions in pemphigus and bullous pemphigoid lesions.

    PubMed

    Sun, Xiu-Kun; Chen, Jun-Fan; Shen, Hong

    2016-08-01

    Pemphigus and bullous pemphigoid (BP) are severe autoimmune skin diseases. Whether innate immunity could be a trigger or a part of the pathogeneses is unknown. Toll-like receptors (TLRs) are important components of the innate immune system, with no previous evaluation of TLRs in autoimmune bullous diseases. This work aims to investigate TLRs 2, 4, and 9 expressions in pemphigus and bullous pemphigoid. Thirty-six patients with pemphigus vulgaris (PV), pemphigus foliaceus (PF), bullous pemphigoid (BP), and six healthy controls were studied. Skin biopsies from the patients and the controls were examined immunohistochemically for TLR2, 4, and 9 expressions. The TLR4 expressed mainly at the basal layer of epidermis in controls, but in the cases with autoimmune bullous diseases, TLR4 staining located at basal layer and suprabasal layer, even superficial layer of epidermis. The immunostaining-intensity-distribution (IID) index of TLR4 in patients with PF (13.83, P = 0.001), PV (13.08, P = 0.003), and BP (11.42, P = 0.042) were significantly higher than that of the controls (6.17). TLR2 and TLR9 showed no significantly changes at epidermal expression (P > 0.05) compared with controls. There was no correlation found between the expressions of these TLRs. This work, thus, shows a re-localization of TLR4 expression sites with increased expression in pemphigus and bullous pemphigoid lesions. Targeting TLR4 signaling is expected to be a novel treatment strategy for autoimmune bullous diseases. PMID:27221282

  8. Herpes simplex encephalitis without cerebrospinal fluid pleocytosis in a patient with bullous pemphigoid: a case report.

    PubMed

    Nakamura, Yoshitsugu; Kakiuti, Kensuke; Tani, Hiroki; Nakajima, Hideto; Kimura, Fumiharu; Hanafusa, Toshiaki

    2016-06-22

    A 78-year-old woman was diagnosed with bullous pemphigoid 2 months ago, and she had been treated with steroid and plasmapheresis. She developed sudden fever, vomiting, disorientation, and abnormal behavior. Diffusion weighted images and fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) images showed high-intensity signals in the right temporal lobe hippocampus and right insular cortex. Cerebrospinal fluid (CSF) examination showed normal cell count (4/mm(3)), but was positive for HSV1-DNA by PCR. She was diagnosed with herpes simplex encephalitis (HSE), and acyclovir was started on the first day of admission. She had complete recovery, and was discharged. She didn't show CSF pleocytosis throughout her course of HSE. No CSF pleocytosis could be due probably to her immunosuppressed state under the steroid therapy for bullous pemphigoid. Because the morbidity and mortality of HSE is drastically reduced by early antiviral treatment, it is important to accelerate the diagnosis and treatment of HSE, especially in immunosuppressed or immunocompromised hosts. PMID:27247185

  9. Development of bullous pemphigoid during treatment of psoriatic onycho-pachydermo periostitis with ustekinumab.

    PubMed

    Nakayama, Chihiro; Fujita, Yasuyuki; Watanabe, Mika; Shimizu, Hiroshi

    2015-10-01

    Ustekinumab is a human monoclonal antibody that specifically binds to the p40 subunit of interleukin (IL)-12 and IL-23, inhibiting the activity of both cytokines, thereby blocking the T-helper (Th)1 and Th17 inflammatory pathways. While biologic agents have dramatically changed the strategies of psoriasis treatment, increasing cases of autoimmune diseases during the use of such agents have been reported. We experienced a case of bullous pemphigoid occurring during treatment of a rare variant of psoriatic arthritis, psoriatic onycho-pachydermo periostitis with ustekinumab. Only six cases of autoimmune blistering diseases during treatment with biologic agents have ever been reported including our case, and we herein review the published work of these cases. Dermatologists must be attentive to the possibility of autoimmune blistering diseases during ustekinumab treatment. PMID:26010891

  10. Aberrant Expression and Secretion of Heat Shock Protein 90 in Patients with Bullous Pemphigoid

    PubMed Central

    Tukaj, Stefan; Kleszczyński, Konrad; Vafia, Katerina; Groth, Stephanie; Meyersburg, Damian; Trzonkowski, Piotr; Ludwig, Ralf J.; Zillikens, Detlef; Schmidt, Enno; Fischer, Tobias W.; Kasperkiewicz, Michael

    2013-01-01

    The cell stress chaperone heat shock protein 90 (Hsp90) has been implicated in inflammatory responses and its inhibition has proven successful in different mouse models of autoimmune diseases, including epidermolysis bullosa acquisita. Here, we investigated expression levels and secretory responses of Hsp90 in patients with bullous pemphigoid (BP), the most common subepidermal autoimmune blistering skin disease. In comparison to healthy controls, the following observations were made: (i) Hsp90 was highly expressed in the skin of BP patients, whereas its serum levels were decreased and inversely associated with IgG autoantibody levels against the NC16A immunodominant region of the BP180 autoantigen, (ii) in contrast, neither aberrant levels of circulating Hsp90 nor any correlation of this protein with serum autoantibodies was found in a control cohort of autoimmune bullous disease patients with pemphigus vulgaris, (iii) Hsp90 was highly expressed in and restrictedly released from peripheral blood mononuclear cells of BP patients, and (iv) Hsp90 was potently induced in and restrictedly secreted from human keratinocyte (HaCaT) cells by BP serum and isolated anti-BP180 NC16A IgG autoantibodies, respectively. Our results reveal an upregulated Hsp90 expression at the site of inflammation and an autoantibody-mediated dysregulation of the intracellular and extracellular distribution of this chaperone in BP patients. These findings suggest that Hsp90 may play a pathophysiological role and represent a novel potential treatment target in BP. PMID:23936217

  11. Bullous Pemphigoid

    MedlinePlus

    ... Sections of the JAOCD JAOCD Archive Published Members Online Dermatology Journals Edit This Favorite Name: Category: Share: Yes ... 2/2017 2017 AOCD Spring Current Concepts in Dermatology Meeting more Latest News ... Surveys About AOCD The AOCD was recognized in ...

  12. Exploring mechanisms of IgE-mediated autoimmunity through the lens of bullous pemphigoid.

    PubMed

    Messingham, Kelly N; Randall, Grant; Fairley, Janet

    2016-04-01

    Bullous pemphigoid (BP) is the most common autoimmune blistering disease characterized by pathogenic autoantibodies targeting collagen XVII (col XVII), a hemidesmosomal adhesion molecule. Early studies utilizing IgG were critical for establishing col XVII-specific antibodies as primary mediators of blister formation; however, these studies lacked key features of the disease, including urticarial erythema and eosinophilic infiltration, which are often associated with IgE. Although it was recognized that BP patients often had elevated circulating IgE, investigations into the pathogenicity of these antibodies was delayed until discovery of col XVII-specific IgE in BP sera. Since then, a variety of in-vivo and in-vitro studies have provided clear evidence that IgE autoantibodies are a key component of BP. Furthermore, studies utilizing IgE receptor blockade in BP patients were the first to confirm a pathogenic role of IgE autoantibodies in human autoimmunity. In this review we will utilize BP as a prototypical autoimmune disease to better understand how IgE autoantibodies participate in human autoimmunity. PMID:26959553

  13. A 14-year paraneoplastic rash: urticarial vasculitis and dermal binding bullous pemphigoid secondary to chronic lymphocytic leukaemia.

    PubMed

    Kassim, J M; Igali, L; Levell, N J

    2015-06-01

    A 72-year-old woman with a 14-year history of urticarial vasculitis (UV) and a 13-year history of bullous pemphigoid (BP) presented with associated progressive chronic lymphocytic leukaemia (CLL). Both skin conditions responded poorly to treatment, until chemotherapy for CLL was commenced. The skin features showed a clear paraneoplastic course, resolving with chemotherapy and recurring when the CLL relapsed and the lymphocyte count rose above 5 × 10(9)/L. No case of UV secondary to CLL, and very few cases of BP related to CLL have been reported, and no paraneoplastic rash of any type lasting 14 years has been reported previously. PMID:25524180

  14. Evaluation of ELISA testing for BP180 and BP230 as a diagnostic modality for bullous pemphigoid: a clinical experience.

    PubMed

    Keller, Jesse J; Kittridge, Ashley L; Debanne, Sara M; Korman, Neil J

    2016-05-01

    Bullous pemphigoid (BP) is a common autoimmune blistering disorder of the elderly. Several diagnostic modalities are available, including clinical impression, histopathology, direct and indirect immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) detection of pathogenic antibodies. In this study, we aim to examine the utility of the newest test, ELISA, in comparison to the constellation of other tests. We describe our clinical experience in which 170 patients diagnosed with bullous pemphigoid had multiple tests performed. BP180 alone showed a sensitivity of 54 % and specificity of 94 %. The positive predictive value (PPV) is 95 % while the negative predictive value (NPV) is 52 %. BP230 alone yielded a sensitivity of 48 % and specificity of 94 %. The PPV is 94 % and the NPV is 49 %. Using both tests in combination yielded a sensitivity of 66 % and specificity of 89 %. The PPV of at least one of two tests returning positive is 92 % while the NPV of dual negative tests is 58 %. Use of ELISAs for suspected cases of BP are an inadequate standalone test, and are only helpful in making the diagnosis should they return positive. However, they would appear to miss about one-third of cases. PMID:26895534

  15. Bullous pemphigoid and neurodegenerative diseases: a study in a setting of a Central European university dermatology department.

    PubMed

    Pietkiewicz, Paweł; Gornowicz-Porowska, Justyna; Bowszyc-Dmochowska, Monika; Bartkiewicz, Paweł; Dmochowski, Marian

    2016-08-01

    Bullous pemphigoid (BP) is an autoimmune blistering dermatosis of the elderly mediated by IgG and IgE antibodies to skin hemidesmosomal proteins, BP180 and/or BP230, that occur physiologically also in neuronal tissue. It was reported that BP is associated with neurodegenerative diseases (ND). We performed a retrospective study in a setting of a Central European university dermatology department on prevalence of ND in 94 BP patients. 26 out of 94 BP patients had at least one ND. ND included: Parkinson's disease, dementia, stroke, hear loss, tinnitus, blindness, vertigo, neurosyphilis, systemic sclerosis, and epilepsy. Since population aging is conceivably responsible for the rising number of BP cases as a result of immunosenescence-related phenomena, the plausible BP-specific immunopathogenetic relationship between BP and ND deserves to be further experimentally explored. PMID:26420424

  16. Current practice in treatment approach for bullous pemphigoid: comparison between national surveys from the Netherlands and the UK.

    PubMed

    Meijer, J M; Jonkman, M F; Wojnarowska, F; Wiliams, H C; Kirtschig, G

    2016-07-01

    Treatment approaches for bullous pemphigoid (BP), the most common autoimmune skin blistering disease, are largely based on national and international guidelines. We conducted a national survey among dermatologists in the Netherlands to explore the current treatment of BP, and compared the results with those of a previously published survey from the UK. Almost all responders in the Netherlands (n = 175) used very potent topical corticosteroids, both as monotherapy and as adjunctive therapy. In contrast to UK dermatologists, the majority recommended whole-body application rather than local application to lesions. Systemic antibiotics were used by > 70% of responders. Half of the responders in the Netherlands considered systemic steroids the first-choice treatment, with the majority also using adjunctive therapy as a routine. Despite many similarities in treatment approach between the two countries, these surveys provide an important insight into the gap between actual and recommended practice at a country level in relation to the best external evidence. PMID:26940484

  17. Possible paraneoplastic syndrome case of bullous pemphigoid with immunoglobulin G anti-BP180 C-terminal domain antibodies associated with psoriasis and primary macroglobulinemia.

    PubMed

    Maki, Nobuki; Demitsu, Toshio; Umemoto, Naoka; Nagashima, Kazutaka; Nakamura, Toshinobu; Kakurai, Maki; Nakamura, Satoshi; Yamada, Tomoko; Ishii, Norito; Hashimoto, Takashi

    2016-05-01

    A 61-year-old Japanese man developed bullous skin lesions during topical therapy for psoriasis vulgaris. Physical examination demonstrated numerous tense bullae and scaly erythemas on the trunk and extremities. Histopathology of the skin biopsy demonstrated subepidermal bullae and lymphocytic infiltration with eosinophils in the dermis. Direct immunofluorescence revealed linear deposits of immunoglobulin (Ig)G, IgA and C3 along the basement membrane zone. Indirect immunofluorescence of 1 mol/L NaCl-split skin showed IgG reactivity with both epidermal and the dermal sides. IgM reactivity with both the epidermal and dermal sides was also detected. Enzyme-linked immunosorbent assays showed negative results for both BP180 and BP230. Immunoelectrophoresis of serum and bone marrow aspiration revealed underlying primary macroglobulinemia with M-proteinemia of IgM-κ type. Immunoblot analysis revealed IgG, but not IgM, antibodies to recombinant protein of BP180 C-terminal domain. We diagnosed the present case as bullous pemphigoid with IgG anti-BP180 C-terminal domain autoantibodies associated with primary macroglobulinemia and psoriasis vulgaris. Systemic administration of prednisolone 30 mg/day resulted in dramatic improvement of both bullous and psoriatic skin lesions. When the bullous and psoriatic lesions relapsed, DRC chemotherapy (dexamethasone, rituximab and cyclophosphamide) for macroglobulinemia was performed. Then, the psoriatic lesions improved and the bullous lesions disappeared. We suggested that the present case may be paraneoplastic syndrome of bullous pemphigoid associated with primary macroglobulinemia and psoriasis vulgaris. PMID:26507447

  18. 92-kD gelatinase is produced by eosinophils at the site of blister formation in bullous pemphigoid and cleaves the extracellular domain of recombinant 180-kD bullous pemphigoid autoantigen.

    PubMed Central

    Ståhle-Bäckdahl, M; Inoue, M; Guidice, G J; Parks, W C

    1994-01-01

    Eosinophils are prominent in bullous pemphigoid (BP), and proteases secreted from these and other inflammatory cells may induce disruption of the basement membrane. We used in situ hybridization and immunohistochemistry to localize the sites of 92-kD gelatinase expression in BP lesions. In all samples (20/20), a strong signal for gelatinase mRNA was detected only in eosinophils and was most pronounced where these cells accumulated at the floor of forming blisters. No other cells were positive for enzyme mRNA. Both eosinophils and neutrophils, however, contained immunoreactive 92-kD gelatinase indicating that active expression occurred only in eosinophils. Degranulated eosinophils were also seen near blisters, and as demonstrated by gelatin zymography, immunoblotting, and ELISA, 92-kD gelatinase protein was prominent in BP blister fluid. No other gelatinolytic activity was specifically detected in BP fluid, and only small amounts of 92-kD gelatinase were present in suction blister fluids. As demonstrated in vitro, 92-kD gelatinase cleaved the extracellular, collagenous domain of recombinant 180-kD BP autoantigen (BP180, BPAG2, HD4, type XVII collagen), a transmembrane molecule of the epidermal hemidesmosome. Our results suggest that production and release 92-kD gelatinase by eosinophils contributes significantly to tissue damage in BP. Images PMID:8182134

  19. Subepidermal Blistering Induced by Human Autoantibodies to BP180 Requires Innate Immune Players in a Humanized Bullous Pemphigoid Mouse Model

    PubMed Central

    Liu, Zhi; Sui, Wen; Zhao, Minglang; Li, Zhuowei; Li, Ning; Thresher, Randy; Giudice, George J.; Fairley, Janet A.; Sitaru, Cassian; Zillikens, Detlef; Ning, Gang; Marinkovich, Peter; Diaz, Luis A.

    2008-01-01

    Bullous pemphigoid (BP) is a cutaneous autoimmune inflammatory disease associated with subepidermal blistering and autoantibodies against BP180, a transmembrane collagen and major component of the hemidesmosome. Numerous inflammatory cells infiltrate the upper dermis in BP. IgG autoantibodies in BP fix complement and target multiple BP180 epitopes that are highly clustered within a non-collagen linker domain, termed NC16A. Anti-BP180 antibodies induce BP in mice. In this study, we generated a humanized mouse strain, in which the murine BP180NC14A is replaced with the homologous human BP180NC16A epitope cluster region. We show that the humanized NC16A (NC16A+/+) mice injected with anti-BP180NC16A autoantibodies develop BP-like subepidermal blisters. The F(ab′)2 fragments of pathogenic IgG fail to activate complement cascade and are no longer pathogenic. The NC16A+/+ mice pretreated with mast cell activation blocker or depleting of complement or neutrophils become resistant to BP. These findings suggest that the humoral response in BP critically depends on innate immune system players. PMID:18922680

  20. Epitope-Dependent Pathogenicity of Antibodies Targeting a Major Bullous Pemphigoid Autoantigen Collagen XVII/BP180.

    PubMed

    Wada, Mayumi; Nishie, Wataru; Ujiie, Hideyuki; Izumi, Kentaro; Iwata, Hiroaki; Natsuga, Ken; Nakamura, Hideki; Kitagawa, Yoshimasa; Shimizu, Hiroshi

    2016-05-01

    In bullous pemphigoid, the common autoimmune blistering disorder, IgG autoantibodies target various epitopes on hemidesmosomal transmembrane collagen XVII (COL17)/BP180. Antibodies (Abs) targeting the extracellular noncollagenous 16th A domain of COL17 may be pathogenic; however, the pathogenic roles of Abs targeting non-noncollagenous 16th A regions are poorly understood. In this study using a pathogenic and a nonpathogenic monoclonal antibody (mAb) targeting the noncollagenous 16th A domain (mAb TS39-3) and the C-terminus domain (mAb C17-C1), respectively, we show that endocytosis of immune complexes after binding of Abs to cell surface COL17 is a key phenomenon that induces skin fragility. Passive transfer of IgG1 mouse mAb TS39-3 but not mAb C17-C1 induces dermal-epidermal separation in neonatal human COL17-expressing transgenic mice. Interestingly, mAb C17-C1 strongly binds with the dermal-epidermal junction of the recipient mice skin, suggesting that binding of Abs with COL17 is insufficient to induce skin fragility. In cultured normal human epidermal keratinocytes treated with these mAbs, mAb TS39-3 but not mAb C17-C1 internalizes immune complexes after binding with cell surface COL17 via macropinocytosis, resulting in reduced COL17 expression. This study shows that pathogenicity of Abs targeting COL17 is epitope dependent, which is associated with macropinocytosis-mediated endocytosis of immune complexes and finally results in the depletion of COL17 expression in basal keratinocytes. PMID:26827765

  1. Human Eosinophils Express the High Affinity IgE Receptor, FcεRI, in Bullous Pemphigoid

    PubMed Central

    Messingham, Kelly N.; Holahan, Heather M.; Frydman, Alexandra S.; Fullenkamp, Colleen; Srikantha, Rupasree; Fairley, Janet A.

    2014-01-01

    Bullous pemphigoid (BP) is an autoimmune blistering disease mediated by autoantibodies targeting BP180 (type XVII collagen). Patient sera and tissues typically have IgG and IgE autoantibodies and elevated eosinophil numbers. Although the pathogenicity of the IgE autoantibodies is established in BP, their contribution to the disease process is not well understood. Our aims were two-fold: 1) To establish the clinical relationships between total and BP180-specific IgE, eosinophilia and other markers of disease activity; and 2) To determine if eosinophils from BP patients express the high affinity IgE receptor, FcεRI, as a potential mechanism of action for IgE in BP. Our analysis of 48 untreated BP patients revealed a correlation between BP180 IgG and both BP180 IgE and peripheral eosinophil count. Additionally, we established a correlation between total IgE concentration and both BP180 IgE levels and eosinophil count. When only sera from patients (n = 16) with total IgE≥400 IU/ml were analyzed, BP180 IgG levels correlated with disease severity, BP230 IgG, total circulating IgE and BP180 IgE. Finally, peripheral eosinophil count correlated more strongly with levels of BP180 IgE then with BP180 IgG. Next, eosinophil FcεRI expression was investigated in the blood and skin using several methods. Peripheral eosinophils from BP patients expressed mRNA for all three chains (α, β and γ) of the FcεRI. Surface expression of the FcεRIα was confirmed on both peripheral and tissue eosinophils from most BP patients by immunostaining. Furthermore, using a proximity ligation assay, interaction of the α- and β-chains of the FcεRI was observed in some biopsy specimens, suggesting tissue expression of the trimeric receptor form in some patients. These studies provide clinical support for the relevance of IgE in BP disease and provide one mechanism of action of these antibodies, via binding to the FcεRI on eosinophils. PMID:25255430

  2. Human eosinophils express the high affinity IgE receptor, FcεRI, in bullous pemphigoid.

    PubMed

    Messingham, Kelly N; Holahan, Heather M; Frydman, Alexandra S; Fullenkamp, Colleen; Srikantha, Rupasree; Fairley, Janet A

    2014-01-01

    Bullous pemphigoid (BP) is an autoimmune blistering disease mediated by autoantibodies targeting BP180 (type XVII collagen). Patient sera and tissues typically have IgG and IgE autoantibodies and elevated eosinophil numbers. Although the pathogenicity of the IgE autoantibodies is established in BP, their contribution to the disease process is not well understood. Our aims were two-fold: 1) To establish the clinical relationships between total and BP180-specific IgE, eosinophilia and other markers of disease activity; and 2) To determine if eosinophils from BP patients express the high affinity IgE receptor, FcεRI, as a potential mechanism of action for IgE in BP. Our analysis of 48 untreated BP patients revealed a correlation between BP180 IgG and both BP180 IgE and peripheral eosinophil count. Additionally, we established a correlation between total IgE concentration and both BP180 IgE levels and eosinophil count. When only sera from patients (n = 16) with total IgE ≥ 400 IU/ml were analyzed, BP180 IgG levels correlated with disease severity, BP230 IgG, total circulating IgE and BP180 IgE. Finally, peripheral eosinophil count correlated more strongly with levels of BP180 IgE then with BP180 IgG. Next, eosinophil FcεRI expression was investigated in the blood and skin using several methods. Peripheral eosinophils from BP patients expressed mRNA for all three chains (α, β and γ) of the FcεRI. Surface expression of the FcεRIα was confirmed on both peripheral and tissue eosinophils from most BP patients by immunostaining. Furthermore, using a proximity ligation assay, interaction of the α- and β-chains of the FcεRI was observed in some biopsy specimens, suggesting tissue expression of the trimeric receptor form in some patients. These studies provide clinical support for the relevance of IgE in BP disease and provide one mechanism of action of these antibodies, via binding to the FcεRI on eosinophils. PMID:25255430

  3. Integrating longitudinal serum IL-17 and IL-23 follow-up, along with autoantibodies variation, contributes to predict bullous pemphigoid outcome.

    PubMed

    Plée, Julie; Le Jan, Sébastien; Giustiniani, Jérôme; Barbe, Coralie; Joly, Pascal; Bedane, Christophe; Vabres, Pierre; Truchetet, François; Aubin, François; Antonicelli, Frank; Bernard, Philippe

    2015-01-01

    Bullous pemphigoid (BP) is an inflammatory autoimmune bullous disease involving cytokines and proteases in the process of blister formation. Recently, IL-17 and IL-23 were evidenced in lesional skin and serum of BP patients at time of diagnosis, but their involvement in disease outcome has still not been investigated yet. We then analysed IL-17 and IL-23 serum levels during the first months of follow-up upon treatment. Compared with age- and sex- matched controls, high levels of IL-23 were observed at baseline in BP patients serum (P < 0.01), while IL-17 levels was not. However, some BP patients expressed high IL-17 serum level, independently of disease severity. In these patients, those with ongoing remission reduced IL-17 concentration upon treatment (P < 0.001), whereas IL-17 level remained elevated in patients who relapsed. Meanwhile, IL-23 serum levels increased during the first month of treatment in BP patients who later relapsed (P < 0.01) and MMP-9 serum level was not controlled. Accordingly, we found that both IL-17 and IL-23 increased MMP-9 secretion from leukocytes in-vitro. Then, we showed that elevated IL-17/IL-23 serum concentrations helped to discriminate BP patients who later relapsed. Such uncontrolled inflammatory response raises the question whether these molecules could become biological target for BP patients resistant to steroid treatment. PMID:26656739

  4. Integrating longitudinal serum IL-17 and IL-23 follow-up, along with autoantibodies variation, contributes to predict bullous pemphigoid outcome

    PubMed Central

    Plée, Julie; Le Jan, Sébastien; Giustiniani, Jérôme; Barbe, Coralie; Joly, Pascal; Bedane, Christophe; Vabres, Pierre; Truchetet, François; Aubin, François; Antonicelli, Frank; Bernard, Philippe

    2015-01-01

    Bullous pemphigoid (BP) is an inflammatory autoimmune bullous disease involving cytokines and proteases in the process of blister formation. Recently, IL-17 and IL-23 were evidenced in lesional skin and serum of BP patients at time of diagnosis, but their involvement in disease outcome has still not been investigated yet. We then analysed IL-17 and IL-23 serum levels during the first months of follow-up upon treatment. Compared with age- and sex- matched controls, high levels of IL-23 were observed at baseline in BP patients serum (P < 0.01), while IL-17 levels was not. However, some BP patients expressed high IL-17 serum level, independently of disease severity. In these patients, those with ongoing remission reduced IL-17 concentration upon treatment (P < 0.001), whereas IL-17 level remained elevated in patients who relapsed. Meanwhile, IL-23 serum levels increased during the first month of treatment in BP patients who later relapsed (P < 0.01) and MMP-9 serum level was not controlled. Accordingly, we found that both IL-17 and IL-23 increased MMP-9 secretion from leukocytes in-vitro. Then, we showed that elevated IL-17/IL-23 serum concentrations helped to discriminate BP patients who later relapsed. Such uncontrolled inflammatory response raises the question whether these molecules could become biological target for BP patients resistant to steroid treatment. PMID:26656739

  5. Juvenile pemphigoid nodularis: Report of a rare case

    PubMed Central

    Das, Dipti; Bandyopadhyay, Debabrata

    2014-01-01

    Bullous pemphigoid is an autoimmune blistering disease that is rare in childhood. Pemphigoid nodularis is a variant of BP that is exceedingly rare in children. Pemphigoid nodularis is characterized by overlapping clinical features of both prurigo nodularis and BP. We report here a case of pemphigoid nodularis in an 11-year-old boy. PMID:24860760

  6. Bullous pemphigoid, an autoantibody-mediated disease, is a novel immune-related adverse event in patients treated with anti-programmed cell death 1 antibodies.

    PubMed

    Hwang, Shelley J E; Carlos, Giuliana; Chou, Shaun; Wakade, Deepal; Carlino, Matteo S; Fernandez-Penas, Pablo

    2016-08-01

    Anti-programmed cell death 1 (anti-PD1) antibodies such as pembrolizumab have shown improved progression-free and overall survival in patients with advanced melanoma. Of 124 patients reviewed in Westmead Hospital from May 2012 to November 2015, treated with pembrolizumab for advanced melanoma, we encountered three cases of bullous pemphigoid (BP). We have previously reported a case of BP. In two recent cases, BP was diagnosed early and treated promptly with potent topical or oral steroid. Patients on anti-PD1 antibodies are at a higher risk of developing cutaneous immune-related adverse events such as lichenoid reactions, eczema and vitiligo. No cases of BP were encountered in the previously published cohort of 260 melanoma patients treated with BRAF inhibitors; as such, it appears that BP is associated with anti-PD1 treatment rather than metastatic melanoma. BP appears to be another immune-related adverse event, and clinicians should have a low threshold for performing cutaneous biopsies and immunofluorescence studies in patients on anti-PD1 therapies. PMID:27031539

  7. Eosinophil localization to the basement membrane zone is autoantibody- and complement-dependent in a human cryosection model of bullous pemphigoid.

    PubMed

    Messingham, Kelly N; Wang, Jeffrey W; Holahan, Heather M; Srikantha, Rupasree; Aust, Samantha C; Fairley, Janet A

    2016-01-01

    Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by antibodies (IgG and IgE) targeting cell-substrate adhesion proteins. A variety of BP models suggest that autoantibody-dependent neutrophil degranulation is essential for blister formation. However, lesional biopsies reveal a predominance of eosinophils and few neutrophils. Our goal was to evaluate the role of antibodies and complement in eosinophil localization, degranulation and split formation at the dermo-epidermal junction (DEJ) utilizing a human skin cryosection model of BP paired with a human eosinophilic cell line, 15HL-60. Expression of receptors for IgG (FcγRII), IgE (FcεRI) and complement (CR1 and CR3) was confirmed on 15HL-60 cells using flow cytometry. 15HL-60 expression of granule protein [eosinophil derived neurotoxin (EDN) and eosinophil peroxidase (EPO)] mRNA and their degranulation in vitro was confirmed using RT-PCR and ELISA, respectively. For cryosection experiments, BP or control sera or IgG and IgE antibodies purified from BP sera were utilized in combination with 15HL-60 cells ± fresh complement. Both BP serum and fresh complement were required for localization of 15-HL60 cells to the DEJ. Interestingly, eosinophil localization to the DEJ was dependent on IgG, but not IgE, and complement. However, no subepidermal split was observed. Additionally, the 15HL-60 cells did not degranulate under any experimental conditions and direct application of cell lysate to cryosections did not result in a split. Our observation that eosinophil localization to the DEJ is dependent on IgG mediated complement fixation provides additional insight into the sequence of events during the development of BP lesions. PMID:26475989

  8. Levels of anti-BP180 NC16A IgE do not correlate with severity of disease in the early stages of bullous pemphigoid.

    PubMed

    Bing, Liu; Xiping, Zhou; Li, Li; Jun, Peng; Yi-Xia, Wang; Min, Yang; Qing, Liu; Qiu-Ning, Sun; Hong-Zhong, Jin; Ya-Gang, Zuo

    2015-11-01

    Bullous pemphigoid (BP), a common autoimmune skin disease, is associated with IgG autoantibodies against the hemidesmosomal proteins, BP180 and BP230. In addition to IgG, IgE has been shown to play a role in the disease. However, the association between disease activity and IgE specific to the NC16A domain of BP180 in blister fluid remains unclear. Our objective was to evaluate the correlation between BP disease activity and BP180 NC16A-specific IgE sera and blister fluid titers, and to analyze changes during treatment. We evaluated the levels of anti-BP180 IgE autoantibodies in the sera and blister fluids of 37 BP patients using an Enzyme-linked immunosorbent assay. We also observed changes in the levels of these antibodies in 2 BP patients at 4 or 5 different time points (day 0 when the patient first visited our hospital, day 5, day 14, day 39 and day 62 for patient 1; day 0, day 4, day 8 and day 17 for patient 2). We also collected extra serum samples from the 2 patients when the disease was controlled (blister disappeared) (day 85, day 104 and day 146 for patient 1 and day 123, day 158 and day 189 for the other patient). IgE anti-BP180 antibodies were detected in the serum of 72.97 % of the patients. There was no correlation between disease activity scores and BP180 NC16A IgE titers in serum (r = -0.077, p > 0.05) or in blister fluid (r = 0.262, p > 0.05). The levels of the autoantibody in serum were positively correlated with that in blister fluid (r = 0.6651, p < 0.001); however, the levels continued to rise despite effective control of the disease in the initial two to 6 weeks of diagnosis. The level of this autoantibody reached a peak on day 39 for patient 1 and on day 17 for patient 2 although the systemic and topical medication of steroid had controlled the disease process effectively. We conclude that levels of anti-BP180 NC16A IgE are higher in the sera than blister fluids. These levels could generally reflect disease severity throughout the course of

  9. Lichen planus pemphigoides associated with pregnancy mimicking pemphigoid gestationis.

    PubMed

    Rullán, Jennifer; Diaz, Nicole C; Vazquez-Botet, Miguel

    2016-06-01

    Lichen planus pemphigoides (LPP) is a rare condition characterized by tense blisters that arise on lesions of lichen planus (LP) and on unaffected skin. We present the case of a 25-year-old pregnant woman at 12 weeks' gestation who developed an acute bullous eruption after 5 months of worsening LP. Similarities to pemphigoid gestationis (PG) included lesions around the periumbilical area and multiple urticarial erythematous papules and plaques in addition to linear C3 and IgM deposition along the basement membrane zone (BMZ) on direct immunofluorescence (DIF). PMID:27416093

  10. Bullous Scabies.

    PubMed

    Luo, Di-Qing; Huang, Mei-Xing; Liu, Juan-Hua; Tang, Wen; Zhao, Yu-Kun; Sarkar, Rashmi

    2016-09-01

    Scabies is a common contagious cutaneous disease and usually affects the young, characterized by polymorphous lesions that may present as burrows, pruritic papules, and inflammatory nodules. Bullous scabies (BS) is its rather rare subtype, mimicking bullous pemphigoid. We report a 15-year-old Chinese boy presenting with 1-month history of pruritic bullae on his penile skin, showing poor response to both topical steroids and systemic antihistamines, but cured by sulfur ointment alone. No recurrence occurred in the 5 years of follow-up. We also reviewed the published cases. Up to date, 44 cases, including the present, have been reported. Of them, 30 were male and 14 were female. The age range was from 1 to 89 years old, with a median age of 70.6 years. The bullous lesions may involve the arms, legs, trunk, genitals, feet, buttocks, thighs, neck, inguinal folds, and may even be generalized. Trunk and extremities are the most common involved locations. Facial or mucosa involvement had never been reported. The histological findings present as a subepidermal split with variable inflammatory infiltrate predominantly neutrophils, and eosinophilic spongiosis, or both. Eighteen of 32 patients showed positive deposition of linear-granular IgG or complement 3 alone or in various combinations, and five of 24 patients revealed circulating IgG. All the 40 cases with therapeutic details were cured by antiscabietic remedy. BS always involves the trunk and extremities. It has a predilection for elderlies and males. The treatments for BS are similar to those of classical scabies. PMID:27402514

  11. A case of crusted scabies combined with bullous scabies

    PubMed Central

    SU, WEN-JING; FANG, SHENG; CHEN, AI-JUN; SHAN, KUI

    2015-01-01

    Scabies is a contagious skin disease that causes extremely itching. It is a parasitic disease caused by the mite Sarcoptes scabiei and characterized by polymorphous lesions. Vesicular and bullous lesions in cases of scabies are rather rare. Bullous scabies has a pemphigoid presentation. Crusted scabies, also known as Norwegian scabies, is a rare and severe form of the disease. The large number of mites present in and on the skin cause scabies to be highly contagious. The present study reports a case of crusted scabies combined with bullous scabies, the clinical and histopathological manifestations of which mimicked those of bullous pemphigoid. Direct and indirect immunofluorescence test results were negative. Bullae recurred and persisted despite systemic corticosteroids and antihistamine medication. The patient was successfully treated with 10% sulfur cream and remained free of recurrence during the 12 months of follow-up. Differential diagnosis with bullous pemphigoid and the mechanism of formation of bullae are also discussed. PMID:26622520

  12. Anti-p200 pemphigoid.

    PubMed

    Goletz, Stephanie; Hashimoto, Takashi; Zillikens, Detlef; Schmidt, Enno

    2014-07-01

    Anti-p200 pemphigoid is a rare subepidermal blistering skin disease. Patients' autoantibodies label the dermal side of 1 mol/L NaCl-split human skin by indirect immunofluorescence microscopy and recognize a 200-kd protein by immunoblotting of human dermal extract. Clinically, anti-p200 pemphigoid is characterized by tense blisters and vesicles, erosions, and urticarial plaques, closely resembling bullous pemphigoid and the inflammatory variant of epidermolysis bullosa acquisita. Recently, 90% of anti-p200 pemphigoid sera were shown to recognize laminin γ1. The C-terminus of laminin γ1 was identified as an immunodominant region and in its recombinant form was used by immunoblotting and enzyme-linked immunosorbent assay for the serologic diagnosis of this disease. Subsequent ex vivo and in vivo studies were, however, unable to show pathogenic activity of antilaminin γ1 antibodies. Both patients' sera and sera depleted from antilaminin γ1 antibodies induced subepidermal splitting in an ex vivo model of autoantibody-mediated leukocyte-dependent neutrophil activation. Antilaminin γ1 antibodies appear to be useful biomarkers that will further facilitate the diagnosis of anti-p200 pemphigoid. The true identity of the pathogenetically relevant autoantigen of this disease, which may either be a yet unknown isoform of laminin γ1 or even another 200-kd protein of the dermoepidermal junction, still needs to be elucidated. PMID:24767733

  13. Cicatricial Pemphigoid

    MedlinePlus

    ... several ways to treat pemphigoid, including tetracycline with niacinamide, cortisone-type drugs that suppress the immune reaction, ... Another alternative is the use of tetracycline and niacinamide, taking one capsule of each, four times daily. ...

  14. Clinical Relevance of Autoantibodies in Patients with Autoimmune Bullous Dermatosis

    PubMed Central

    Mihályi, Lilla; Kiss, Mária; Dobozy, Attila; Kemény, Lajos; Husz, Sándor

    2012-01-01

    The authors present their experience related to the diagnosis, treatment, and followup of 431 patients with bullous pemphigoid, 14 patients with juvenile bullous pemphigoid, and 273 patients with pemphigus. The detection of autoantibodies plays an outstanding role in the diagnosis and differential diagnosis. Paraneoplastic pemphigoid is suggested to be a distinct entity from the group of bullous pemphigoid in view of the linear C3 deposits along the basement membrane of the perilesional skin and the “ladder” configuration of autoantibodies demonstrated by western blot analysis. It is proposed that IgA pemphigoid should be differentiated from the linear IgA dermatoses. Immunosuppressive therapy is recommended in which the maintenance dose of corticosteroid is administered every second day, thereby reducing the side effects of the corticosteroids. Following the detection of IgA antibodies (IgA pemphigoid, linear IgA bullous dermatosis, and IgA pemphigus), diamino diphenyl sulfone (dapsone) therapy is preferred alone or in combination. The clinical relevance of autoantibodies in patients with autoimmune bullous dermatosis is stressed. PMID:23320017

  15. Case with Brunsting-Perry-like localized subepidermal blister formations and immunoglobulin G antibodies against unidentified basement membrane zone antigen.

    PubMed

    Sato-Shibuya, Mami; Dainichi, Teruki; Egawa, Gyohei; Honda, Tetsuya; Otsuka, Atsushi; Ishii, Norito; Hashimoto, Takashi; Miyachi, Yoshiki; Kabashima, Kenji

    2016-04-01

    Brunsting-Perry type bullous pemphigoid is defined by the blister formation limited to the head and neck, and autoantibodies to type VII collagen are detected in several cases. However, the pathomechanisms and autoantigens in this condition remain unknown. We report a 20-year-old female patient with a more than 2-year history of recurrent tense blisters localized on the face with no distinct atrophic scar formation. The patient had neither extensive sun exposure nor a history suggestive of contact dermatitis. Oral betamethasone was effective on the skin lesions. Histopathology revealed subepidermal blister formation with dermal infiltrates of neutrophils. Although direct and indirect immunofluorescence tests detected immunoglobulin G antibodies to the basement membrane zone (BMZ), no known dermal or epidermal autoantigens were detected in immunoblot analyses. Therefore, this case may be a rare variant of Brunsting-Perry type localized bullous pemphigoid with autoantibodies to an undetermined BMZ antigen. PMID:26362108

  16. Why human pemphigoid autoantibodies do not trigger disease by the passive transfer into mice?

    PubMed

    Sesarman, Alina; Oswald, Eva; Chiriac, Mircea T; Csorba, Kinga; Vuta, Vlad; Feldrihan, Vasile; Baican, Adrian; Bruckner-Tuderman, Leena; Sitaru, Cassian

    2012-03-30

    The recapitulation of disease features in animals by the transfer of patient autoantibodies has been used to demonstrate the autoimmune nature of several diseases. Failure of disease induction by the passive transfer of autoantibodies has been assigned to a limited cross-reactivity of the autoantibodies with the murine tissue. However, the possibility that the passively transferred "inflammatory" patient autoantibodies may not be able to unfold their pathogenic potential due to restricted Fc-dependent effector functions has not yet been systematically explored. In this study we analyze the interaction of patients' autoantibodies with murine complement and granulocytes. Bullous pemphigoid is a blistering disease associated with autoantibodies, which are thought to induce subepidermal blistering by activating complement and granulocytes. The passive transfer of patients autoantibodies failed to induce skin blistering in wild type mice. The cross-reactivity of pemphigoid autoantibodies with murine antigens was analyzed in silico, ex vivo and by the passive transfer of IgG in vivo. Complement-fixing ability of patients' autoantibodies was evaluated by complement-binding test. Granulocyte activation was assessed by reactive oxygen species production assay and the cryosection model. We have found that although pemphigoid autoantibodies bound to murine skin in vitro and in vivo, they showed a lower capacity to fix murine complement and a reduced ability to activate murine granulocytes when compared with human complement and cells, respectively. These results indicate that for disease models using the passive transfer of patient autoantibodies, their interaction with the innate factors of the host should be optimized to match the human situation. PMID:22305931

  17. Linear immunoglobulin A (IgA) bullous dermatosis of childhood: identification of the target antigens and study of the cellular sources.

    PubMed

    Yamane, Y; Sato, H; Higashi, K; Yaoita, H

    1996-11-01

    A 4-year-old girl developed numerous tense blisters on the body. The blisters healed without scarring. Histopathological and immunofluorescence studies showed findings consistent with linear immunoglobulin A (IgA) bullous dermatosis of childhood. Immunoelectron microscopy revealed deposition of IgA in the lamina lucida of the basement membrane zone of the dermal-epidermal junction. Circulating IgA autoantibody was positive at the titre of 1 : 128 and recognized the antigens located on epidermal sites of 1 mol/l NaCl-split skin. Immunofluorescence staining of cultured normal human fibroblasts and cultured DJM-1 cells (derived from human squamous cell carcinoma of skin) with the patient's sera demonstrated that both of these cells synthesize the antigens in vitro, although fibroblasts produce the antigens more abundantly. When DJM-1 cells were injected intracutaneously into nude mice, the antigens recognized by the sera were present mainly around the tumour cell islands in a linear pattern, while the dermal-epidermal junction of mouse skin was negative, suggesting that epidermal cells may contribute directly to synthesis and deposition of the antigens at the basement membrane. By immunoprecipitation using cultured normal human fibroblasts, the patient's sera could precipitate at least two specific molecules at 100-kDa and 145-kDa molecular weight. PMID:8977683

  18. Pregnancy with Pemphigoid Gestationis: A Rare Entity

    PubMed Central

    Shree, Sneha; Mehta, Sumita

    2016-01-01

    Pemphigoid Gestationis (PG) is a rare autoimmune blistering disease with an incidence of 1/50000 pregnancies. Presentation in the second or third trimester is most common and tends to recur in subsequent pregnancies with earlier onset and a more severe course. Direct Immunofluorescence (DIF) staining is confirmatory on skin biopsy specimen. A 24-year-old female presented at 6 months period of gestation with increased blood pressure records. On examination, there were fresh bullous lesions along with old healed scar marks on the abdomen and limbs. Termination of pregnancy was done due to high BP. Patient delivered a fresh still birth weighing 750 gm. No postpartum flare ups were seen and she was discharged on prednisolone in a satisfactory condition.

  19. Development of an ELISA for sensitive and specific detection of IgA autoantibodies against BP180 in pemphigoid diseases

    PubMed Central

    2011-01-01

    Background Pemphigoids are rare diseases associated with IgG, IgE and IgA autoantibodies against collagen XVII/BP180. An entity of the pemphigoid group is the lamina lucida-type of linear IgA disease (IgA pemphigoid) characterized by IgA autoantibodies against BP180. While for the detection of IgG and IgE autoantibodies specific to collagen XVII several ELISA systems have been established, no quantitative immunoassay has been yet developed for IgA autoantibodies. Therefore, the aim of the present study was to develop an ELISA to detect IgA autoantibodies against collagen XVII in the sera of patients with pemphigoids. Methods We expressed a soluble recombinant form of the collagen XVII ectodomain in mammalian cells. Reactivity of IgA autoantibodies from patients with IgA pemphigoid was assessed by immunofluorescence microscopy and immunoblot analysis. ELISA test conditions were determined by chessboard titration experiments. The sensitivity, specificity and the cut-off were determined by receiver-operating characteristics analysis. Results The optimized assay was carried out using sera from patients with IgA pemphigoid (n = 30) and healthy donors (n = 105). By receiver operating characteristics (ROC) analysis, an area under the curve of 0.993 was calculated, indicating an excellent discriminatory capacity. Thus, a sensitivity and specificity of 83.3% and 100%, respectively, was determined for a cut-off point of 0.48. As additional control groups, sera from patients with bullous pemphigoid (n = 31) and dermatitis herpetiformis (n = 50), a disease associated with IgA autoantibodies against epidermal transglutaminase, were tested. In 26% of bullous pemphigoid patients, IgA autoantibodies recognized the ectodomain of collagen XVII. One of 50 (2%) of dermatitis herpetiformis patients sera slightly topped the cut-off value. Conclusions We developed the first ELISA for the specific and sensitive detection of serum IgA autoantibodies specific to collagen XVII in patients

  20. Suppressor cell function is preserved in pemphigus and pemphigoid

    SciTech Connect

    King, A.J.; Schwartz, S.A.; Lopatin, D.; Voorhees, J.J.; Diaz, L.A.

    1982-09-01

    Human peripheral blood lymphocytes (PBL) are activated to become suppressor T cells (S-T-C) by incubation with Concanavalin-A (Con-A). This has become the standard method for evaluation of suppressor function in patients. S-T-C function has been found to be impaired in several autoimmune diseases, including systemic lupus erythematosus (SLE). Using this assay, we have investigated suppressor-cell function in 2 autoimmune disorders, bullous pemphigoid (BP) and pemphigus vulgaris (PV), studying 6 patients from each group. Three patients with active SLE (positive controls), and 11 normal donors (negative controls) were also included. None of these patients had received systemic therapy with the exception of 2 patients with PV who were treated with gold in the past. PBL from these patients were incubated with and without 40 micrograms/ml Con-A for 72 hr to generate suppressor cells. Both groups of PBL were then irradiated wih 1500 r cobalt. Co-cultures were set up in sextuplicate using normal PBL as responders. Responder PBL were stimulated with 0.5, 1.0, and 2.0 micrograms/ml of phytohemagglutin (PHA) and 5.0, 10.0, and 20.0 micrograms/ml of Con-A. Cultures were pulsed on day 3 with /sup 3/H-thymidine and harvested on day 4. Data were analyzed using Student's t-test. S-T-C function was found to be significantly impaired in SLE vs normal (p . 0.0316). No statistically significant difference was seen in BP (p . 0.5883) and PV (p . 0.0921) as compared with normals. A defect in suppressor cell function may still be present in patients with PV and BP for the defect may be antigen-specific and therefore remain undetected by the Con-A suppressor assay.

  1. Case of paraneoplastic pemphigus with immunoglobulin (Ig)G and IgA antibodies to various antigens.

    PubMed

    Otsuka, Yohei; Ueno, Takashi; Yamase, Aya; Ito, Michiko; Osada, Shinichi; Kawana, Seiji; Funasaka, Yoko; Teye, Kwesi; Ishii, Norito; Hashimoto, Takashi; Saeki, Hidehisa

    2016-08-01

    A 63-year-old Japanese man with non-Hodgkin B-cell lymphoma presented with erythematous skin lesions on his entire body, with oral, ocular and anal mucosal lesions. The patient was diagnosed with paraneoplastic pemphigus. Immunofluorescence showed both immunoglobulin (Ig)G and IgA antibodies to keratinocyte cell surfaces. Various immunoblot and enzyme-linked immunosorbent assays showed both IgG and IgA antibodies to various autoantigens, including desmogleins, desmocollins, envoplakin, periplakin and bullous pemphigoid antigens. This was a unique case with a very rare autoantibody profile in paraneoplastic pemphigus. PMID:26969813

  2. Mucous Membrane Pemphigoid with Tracheal Involvement

    PubMed Central

    Minaie, Arash; Surani, Salim R.

    2016-01-01

    34-year-old African American female with history of pemphigoid presented with hemoptysis. Patient was found to have mucous membrane pemphigoid involving the oropharynx and extending to trachea, till just above main stem carina. Four other cases described mucosal pemphigoid involving the trachea. We hereby present a brief review of current consensus on management of mucous membrane pemphigoid with airway involvement. PMID:26955496

  3. Genetic polymorphisms of CYP2D6 oxidation in patients with autoimmune bullous diseases

    PubMed Central

    Rychlik-Sych, Mariola; Baranska, Małgorzata; Waszczykowska, Elzbieta; Torzecka, Jolanta Dorota; Skretkowicz, Jadwiga

    2013-01-01

    Introduction Bullous skin diseases, which include, among others pemphigoid, pemphigus, and dermatitis herpetiformis are classified as severe autoimmune dermatoses. It has been shown that a pattern of xenobiotic metabolism may play a role in the pathogenesis of autoimmune diseases. Aim To estimate whether the CYP2D6 genotype may be considered a predisposing factor in autoimmune bullous diseases induction. Material and methods The study included 72 patients with autoimmune bullous diseases: 37 with pemphigoid, 21 with pemphigus, and 14 with dermatitis herpetiformis (DH). The CYP2D6 genotypes were analyzed by the polymerase chain reaction fragment length polymorphism (PCR-RFLP) method. Results Relative risk of DH development for particular genotype carriers expressed by odds ratio (OR) was statistically significantly higher for subjects with CYP2D6*1/CYP2D6*4 (OR = 4.2; p = 0.0104) and 2-fold higher for subjects with CYP2D6*4 (OR = 2.3; p = 0.0351). Conclusions The results of the present study show that the CYP2D6 oxidation polymorphism cannot be considered a risk factor for development of pemphigoid and pemphigus, however it might have an impact on dermatitis herpetiformis. PMID:24278077

  4. Lichen Planus Pemphigoides Presenting Preferentially Over Preexisting Scars: A Rare Instance of Isotopic Phenomenon

    PubMed Central

    Kumar, Piyush; Savant, Sushil S; Das, Anupam; Hassan, Shahid; Barman, Panchami Deb

    2015-01-01

    An 18-year-old girl presented with multiple itchy hyperpigmented papules and plaques, along with tense blisters over the lower limbs and buttocks for last 3 months. These papules, plaques, and bullae were mostly localized to preexisting scars. The histopathological findings from papule and bulla were consistent with lichen planus (LP) and bullous pemphigoid, respectively. Direct immunofluorescence (DIF) of perilesional skin around bulla showed linear deposition of IgG and C3. Considering clinical, histopathological and DIF findings, diagnosis of LP pemphigoides (LPP) was made. The preferential localization of LPP lesions over preexisting scars was a very interesting finding in our case an extremely rare instance of the isotopic phenomenon. PMID:26677275

  5. Lichen Planus Pemphigoides Presenting Preferentially Over Preexisting Scars: A Rare Instance of Isotopic Phenomenon.

    PubMed

    Kumar, Piyush; Savant, Sushil S; Das, Anupam; Hassan, Shahid; Barman, Panchami Deb

    2015-01-01

    An 18-year-old girl presented with multiple itchy hyperpigmented papules and plaques, along with tense blisters over the lower limbs and buttocks for last 3 months. These papules, plaques, and bullae were mostly localized to preexisting scars. The histopathological findings from papule and bulla were consistent with lichen planus (LP) and bullous pemphigoid, respectively. Direct immunofluorescence (DIF) of perilesional skin around bulla showed linear deposition of IgG and C3. Considering clinical, histopathological and DIF findings, diagnosis of LP pemphigoides (LPP) was made. The preferential localization of LPP lesions over preexisting scars was a very interesting finding in our case an extremely rare instance of the isotopic phenomenon. PMID:26677275

  6. Relationship between target antigens and major histocompatibility complex (MHC) class II genes in producing two pathogenic antibodies simultaneously

    PubMed Central

    Zakka, L R; Keskin, D B; Reche, P; Ahmed, A R

    2010-01-01

    In this report, we present 15 patients with histological and immunopathologically proven pemphigus vulgaris (PV). After a mean of 80 months since the onset of disease, when evaluated serologically, they had antibodies typical of PV and pemphigoid (Pg). Similarly, 18 patients with bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP) were diagnosed on the basis of histology and immunopathology. After a mean of 60 months since the onset of disease, when their sera were evaluated they were found to have Pg and PV autoantibodies. In both groups of patients the diseases were characterized by a chronic course, which included several relapses and recurrences and were non-responsive to conventional therapy. The major histocompatibility complex class II (MHC II) genes were studied in both groups of patients and phenotypes associated typically with them were observed. Hence, in 33 patients, two different pathogenic autoantibodies were detected simultaneously. The authors provide a computer model to show that each MHC II gene has relevant epitopes that recognize the antigens associated with both diseases. Using the databases in these computer models, the authors present the hypothesis that these two autoantibodies are produced simultaneously due to the phenomena of epitope spreading. PMID:21069937

  7. The Use of Traditional Chinese Medicine in Some Dermatologic Diseases: Part II--Autoimmune Bullous Disorders and Lichen Planus.

    PubMed

    Baroni, Adone; Ruocco, Eleonora; Russo, Teresa; Piccolo, Vincenzo; Geng, Long; Zhou, Hongbo; Chen, Hong-Duo; Gao, Xing-Hua

    2015-01-01

    Over the centuries, traditional Chinese medicine (TCM) and Western medicine have traveled along parallel lines with no opportunity for collaboration. In recent decades, while an interest in TCM has been growing among Western clinicians, progress has been made in the comprehension of pathogenic mechanisms of skin disorders, and the communication between Western and Eastern medicines has become more and more intensive. In this paper, the authors discuss TCM remedies used in the treatment of autoimmune bullous disorders (pemphigus and bullous pemphigoid) and lichen planus. Future studies on the active components of the TCM will certainly shed new light on the still obscure aspects of some dermatologic diseases. PMID:26380506

  8. Is There a Relation between ABO Blood Groups and Clinical Outcome in Patients with Pemphigoid? A Case-Control Study

    PubMed Central

    Bakhtiari, Sedigheh; Toosi, Parviz; Azimi, Somayyeh; Esmaili, Nafiseh; Montazami, Ali

    2016-01-01

    Background. Relationship between blood groups and dermatologic diseases remains controversial and was not yet fully elucidated nor explained clearly. The aim of this study was to examine if any relation exists between different types of pemphigoid diseases and ABO blood group. Methods. In this case-control study, 159 pemphigoid patients and 152 healthy matched-controls were evaluated. All blood group (including Rh status) data for the study was obtained from the hospital medical records. Statistical comparisons were completed with chi-square test and logistic regression. Results. Blood group “O” was found in 32.9% of patients and 38.2% of control group. Blood group “A” was found among 30.8% of patients and 34.2% of control group, while group “B” was reported in 27.4% of cases and 21.1% of controls and “AB” was identified among 8.9% of patients and 6.6% of control group. 84.9% of patients were Rh positive, while in the control group 86.2% of patients were Rh positive. No significant differences were found regarding ABO blood groups (P = 0.46) or Rh (P = 0.76) between pemphigoid patients and control group. Also, older females had the higher risk of developing bullous pemphigoid. Conclusion. We found no relationship between ABO blood groups and pemphigoid disease. PMID:27437000

  9. Pathogenicity of Autoantibodies in Anti-p200 Pemphigoid

    PubMed Central

    Beckmann, Tina; Hirose, Misa; Dworschak, Jenny; Recke, Andreas; Ludwig, Ralf J.; Hashimoto, Takashi; Zillikens, Detlef; Schmidt, Enno

    2012-01-01

    Recently, the C-terminus of laminin γ1 has been identified as target antigen in anti-p200 pemphigoid and the disease was renamed as anti-laminin γ1 pemphigoid. However, the pathogenic relevance of these autoantibodies has not yet been demonstrated. Therefore, we employed an ex vivo model of autoantibody-mediated leukocyte-dependent neutrophil activation and dermal-epidermal separation (DES) using cryosections of human skin. We showed that anti-p200 pemphigoid sera (n = 7) induced DES in a time-dependent manner, in contrast to sera from healthy controls. Furthermore, laminin γ1-specific IgG and serum depleted from anti-laminin γ1 reactivity were generated using the recombinant C-terminus of laminin γ1 (LAMC1-term; amino acids 1364 to 1609). Interestingly, both fractions labeled the dermal-epidermal-junction (DEJ) by indirect immunofluorescence microscopy on human foreskin and recognized a 200 kDa protein by immunoblotting with dermal extract. Human and rabbit IgG against LAMC1-cterm failed to attract neutrophils at the DEJ and to induce DES. In contrast, patient serum depleted from LAMC1-cterm reactivity led to the same extent of DES as non-depleted IgG. Repeated injection of rabbit anti-murine LAMC1-cterm IgG into both neonatal and adult C57BL/6mice as well as repetitive immunization of various mouse strains with murine LAMC1-cterm failed to induce macro- and microscopic lesions. In all mice, circulating anti-LAMC1-cterm antibodies were present, but only in some mice, IgG deposits were seen at the DEJ. We conclude that autoantibodies in anti-p200 pemphigoid sera are pathogenic while pathogenicity is not mediated by autoantibodies against laminin γ1. Further studies are needed to identify the pathogenically relevant autoantigen in anti-p200 pemphigoid. PMID:22911854

  10. Linear IgA Bullous Dermatosis

    PubMed Central

    Chaudhari, Soham

    2015-01-01

    Linear immunoglobulin A bullous dermatosis is a rare autoimmune mucocutaneous disorder caused by immunoglobulin A autoantibodies produced against several different antigens in the basement membrane zone. Clinically, it is characterized by tense vesicles or bullae, which on histopathological exam demonstrate subepidermal blister with a predominantly neutrophilic infiltrate. A smooth, linear pattern of immunoglobulin A deposition in the basement membrane zone on direct immunofluorescence is considered the gold standard for establishing a diagnosis. Treatment consists of dapsone or sulfapyridine. The authors report a 60-year-old woman who presented with pruritic erythematous patches and plaques on her trunk, back, and legs without blisters, who was diagnosed with eczema for several months with no response to prior treatments. A biopsy was performed, which was consistent with linear immunoglobulin A bullous dermatosis and later confirmed by direct immunofluorescence studies. The authors present this case to increase awareness of this rare disease, which could manifest in a nonclassical, nonblistering fashion. PMID:26557220

  11. Therapy of autoimmune bullous diseases

    PubMed Central

    Mutasim, Diya F

    2007-01-01

    Autoimmune bullous diseases result from an immune response to molecular components of the desmosome or basement membrane. Bullous diseases are associated with a high degree of morbidity and occasional mortality. Therapy of bullous diseases consists of suppressing the immune system, controlling inflammation and improving healing of erosions. The therapeutic agents used in the treatment of bullous diseases may be associated with high morbidity and occasional mortality. Successful treatment requires understanding of the pathophysiology of the disease process and the pharmacology of the drugs being used. PMID:18360613

  12. Bullous dermatitis artefacta.

    PubMed

    Sokumbi, Olayemi; Comfere, Nneka I; McEvoy, Marian T; Peters, Margot S

    2013-02-01

    Bullous artefactual dermatoses are rare and may be induced by various techniques, including chemicals, heat, or electrical current. Proving a factitial etiology and identifying the mechanism of injury may be difficult. We describe the clinical features and histopathology of 2 patients with bullous disease induced by electrical current or heat. Physical examination in both patients demonstrated geometrically shaped tense bullae. Skin biopsies revealed epidermal necrosis overlying a pauci-inflammatory subepidermal cleft, with homogenization of underlying superficial dermal collagen. In 1 of the 2 patients, there was prominent vertical elongation of keratinocyte nuclei and also of cytoplasmic processes. Direct immunofluorescence study of skin plus testing of serum by indirect immunofluorescence and enzyme-linked immunosorbent assay for BP180 and BP230 antibodies revealed no evidence for immunobullous disease in either patient. Vertical elongation of keratinocyte nuclei, often attributed to a polarization effect of electrical current, is characteristic of electrical burn but also may be induced by thermal injury. These 2 patients highlight the importance of histopathology in confirming a diagnosis of bullous dermatitis artefacta. PMID:22771895

  13. Clinical and Immunological Studies of 332 Japanese Patients Tentatively Diagnosed as Anti-BP180-type Mucous Membrane Pemphigoid: A Novel BP180 C-terminal Domain Enzyme-linked Immunosorbent Assay.

    PubMed

    Yasukochi, Atsushi; Teye, Kwesi; Ishii, Norito; Hashimoto, Takashi

    2016-08-23

    Diagnosis of anti-BP180-type mucous membrane pemphigoid (BP180-MMP) is frustrated by the difficulty of detecting BP180 reactivity. A total of 721 patients with suspected MMP, selected from a cohort of 4,698 patients with autoimmune bullous disease (AIBD), were included in this study. Of these, 332 patients were tentatively diagnosed as BP180-MMP if they showed IgG/IgA reactivity with the epidermal side of 1M NaCl-split-skin and/or positive reactivity with BP180 in at least one of our antigen detection methods. Clinically, a predominance of female patients was found. Oral mucosal and cutaneous lesions were found in 85.5% and 41.0% of patients, respectively, and frequent treatments were systemic steroids, tetracycline/minocycline and diaminodiphenyl sulfone. Various immunological methods, including a newly developed BP180 C-terminal domain enzyme-linked immunosorbent assay (ELISA), revealed frequent reactivity with BP180 C-terminal and NC16a domains. Some patients reacted with BP180 and other antigens, indicating that BP180-MMP tends to concur with other AIBDs. This large study of patients with suspected BP180-MMP indicates the difficulty of diagnosis of BP180-MMP and the diagnostic usefulness of BP180 C-terminal domain ELISA. PMID:26984589

  14. Nursing diagnoses in patients with immune-bullous dermatosis 1

    PubMed Central

    Brandão, Euzeli da Silva; dos Santos, Iraci; Lanzillotti, Regina Serrão; Ferreira, Adriano Menis; Gamba, Mônica Antar; Azulay-Abulafia, Luna

    2016-01-01

    ABSTRACT Objective: identify nursing diagnoses in patients with immune-bullous dermatosis. Method: a quantitative and descriptive research, carried out in three institutions located in Rio de Janeiro and Mato Grosso do Sul, Brazil, using the Client Assessment Protocol in Dermatology during a nursing consultation. Simple descriptive statistics was used for data analysis. Results: 14 subjects participated in the study, nine with a diagnosis of pemphigus vulgaris, pemphigus two and three of bullous pemphigoid. The age ranged between 27 and 82 years, predominantly females (11). 14 nursing diagnoses were discussed and identified from a clinical rationale in all study participants, representing the most common human responses in this sample. The application of the Assessment Protocol in Dermatology facilitated the comprehensive assessment, in addition to providing the identification of diagnostics according to the North American Nursing Diagnosis Association International. Conclusion: the nursing diagnoses presented confirm the necessity of interdisciplinary work during the care for this clientele. For better description of the phenomena related to the client in question, it is suggested the inclusion of two risk factors related in three diagnoses of this taxonomy. It is worth noting the contribution of the findings for the care, education and research in nursing in dermatology. PMID:27533274

  15. Serological diagnosis of autoimmune bullous skin diseases: Prospective comparison of the BIOCHIP mosaic-based indirect immunofluorescence technique with the conventional multi-step single test strategy

    PubMed Central

    2012-01-01

    Background Various antigen-specific immunoassays are available for the serological diagnosis of autoimmune bullous diseases. However, a spectrum of different tissue-based and monovalent antigen-specific assays is required to establish the diagnosis. BIOCHIP mosaics consisting of different antigen substrates allow polyvalent immunofluorescence (IF) tests and provide antibody profiles in a single incubation. Methods Slides for indirect IF were prepared, containing BIOCHIPS with the following test substrates in each reaction field: monkey esophagus, primate salt-split skin, antigen dots of tetrameric BP180-NC16A as well as desmoglein 1-, desmoglein 3-, and BP230gC-expressing human HEK293 cells. This BIOCHIP mosaic was probed using a large panel of sera from patients with pemphigus vulgaris (PV, n = 65), pemphigus foliaceus (PF, n = 50), bullous pemphigoid (BP, n = 42), and non-inflammatory skin diseases (n = 97) as well as from healthy blood donors (n = 100). Furthermore, to evaluate the usability in routine diagnostics, 454 consecutive sera from patients with suspected immunobullous disorders were prospectively analyzed in parallel using a) the IF BIOCHIP mosaic and b) a panel of single antibody assays as commonly used by specialized centers. Results Using the BIOCHIP mosaic, sensitivities of the desmoglein 1-, desmoglein 3-, and NC16A-specific substrates were 90%, 98.5% and 100%, respectively. BP230 was recognized by 54% of the BP sera. Specificities ranged from 98.2% to 100% for all substrates. In the prospective study, a high agreement was found between the results obtained by the BIOCHIP mosaic and the single test panel for the diagnosis of BP, PV, PF, and sera without serum autoantibodies (Cohen’s κ between 0.88 and 0.97). Conclusions The BIOCHIP mosaic contains sensitive and specific substrates for the indirect IF diagnosis of BP, PF, and PV. Its diagnostic accuracy is comparable with the conventional multi-step approach. The highly

  16. Nutrition and bullous skin diseases.

    PubMed

    Fedeles, Flavia; Murphy, Michael; Rothe, Marti J; Grant-Kels, Jane M

    2010-01-01

    Autoimmune and nonautoimmune bullous diseases can both be associated with significant morbidity and mortality. Although our understanding of the pathogenic mechanisms of these diseases has increased tremendously, there is still much to learn about the various factors affecting their onset, course, and therapy. In recent years, increasing information has been published about the effect of vitamins, minerals, and other nutrients on bullous skin diseases. Some factors are believed to be inducers (thiol and phenol-containing foods in pemphigus), whereas others are believed to be protective (antioxidants in cutaneous porphyrias). This contribution reviews the evidence in the literature of the role of various dietary factors in bullous diseases, including the nonautoimmune and the deficiency dermatoses. Additional studies and new investigations are needed to provide a better understanding of the specific associations of dietary factors with bullous diseases and better management for patients affected by these conditions. PMID:21034987

  17. Immunopathological diagnosis of cicatricial pemphigoid with desquamative gingivitis. A case report.

    PubMed

    Kurihara, M; Nishimura, F; Hashimoto, T; Komai, A; Ueda, H; Kokeguchi, S; Takashiba, S; Murayama, Y

    2001-02-01

    Cicatricial pemphigoid (CP) is a chronic subepidermal bullous dermatosis which primarily involves the mucous membranes. The oral cavity and the eye are most frequently involved. Since extension of the lesion into the pharynx and esophagus causes sore throat and dysphagia and progressive ocular lesions may cause blindness, early and valid diagnosis is very important. Here we present a case of cicatricial pemphigoid with onset at age 45 in a patient who manifested severe periodontal disease and showed the lesion on the mucous membranes of the mouth (desquamative gingivitis), skin, and eyes. Since definite diagnosis is very important, we describe how we made a differential diagnosis from other diseases which also accompany desquamative gingivitis. We examined the clinical manifestations, blood test results, HLA-genotype, histopathologic findings of the affected tissue, and immunological findings in relation to autoimmunity. Since many of the CP cases are first referred to periodontists or dentists, we believe that the diagnostic strategy described in the present study will be quite informative for making rapid and definite diagnoses of similar cases. PMID:11288799

  18. [Bullous autoimmune disorders in children].

    PubMed

    Sárdy, M; Kasperkiewicz, M

    2013-06-01

    We review the pathogenesis, clinical features, diagnosis, differential diagnosis, and therapy of autoimmune bullous skin diseases of childhood, especially of the most common linear IgA dermatosis. In autoimmune bullous diseases, autoantibodies are formed against different adhesion molecules of the skin. These are not only pathophysiologically relevant, but also serve as basis for diagnosis and follow-up of these diseases. In case an autoimmune bullous disease is suspected, histopathology and immunohistopathology (direct immunofluorescence microscopy) as well as serological tests (indirect immunofluorescence microscopy, ELISA, immunoblot) should be performed. Therapy depends on the diagnosis. In IgA-mediated pathogenesis, dapsone can be successfully used. In IgG-mediated diseases, immunosuppression with corticosteroids and steroid-sparing agents should be initiated, although only local therapy is sufficient to control a self-limiting pemphigus neonatorum. In dermatitis herpetiformis, a life-long gluten-free diet is recommended. PMID:23677541

  19. Development of a disease registry for autoimmune bullous diseases: initial analysis of the pemphigus vulgaris subset.

    PubMed

    Shah, Amit Aakash; Seiffert-Sinha, Kristina; Sirois, David; Werth, Victoria P; Rengarajan, Badri; Zrnchik, William; Attwood, Kristopher; Sinha, Animesh A

    2015-01-01

    Pemphigus vulgaris (PV) is a rare, potentially life threatening, autoimmune blistering skin disease. The International Pemphigus and Pemphigoid Foundation (IPPF) has recently developed a disease registry with the aim to enhance our understanding of autoimmune bullous diseases with the long-term goal of acquiring information to improve patient care. Patients were recruited to the IPPF disease registry through direct mail, e-mail, advertisements, and articles in the IPPF-quarterly, -website, -Facebook webpage, and IPPF Peer Health Coaches to complete a 38-question survey. We present here the initial analysis of detailed clinical information collected on 393 PV patients. We report previously unrecognized gender differences in terms of lesion location, autoimmune comorbidity, and delay in diagnosis. The IPPF disease registry serves as a useful resource and guide for future clinical investigation. PMID:24691863

  20. Urban legend series: mucous membrane pemphigoid.

    PubMed

    Di Zenzo, G; Carrozzo, M; Chan, L S

    2014-01-01

    Mucous membrane pemphigoid (MMP) is a heterogeneous group of autoimmune subepithelial blistering diseases affecting primarily mucous membranes showing marked degree of clinical and immunological variability. We investigated four controversial topics: (i) Does oral pemphigoid (OP) really exist as a separate entity? (ii) Is mucous membrane pemphigoid curable? (iii) What is the best therapeutic option for MMP? (iv) Does exclusive oral IgA dermatitis exist as a distinct entity from MMP? Results from extensive literature searches suggested that (i) it is still unclear whether patients with OP could be considered as a distinct subset of MMP with specific clinical and immunological features; (ii) it is uncertain whether treatment regimens that get MMP under control can be eliminated to allow patients to be in drug-free remission or they should be continuously administered in some capacities; (iii) there is a concerning paucity of good-quality trials on MMP and available recommendations are solely based on generally small patients' cohorts or case series. Some of the 2002 consensus experts' opinions should be possibly updated, particularly regarding the safety of sulfa drugs; (iv) we did not find any strong evidence to support an exclusive oral (and perhaps also mucosal) form of LAD as a separate entity. PMID:24320968

  1. Autoimmune dermatologic toxicities from immune checkpoint blockade with anti-PD-1 antibody therapy: a report on bullous skin eruptions.

    PubMed

    Jour, George; Glitza, Isabella C; Ellis, Rachel M; Torres-Cabala, Carlos A; Tetzlaff, Michael T; Li, Janet Y; Nagarajan, Priyadharsini; Huen, Auris; Aung, Phyu P; Ivan, Doina; Drucker, Carol R; Prieto, Victor G; Rapini, Ronald P; Patel, Anisha; Curry, Jonathan L

    2016-08-01

    Monoclonal antibodies against the immune checkpoint programmed cell death receptor 1 (PD-1) improve the hosts' antitumor immune response and have showed tremendous promise in the treatment of advanced solid tumors and hematologic malignancies. Reports of serious autoimmune dermatologic toxicities from immune checkpoint blockade therapy, however, are emerging. We report our experience with five patients who presented with pruritic vesicles and blisters on the skin while treated with anti-PD-1 antibody immunotherapy with either nivolumab or pembrolizumab. Four of the patients' skin biopsies revealed subepidermal bullae with immunohistochemical study for type IV collagen labeling the floor of the blister cavity and direct immunofluorescence studies (in three of the four patients tested) decorated linear IgG and C3 immune deposits on the blister roof, diagnostic of bullous pemphigoid. One patient developed bullous erythema multiforme. All patients had partial or complete resolution of skin lesions following treatment with systemic corticosteroid and cessation of checkpoint blockade. Recognition and treatment of rare immune-related bullous dermatologic toxicities will become increasingly important as more patients are treated with effective and newer immune checkpoint blockade therapy. PMID:27086658

  2. Heat shock protein 90: a pathophysiological factor and novel treatment target in autoimmune bullous skin diseases.

    PubMed

    Tukaj, Stefan; Zillikens, Detlef; Kasperkiewicz, Michael

    2015-08-01

    The chaperone heat shock protein 90 (Hsp90), a cell stress-inducible molecule that regulates activity of many client proteins responsible for cellular growth, differentiation and apoptosis, has been proposed as an important therapeutic target in patients with malignancies. More recently, its active participation in (auto)immune processes has been recognized as evidenced by amelioration of inflammatory disease pathways through pharmacological inhibition of Hsp90 in rodent models of autoimmune encephalomyelitis, rheumatoid arthritis and systemic lupus erythematosus. Based on own current research results, this viewpoint essay provides important insights that Hsp90 is also involved as a notable pathophysiological factor in autoimmune blistering dermatoses including epidermolysis bullosa acquisita, bullous pemphigoid and possibly dermatitis herpetiformis. The observed in vitro, ex vivo and in vivo efficacy of anti-Hsp90 treatment in experimental models of autoimmune bullous diseases and its underlying multimodal anti-inflammatory mechanisms of interference with key contributors to autoimmune-mediated blister formation supports the introduction of selective non-toxic Hsp90 inhibitors into the clinical setting for the treatment of patients with these disorders. PMID:25980533

  3. [Bullous mastocytosis in infancy: a rare presentation].

    PubMed

    Deverrière, G; Carré, D; Nae, I; Cailliez, D; Boulloche, J

    2012-07-01

    Mastocytosis is a rare condition related to an abnormal proliferation of mast cells and their accumulation in tissues. Cutaneous mastocytosis is the most common form and mainly affects newborns and infants. The symptoms are caused by the release of mediators contained in mast cells, including histamine. Mastocytosis may be associated with a mutation in the gene encoding the c-kit receptor. Clinically, there are different dermatological findings, which combine acute cutaneous, digestive, or even hemodynamic manifestations in varying degrees. The diagnosis is confirmed by the histological study of a skin sample. We report here the case of a 4-month-old infant suffering from diffuse cutaneous bullous mastocytosis, a very rare variety of mastocytosis. This infant had an erosive and bullous manifestation of dermatosis, initially confused with impetigo. The proliferation of bullous lesions led to her hospitalization. Codeine intake for pain was responsible for a large and extensive bullous reaction associated with anaphylactic shock. This context of bullous spread occurring after taking codeine led to the suspicion of bullous diffuse cutaneous mastocytosis, a diagnosis that was confirmed histologically. This observation demonstrates the difficulty of mastocytosis diagnosis, mostly due to its rarity, especially in its diffuse bullous forms. The rapid deterioration of this patient, after the codeine prescription, emphasizes the importance of the eviction of histamine-releaser compounds in the management of this disease. PMID:22664234

  4. Profibrotic Phenotype of Conjunctival Fibroblasts from Mucous Membrane Pemphigoid

    PubMed Central

    Saw, Valerie P.J.; Schmidt, Enno; Offiah, Ifeoma; Galatowicz, Grazyna; Zillikens, Detlef; Dart, John K.G.; Calder, Virginia L.; Daniels, Julie T.

    2011-01-01

    Ocular mucous membrane pemphigoid is an immunobullous disease in which excessive conjunctival fibrosis causes blindness, and the pathogenesis of scarring is incompletely understood. To establish whether profibrotic fibroblasts with an altered phenotype exist in ocular mucous membrane pemphigoid, we compared the functional characteristics of pemphigoid conjunctival fibroblasts to normal conjunctival fibroblasts with respect to cell division; migration; collagen contraction; matrix metalloproteinase, secretion of collagen and chemokines; and myofibroblast differentiation. We found that pemphigoid fibroblasts showed increased cell division (P = 0.01), increased migration in serum-free medium (72 ± 18 migrated cells versus 33 ± 11, P = 0.04), increased collagen contraction in the presence of 10 ng/ml tumor necrosis factor-α, increased collagen type I secretion (P = 0.03), increased secretion of matrix metalloproteinase-3 (P = 0.03), and increased secretion of eotaxin in response to interleukin-13 (P = 0.04). Differences between pemphigoid and normal conjunctival fibroblasts with respect to collagen contraction and MMP secretion in the presence of interleukin-13 were also observed. Together, these findings indicate that pemphigoid conjunctival fibroblasts have a profibrotic phenotype that is maintained in vitro. No differences between pemphigoid fibroblasts obtained from acutely inflamed versus clinically uninflamed conjunctiva were observed. Developing effective antifibrotic therapies will require understanding of the mechanisms that both induce and maintain the profibrotic phenotype. PMID:21224056

  5. Bullous leukemia cutis mimicking facial cellulitis*

    PubMed Central

    Caldato, Luciana de Sales; Britto, Juliana de Sousa; Niero-Melo, Ligia; Miot, Hélio Amante

    2016-01-01

    Bullous leukemia cutis is an uncommon clinical manifestation of cutaneous infiltration by leukemic cells, from B-cell chronic lymphocytic leukemia. We present the case of a 67-year-old, female, chronic lymphocytic leukemia patient. She was taking chlorambucil and developed facial edema with erythema and warmth, misjudged as facial cellulitis. Two days later, she developed bullous lesions in the arms, legs, neck and face. The histopathology of facial and bullous lesions confirmed leukemia cutis. All lesions disappeared following the administration of rituximab combined with cycles of fludarabine and cyclophosphamide. Although soft tissue infections are common complications in patients undergoing chemotherapy, leukemia cutis can also resemble cellulitis. PMID:27192532

  6. Ocular cicatricial pemphigoid masquerading as chronic conjunctivitis: a case report

    PubMed Central

    DaCosta, Joanna

    2012-01-01

    Conjunctivitis is often considered an innocuous condition which is self-limiting. This report describes misdiagnosis of ocular cicatricial pemphigoid as chronic conjunctivitis. Ocular cicatricial pemphigoid is a rare autoimmune condition. The clinical features which are useful to distinguish this condition from infective conjunctivitis are discussed. The investigation and treatment of ocular cicatricial pemphigoid is discussed. It is important to recognize nonocular symptoms and signs that may indicate the presence of a more serious underlying pathological condition necessitating specialized ophthalmic referral and subsequent investigation and treatment. PMID:23269857

  7. Antigen

    MedlinePlus

    An antigen is any substance that causes your immune system to produce antibodies against it. This means your immune ... and is trying to fight it off. An antigen may be a substance from the environment, such ...

  8. Azithromycin induced bullous fixed drug eruption

    PubMed Central

    Das, Anupam; Sancheti, Karan; Podder, Indrashis; Das, Nilay Kanti

    2016-01-01

    Fixed drug eruption (FDE) is a common type of drug eruption seen in skin clinics. It is characterized by solitary or multiple, round to oval erythematous patches with dusky red centers, some of which may progress to bulla formation. Bullous FDE may be caused by a number of drugs. We hereby describe a case of azithromycin-induced bullous FDE; to the best of our knowledge, this is the first such case being reported. PMID:26997729

  9. Phototherapeutic keratectomy for bullous keratopathy.

    PubMed Central

    Thomann, U; Meier-Gibbons, F; Schipper, I

    1995-01-01

    AIMS--This study was designed to investigate the therapeutic potential of excimer laser for recurrent painful erosions in patients not suited to treatment with penetrating keratoplasty. METHODS--Phototherapeutic keratectomy (PTK) with the excimer laser was performed prospectively on a series of 13 eyes of 12 patients with recurrent corneal erosions in connection with bullous keratopathy of varied aetiology. The main complaint of the patients before the treatment was frequent attacks of pain. The patients selected either refused corneal grafting or could not for a variety of reasons expect to profit visually from an operation. The treatment was performed with the MEL 60 Aesculap Meditec excimer laser using either a spot mode (five cases), a scanning mode (three cases), or a combination of both (five cases). RESULTS--All patients responded well to the treatment, and the pain subsided after a couple of weeks. In five cases (38.5%) a second treatment was necessary because of persistent pain, which was, however, much less than before the initial treatment. In four of these five patients small corneal bullae persisted. The visual performance of the seven patients with visual acuity better than 20/200 ameliorated in two cases and remained unchanged in four cases. One patient lost two Snellen lines after the laser treatment for terminal glaucoma. The mean follow up was 14.1 months (range 1-28 months). No complications were seen so far. CONCLUSION--It was concluded that PTK is a very promising and effective outpatient treatment for patients with bullous keratopathy. This therapeutic approach is not thought to have been described before. Images PMID:7742278

  10. Bullous Systemic Lupus Erythematosus: Case report

    PubMed Central

    Miziara, Ivan Dieb; Mahmoud, Ali; Chagury, Azis Arruda; Alves, Ricardo Dourado

    2013-01-01

    Summary Introduction: Bullous systemic lupus erythematosus (BSLE) is an autoantibody-mediated disease with subepidermal blisters. It is a rare form of presentation of SLE that occurs in less than 5% of cases of lupus. Case Report: A 27-year-old, female, FRS patient reported the appearance of painful bullous lesions in the left nasal wing and left buccal mucosa that displayed sudden and rapid growth. She sought advice from emergency dermatology staff 15 days after onset and was hospitalized with suspected bullous disease. Intravenous antibiotics and steroids were administered initially, but the patient showed no improvement during hospitalization. She displayed further extensive injuries to the trunk, axillae, and vulva as well as disruption of the bullous lesions, which remained as hyperemic scars. Incisional biopsy of a lesion in the left buccal mucosa was performed, and pathological results indicated mucositis with extensive erosion and the presence of a predominantly neutrophilic infiltrate with degeneration of basal cells and apoptotic keratinocytes. Under direct immunofluorescence, the skin showed anti-IgA, anti-IgM, and anti-IgG linear fluorescence on the continuous dermal side of the cleavage. Indirect immunofluorescence of the skin showed conjugated anti-IgA, was anti-IgM negative, and displayed pemphigus in conjunction with anti-IgG fluorescence in the nucleus of keratinocytes, consistent with a diagnosis of bullous lupus erythematosus. Discussion: BSLE is an acquired autoimmune bullous disease caused by autoantibodies against type VII collagen or other components of the junctional zone, epidermis, and dermis. It must be differentiated from the secondary bubbles and vacuolar degeneration of the basement membrane that may occur in acute and subacute cutaneous lupus erythematosus. PMID:25992032

  11. [Chronic bullous dermatosis in childhood (linear IgA dermatosis)].

    PubMed

    Wilk, M; Biwer, E

    1993-07-01

    A 5-year-old boy presented with disseminated, partly grouped blisters indicative of chronic bullous dermatosis of childhood (CBDC) following a gastrointestinal infection 2 weeks earlier. CBDC has long been differentiated from adult linear IgA disease. Clinical and laboratory studies revealed substantial clinical and immunological overlap between the two blistering disorders, whereas recent investigations suggest heterogeneity of the target antigen involved. Pathohistological and immunofluorescence-microscopical characteristics of a subepidermal blister and linear IgA and granular C3 deposition at the basement membrane together with the typical history and clinical signs were decisive in the differential diagnosis. The disease promptly cleared up after daily administration of 16 mg methylprednisolone-21-acetate tapering and 25 mg dapsone. Immunohistological detection of collagen IV at the base of a blister made it possible to localize the split above the lamina densa. The demonstration of collagen IV stresses the importance of immunodermatopathology in the differential diagnosis of subepidermal blistering diseases. PMID:8365883

  12. Anti-BP180-type mucous membrane pemphigoid immunoglobulin G shows heterogeneity of internalization of BP180/collagen XVII into keratinocyte cytoplasm.

    PubMed

    Imanishi, Akiko; Imanishi, Hisayoshi; Hiroyasu, Sho; Ozawa, Toshiyuki; Koga, Hiroshi; Ishii, Norito; Kitajima, Yasuo; Hashimoto, Takashi; Tsuruta, Daisuke

    2016-06-01

    Anti-BP180-type mucous membrane pemphigoid (BP180-MMP) is a rare autoimmune subepidermal blistering disease that targets the C terminus of BP180/collagen XVII. Currently, the pathomechanism of BP180-MMP is not well understood. We reported previously that immunoglobulin G (IgG) from patients with bullous pemphigoid (BP) can induce internalization of BP180 via a macropinocytic pathway, which depletes BP180 and weakens epidermal cell-matrix integrity. The purpose of the present study was to elucidate the pathomechanism of BP180-MMP. Immunohistochemistry of biopsy specimens from two patients with BP180-MMP revealed that one patient had BP180 internalization, but the other did not. In live-cell imaging using IgG from patients with BP180-MMP on several keratinocyte cell lines, IgG from only three out of the seven patients was associated with BP180 internalization into the cytoplasm. Our results suggest that IgG from patients with BP180-MMP shows heterogeneity of internalization of BP180. This variability in BP180 internalization in patients with BP or BP180-MMP may lead to differences in clinical presentation. PMID:26658728

  13. Vesiculo-Bullous Disorders in Childhood

    PubMed Central

    McKay, Roberta M.

    1987-01-01

    This is the second of three articles outlining the diagnoses to be considered when vesiculo-bullous lesions are identified in the neonate, children, and adults. This paper deals with a number of blistering disorders which can arise throughout infancy and childhood. Both inherited and acquired diseases are considered, and general guidelines for diagnosis and management are discussed. PMID:21264002

  14. Bullous hemorrhagic dermatosis induced by enoxaparin.

    PubMed

    Gouveia, Ana Isabel; Lopes, Leonor; Soares-Almeida, Luis; Filipe, Paulo

    2016-06-01

    The bullous hemorrhagic dermatosis induced by enoxaparin is a rare adverse reaction, which may be under-reported given its favorable evolution. We report a 71-year-old man who developed hemorrhagic bullae at sites distant from subcutaneous enoxaparin injections. It is important that clinicians be aware of the different adverse reactions of these widely used drugs. PMID:25942690

  15. Linear IgA Bullous Dermatosis: A Rare Clinicopathologic Entity with an Unusual Presentation.

    PubMed

    Chaudhari, Soham; Mobini, Narciss

    2015-10-01

    Linear immunoglobulin A bullous dermatosis is a rare autoimmune mucocutaneous disorder caused by immunoglobulin A autoantibodies produced against several different antigens in the basement membrane zone. Clinically, it is characterized by tense vesicles or bullae, which on histopathological exam demonstrate subepidermal blister with a predominantly neutrophilic infiltrate. A smooth, linear pattern of immunoglobulin A deposition in the basement membrane zone on direct immunofluorescence is considered the gold standard for establishing a diagnosis. Treatment consists of dapsone or sulfapyridine. The authors report a 60-year-old woman who presented with pruritic erythematous patches and plaques on her trunk, back, and legs without blisters, who was diagnosed with eczema for several months with no response to prior treatments. A biopsy was performed, which was consistent with linear immunoglobulin A bullous dermatosis and later confirmed by direct immunofluorescence studies. The authors present this case to increase awareness of this rare disease, which could manifest in a nonclassical, nonblistering fashion. PMID:26557220

  16. Autoimmune Bullous Skin Disorders with Immune Checkpoint Inhibitors Targeting PD-1 and PD-L1.

    PubMed

    Naidoo, Jarushka; Schindler, Katja; Querfeld, Christiane; Busam, Klaus; Cunningham, Jane; Page, David B; Postow, Michael A; Weinstein, Alyona; Lucas, Anna Skripnik; Ciccolini, Kathryn T; Quigley, Elizabeth A; Lesokhin, Alexander M; Paik, Paul K; Chaft, Jamie E; Segal, Neil H; D'Angelo, Sandra P; Dickson, Mark A; Wolchok, Jedd D; Lacouture, Mario E

    2016-05-01

    Monoclonal antibodies (mAb) targeting immune checkpoint pathways such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) may confer durable disease control in several malignancies. In some patients, immune checkpoint mAbs cause cutaneous immune-related adverse events. Although the most commonly reported cutaneous toxicities are mild, a subset may persist despite therapy and can lead to severe or life-threatening toxicity. Autoimmune blistering disorders are not commonly associated with immune checkpoint mAb therapy. We report a case series of patients who developed bullous pemphigoid (BP), an autoimmune process classically attributed to pathologic autoantibody formation and complement deposition. Three patients were identified. Two patients developed BP while receiving the anti-PD-1 mAb nivolumab, and one while receiving the anti-PD-L1 mAb durvalumab. The clinicopathologic features of each patient and rash, and corresponding radiologic findings at the development of the rash and after its treatment, are described. Patients receiving an anti-PD-1/PD-L1 mAb may develop immune-related BP. This may be related to both T-cell- and B-cell-mediated responses. Referral to a dermatologist for accurate diagnosis and management is recommended. Cancer Immunol Res; 4(5); 383-9. ©2016 AACR. PMID:26928461

  17. Literature-based immunization recommendations for patients requiring immunosuppressive medications for autoimmune bullous dermatoses.

    PubMed

    Laniosz, Valerie; Lehman, Julia S; Poland, Gregory A; Wetter, David A

    2016-06-01

    Autoimmune bullous diseases, such as pemphigus, pemphigoid, and dermatitis herpetiformis, are uniquely associated with vulnerability in the mucocutaneous barrier against infection. The management of immunobullous diseases is complex and may at times require immunosuppressive medications. Iatrogenic immunosuppression may increase susceptibility to vaccine-preventable illnesses. Currently, there are no guidelines to assist the clinician treating patients with immunobullous disease regarding the delivery of various vaccinations. The aim of this review is to provide recommendations for immunization in the unique setting of immunobullous disease. Recommendations are based on careful review of the literature in other conditions requiring iatrogenic immunosuppression, as well as the most recent Centers for Disease Control and Prevention guidelines. Immunization with nonlive vaccines appears to be a safe and effective strategy for preventing infection in the particularly susceptible patient with immunobullous disease. Opportunities for live vaccine administration may become available at lower levels of immune suppression or during clinical remission when immunosuppressive regimens can be reduced. Anticipatory vaccination before the initiation of iatrogenic immunosuppression is ideal. Although immunologic response to vaccination may be suboptimal during immunosuppression, nonlive vaccination is strongly recommended for this patient population. PMID:26711431

  18. Heat shock protein 90 inhibition: A potential double- or triple-edged sword in the treatment of mucous membrane pemphigoid.

    PubMed

    Kasperkiewicz, Michael; Płatkowska, Anna; Zalewska, Anna; Zillikens, Detlef

    2015-10-01

    Mucous membrane pemphigoid (MMP) is a subtype of autoimmune subepidermal blistering diseases characterized by autoantibodies to structural components of the hemidesmosome primarily affecting mucous membranes. Inflammation-related progressive scarring can lead to serious complications, including blindness, and the disease may be associated with malignancy. Conventional immunosuppressive treatment is often insufficiently effective and limited due to side effects, warranting new therapeutic options ideally targeting both inflammation and extensively recalcitrant cicatrization. Heat shock protein 90 (Hsp90) is a cell stress-inducible chaperone required for the function of a large number of client proteins, and its pharmacological inhibition has proven to be effective and relatively safe in patients with cancer. Recent observations also suggest a promising role of Hsp90 as drug target in preclinical in vivo murine models of autoimmune diseases such as subepidermal bullous and fibrotic autoimmune disorders comprising epidermolysis bullosa acquisita and systemic sclerosis, respectively, which exhibit some pathophysiological features reminiscent of MMP. This article thus hypothesizes that Hsp90 blockade could represent a double-edged sword in MMP treatment by targeting pathogenic factors of inflammatory blister and fibrosis formation. Moreover, Hsp90 inhibitors could even be proclaimed as a triple-edged sword in case of an underlying malignancy. Future studies investigating the role of Hsp90 in MMP are needed to clarify whether Hsp90 inhibition could become a novel treatment approach for patients with this potentially devastating disease. PMID:26152650

  19. Staphylococcal bullous impetigo in a neonate.

    PubMed

    Duggal, Shalini Dewan; Bharara, Tanisha; Jena, Pragnya Paramita; Kumar, Avinash; Sharma, Abha; Gur, Renu; Chaudhary, Sanjay

    2016-07-16

    An otherwise healthy, full-term neonate presented at day 15 of life to the pediatric emergency with generalized papulo-pustular rash for 2 d. This was finally diagnosed as bullous impetigo caused by Staphylococcus aureus (S. aureus). The skin lesions decreased significantly after starting antibiotic therapy and drainage of blister fluid. There was no recurrence of the lesions on follow-up. This case of generalized pustular eruption due to S. aureus in a neonate is reported, as it poses a diagnostic dilemma and can have serious consequences if left untreated. PMID:27458596

  20. Staphylococcal bullous impetigo in a neonate

    PubMed Central

    Duggal, Shalini Dewan; Bharara, Tanisha; Jena, Pragnya Paramita; Kumar, Avinash; Sharma, Abha; Gur, Renu; Chaudhary, Sanjay

    2016-01-01

    An otherwise healthy, full-term neonate presented at day 15 of life to the pediatric emergency with generalized papulo-pustular rash for 2 d. This was finally diagnosed as bullous impetigo caused by Staphylococcus aureus (S. aureus). The skin lesions decreased significantly after starting antibiotic therapy and drainage of blister fluid. There was no recurrence of the lesions on follow-up. This case of generalized pustular eruption due to S. aureus in a neonate is reported, as it poses a diagnostic dilemma and can have serious consequences if left untreated. PMID:27458596

  1. Bullous pilomatricoma: a stage in transition to secondary anetoderma?

    PubMed

    Bhushan, Premanshu; Hussain, Syed N

    2012-01-01

    Pilomatricoma is an uncommon hamartomatous tumor of the hair matrix. Bullous and anetodermic changes over pilomatricoma are rare. We report an 18-year-old male with an asymptomatic nodule with overlying cystic changes on the left arm of 6-month duration with clinical and histological features of both bullous and anetodermic modifications. We also reviewed the associated literature to conclude that there is sufficient overlap in these two entities. Both variants show a bullous or pseudobullous appearance clinically and loss of elastin, sparse collagen bundles separated by intense edema, and dilated lymphatics/blood vessels in the dermis overlying the tumor mass histologically. We therefore propose that bullous, pseudoampullary, anetodermic, and lymphangiectatic forms should be considered as synonymous or transitional to the ultimate scar-like anetodermic appearance. PMID:22772621

  2. Bullous impetigo caused by Streptococcus salivarius: a case report.

    PubMed Central

    Brook, I

    1980-01-01

    A 19-month-old child presented with bullous impetigo around the perineal region, penis, and left foot. Streptococcus salivarius was the only isolate recovered from the lesions. The child was treated with parenteral penicillin, debridement of the bulli, and local application of silver sulphadiazine cream. This case of bullous impetigo illustrates another aspect of the pathogenicity of Strep. salivarius. Images Fig. 1 Fig. 2 PMID:7002959

  3. Bullous variant of idiopathic central serous chorioretinopathy

    PubMed Central

    Sahu, D.; Namperumalsamy, P; Hilton, G.; de Sousa, N. F

    2000-01-01

    BACKGROUND—Spontaneous bullous serous retinal detachment (RD) with subretinal exudation complicating idiopathic central serous chorioretinopathy (ICSC) is a rare and infrequently described clinical entity. Clinical observations are described on this variant form in 11 patients, the largest series reported to date.
METHODS—13 eyes of 11 Indian patients having this entity were followed up clinically and angiographically for 12-24 months (retrospective, longitudinal). None of the patients had any previous history of other diseases nor were they on any medications. Four eyes received laser treatment (group A); nine eyes were not treated (group B).
RESULTS—All 11 patients were male, aged 23-49 years (median 37 years). The clinical and photographic records revealed subretinal exudation and inferior bullous serous RD complicating ICSC with evidence of large, single or multiple, leaking retinal pigment epithelial detachments (PEDs) in all the cases. In group A, resolution of serous RD occurred in 12 weeks (median) with a visual recovery of ⩾20/30 in three out of four eyes while in group B resolution of serous retinal detachment was observed in 14 weeks (median) with eight out of nine eyes achieving a visual acuity of ⩾20/30. Subretinal fibrosis developed in two eyes in group A and none of the eyes in group B.
CONCLUSION—The disease is an exaggerated form of ICSC and can occur spontaneously without any history of corticosteroid therapy. Recognition of this atypical presentation is important to avoid inappropriate treatment. These observations suggest that with respect to the duration of the disease and the final visual outcome laser therapy offers no additional benefit over the natural course of this variant form of ICSC.

 PMID:10781512

  4. Concomitant pemphigus vulgaris and pemphigoid gestationis: a case report and review of the literature.

    PubMed

    Vin, Harina; Seyfer, Sarah J; McClain, Colt M; Hsu, Sylvia

    2016-01-01

    Pemphigus and pemphigoid are two unique acquired immunobullous diseases with distinct clinical presentations, histological findings, and characteristic serology; they are rarely reported to coexist in the same patient. Herein we present a 29-year-old woman with a history of pemphigus vulgaris, diagnosed by histology and positive desmoglein-3 antibodies on ELISA. She presented to our clinic shortly after the delivery of her first child with tense vesicles and bullae on an erythematous base on her abdomen. Biopsy was consistent with pemphigoid gestationis and direct immunofluorescence confirmed the diagnosis. To our knowledge, there are no other reported cases of pemphigoid gestationis occurring in a patient with pemphigus vulgaris. PMID:26990471

  5. Systemic minocycline as a therapeutic option in predominantly oral mucous membrane pemphigoid: a cautionary report.

    PubMed

    Carrozzo, M; Arduino, P; Bertolusso, G; Cozzani, E; Parodi, A

    2009-10-01

    The aim of this study was to evaluate the therapeutic benefit of minocycline in mucous membrane pemphigoid (MMP) predominantly involving the oral cavity. A descriptive, open clinical study with no control group, including 9 patients, was developed. The diagnosis was confirmed by histopathological examination and direct and salt-split-skin indirect immunofluorescence analysis. Target antigens were sought by immunoblotting. Patients received minocycline (200mg/day) for a variable period. All patients were followed up for at least 2 years after initial diagnosis. Therapeutic response was assessed by clinical improvement in three categories: major response, minor response and no response. A major response was observed in 3 patients (33%), a minor response in 4 (44%) and 2 (22%) patients showed no improvement. Two of the 3 patients with a major response showed no immunoblot reactivity; 80% of patients with circulating autoantibodies (autoAb) against BP180 had a minor or no response. Permanent remission of signs with no relapse was only obtained in one patient. 5 patients (55%) stopped the drug because of adverse effects, such as vertigo and gastralgia. The results revealed temporary clinical benefits in MMP predominantly involving the oral cavity with minocycline, although frequently side effects led to drug withdrawal. PMID:19628373

  6. Benign mucous membrane pemphigoid with advanced periodontal involvement: diagnosis and therapy.

    PubMed

    Lilly, J P; Spivey, J D; Fotos, P G

    1995-08-01

    This paper describes a case of benign mucous membrane pemphigoid which affected the periodontal tissues and complicated ocular prosthesis placement. The clinical findings, diagnostic criteria, and therapeutic management of this disorder are reviewed. PMID:7473017

  7. A clinical study of oral mucous membrane pemphigoid.

    PubMed

    Alkan, A; Günhan, O; Alkan, A; Otan, F

    2003-01-01

    We present 13 cases of oral mucous membrane pemphigoid (MMP) and review the literature. The cases were retrieved from the archives of Ondokuz Mayis University and Gülhane Military Medical Academy, Turkey, between 1997 and 2002. Inclusion criteria were clinical findings of oral MMP verified by histological and immunofluorescent examination. Thirteen patients (two males and 11 females), aged 16-72 years, were identified. Involvement was confined to the mouth in all cases except one, in which the conjunctiva was also affected. Two individuals in the study were < 20 years old, an age group rarely affected. The oral mucosa is often the initial site of MMP lesions, so it is important that dentists as well as physicians are aware of the symptoms and signs. A swift diagnosis, made in consultation with other specialists such as ophthalmologists and dermatologists, is needed in order to prevent a delay in treatment. PMID:12964512

  8. A Fatal Case of "Bullous Erysipelas-like" Pseudomonas Vasculitis.

    PubMed

    Yang, Sam Shiyao; Chandran, Nisha Suyien; Huang, Jing Xiang; Tan, Kong-Bing; Aw, Derrick Chen-Wee

    2016-01-01

    Erysipelas is a generally benign superficial bacterial skin infection, and its bullous form constitutes a rare and more severe variant. We describe the first and fatal case of "bullous erysipelas-like" septic vasculitis due to Pseudomonas bacteremi. A 69-year-old Chinese man presenting with diarrhea and septic shock initially began to rapidly develop sharply defined erythematous plaques with non-hemorrhagic bullae over his lower limbs. Culture of the aspirate from the bullae was positive for Pseudomonas aeruginosa. This was also consistent with his blood cultures showing Pseudomonas bacteremia. Histology of the skin lesion showed microthrombi and neutrophilic infiltrates in blood vessels with Gram-negative bacilli extruding from the vessel walls, characteristic of septic vasculitis. The bullous erysipelas-like lesions seen in this patient represents a rare manifestation of both septic vasculitis and Pseudomonas infection. PMID:26955132

  9. Extragenital bullous lichen sclerosus in a pediatric patient: a case report and literature review.

    PubMed

    Shiver, Mallory; Papasakelariou, Catherine; Brown, Jameel Ahmad; Wirges, Marla; Kincannon, Jay

    2014-01-01

    A 14-year-old girl presented with a 1-year history of a pruritic, bullous lesion on her posterior neck. A biopsy revealed bullous lichen sclerosus. Although unusual, this bullous variant of lichen sclerosus is well recognized in the adult literature, but extragenital bullous and hemorrhagic lesions are rare in children. A review of this case and the literature describes the clinical features, pathophysiology, and treatment options for this extragenital bullous variant in an effort to raise awareness of this rare clinical presentation. PMID:23171125

  10. Ciprofloxacin induced bullous fixed drug reaction: three case reports

    PubMed Central

    Nair, Pragya A.

    2015-01-01

    Cutaneous adverse drug reactions (ADRs) are seen in about 1–2% cases. Fixed drug reaction (FDR) is responsible for about 10% of all ADRs. It is a delayed type of hypersensitivity reaction that occurs as lesions recurs at the same skin site due to repeated intake of an offending drug. The most common drugs causing fixed drug eruption (FDE) are analgesics, antibiotics, muscle relaxants and anticonvulsants. FDE due to ciprofloxacin has been reported earlier also, but bullous variant of FDR is rare. We hereby report three case reports of bullous FDR caused due to ciprofloxacin. PMID:25949980

  11. Bullous Fixed Drug Eruption Probably Induced by Paracetamol

    PubMed Central

    Agarwala, Manoj Kumar; Mukhopadhyay, Sramana; Sekhar, M Raja; Peter, CV Dincy

    2016-01-01

    We report a case of a 42-year-old male who presented with second episode of bullous eruptions after ingestion of paracetamol. There were no systemic complaints. The temporal correlation with the drug, history of a similar episode and the quick improvement led us to a diagnosis of bullous fixed drug due to paracetamol. Applying Naranjo's algorithm, a causality score of 8 was obtained and was categorized as probable reaction to paracetamol. Clinicians should be vigilant of the possible adverse reactions to drugs with robust safety profiles. Drug alert cards could play an important role in preventing recurrences. PMID:26951737

  12. Bullous impetigo associated with Abiotrophia defectiva in an immunocompetent adult.

    PubMed

    Anderson, Heather M; Miller, Cathy; Kemp, Earl; Huntington, Mark K

    2012-07-01

    Infection of humans by Abiotrophia defectiva, a nutritionally variant streptococcus, most commonly takes the form of endocarditis, though a variety of other manifestations ranging from central nervous system abscesses to orthopaedic infections have been seen. We report here what we believe is the first case of bullous impetigo associated with this organism. PMID:22493280

  13. Bullous reactions to bed bug bites reflect cutaneous vasculitis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study evaluates bullous cutaneous reactions and sequential histopathology in an individual sensitized to bed bug bites in an effort to better understand the allergic response and histology associated with these bites. There was a progression of the inflammatory response across time ranging from...

  14. Localized bullous eruption in a patient with anasarca.

    PubMed

    Bernardes Filho, Fred; Kac, Bernard Kawa

    2016-01-01

    The diagnosis of bullae can be a challenge. The proper diagnosis and prompt treatment is mandatory because most of these diseases are associated with a significant degree of morbidity. The authors present the case of a 76-year-old woman admitted for treatment of anasarca. She also exhibited a bullous eruption localized to the right upper limb. PMID:27136638

  15. Desquamative gingivitis as only presenting sign of mucous membrane pemphigoid.

    PubMed

    Vijayan, Veena; Paul, Ajish; Babu, Kennedy; Madhan, Balasubramanian

    2016-01-01

    Desquamative gingivitis (DG) is a clinical condition in which the gingiva appears reddish, glazed, and friable with loss of superficial epithelium. DG is considered a clinical manifestation of many gingival diseases and hence not identified as a diagnosis itself. Mucous membrane pemphigoid (MMP) is an autoimmune vesiculobullous disorder of mucous membrane characterized by subepithelial bullae formation. MMP can affect the mucous membranes of oral cavity, conjunctiva, nasopharynx, larynx, esophagus, genitourinary tract, and anus and vary in its severity. The most commonly affected sites are oral cavity and conjunctiva. Since DG may be the early sign or only presenting sign of these conditions, most of the times, dental surgeon plays a key role in the diagnosis and prevention of the systemic complications of these diseases. We report a case of a 41-year-old male patient presented with DG. Histopathological examination revealed subepithelial clefting suggestive of MMP. The patient was treated with topical application of triamcinolone acetonide 0.1% 3-4 times a day for 1 month. PMID:27563211

  16. Desquamative gingivitis as only presenting sign of mucous membrane pemphigoid

    PubMed Central

    Vijayan, Veena; Paul, Ajish; Babu, Kennedy; Madhan, Balasubramanian

    2016-01-01

    Desquamative gingivitis (DG) is a clinical condition in which the gingiva appears reddish, glazed, and friable with loss of superficial epithelium. DG is considered a clinical manifestation of many gingival diseases and hence not identified as a diagnosis itself. Mucous membrane pemphigoid (MMP) is an autoimmune vesiculobullous disorder of mucous membrane characterized by subepithelial bullae formation. MMP can affect the mucous membranes of oral cavity, conjunctiva, nasopharynx, larynx, esophagus, genitourinary tract, and anus and vary in its severity. The most commonly affected sites are oral cavity and conjunctiva. Since DG may be the early sign or only presenting sign of these conditions, most of the times, dental surgeon plays a key role in the diagnosis and prevention of the systemic complications of these diseases. We report a case of a 41-year-old male patient presented with DG. Histopathological examination revealed subepithelial clefting suggestive of MMP. The patient was treated with topical application of triamcinolone acetonide 0.1% 3–4 times a day for 1 month. PMID:27563211

  17. Recognizing Presentations of Pemphigoid Gestationis: A Case Study

    PubMed Central

    2014-01-01

    Introduction. Pemphigoid gestationis (PG) is an autoimmune blistering disease that occurs in approximately 1 in 50,000 pregnancies. Failing to recognize PG may lead to inadequate maternal treatment and possible neonatal complications. Case Report. At 18 weeks of gestation, a 36-year-old otherwise healthy Caucasian G4P1 presented with pruritic papules on her anterior thighs, initially treated with topical steroids. At 31 weeks of gestation, she was switched to oral steroids after her rash and pruritus worsened. The patient had an uncomplicated SVD of a healthy female infant at 37 weeks of gestation and was immediately tapered off steroid treatment, resulting in a severe postpartum flare of her disease. Discussion. This case was similar to reported cases of pruritic urticarial papules followed by blisters; however, this patient had palm, sole, and mucous membrane involvement, which is rare. Biopsy for direct immunofluorescence or ELISA is the preferred test for diagnosis. Previous case reports describe severe postdelivery flares that require higher steroid doses. Obstetrical providers need to be familiar with this disease although it is rare, as this condition can be easily confused with other dermatoses of pregnancy. Adequate treatment is imperative for the physical and psychological well-being of the mother and infant. PMID:25506008

  18. Ulcers caused by bullous morphea: successful therapy with N-acetylcysteine and topical wound care.

    PubMed

    Rosato, E; Veneziano, M L; Di Mario, A; Molinaro, I; Pisarri, S; Salsano, F

    2013-01-01

    Bullous morphea is an uncommon form of localized scleroderma. The pathogenesis is unknown and treatment of coexistent ulcers is difficult. The pathogenesis of bullae formation in morphea is multifactorial, but reactive oxygen species production appears to play a key role. We report a patient with bullous morphea with long-standing ulcers whom we successfully treated with N-acetylcysteine and topical wound care. N-acetylcysteine, an antioxidant sulfhydryl substance, promotes the healing of ulcers in patients with bullous morphea. PMID:23527731

  19. A breath from Houdini - A case of giant bullous emphysema.

    PubMed

    Tay, Chee Kiang; Ng, Yuen Li

    2015-01-01

    We describe a case of a young man presenting with exertional dyspnea. His chest radiograph showed hyperlucency in his left lung, and he was subsequently diagnosed to have giant bullous emphysema. An approach to lesions of decreased attenuation on computed tomography of the chest, with a focus on cystic lung diseases is discussed. This is followed by a literature review of the clinical presentation, natural history, radiology and management of giant bullous emphysema. Although this is an uncommon condition, a clinician has to be cognizant of the fact that it may mimic other common respiratory diseases. This review highlights the importance of these caveats as misguided treatment options may lead to devastating consequences. PMID:26029573

  20. Oral bullous lichen planus: Case report and review of management

    PubMed Central

    Patil, Archana; Prasad, Shiva; Ashok, L.; Sujatha, G. P.

    2012-01-01

    A 34-year-old female patient with the chief complaint of burning sensation in the oral cavity associated with generalized pruritis, scalp and skin lesions diagnosed as Bullous lichen planus and treated with systemic prednisolone, levamisole, benzydamine oral rinse. Patient is in follow up since 1 year and free of lesions. Here we report the case and review current modalities in the management of oral lichen planus. PMID:23293497

  1. A Case of Lichen Sclerosus et Atrophicus Accompanying Bullous Morphea

    PubMed Central

    Yasar, Sirin; Serdar, Zehra Asiran; Gunes, Pembegul

    2011-01-01

    Bullous morphea is a rare form of morphea characterized with bullae on or around atrophic morphea plaques. Whereas lichen sclerosus et atrophicus (LSA) is a disease the etiology of which is not fully known, and which is characterized with sclerosis. Coexistence of morphea and LSA has been identified in some cases. Some authors believe that these two diseases are different manifestations which are on the same spectrum. The 70-year-old patient stated herein, presented to us for 6 months with annular, atrophic plaques, ivory color in the middle, surrounded by living erythema, on the front and back of the trunk. Occasionally bulla formation on the plaques on the trunk lateral was identified. Fibrotic and atrophic plaques of ligneous hardness were present on the front side of tibia of both legs. In the histopathologic examination, the lesions were found concordant with bullous morphea and LSA. With colchicine 1.5 mg/day, pentoxifylline 1,200 mg/day, topical calcipotriol ointment and clobetasol propionate cream, the erythema in the patient's lesions faded and softening in the fibrotic plaques was observed. Concomitance of bullous morphea and LSA is a rarely seen, interesting coexistence which suggests a common, as yet unknown, underlying pathogenesis. PMID:22346277

  2. Annular bullous lesions with atypical erythema multiforme in leprosy.

    PubMed

    Shah, Aishani; Mahajan, Rashmi; Ninama, Kishan; Bilimoria, Freny

    2014-09-01

    Erythema nodosum leprosum (ENL) is an immune complex-mediated reaction that may complicate the course of multibacillary leprosy. Bullous lesions in Type II reaction, though reported, are exceedingly rare. We report the case of a 32 year old female patient who presented initially at our OPD with erythema nodosum. Cutaneous examination revealed impaired sensation over dorsum of right foot and thickened right lateral popliteal nerve. Slit skin smear (SSS) from ear lobes revealed AFB with a bacteriological index of 2+. She was started on MDT, tablet ofloxacin 200 mg twice a day, and 30 mg oral prednisolone. Two months later, she presented with generalised pruritus, large target lesions over the back, and hemorrhagic bullae over lower extremities and annular pattern of bullae, over both arms. A SSS was repeated which was positive for AFB. Histopathology from bullous lesions was consistent with ENL. Direct Immunofluorescence (DIF) study was negative. Our patient improved rapidly after she was started on thalidomide 100 mg twice daily, with withdrawal of ofloxacin. Erythema Multiforme (EMF) and annular bullous lesions have been reported in patients on treatment with ofloxacin. This case is being presented due to the unusual and varied manifestation of Type II lepra reaction in a 34 year old female patient. PMID:25509721

  3. Bleb point: mimicker of pneumothorax in bullous lung disease.

    PubMed

    Gelabert, Christopher; Nelson, Mathew

    2015-05-01

    In patients presenting with severe dyspnea, several diagnostic challenges arise in distinguishing the diagnosis of pneumothorax versus several other pulmonary etiologies like bullous lung disease, pneumonia, interstitial lung disease, and acute respiratory distress syndrome. Distinguishing between large pulmonary bullae and pneumothorax is of the utmost importance, as the acute management is very different. While multiple imaging modalities are available, plain radiographs may be inadequate to make the diagnosis and other advanced imaging may be difficult to obtain. Ultrasound has a very high specificity for pneumothorax. We present a case where a large pulmonary bleb mimics the lung point and therefore inaccurately suggests pneumothorax. PMID:25987927

  4. Quality of life in patients with bullous dermatoses

    PubMed Central

    Sebaratnam, Deshan F.; McMillan, James R.; Werth, Victoria P.; Murrell, Dédée F.

    2013-01-01

    Genetic and acquired bullous dermatoses can severely affect multiple domains of a patient’s quality of life (QOL). Integrating formal evaluation of QOL into the clinical evaluation of patients facilitates an objective assessment of disease severity, mapping of disease trajectory, and captures therapeutic intervention outcomes. There have been 5 studies evaluating QOL in autoimmune dermatoses and 4 studies reviewing QOL in the genodermatoses. All literature to date indicates a significant disease burden in this setting. The development of formal QOL instruments has facilitated quantification of QOL deficits in this arena and offers promising tools for patient assessment in the future. PMID:22137233

  5. Unilateral Oral Mucous Membrane Pemphigoid: Refractory Atypical Presentation Successfully Treated with Intravenous Immunoglobulins

    PubMed Central

    Laureano, André; Cardoso, Jorge

    2015-01-01

    A 57-year-old male presented with a 6-month history of blisters and painful erosions on the right buccal mucosa. No skin or other mucosal involvement was seen. The findings of histopathological and direct immunofluorescence examinations were sufficient for the diagnosis of oral mucous membrane pemphigoid in the context of adequate clinical correlation. No response was seen after topical therapies and oral corticosteroids or dapsone. Intravenous immunoglobulin was started and repeated every three weeks. Complete remission was achieved after three cycles and no recurrence was seen after two years of follow-up. The authors report a rare unilateral presentation of oral mucous membrane pemphigoid on the right buccal and hard palate mucosa, without additional involvement during a period of five years. Local trauma or autoimmune factors are possible etiologic factors for this rare disorder, here with unique presentation. PMID:25785208

  6. Bullous skin reaction seen after extravasation of calcium gluconate.

    PubMed

    Celbek, G; Gungor, A; Albayrak, H; Kir, S; Guvenc, S C; Aydin, Y

    2013-03-01

    Intravenous (IV) calcium is usually given to temporarily treat the effects of hyperkalaemia on muscle and heart. When extravasation of a calcium gluconate infusion occurs, there may be rapid and marked swelling and erythema, with signs of soft-tissue necrosis or infection, and ensuing extensive local calcification, called calcinosis cutis. We report a 26-year-old woman who was hospitalized for exacerbation of acute intermittent porphyria. She had a history of hypertension and chronic renal failure. On the second day of her hospitalization, she developed hyperpotassaemia (6.7 mEq/L potassium; normal range 3.5-5 mEq/L). She was given an IV infusion of 10 mL calcium gluconate into the left dorsal pedal vein. Bullous skin reactions occurred in the infusion area nearly 2 h after administration. The patient's leg was elevated and the lesions cleaned with 0.9% saline. By day 9 of hospitalization, the lesions had markedly regressed. Several drugs have been associated with dermoepidermal blistering as an adverse drug reaction, but there is only one existing report in the literature about this side-effect associated with calcium gluconate. Clinicians should be alert to the possibility of bullous skin reactions, which may be a predictor of extravasation and necrosis, when treating patients with IV calcium gluconate. PMID:22830330

  7. Bullous delayed pressure urticaria: pathogenic role for eosinophilic granulocytes?

    PubMed

    Kerstan, A; Rose, C; Simon, D; Simon, H-U; Bröcker, E-B; Trautmann, A; Leverkus, M

    2005-08-01

    Bullous delayed pressure urticaria (DPU) is a rare variant of DPU. Treatment of DPU is difficult and the underlying pathogenic mechanism of DPU remains elusive. We report a 72-year-old man with DPU and associated chronic urticaria as well as delayed urticarial dermographism. Pressure challenge gave rise to a deep weal covered by multiple vesicles and bullae after 24 h. Histological examination of a skin biopsy specimen obtained 24 h after pressure challenge demonstrated intraepidermal bullae filled with eosinophils accompanied by a dense, predominantly eosinophilic infiltrate in the dermis. Whereas the numbers and morphology of mast cells were unaltered, the extracellular deposition of eosinophil cationic protein revealed evidence for eosinophil activation. Concomitantly, both CD4+ and CD8+ T lymphocytes were present in the infiltrate and expressed interleukin 5. As bullous DPU may represent the maximal variant of DPU, the investigation of the cellular infiltrate and the chemokines/cytokines released may reveal potential pathogenic mechanisms. A possible effector role of eosinophilic granulocytes, T-cell subsets and mast cells is discussed. PMID:16086763

  8. Bullous mastocytosis in an infant associated with the use of a nonprescription cough suppressant.

    PubMed

    Cook, J; Stith, M; Sahn, E E

    1996-01-01

    Bullous mastocytosis is an unusual expression of mastocytosis typically seen in young children, and many causes of the acute mast cell degranulation with bulla formation have been identified. We report a 6-month-old boy with urticaria pigmentosa and an extensive bullous eruption associated with the ingestion of a nonprescription cough suppressant containing dextromethorphan. The pathogenesis of mastocytosis and the care of patients with this disease are discussed. PMID:8893244

  9. Recommendations for the use of immunoapheresis in the treatment of autoimmune bullous diseases.

    PubMed

    Zillikens, Detlef; Derfler, Kurt; Eming, Rüdiger; Fierlbeck, Gerhard; Goebeler, Matthias; Hertl, Michael; Hofmann, Silke C; Karlhofer, Franz; Kautz, Ocko; Nitschke, Martin; Opitz, Andreas; Quist, Sven; Rose, Christian; Schanz, Stefan; Schmidt, Enno; Shimanovich, Iakov; Michael, Michael; Ziller, Fabian

    2007-10-01

    Despite the use of high-dose systemic corticosteroids in combination with other immunosuppressants, in some patients with autoimmune bullous diseases only insufficient improvement is achieved. In these cases and in acute severe disease, adjuvant immunoapheresis has been increasingly used. A consensus meeting was held in mid-2005 in Hamburg, aiming at developing guidelines for the use of immunoapheresis in the treatment of autoimmune bullous diseases. This paper summarizes the experts' recommendations. PMID:17910670

  10. Exfoliative Epitheliopathy of Bullous Keratopathy with Breaches in the MUC16 Glycocalyx

    PubMed Central

    Glasgow, Ben J.; Gasymov, Oktay K.; Casey, Richard C.

    2009-01-01

    Purpose Expression of cellular adhesion molecules is altered in bullous keratopathy. The hypothesis that epithelial alterations in bullous keratopathy compromise the surface of the cornea and its glycocalyx was tested. Methods Studies were performed on eight cases each of pseudophakic bullous keratopathy and healthy corneas. The number of epithelial cell layers was determined with a stereological method of point counting. The minimum distance between points was established by estimates of cell size with variable pressure scanning electron microscopy performed in backscatter mode. The mean number of cell layers with mucin expression was identified by immunohistochemistry with mouse monoclonal antibodies for MUC1 and MUC16. Data were analyzed by Student's t-test if values showed a normal distribution or, alternatively, by the Wilcoxon rank-sum test. Results Mean numbers of wing cell and superficial cell layers were lower in bullous keratopathy specimens (1.6 vs. 2.0; P < 0.0001) than in controls (1.1 vs. 1.8; P < 0.000001). The number of exfoliated cell layers evident in sections was increased in the bullous keratopathy specimens compared with controls (0.36 vs. 0.03; P < 0.0001). The number of cell layers decorated with antibodies to MUC16 was lower in bullous keratopathy specimens than in controls (0.5 vs. 1.2; P < 0.025). The reduction of layers expressing MUC1 in bullous keratopathy was not statistically significant. Conclusions Pseudophakic bullous keratopathy manifests an abnormal corneal ocular surface in which superficial cell layers are exfoliated, leaving breaches in the protective MUC16 glycocalyx. The results provide a morphologic correlate for the surface epithelial abnormalities noted clinically in these patients. PMID:19420336

  11. Enoxaparin-induced hemorrhagic bullous dermatosis in a leprosy patient.

    PubMed

    Öztürk, Savaş; Can, Ilkay; Erden, Ilker; Akyol, Hadice; Solmaz, Ozgen Aslan

    2015-01-01

    Enoxaparin is a low-molecular-weight heparin that has been used widely to prevent and treat thromboembolic disorders for at least 30 years. The most common adverse skin reactions to enoxaparin are ecchymosis and skin necrosis due to vasculitis, urticaria, angioedema and erythema. Side effects from heparin administration are rare and usually located at the injection site. However, recent reports have suggested that they can also occur at a distance from the site of injection. Moreover, the etiopathogenesis has not been fully explained. In this article, we present a case of hemorrhagic bullous dermatosis associated with enoxaparin for the treatment of ischemic heart disease that developed in a patient with a past history of lepromatous leprosy. PMID:25198402

  12. Bullous pyoderma gangrenosum associated with pancytopenia of unknown origin

    PubMed Central

    Wolska, Katarzyna; Michalska-Jakubus, Małgorzata; Pucuła, Joanna; Chodorowska, Grażyna; Dzida, Grzegorz; Mosiewicz, Jerzy; Prystupa, Andrzej; Podhorecka, Monika

    2014-01-01

    Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unknown origin. Clinically it starts with a pustule, nodule or bulla that rapidly progresses and turns into a painful ulcer with raised, undermined borders. The etiopathogenesis of PG remains unknown. However it is frequently associated with systemic diseases such as inflammatory bowel disease (IBD), haematological disorders or arthritis. The latest multicentric retrospective analysis published by Ghazal et al. shows that anaemia has been observed very often in German patients suffering from PG (in 45.6% of 259) so this disorder is supposed to be a possible cofactor in the pathogenesis of PG. According to its progressive course, patients require intensive diagnostic procedures and rapid initiation of the treatment. In this article, we report a case of bullous pyoderma gangrenosum in association with pancytopenia of unknown origin, according to its diagnostic and therapeutic difficulties. PMID:25254015

  13. [Wounds in autoimmune bullous dermatoses and systemic connective tissue diseases].

    PubMed

    Marinović, Branka; Jukić, Ines Lakos; Lipozencić, Jasna

    2012-10-01

    Autoimmune bullous dermatoses are a group of skin and/or mucous membrane diseases characterized by blisters and erosions, which are the results of autoantibodies directed to structural components of desmosomes and structural proteins of the basement membrane zone. In this group of diseases, the diagnosis is based on history, clinical presentation, histopathologic findings, findings of direct and indirect immunofluorescence, and specific evidence of circulating antibodies by the enzyme linked immunosorbent assay (ELISA) method. Connective tissue diseases are a heterogeneous group of diseases with some common pathogenetic mechanisms and frequent involvement of the skin. This group of diseases commonly includes lupus erythematosus, dermatomyositis/polymyositis, localized and systemic scleroderma. As most of the diseases in this group have positive one of the antinuclear antibodies, in clinical practice these diseases are often called autoimmune connective tissue diseases. In the group of autoimmune bullous dermatoses, wounds occur as the result of breaking of blisters, and consequently affect the epidermis alone or epidermis and upper dermis, while in the group of systemic diseases of connective tissue, wounds occur in advanced stages of disease as a result of vascular tissue damage, causing necrosis of tissue and wounds. When wounds in these diseases last for a longer period (longer than 3 months), they are considered as chronic wounds and in these cases it is necessary to determine the reason for slow healing. In patients with wounds as a symptom of disease, besides systemic therapy, special attention should be paid to local therapy in order to prevent superinfection and accelerate epithelialization and wound healing. PMID:23193815

  14. Dermatological Diseases Associated with Pregnancy: Pemphigoid Gestationis, Polymorphic Eruption of Pregnancy, Intrahepatic Cholestasis of Pregnancy, and Atopic Eruption of Pregnancy

    PubMed Central

    Sävervall, Christine; Sand, Freja Lærke; Thomsen, Simon Francis

    2015-01-01

    Dermatoses unique to pregnancy are important to recognize for the clinician as they carry considerable morbidity for pregnant mothers and in some instances constitute a risk to the fetus. These diseases include pemphigoid gestationis, polymorphic eruption of pregnancy, intrahepatic cholestasis of pregnancy, and atopic eruption of pregnancy. This review discusses the pathogenesis, clinical importance, and management of the dermatoses of pregnancy. PMID:26609305

  15. Azathioprine-induced bullous Sweet's syndrome: a rare association.

    PubMed

    Biswas, Sugata Narayan; Chakraborty, Partha Pratim; Gantait, Kripasindhu; Bar, Chittaranjan

    2016-01-01

    A 52-year-old man presented with high-grade fever, headache and painful vesicular skin rash involving the upper trunk and upper extremities, 8 days after initiation of chemotherapy with azathioprine (50 mg/day), which had been prescribed for acral vitiligo. There was neither any history of preceding respiratory or gastrointestinal tract infection, nor was the patient known to have malignancy, drug hypersensitivity, inflammatory bowel disease, vasculitis or other autoimmune disease. Laboratory results revealed leucocytosis with neutrophilia and markedly elevated acute phase reactants. Antinuclear antibody, perinuclear and cytoplasmic antineutrophil cytoplasmic antibody were found negative. Punch biopsy from skin of the upper trunk revealed dense neutrophilic infiltration of dermis without signs of vasculitis, suggestive of Sweet's syndrome. In view of the temporal association with azathioprine and absence of an obvious alternative aetiology, provisional diagnosis of drug-induced bullous Sweet's syndrome was made. Azathioprine was discontinued and high-dose oral prednisolone initiated. The response was dramatic with resolution of skin lesions within 72 h without further recurrence at fourth week of follow-up. PMID:27090551

  16. A Fatal Case of “Bullous Erysipelas-like” Pseudomonas Vasculitis

    PubMed Central

    Yang, Sam Shiyao; Chandran, Nisha Suyien; Huang, Jing Xiang; Tan, Kong-Bing; Aw, Derrick Chen-Wee

    2016-01-01

    Erysipelas is a generally benign superficial bacterial skin infection, and its bullous form constitutes a rare and more severe variant. We describe the first and fatal case of “bullous erysipelas-like” septic vasculitis due to Pseudomonas bacteremi. A 69-year-old Chinese man presenting with diarrhea and septic shock initially began to rapidly develop sharply defined erythematous plaques with non-hemorrhagic bullae over his lower limbs. Culture of the aspirate from the bullae was positive for Pseudomonas aeruginosa. This was also consistent with his blood cultures showing Pseudomonas bacteremia. Histology of the skin lesion showed microthrombi and neutrophilic infiltrates in blood vessels with Gram-negative bacilli extruding from the vessel walls, characteristic of septic vasculitis. The bullous erysipelas-like lesions seen in this patient represents a rare manifestation of both septic vasculitis and Pseudomonas infection. PMID:26955132

  17. Bullous emphysema as first presentation of Ehlers-Danlos syndrome in monozygotic twins.

    PubMed

    Ruggeri, Paolo; Calcaterra, Salvatore; Girbino, Giuseppe

    2015-01-01

    Ehlers-Danlos syndrome, characterized by hyperextensible skin, hypermobile joints, and fragile vessels, is the most common heritable disorder of connective tissue and has an estimated prevalence of 1 in 5000. Pulmonary involvement with signs of lung destruction (bullous emphysema) as first presentation is unusual. We report a case of monozygotic twins 37 years old men with occasional evidence of bullous emphysema with previously undiagnosed Ehlers-Danlos syndrome type IV. We emphasize the importance of considering uncommon genetic causes of emphysema in young adults, discuss underlining pathophysiological mechanisms and propose a conservative management and follow-up. PMID:26029576

  18. Dental Treatment of a Child Suffering from Non-bullous Congenital Ichthyosiform Erythroderma under General Anesthesia.

    PubMed

    Choudhary, Rahul; Satish, V

    2015-01-01

    Non-bullous congenital ichthyosiform erythroderma (NBCIE) is an autosomal recessive form of inherited icthyosis appears as fine white scales that gradually replace collodion membrane. This case report describes management of 5 years and 11-month-old child with NBCIE suffering from early childhood caries (ECC) under general anesthesia. How to cite this article: Choudhary R, Satish V. Dental Treatment of a Child Suffering from Non-bullous Congenital Ichthyosiform Erythroderma under General Anesthesia. Int J Clin Pediatr Dent 2015;8(2):157-162. PMID:26379388

  19. A rare case of unilateral severe bullous emphysema in a 32-year-old female.

    PubMed

    Lim, Hui Jun; Lim, Chong Hee

    2016-07-01

    Congenital bullous emphysema is defined as large bullae involving at least one-third of a hemithorax. We describe the case of a 32-year-old female who presented with increasing shortness of breath. Radiological investigations revealed severe emphysema with hyperexpansion of the right lung and a mediastinal shift to the left. A lung perfusion scan showed reduced perfusion in the right lung. The patient underwent a right pneumonectomy with a diagnosis of congenital bullous emphysema. She was doing well 6 years later. PMID:27206777

  20. Intravenous immunoglobulin for treatment of severe acquired bullous epidermolysis refractory to conventional immunosuppressive therapy.

    PubMed

    Mosqueira, Carolina Balbi; Furlani, Laura de Albuquerque; Xavier, Augusto Frederico de Paula; Cunha, Paulo Rowilson; Galvão, Alda Maria Penna

    2010-01-01

    Acquired bullous epidermolysis is a chronic and rare bullous subepidermal disease. It usually begins in adulthood and its etiology is unknown although it is associated with antibodies against type VII collagen. There are spontaneous and trauma induced formation of blisters that may cause serious complications. Treatment is disappointing and difficult. Apart from conventional therapy with systemic corticosteroid, new therapeutic modalities such as intravenous immunoglobulin are currently being used. This report highlights the extremely difficult clinical management of this rare disease and the important improvement provided by intravenous immunoglobulin. PMID:20944913

  1. Dental Treatment of a Child Suffering from Non-bullous Congenital Ichthyosiform Erythroderma under General Anesthesia

    PubMed Central

    Satish, V

    2015-01-01

    ABSTRACT Non-bullous congenital ichthyosiform erythroderma (NBCIE) is an autosomal recessive form of inherited icthyosis appears as fine white scales that gradually replace collodion membrane. This case report describes management of 5 years and 11-month-old child with NBCIE suffering from early childhood caries (ECC) under general anesthesia. How to cite this article: Choudhary R, Satish V. Dental Treatment of a Child Suffering from Non-bullous Congenital Ichthyosiform Erythroderma under General Anesthesia. Int J Clin Pediatr Dent 2015;8(2):157-162. PMID:26379388

  2. Evidence of increased keratinocyte proliferation in air-liquid interface cultures of non-bullous congenital ichthyosiform erythroderma.

    PubMed

    Amsellem, C; Haftek, M; Hoyo, E; Thivolet, J; Schmitt, D

    1993-08-01

    Modern pharmacological and dermatological research requires the use of appropriate in vitro models which permit a faithful reproduction of various aspects of the in situ situation. The air-exposed culture of keratinocytes on dead de-epidermized dermis is one of the best models of in vitro epidermal differentiation known at the moment. In this study, we verified the model's validity for the reproduction of a hyperproliferative genodermatosis: non-bullous congenital ichthyosiform erythroderma. We used subcultured epidermal keratinocytes originating from normal and ichthyotic patients. Light and electron microscopy of pathological cultures disclosed, on day 14, a terminally differentiated epidermis with a marked granular layer and hyperkeratosis which, however, was not dramatically different from the normal controls. On day 25, the normal cultures displayed an even more pronounced hyperkeratosis and hypergranulosis, whereas the reconstructed epidermis of pathological origin presented a considerable reduction of the viable non-keratinized compartment and a focal parakeratosis. Indirect immunofluorescence revealed the expression of several differentiation markers which were not observed in the immersed culture models (e.g. the desmosome- and differentiation-related antigens KM48 and G36-19). Abundant keratohyalin granules were stained with AKH1 antibody and observed even in the deep epidermal layers, but no profilaggrin-filaggrin conversion could be detected biochemically.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7506468

  3. Diagnostic value of Tzanck smear in various erosive, vesicular, and bullous skin lesions

    PubMed Central

    Yaeen, Atiya; Ahmad, Qazi Masood; Farhana, Anjum; Shah, Parveen; Hassan, Iffat

    2015-01-01

    Background: Cutaneous cytology has long been shown to be useful in the diagnosis of several erosive, vesicular, and bullous skin lesions. The Tzanck smear although an old tool, still remains a simple, rapid, easily applied, and inexpensive test for these skin lesions. Aims and Objectives: The aim of this study was to evaluate the diagnostic value of Tzanck smear by determining its sensitivity and specificity in various erosive, vesicular, and bullous skin lesions. Materials and Methods: One hundred and forty-two patients with erosive, vesicular, and/or bullous skin lesions were included in the study. Four groups of disorders were identified: infections, immunologic disorders, genodermatosis, and spongiotic dermatitis. All the study cases were evaluated by Tzanck smear. Definitive diagnosis was established by standard diagnostic techniques (including when appropriate, viral serology, bacterial culture, histopathology, direct immunoflourescence). Results: The sensitivity and specificity of cytologic findings was respectively 86.36% and 91.30% for viral infections; for bacterial infections, it was 85.7% and 66.6%. The sensitivity and specificity of Tzanck smear was respectively 85.0% and 83.33% for pemphigus; for bullous pemhigoid it was 11.11% and 100.0%. Tzanck smear sensitivity in genodermatoses was 100%. The sensitivity and specificity of the test in spongiotic dermatitis could not be calculated due to an insufficient number of patients. Conclusion: The Tzanck smear is a quick and reliable tool for the evaluation of various erosive and vesiculobullous skin lesions. PMID:26751561

  4. Autologous Tragal Perichondrium Transplantation: A Novel Approach for the Management of Painful Bullous Keratopathy

    PubMed Central

    Kim, Kyoung Woo; Chun, Yeoun Sook

    2013-01-01

    Purpose To introduce autologous tragal perichondrium transplantation as a novel surgical modality for the management of intractable symptomatic bullous keratopathy. Methods In three eyes of three patients with painful bullous keratopathy, autologous tragal perichondria were transplanted on the corneal surface with the human amniotic membrane transplanted above. We included an additional three eyes of three patients with painful bullous keratopathy who received amniotic membrane transplantation only to serve as controls. Clinical symptom outcomes were assessed using a visual analogue scale at postsurgical months 1, 3, 5, 7, and 9. In addition, transplanted tragal perichondrium and amniotic membrane complex tissue button obtained from one patient who underwent penetrating keratoplasty was evaluated by immunohistochemical analysis of CD34, vimentin, and alcian blue staining. Results All three patients who underwent autologous tragal perichondrium and human amniotic membrane co-transplantation showed improvements in pain and tearing. However, all three patients in the control group experienced aggravation of tearing and no further improvement of pain 3 months after surgery. In addition, one patient in the control group developed premature degradation of the amniotic membrane. Histopathologic and immunohistochemical analysis showed intact surface epithelization and positive CD34, vimentin and alcian blue staining of transplanted tragal perichondria. Conclusions The tragal perichondrium has a high mechanical structural force and high potency due to well-organized epithelization and the presence of mesenchymal stem cells. Autologous tragal perichondrium transplantation may be an effective modality for the management of painful bullous keratopathy. PMID:23730105

  5. A breath from Houdini – A case of giant bullous emphysema

    PubMed Central

    Tay, Chee Kiang; Ng, Yuen Li

    2014-01-01

    We describe a case of a young man presenting with exertional dyspnea. His chest radiograph showed hyperlucency in his left lung, and he was subsequently diagnosed to have giant bullous emphysema. An approach to lesions of decreased attenuation on computed tomography of the chest, with a focus on cystic lung diseases is discussed. This is followed by a literature review of the clinical presentation, natural history, radiology and management of giant bullous emphysema. Although this is an uncommon condition, a clinician has to be cognizant of the fact that it may mimic other common respiratory diseases. This review highlights the importance of these caveats as misguided treatment options may lead to devastating consequences. PMID:26029573

  6. Association of DQw7 (DQB1*0301) with ocular cicatricial pemphigoid.

    PubMed Central

    Ahmed, A R; Foster, S; Zaltas, M; Notani, G; Awdeh, Z; Alper, C A; Yunis, E J

    1991-01-01

    Ocular cicatricial pemphigoid (OCP) is an autoimmune blistering disease that affects the conjunctiva and multiple mucous membranes. Class I and II and complement genetic markers of the major histocompatibility complex were studied in 20 Caucasian OCP patients and members of their families. Frequencies of individual alleles and common fixed or extended haplotypes in the patients were compared with those in normal family control haplotypes and with overall normal Caucasian haplotypes. The most striking increase compared with overall controls was noted in HLA-DQw3 (P = 0.006), unassociated with any extended haplotype. All but 1 of the 20 patients carried DQw3 in linkage with HLA-DR4 (increased significantly with P = 0.042 compared with overall normal genotype controls) or DR5. The DQw3, on analysis by restriction fragment length polymorphism in genomic DNA, was, in every instance, DQw7 (3.1, DQB1*0301). The frequency of DQB1*0301 in patient haplotypes compared with overall normal DR4 and DR5 DQw3-bearing haplotypes was statistically significantly increased (P less than 0.003, relative risk = 9.6). The distribution of homozygotes and heterozygotes for DQB1*0301 among the patients was consistent with dominant but not recessive inheritance of DQB1*0301 or a gene, probably a class II allele, in linkage disequilibrium with it as the major histocompatibility complex susceptibility gene for OCP. Images PMID:1763074

  7. Effect of Glyceraldehyde Cross-Linking on a Rabbit Bullous Keratopathy Model

    PubMed Central

    Wang, Mengmeng

    2015-01-01

    Background. To evaluate the effects of corneal glyceraldehyde CXL on the rabbit bullous keratopathy models established by descemetorhexis. Methods. Fifteen rabbits were randomly divided into five groups. Group A (n = 3) is the control group. The right eyes of animals in Groups B,C, D, and E (n = 3, resp.) were suffered with descemetorhexis procedures. From the 8th day to the 14th day postoperatively, the right eyes in Groups C and D were instilled with hyperosmolar drops and glyceraldehyde drops, respectively; the right eyes in Group E were instilled with both hyperosmolar drops and glyceraldehyde drops. Central corneal thickness (CCT), corneal transparency score, and histopathological analysis were applied on the eyes in each group. Results. Compared with Group A, statistically significant increase in CCT and corneal transparency score was found in Groups B, C, D, and E at 7 d postoperatively (P < 0.05) and in Groups C, D, and E at 14 d postoperatively (P < 0.05). Conclusion. Chemical CXL technique using glyceraldehyde improved the CCT and corneal transparency of the rabbit bullous keratopathy models. Topical instillation with glyceraldehyde and hyperosmolar solutions seems to be a good choice for the bullous keratopathy treatment. PMID:26509077

  8. Bullous melanoma: a rare variant of melanoma causing practical problems in determination of tumor thickness.

    PubMed

    Woltsche, Nora M; Cota, Carlo; Fink-Puches, Regina; Requena, Luis; Cerroni, Lorenzo

    2015-02-01

    Bullous melanoma represents a rare variant of melanoma characterized by variably large subepidermal, basilar, or suprabasilar blisters. We present 7 cases of bullous melanoma (M:F = 4:3; median age, 57 years; age range, 38-86) located on the heel (n = 2), foot (n = 2), arm (n = 2), and back (n = 1). In 5/7 cases, the bulla was due to dyscohesiveness of basilar or suprabasilar melanocytes with subsequent acantholytic features simulating pemphigus vulgaris or Hailey-Hailey disease, whereas in the last 2 cases a subepidermal bulla without clear-cut relation to the melanocytic complexes was observed. Direct and indirect immunfluorescence studies performed in 4 patients on skin near the original surgical scar (including those with subepidermal bullae) were negative. Measurement of the Breslow index in all 7 cases was affected by the presence of the bulla, and in 5 of them, the TNM classification was different depending on the method of measurement (with or without the bulla). We suggest that the Breslow index in these cases should be measured detracting the thickness of the bulla from the total thickness, but follow-up data on larger numbers of patients are necessary to establish whether the presence of bullous features has any prognostic implication. PMID:25079203

  9. Desquamative gingivitis - A clinical sign in mucous membrane pemphigoid: Report of a case and review of literature

    PubMed Central

    Hasan, Shamimul

    2014-01-01

    Gingival desquamation is a clinical sign in which the gingiva appears reddish, glazed and friable with destruction of the epithelium. Gingival desquamation may be the result of various disease processes in gingiva. Mucous membrane pemphigoid (MMP), oral lichen planus and pemphigus vulgaris accounts for the major causes of gingival desquamation. MMP is a rare, chronic autoimmune blistering disorder characterized by subepithelial bullae. The condition frequently involves mucous membranes, with rare skin involvement. Oral cavity is mostly affected and desquamative gingivitis is the most common manifestation. Hereby, we present an interesting case of MMP manifesting as desquamative gingivitis, along with a brief review of the literature. PMID:24741281

  10. Vancomycin-induced Linear IgA Bullous Dermatosis: A Case Report and Review of the Literature

    PubMed Central

    Kang, Min Ju; Kim, Hyung Ok

    2008-01-01

    Linear IgA bullous dermatosis (LABD) is a rare autoimmune bullous disease that can either occur without any apparent cause or be induced by the administration of certain drugs, the most common of which is vancomycin. We present a case of a 45-year-old woman who was diagnosed with vancomycin-induced LABD by the presence of a characteristic linear band of IgA along the basement membrane zone on direct immunofluorescence microscopy. Our patient showed complete recovery after a 2-week period during which vancomycin administration was discontinued. PMID:27303171

  11. Bullous Dermatitis Artefacta in a 17 Year-old Girl Induced by a Native Herb

    PubMed Central

    Zarei, Mina; Kamali, Mohammad; Bidaki, Reza

    2013-01-01

    Dermatitis artifacta is a factitious dermatological disorder with many forms of presentation of self inflicted skin lesions in any part of the body. Dermatitis artefacta is a rare and difficult condition for diagnosis and treatment mostly because of the patient's denial. The liaison among primary care physicians, psychiatrists and dermatologists can be important in the management of these patients. In this report we describe a 17-year-old girl with dermatitis artefacta which was presented as bullous lesions on her face induced with a native herb combining with fake headaches. PMID:24616800

  12. Bullous Dermatitis Artefacta in a 17 Year-old Girl Induced by a Native Herb.

    PubMed

    Zarei, Mina; Kamali, Mohammad; Bidaki, Reza

    2013-09-01

    Dermatitis artifacta is a factitious dermatological disorder with many forms of presentation of self inflicted skin lesions in any part of the body. Dermatitis artefacta is a rare and difficult condition for diagnosis and treatment mostly because of the patient's denial. The liaison among primary care physicians, psychiatrists and dermatologists can be important in the management of these patients. In this report we describe a 17-year-old girl with dermatitis artefacta which was presented as bullous lesions on her face induced with a native herb combining with fake headaches. PMID:24616800

  13. Clinical features and in vivo confocal microscopy assessment in 12 patients with ocular cicatricial pemphigoid

    PubMed Central

    Long, Qin; Zuo, Ya-Gang; Yang, Xue; Gao, Ting-Ting; Liu, Jie; Li, Ying

    2016-01-01

    AIM To describe the clinical features and microstructural characteristics assessed by in vivo confocal microscopy (IVCM) in patients with ocular cicatricial pemphigoid (OCP). METHODS A descriptive, uncontrolled case series study. Patients diagnosed with OCP were examined by clinical history, slit-lamp biomicroscopy features and IVCM images. The results of direct immunofluorescence (DIF) biopsies and indirect immunofluorescence (IIF) were also recorded. Local and systemic immunosuppressive therapy were administered and adjusted according to response. RESULTS A total of 12 consecutive OCP patients (7 male, 5 female; mean age 60.42±10.39y) were recruited. All patients exhibited bilateral progressive conjunctival scarring and recurrent chronic conjunctivitis was the most frequent clinical pattern. The mean duration of symptoms prior to diagnosis of OCP was 2.95±2.85y (range: 5mo to 10y). The Foster classification varied from stage I to IV and 20 eyes (83%) were within or greater than Foster stage III on presentation. Two of the 12 patients (17%) demonstrated positive DIF; 3 of the 12 (25%) patients reported positive IIF. The mean duration of the follow-up period was 20.17±11.88mo (range: 6 to 48mo). IVCM showed variable degrees of abnormality in the conjuctiva-cornea and conjuctival scarring was detected in all the involved eyes. Corneal stromal cell activation and dendritic cell infiltration presented as ocular surface inflammation, ocular surface keratinization along with the destroyed Vogt palisades was noted in eyes with potential limbal stem cell deficiency. After treatment, remission of ocular surface inflammation was achieved in all the patients, 18 eyes (75%) remained stable, 6 eyes (25%) had recurrent conjunctivitis and cicatrization in 2 eyes (8%) was progressing. CONCLUSION As an autoimmune disease, OCP manifests as variable degrees of clinical and laboratory abnormalities with both local and systemic immunosuppressive treatment playing important roles

  14. Multifocal Bullous Fixed Drug Erruption Due To Phenytoin: A Lesson Learned!

    PubMed Central

    Gupta, Naresh

    2015-01-01

    Antiepileptic drugs (AED) are a common culprit of cutaneous eruptions in clinical practice. Phenytoin, lamotrigine and carbamazepine are the commonest offenders. Maculopapular eruptions are the most frequently reported events. However, multifocal bullous fixed drug eruptions have rarely been described in association with AED use. The risk factors for skin rash including its association with the rate of drug administration are unclear in the literature. We report a case of a young alcoholic man, on long term phenytoin therapy since 3 years, who presented to our emergency department with a breakthrough seizure episode. Patient’s routine investigations including serum biochemistry, imaging and toxicology screen were normal. Patient was found to have sub-therapeutic serum phenytoin levels and was prescribed loading with intravenous phenytoin (15mg/kg body weight), which was mistakenly infused at a rapid rate (60mg/minute). Patient developed multifocal bullous lesions over muco-cutaneous regions after 6 hours of drug administration which healed after its discontinuation leaving behind residual hyperpigmentation. Patient was managed conservatively, switched to oral levetiracetam and discharged in a stable condition after one week of hospital stay. Present case highlights a yet uncommon reaction to a commonly used drug and tries to establish the relation between rate of drug infusion and the risk of skin reaction. PMID:26816935

  15. Multifocal Bullous Fixed Drug Erruption Due To Phenytoin: A Lesson Learned!

    PubMed

    Jain, Ankur; Gupta, Naresh

    2015-12-01

    Antiepileptic drugs (AED) are a common culprit of cutaneous eruptions in clinical practice. Phenytoin, lamotrigine and carbamazepine are the commonest offenders. Maculopapular eruptions are the most frequently reported events. However, multifocal bullous fixed drug eruptions have rarely been described in association with AED use. The risk factors for skin rash including its association with the rate of drug administration are unclear in the literature. We report a case of a young alcoholic man, on long term phenytoin therapy since 3 years, who presented to our emergency department with a breakthrough seizure episode. Patient's routine investigations including serum biochemistry, imaging and toxicology screen were normal. Patient was found to have sub-therapeutic serum phenytoin levels and was prescribed loading with intravenous phenytoin (15mg/kg body weight), which was mistakenly infused at a rapid rate (60mg/minute). Patient developed multifocal bullous lesions over muco-cutaneous regions after 6 hours of drug administration which healed after its discontinuation leaving behind residual hyperpigmentation. Patient was managed conservatively, switched to oral levetiracetam and discharged in a stable condition after one week of hospital stay. Present case highlights a yet uncommon reaction to a commonly used drug and tries to establish the relation between rate of drug infusion and the risk of skin reaction. PMID:26816935

  16. Frequent Occurrence of Aplasia Cutis Congenita in Bullous Dermolysis of the Newborn.

    PubMed

    Diociaiuti, Andrea; Castiglia, Daniele; Giancristoforo, Simona; Guerra, Liliana; Proto, Vittoria; Dotta, Andrea; Boldrini, Renata; Zambruno, Giovanna; El Hachem, Maya

    2016-08-23

    Bullous dermolysis of the newborn (BDN) is a subtype of dystrophic epidermolysis bullosa characterized by rapid improvement in skin fragility within the first months of life, associated with typical immunofluorescence and ultrastructural features. Inheritance can be autosomal dominant or recessive. We report here 4 cases of BDN, 2 of which presented with aplasia cutis congenita of the lower extremities. All patients improved rapidly and blister formation ceased by the third month of life in 3 cases. In these patients only residual milia, nail dystrophies and atrophic scarring at sites of aplasia cutis were visible by one year. Family history indicated dominant inheritance in 2 cases, confirmed by identification of COL7A1 mutation. Molecular analysis also revealed recessive inheritance in the 2 sporadic cases. A literature search identified several patients with BDN born with skin defects localized to the lower extremities. In conclusion, these findings indicate that aplasia cutis congenita is not an infrequent manifestation of BDN. PMID:26864810

  17. Bullous Lesions After Use of a Commercial Therapeutic Hypothermia Temperature Management System: A Possible Burn Injury?

    PubMed Central

    Wells, James M.; Rizk, Dana V.

    2013-01-01

    Therapeutic hypothermia (TH) is a novel technique for improving the likelihood of survival with good neurologic outcome after cardiopulmonary arrest. While commercial temperature management systems (TMS) are intended to facilitate cooling of the body during TH, their operation also involves body exposure to heat. We describe the case of a 72-year-old female postarrest patient who underwent TH using a commercial water-circulating TMS and concurrent continuous renal replacement therapy. The patient developed bullous lesions on the thigh and torso suspected to constitute a scald burn injury from the TMS. Clinicians must be aware of this important adverse event when providing TH, especially in the setting of concurrent hemodialysis therapy. PMID:24066269

  18. A case of bullous dermatitis artefacta possibly induced by a deodorant spray.

    PubMed

    Ikenaga, Satsuki; Nakano, Hajime; Umegaki, Noriko; Moritsugu, Ryuta; Aizu, Takayuki; Kuribayashi, Michihito; Hanada, Katsumi

    2006-01-01

    Dermatitis artefacta is one of a spectrum of factitious diseases etiologically responsible for skin lesions denied by patients. These factors often make it difficult to identify the causative agents of the condition. Herein, we report a case of bullous dermatitis artefacta in a 12-year-old girl, for which a deodorant spray was suspected as the probable cause. Pathological examination revealed subepidermal blistering with full-thickness necrosis of the epidermis, suggesting a thermo- or cryo-induced injury. Psychological testing demonstrated her immaturity and dependence. In searching for the causative agent, we suspected a deodorant spray as a blister-inducing agent. We succeeded in reproducing a similar blister lesion on the volunteer's healthy skin using the same spray. Psychiatric involvement significantly complicates the treatment of factitious diseases, including dermatitis artefacta. Cooperation among dermatologists, psychiatrists and the patient's family members is required for ensuring a favorable prognosis. PMID:16469083

  19. Bullous Keratopathy

    MedlinePlus

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  20. Conjunctival Interleukin-13 Expression in Mucous Membrane Pemphigoid and Functional Effects of Interleukin-13 on Conjunctival Fibroblasts in Vitro

    PubMed Central

    Saw, Valerie P.J.; Offiah, Ifeoma; Dart, Robin J.; Galatowicz, Grazyna; Dart, John K.G.; Daniels, Julie T.; Calder, Virginia L.

    2009-01-01

    Interleukin-13 (IL-13) is the dominant effector cytokine of fibrosis in pulmonary and liver disease. Excessive conjunctival fibrosis in the immunobullous disease ocular mucous membrane pemphigoid (MMP) causes blindness; the pathogenesis of scarring in this disease is incompletely understood. To determine whether IL-13 is involved in conjunctival fibrosis in MMP, we studied the expression of IL-13 in ocular MMP patients before and after systemic immunosuppression and examined the effects of IL-13 on normal human conjunctival fibroblasts. We found high stromal cell expression of IL-13 in active ocular MMP by immunohistochemistry; 80% of these cells were CD3-positive T cells. Following immunosuppression, in clinically uninflamed, treated, ocular MMP patients, the number of IL-13 positive cells was significantly reduced, but this was still fourfold greater than in normal conjunctiva. IL-13 stimulated collagen lattice contraction and migration, and decreased production of mmp-3 and mmp-10 by human conjunctival fibroblasts. The addition of T cell culture supernatant to IL-13 synergistically augmented fibroblast migration. IL-13 also up-regulated surface expression of HLA-DR, CD80, CD40, and CD154 by conjunctival fibroblasts, suggesting a potential mechanism for fibroblast-T cell cross talk, via which fibroblasts may actively engage in perpetuating chronic inflammation and continued fibrosis. Together, these findings suggest that IL-13 is involved in conjunctival fibrosis in MMP, and that IL-13 has both profibrotic and pro-inflammatory effects on human conjunctival fibroblasts. PMID:19910508

  1. Antigenic sites in carcinoembryonic antigen.

    PubMed

    Hammarstrom, S; Shively, J E; Paxton, R J; Beatty, B G; Larsson, A; Ghosh, R; Bormer, O; Buchegger, F; Mach, J P; Burtin, P

    1989-09-01

    The epitope reactivities of 52 well-characterized monoclonal antibodies (Mabs) against carcinoembryonic antigen from 11 different research groups were studied using competitive solid-phase immunoassays. About 60% of all possible combinations of Mabs as inhibitors and as the primary binding antibody were investigated. The inhibition data were analyzed by a specially developed computer program "EPITOPES" which measures concordance and discordance in inhibition patterns between Mabs. The analysis showed that 43 of the 52 Mabs (83%) could be classified into one of five essentially noninteracting epitope groups (GOLD 1-5) containing between four and 15 Mabs each. The epitopes recognized by the Mabs belonging to groups 1 to 5 were peptide in nature. With one or two possible exceptions non-classifiable Mabs were either directed against carbohydrate epitopes (4 Mabs) or were inactive in the tests used. Within epitope groups GOLD 1, 4, and 5 two partially overlapping subgroups were distinguished. Mabs with a high degree of carcinoembryonic antigen specificity generally belonged to epitope groups GOLD 1 and 3. PMID:2474375

  2. Ciprofloxacin-induced acute generalized exanthematous pustulosis mimicking bullous drug eruption confirmed by a positive patch test.

    PubMed

    Hausermann, P; Scherer, K; Weber, M; Bircher, A J

    2005-01-01

    We report the case of an 80-year-old woman presenting with ciprofloxacin-induced acute generalized exanthematous pustulosis (AGEP) confirmed by a positive patch test. Cutaneous morphology, course and histological findings were consistent with a definite diagnosis according to the AGEP validation score of the EuroSCAR study group. We point to the rarity of quinolone-induced AGEP and discuss immunological mechanisms, the value of in vivo and in vitro tests as well as the main differential diagnosis. Furthermore, we highlight in this particular case the challenging differentiation from bullous drug eruption. PMID:16205075

  3. Non-Descemet Stripping Automated Endothelial Keratoplasty for Bullous Keratopathy in Buphthalmic Eye

    PubMed Central

    Hirano, Koji; Kachi, Shu; Matsuura, Masako; Kawase, Kazuhide

    2016-01-01

    Purpose To report the 2-year follow-up findings in a patient with buphthalmic bullous keratopathy (BK) who was successfully treated with non-Descemet stripping automated endothelial keratoplasty (nDSAEK). Methods A 39-year-old man had an endothelial graft of 8.0 mm diameter placed uneventfully using the nDSAEK method for phakic BK with buphthalmos of the left eye. He had had a penetrating keratoplasty in the right eye due to aphakic BK 5 years earlier, which, however, resulted in the invasion of blood vessels and graft failure. Since the left eye was phakic, Descemetorhexis was not performed because the instruments might touch the crystalline lens. The best-corrected visual acuity (BCVA), intraocular pressure (IOP), and endothelial cell density (ECD) were determined at 2 weeks, and at 1, 3, 6, 12, 18 and 24 months after nDSAEK. Results Twenty-four months after nDSAEK, his left cornea and lens remained clear, and the decimal BCVA was 0.8. However, the ECD of the graft had decreased from 2,274 cells/mm2 before nDSAEK to 539 cells/mm2 24 months after the surgery, and the rate of decrease appeared to be slightly faster than that of former reports. An IOP of $1003e;30 mm Hg was recorded at around 2 months after the surgery, but was well controlled by tapering the topical steroids and the addition of topical brinzolamide and latanoprost. Conclusion Our findings show that nDSAEK can be successfully used to treat buphthalmic BK. We recommend that nDSAEK be considered especially in phakic eyes with a smooth posterior surface around the pupillary area. PMID:27462256

  4. Wound healing in porcine skin following low-output carbon dioxide laser irradiation of the incision

    SciTech Connect

    Robinson, J.K.; Garden, J.M.; Taute, P.M.; Leibovich, S.J.; Lautenschlager, E.P.; Hartz, R.S.

    1987-06-01

    Wound healing of scalpel incisions to the depth of adipose tissue closed with conventional methods was compared with closure by low-output carbon dioxide laser irradiation. In 3 Pitman-Moore minipigs wound healing was evaluated at intervals from 1 to 90 days by the following methods: clinical variables of wound healing; formation of the basement membrane components bullous pemphigoid antigen, laminin, and fibronectin; and histological evaluation of the regeneration of the epidermis, neovascularization, and elastin and collagen formation. There was no significant difference in healing between wounds closed by the various conventional methods and by the low-output carbon dioxide laser.

  5. Rotavirus antigen test

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003349.htm Rotavirus antigen test To use the sharing features on this page, please enable JavaScript. The rotavirus antigen test detects rotavirus in the feces. This ...

  6. PD-1 inhibitors induced bullous lichen planus-like reactions: a rare presentation and report of three cases.

    PubMed

    Wakade, Deepal V; Carlos, Giuliana; Hwang, Shelley J E; Chou, Shaun; Hui, Rina; Fernandez-Peñas, Pablo

    2016-08-01

    The introduction of immunotherapy such as antiprogrammed death1 (anti-PD1) monoclonal antibodies has changed the scenario of treatment in cancer. Apart from their impressive efficacy profiles, they are better tolerated than the anticytotoxic T-lymphocyte-associated protein 4 antibodies. Dermatological adverse events such as pruritus and rash have been reported in various clinical trials. We report three cases of anti-PD1-induced bullous lichen planus (LP)-like reactions encountered in our institution. These patients developed LP-like papules and annular plaques with vesicles or crusted centres. Histology showed LP-like changes with negative immunofluorescence. Vesiculobullous lesions in patients treated with anti-PD1 therapies require a careful clinicopathological evaluation. PMID:27135655

  7. Homozygous ALOXE3 Nonsense Variant Identified in a Patient with Non-Bullous Congenital Ichthyosiform Erythroderma Complicated by Superimposed Bullous Majocchi’s Granuloma: The Consequences of Skin Barrier Dysfunction

    PubMed Central

    Wang, Tao; Xu, Chenchen; Zhou, Xiping; Li, Chunjia; Zhang, Hongbing; Lian, Bill Q.; Lee, Jonathan J.; Shen, Jun; Liu, Yuehua; Lian, Christine Guo

    2015-01-01

    Non-bullous congenital ichthyosiform erythroderma (NBCIE) is a hereditary disorder of keratinization caused by pathogenic variants in genes encoding enzymes important to lipid processing and terminal keratinocyte differentiation. Impaired function of these enzymes can cause pathologic epidermal scaling, significantly reduced skin barrier function. In this study, we have performed a focused, genetic analysis of a probrand affected by NBCIE and extended this to his consanguineous parents. Targeted capture and next-generation sequencing was performed on NBCIE associated genes in the proband and his unaffected consanguineous parents. We identified a homozygous nonsense variant c.814C>T (p.Arg272*) in ALOXE3 (NM_001165960.1) in the proband and discovered that his parents are both heterozygous carriers of the variant. The clinical manifestations of the proband’s skin were consistent with NBCIE, and detailed histopathological assessment revealed epidermal bulla formation and Majocchi’s granuloma. Infection with Trichophyton rubrum was confirmed by culture. The patient responded to oral terbinafine antifungal treatment. Decreased skin barrier function, such as that caused by hereditary disorders of keratinization, can increase the risk of severe cutaneous fungal infections and the formation of Majocchi’s granuloma and associated alopecia. Patients with NBCIE should be alerted to the possible predisposition for developing dermatophytoses and warrant close clinical follow-up. PMID:26370990

  8. Transcutaneous antigen delivery system

    PubMed Central

    Lee, Mi-Young; Shin, Meong-Cheol; Yang, Victor C.

    2013-01-01

    Transcutaneous immunization refers to the topical application of antigens onto the epidermis. Transcutaneous immunization targeting the Langerhans cells of the skin has received much attention due to its safe, needle-free, and noninvasive antigen delivery. The skin has important immunological functions with unique roles for antigen-presenting cells such as epidermal Langerhans cells and dermal dendritic cells. In recent years, novel vaccine delivery strategies have continually been developed; however, transcutaneous immunization has not yet been fully exploited due to the penetration barrier represented by the stratum corneum, which inhibits the transport of antigens and adjuvants. Herein we review recent achievements in transcutaneous immunization, focusing on the various strategies for the enhancement of antigen delivery and vaccination efficacy. [BMB Reports 2013; 46(1): 17-24] PMID:23351379

  9. The relevance of the IgG subclass of autoantibodies for blister induction in autoimmune bullous skin diseases

    PubMed Central

    Mihai, Sidonia; Zillikens, Detlef

    2007-01-01

    Autoimmune bullous skin diseases are characterized by autoantibodies and T cells specific to structural proteins maintaining cell–cell and cell–matrix adhesion in the skin. Existing clinical and experimental evidence generally supports a pathogenic role of autoantibodies for blister formation. These autoantibodies belong to several IgG subclasses, which associate with different functional properties and may thus determine the pathogenic potential of IgG antibodies. In pemphigus diseases, binding of IgG to keratinocytes is sufficient to cause intraepidermal blisters without engaging innate immune effectors and IgG4 autoantibodies seem to mainly mediate acantholysis. In contrast, in most subepidermal autoimmune blistering diseases, complement activation and recruitment and activation of leukocytes by autoantibodies are required for blister induction. In these conditions, tissue damage is thought to be mainly mediated by IgG1, but not IgG4 autoantibodies. This review summarizes the current knowledge on the pathogenic relevance of the IgG subclass of autoantibodies for blister formation. Characterization of the pathogenically relevant subclass(es) of autoantibodies not only provides mechanistic insights, but should greatly facilitate the development of improved therapeutic modalities of autoimmune blistering diseases. PMID:17277959

  10. NGF Modulates trkANGFR/p75NTR in αSMA-Expressing Conjunctival Fibroblasts from Human Ocular Cicatricial Pemphigoid (OCP)

    PubMed Central

    Di Zazzo, Antonio; Sgrulletta, Roberto; Cortes, Magdalena; Normando, Eduardo Maria; Lambiase, Alessandro; Bonini, Stefano

    2015-01-01

    Objective In a previous study, we reported the upregulation of Nerve Growth Factor (NGF) and trkANGFR expression in Ocular Cicatricial Pemphigoid (OCP), an inflammatory and remodeling eye disease. Herein, we hypothesize a potential NGF-driven mechanism on fibroblasts (FBs) during OCP remodeling events. To verify, human derived OCP-FBs were isolated and characterized either at baseline or after NGF exposure. Materials and Methods Conjunctival biopsies were obtained from 7 patients having OCP and 6 control subjects (cataract surgery). Both conjunctivas and primary FB cultures were characterised for αSMA, NGF and trkANGFR/p75NTR expression. Subcultures were exposed to NGF and evaluated for αSMA, NGF, trkANGFR/p75NTR expression as well as TGFβ1/IL4 release. For analysis, early and advanced subgroups were defined according to clinical parameters. Results OCP-conjunctivas showed αSMA-expressing FBs and high NGF levels. Advanced OCP-FBs showed higher αSMA expression associated with higher p75NTR and lower trkANGFR expression, as compared to early counterparts. αSMA expression was in keeping with disease severity and correlated to p75NTR. NGF exposure did not affect trkANGFR levels in early OCP-FBs while decreased both αSMA/p75NTR expression and TGFβ1/IL4 release. These effects were not observed in advanced OCP-FBs. Conclusions Taken together, these data are suggestive for a NGF/p75NTR task in the potential modulation of OCP fibrosis and encourages further studies to fully understand the underlying mechanism occurring in fibrosis. NGF/p75NTR might be viewed as a potential therapeutic target. PMID:26569118

  11. Epidermolysis Bullosa Acquisita: From Pathophysiology to Novel Therapeutic Options.

    PubMed

    Kasperkiewicz, Michael; Sadik, Christian D; Bieber, Katja; Ibrahim, Saleh M; Manz, Rudolf A; Schmidt, Enno; Zillikens, Detlef; Ludwig, Ralf J

    2016-01-01

    Epidermolysis bullosa acquisita (EBA) is a prototypic organ-specific autoimmune disease induced by autoantibodies to type VII collagen causing mucocutaneous blisters. In the inflammatory (bullous pemphigoid-like) EBA variant, autoantibody binding is followed by a lesional inflammatory cell infiltration, and the overall clinical picture may be indistinguishable from that of bullous pemphigoid, the latter being the most common autoimmune bullous disease. The last decade witnessed the development of several mouse models of inflammatory EBA that facilitated the elucidation of the pathogenesis of autoantibody-induced, cell-mediated subepidermal blistering diseases and identified new therapeutic targets for these and possibly other autoantibody-driven disorders. PMID:26763420

  12. Blisters - an unusual effect during radiotherapy.

    PubMed

    Höller, U; Schubert, T; Budach, V; Trefzer, U; Beyer, M

    2013-11-01

    The skin reaction to radiation is regularly monitored in order to detect enhanced radiosensitivity of the patient, unexpected interactions (e.g. with drugs) or any inadvertent overdosage. It is important to distinguish secondary disease from radiation reaction to provide adequate treatment and to avoid unnecessary discontinuation of radiotherapy. A case of bullous eruption or blisters during radiotherapy of the breast is presented. Differential diagnoses bullous pemphigoid, pemphigus vulgaris, and bullous impetigo are discussed and treatment described. PMID:24158604

  13. Presentation of hepatocellular antigens

    PubMed Central

    Grakoui, Arash; Crispe, Ian Nicholas

    2016-01-01

    The liver is an organ in which antigen-specific T-cell responses manifest a bias toward immune tolerance. This is clearly seen in the rejection of allogeneic liver transplants, and multiple other phenomena suggest that this effect is more general. These include tolerance toward antigens introduced via the portal vein, immune failure to several hepatotropic viruses, the lack of natural liver-stage immunity to malaria parasites, and the frequent metastasis of cancers to the liver. Here we review the mechanisms by which T cells engage with hepatocellular antigens, the context in which such encounters occur, and the mechanisms that act to suppress a full T-cell response. While many mechanisms play a role, we will argue that two important processes are the constraints on the cross-presentation of hepatocellular antigens, and the induction of negative feedback inhibition driven by interferons. The constant exposure of the liver to microbial products from the intestine may drive innate immunity, rendering the local environment unfavorable for specific T-cell responses through this mechanism. Nevertheless, tolerance toward hepatocellular antigens is not monolithic and under specific circumstances allows both effective immunity and immunopathology. PMID:26924525

  14. Pathways of Antigen Processing

    PubMed Central

    Blum, Janice S.; Wearsch, Pamela A.; Cresswell, Peter

    2014-01-01

    T cell recognition of antigen presenting cells depends on their expression of a spectrum of peptides bound to Major Histocompatibility Complex class I (MHC-I) and class II (MHC-II) molecules. Conversion of antigens from pathogens or transformed cells into MHC-I and MHC-II-bound peptides is critical for mounting protective T cell responses, and similar processing of self proteins is necessary to establish and maintain tolerance. Cells use a variety of mechanisms to acquire protein antigens, from translation in the cytosol to variations on the theme of endocytosis, and to degrade them once acquired. In this review we highlight the aspects of MHC-I and MHC-II biosynthesis and assembly that have evolved to intersect these pathways and sample the peptides that are produced. PMID:23298205

  15. Lipid antigens in immunity

    PubMed Central

    Dowds, C. Marie; Kornell, Sabin-Christin

    2014-01-01

    Lipids are not only a central part of human metabolism but also play diverse and critical roles in the immune system. As such, they can act as ligands of lipid-activated nuclear receptors, control inflammatory signaling through bioactive lipids such as prostaglandins, leukotrienes, lipoxins, resolvins, and protectins, and modulate immunity as intracellular phospholipid- or sphingolipid-derived signaling mediators. In addition, lipids can serve as antigens and regulate immunity through the activation of lipid-reactive T cells, which is the topic of this review. We will provide an overview of the mechanisms of lipid antigen presentation, the biology of lipid-reactive T cells, and their contribution to immunity. PMID:23999493

  16. Antigen detection systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infectious agents or their constituent parts (antigens or nucleic acids) can be detected in fresh, frozen, or fixed tissue using a variety of direct or indirect assays. The assays can be modified to yield the greatest sensitivity and specificity but in most cases a particular methodology is chosen ...

  17. Antigen smuggling in tuberculosis.

    PubMed

    Hudrisier, Denis; Neyrolles, Olivier

    2014-06-11

    The importance of CD4 T lymphocytes in immunity to M. tuberculosis is well established; however, how dendritic cells activate T cells in vivo remains obscure. In this issue of Cell Host & Microbe, Srivastava and Ernst (2014) report a mechanism of antigen transfer for efficient activation of antimycobacterial T cells. PMID:24922567

  18. Antigen detection systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infectious agents or their constituent parts (antigens or nucleic acids) can be detected in fresh, frozen, or fixed tissues or other specimens, using a variety of direct or indirect assays. The assays can be modified to yield the greatest sensitivity and specificity but in most cases a particular m...

  19. Aspergillus antigen skin test (image)

    MedlinePlus

    The aspergillus antigen skin test determines whether or not a person has been exposed to the mold aspergillus. It is performed by injecting an aspergillus antigen under the skin with a needle. After 48 ...

  20. Cancer testis antigen and immunotherapy

    PubMed Central

    Krishnadas, Deepa Kolaseri; Bai, Fanqi; Lucas, Kenneth G

    2013-01-01

    The identification of cancer testis (CT) antigens has been an important advance in determining potential targets for cancer immunotherapy. Multiple previous studies have shown that CT antigen vaccines, using both peptides and dendritic cell vaccines, can elicit clinical and immunologic responses in several different tumors. This review details the expression of melanoma antigen family A, 1 (MAGE-A1), melanoma antigen family A, 3 (MAGE-A3), and New York esophageal squamous cell carcinoma-1 (NY-ESO-1) in various malignancies, and presents our current understanding of CT antigen based immunotherapy.

  1. Human leucocyte antigens in tympanosclerosis.

    PubMed

    Dursun, G; Acar, A; Turgay, M; Calgüner, M

    1997-02-01

    This study was designed to evaluate the association between certain HLA antigens and tympanosclerosis. The serum concentrations of HLA antigens were measured by a microlymphocytotoxicity technique in patients with tympanosclerosis and compared with a healthy control group. The serum levels of HLA-B35 and -DR3 were significantly higher in the patients with tympanosclerosis. This result suggests that certain types of HLA antigens may play an important role as an indicator or mediator in the pathogenesis of tympanosclerosis. PMID:9088683

  2. Novel antigen delivery systems.

    PubMed

    Trovato, Maria; De Berardinis, Piergiuseppe

    2015-08-12

    Vaccines represent the most relevant contribution of immunology to human health. However, despite the remarkable success achieved in the past years, many vaccines are still missing in order to fight important human pathologies and to prevent emerging and re-emerging diseases. For these pathogens the known strategies for making vaccines have been unsuccessful and thus, new avenues should be investigated to overcome the failure of clinical trials and other important issues including safety concerns related to live vaccines or viral vectors, the weak immunogenicity of subunit vaccines and side effects associated with the use of adjuvants. A major hurdle of developing successful and effective vaccines is to design antigen delivery systems in such a way that optimizes antigen presentation and induces broad protective immune responses. Recent advances in vector delivery technologies, immunology, vaccinology and system biology, have led to a deeper understanding of the molecular and cellular mechanisms by which vaccines should stimulate both arms of the adaptive immune responses, offering new strategies of vaccinations. This review is an update of current strategies with respect to live attenuated and inactivated vaccines, DNA vaccines, viral vectors, lipid-based carrier systems such as liposomes and virosomes as well as polymeric nanoparticle vaccines and virus-like particles. In addition, this article will describe our work on a versatile and immunogenic delivery system which we have studied in the past decade and which is derived from a non-pathogenic prokaryotic organism: the "E2 scaffold" of the pyruvate dehydrogenase complex from Geobacillus stearothermophilus. PMID:26279977

  3. Stool Test: H. Pylori Antigen

    MedlinePlus

    ... Things to Know About Zika & Pregnancy Stool Test: H. Pylori Antigen KidsHealth > For Parents > Stool Test: H. Pylori Antigen Print A A A Text Size ... en español Muestra de materia fecal: antígeno de H. pylori What It Is Helicobacter pylori ( H. pylori ) ...

  4. Novel antigen delivery systems

    PubMed Central

    Trovato, Maria; Berardinis, Piergiuseppe De

    2015-01-01

    Vaccines represent the most relevant contribution of immunology to human health. However, despite the remarkable success achieved in the past years, many vaccines are still missing in order to fight important human pathologies and to prevent emerging and re-emerging diseases. For these pathogens the known strategies for making vaccines have been unsuccessful and thus, new avenues should be investigated to overcome the failure of clinical trials and other important issues including safety concerns related to live vaccines or viral vectors, the weak immunogenicity of subunit vaccines and side effects associated with the use of adjuvants. A major hurdle of developing successful and effective vaccines is to design antigen delivery systems in such a way that optimizes antigen presentation and induces broad protective immune responses. Recent advances in vector delivery technologies, immunology, vaccinology and system biology, have led to a deeper understanding of the molecular and cellular mechanisms by which vaccines should stimulate both arms of the adaptive immune responses, offering new strategies of vaccinations. This review is an update of current strategies with respect to live attenuated and inactivated vaccines, DNA vaccines, viral vectors, lipid-based carrier systems such as liposomes and virosomes as well as polymeric nanoparticle vaccines and virus-like particles. In addition, this article will describe our work on a versatile and immunogenic delivery system which we have studied in the past decade and which is derived from a non-pathogenic prokaryotic organism: the “E2 scaffold” of the pyruvate dehydrogenase complex from Geobacillus stearothermophilus. PMID:26279977

  5. Radioimmunoassays of hidden viral antigens

    SciTech Connect

    Neurath, A.R.; Strick, N.; Baker, L.; Krugman, S.

    1982-07-01

    Antigens corresponding to infectious agents may be present in biological specimens only in a cryptic form bound to antibodies and, thus, may elude detection. We describe a solid-phase technique for separation of antigens from antibodies. Immune complexes are precipitated from serum by polyethylene glycol, dissociated with NaSCN, and adsorbed onto nitrocellulose or polystyrene supports. Antigens remain topographically separated from antibodies after removal of NaSCN and can be detected with radiolabeled antibodies. Genomes from viruses immobilized on nitrocellulose can be identified by nucleic acid hybridization. Nanogram quantities of sequestered hepatitis B surface and core antigens and picogram amounts of hepatitis B virus DNA were detected. Antibody-bound adenovirus, herpesvirus, and measles virus antigens were discerned by the procedure.

  6. [Effect of dithranol therapy on membrane, basement membrane and nuclear markers in psoriasis lesions].

    PubMed

    Wollina, U; Schlesier, F; Schaarschmidt, H; Knopf, B; Hipler, C; Henkel, U; Roth, H; Bartá, U

    1987-02-15

    We investigated the effects of anti-psoriatic therapy with dithranol (1/20-1%) in salicylic acid (0.5%) in white petrolatum on lesional skin. FITC-labeled lectins and pemphigus vulgaris antibodies (PV) served as analytical means to study the glycocalyx. Antibodies of bullous pemphigoid (BP) were used as basal membrane markers. Nuclear antigens were recorded according to the binding of speckled, anti-nuclear antibodies (ANA) as well as antibodies to dsDNA. With some lectins, dithranol therapy resulted in pronounced fluorescence of the lower parts of the basal cells. ConA was fixed by the basal cell layer. To a lesser degree, ANA were fixed by nuclei of keratinocytes. PV antibodies were not fixed at all. PMID:3554801

  7. The role of lymphocytes, granulocytes, mast cells and their related cytokines in lesional skin of linear IgA bullous dermatosis.

    PubMed

    Caproni, M; Rolfo, S; Bernacchi, E; Bianchi, B; Brazzini, B; Fabbri, P

    1999-06-01

    Linear IgA bullous dermatosis (LAD) is an acquired, heterogeneous, subepidermal blistering disease characterized by linear IgA deposits at the dermoepidermal basement membrane zone (BMZ), often with circulating IgA antibodies to the BMZ. The pathogenetic mechanism, possibly related to the immunophenotype of infiltrating cells, as well as the potential role of cytokines in determining bullous lesions, have not yet been elucidated. An immunohistochemical study was performed with a large panel of monoclonal antibodies [to CD3, CD4, CD8, CD25, CD1a, CD30, CD54, CD50, endothelial leucocyte adhesion molecule-1, vascular cell adhesion molecule-1, myeloperoxidase (MPO), eosinophil cationic protein EG1 and EG2, tryptase, HLA-DR, human interleukin (IL)-3, human IL-5, human IL-8, human IL-4, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma and granulocyte/macrophage colony-stimulating factor] using the alkaline phosphatase-antialkaline phosphatase procedure on lesional and perilesional skin of nine patients (one male, eight female; age range 8 months-80 years) with clinical, histological and immunofluorescent proven LAD. The predominant infiltrating cells, distributed mostly inside and below the bullae, were neutrophils and eosinophils which showed intense activation (MPO +, EG1 +, EG2 +). The lymphocytic infiltrate, consisting principally of CD4 +, HLA-DR + and CD30 + T cells, had a predominantly perivascular distribution. Proinflammatory cytokines, such as TNF-alpha and IFN-gamma, showed a moderate focal expression on the dermal perivascular sites; IL-8 was found to have a particularly intense staining on all the epidermal cell layers and at perivascular and vascular sites. Other cytokines, such as IL-4 and IL-5, showed a prevalent intracytoplasmic staining on some cells of the dermal infiltrate (probably mastocytes and lymphocytes), and at the dermal-epidermal separation sites there was also an intense scattered distribution of IL-5. The specific tissue lesions

  8. [Antigenic response against PPD and antigen 60 in tubercular patients: single antigen versus the combined test].

    PubMed

    Máttar, S; Broquetas, J M; Gea, J; Aran, X; el-Banna, N; Sauleda, J; Torres, J M

    1992-05-01

    We analyze serum samples from 70 patients with pulmonary tuberculosis and 50 healthy individuals. The antigenic activity (IgG) against protein purified antigen (PPD) and antigen 60 (A60) from M. tuberculosis. Thirteen patients were also HIV infected, and three patients had AIDS defined by the presence of disseminated tuberculosis. The test using antigen alone showed a 77% sensitivity and 74% specificity when PPD is used. When A60 was used, both values improved (81% sensitivity, 94% specificity). The use of a combined test (PPD and A60) improves the sensitivity (89%) but reduces the specificity (82%). The HIV infected patients showed similar responses to those of other patients. The combined use of different antigens might be useful for diagnosing tuberculosis. PMID:1390996

  9. Altering the antigenicity of proteins.

    PubMed Central

    Alexander, H; Alexander, S; Getzoff, E D; Tainer, J A; Geysen, H M; Lerner, R A

    1992-01-01

    To better understand the binding interaction between antigen and antibody we need to distinguish protein residues critical to the binding energy and mechanism from residues merely localized in the interface. By analyzing the binding of monoclonal antibodies to recombinant wild-type and mutant myohemerythrin (MHr) proteins, we were able to test the role of individual critical residues at the highly antigenic site MHr-(79-84), within the context of the folded protein. The results directly show the existence of antigenically critical residues, whose mutations significantly reduce antibody binding to the folded protein, thus verifying peptide-based assignments of these critical residues and demonstrating the ability of buried side chains to influence antigenicity. Taken together, these results (i) distinguish the antigenic surface from the solvent-exposed protein surface before binding, (ii) support a two-stage interaction mechanism allowing inducible changes in protein antigens by antibody binding, and (iii) show that protein antigenicity can be significantly reduced by alteration of single critical residues without destroying biological activity. Images PMID:1373498

  10. 7th International Immunoglobulin Conference: Immunomodulation

    PubMed Central

    Danieli, M G; Shoenfeld, Y

    2014-01-01

    Immunomodulation uses synthetic, natural and recombinant preparations to modify the immune response to a desired level, typically to treat specific autoimmune diseases, as will be discussed in this section. Rheumatoid arthritis (RA) is a common systemic autoimmune disease, affecting 1% of the population worldwide. Currently, a first-line disease-modifying therapy for RA is methotrexate; however, more than 40 monoclonal antibodies are in use or under investigation for the treatment of RA. This panoply of biological disease-modifying agents means that clinicians can make use of drugs with different mechanisms of action should one type become ineffective. In autoimmune pemphigus conditions, identification of pathogenic autoantibodies against intercellular cadherin desmoglein 1 and/or 3 antigens is one of the criteria for appropriate diagnosis. In pemphigoid conditions, autoantibodies are directed against bullous pemphigoid antigens BP230 and BP180, and in both types of immunobullous disease intravenous immunoglobulin (IVIg), as adjuvant therapy in combination with a cytotoxic drug, is effective in reducing autoantibody levels, disease severity and background steroid use. Further studies are required to establish the role of monoclonal antibodies in the treatment of autoimmune bullous disease. IVIg may also be effective in another at-risk population with autoimmune disease, namely secondary recurrent miscarriage (RM). However, the mechanism of action of IVIg in secondary RM is largely unknown, although levels of natural killer cell biomarkers, particularly CD56+, have been shown to decline after IVIg treatment [1-6]. Data from meta-analyses of heterogeneous placebo-controlled trials indicate that IVIg may be effective in secondary RM, but most trials to date have used immunomodulatory doses lower than those considered to be efficient in autoimmune disease. The results of a recently completed study may help to address this question. PMID:25546784

  11. 7th International Immunoglobulin Conference: Immunomodulation.

    PubMed

    Danieli, M G; Shoenfeld, Y

    2014-12-01

    Immunomodulation uses synthetic, natural and recombinant preparations to modify the immune response to a desired level, typically to treat specific autoimmune diseases, as will be discussed in this section. Rheumatoid arthritis (RA) is a common systemic autoimmune disease, affecting 1% of the population worldwide. Currently, a first-line disease-modifying therapy for RA is methotrexate; however, more than 40 monoclonal antibodies are in use or under investigation for the treatment of RA. This panoply of biological disease-modifying agents means that clinicians can make use of drugs with different mechanisms of action should one type become ineffective. In autoimmune pemphigus conditions, identification of pathogenic autoantibodies against intercellular cadherin desmoglein 1 and/or 3 antigens is one of the criteria for appropriate diagnosis. In pemphigoid conditions, autoantibodies are directed against bullous pemphigoid antigens BP230 and BP180, and in both types of immunobullous disease intravenous immunoglobulin (IVIg), as adjuvant therapy in combination with a cytotoxic drug, is effective in reducing autoantibody levels, disease severity and background steroid use. Further studies are required to establish the role of monoclonal antibodies in the treatment of autoimmune bullous disease. IVIg may also be effective in another at-risk population with autoimmune disease, namely secondary recurrent miscarriage (RM). However, the mechanism of action of IVIg in secondary RM is largely unknown, although levels of natural killer cell biomarkers, particularly CD56(+) , have been shown to decline after IVIg treatment. Data from meta-analyses of heterogeneous placebo-controlled trials indicate that IVIg may be effective in secondary RM, but most trials to date have used immunomodulatory doses lower than those considered to be efficient in autoimmune disease. The results of a recently completed study may help to address this question. PMID:25546784

  12. Antigen Retrieval Immunohistochemistry

    PubMed Central

    Shi, Shan-Rong; Shi, Yan; Taylor, Clive R.

    2011-01-01

    As a review for the 20th anniversary of publishing the antigen retrieval (AR) technique in this journal, the authors intend briefly to summarize developments in AR-immunohistochemistry (IHC)–based research and diagnostics, with particular emphasis on current challenges and future research directions. Over the past 20 years, the efforts of many different investigators have coalesced in extending the AR approach to all areas of anatomic pathology diagnosis and research and further have led to AR-based protein extraction techniques and tissue-based proteomics. As a result, formalin-fixed paraffin-embedded (FFPE) archival tissue collections are now seen as a literal treasure of materials for clinical and translational research to an extent unimaginable just two decades ago. Further research in AR-IHC is likely to focus on tissue proteomics, developing a more efficient protocol for protein extraction from FFPE tissue based on the AR principle, and combining the proteomics approach with AR-IHC to establish a practical, sophisticated platform for identifying and using biomarkers in personalized medicine. PMID:21339172

  13. Natural Selection Promotes Antigenic Evolvability

    PubMed Central

    Graves, Christopher J.; Ros, Vera I. D.; Stevenson, Brian; Sniegowski, Paul D.; Brisson, Dustin

    2013-01-01

    The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed ‘cassettes’ that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios) and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish chronic infections

  14. Aptamer-targeted Antigen Delivery

    PubMed Central

    Wengerter, Brian C; Katakowski, Joseph A; Rosenberg, Jacob M; Park, Chae Gyu; Almo, Steven C; Palliser, Deborah; Levy, Matthew

    2014-01-01

    Effective therapeutic vaccines often require activation of T cell-mediated immunity. Robust T cell activation, including CD8 T cell responses, can be achieved using antibodies or antibody fragments to direct antigens of interest to professional antigen presenting cells. This approach represents an important advance in enhancing vaccine efficacy. Nucleic acid aptamers present a promising alternative to protein-based targeting approaches. We have selected aptamers that specifically bind the murine receptor, DEC205, a C-type lectin expressed predominantly on the surface of CD8α+ dendritic cells (DCs) that has been shown to be efficient at facilitating antigen crosspresentation and subsequent CD8+ T cell activation. Using a minimized aptamer conjugated to the model antigen ovalbumin (OVA), DEC205-targeted antigen crosspresentation was verified in vitro and in vivo by proliferation and cytokine production by primary murine CD8+ T cells expressing a T cell receptor specific for the major histocompatibility complex (MHC) I-restricted OVA257–264 peptide SIINFEKL. Compared with a nonspecific ribonucleic acid (RNA) of similar length, DEC205 aptamer-OVA-mediated antigen delivery stimulated strong proliferation and production of interferon (IFN)-γ and interleukin (IL)-2. The immune responses elicited by aptamer-OVA conjugates were sufficient to inhibit the growth of established OVA-expressing B16 tumor cells. Our results demonstrate a new application of aptamer technology for the development of effective T cell-mediated vaccines. PMID:24682172

  15. [Scarring linear IgA dermatosis in the adult].

    PubMed

    Kurz, K; Mahrle, G

    1986-10-15

    A 54-year-old woman had a six-months history of a scarring blistering disease with clinical signs of dermatitis herpetiformis and bullous pemphigoid. Direct immunofluorescence examination showed homogeneously linear deposits of IgA along the dermo-epidermal junction. Electron microscopic studies revealed blistering above and beneath the lamina densa. Referring to this new case of a scarring linear IgA disease we discuss some other forms of scarring bullous diseases in adults. PMID:3541412

  16. Surface antigens of smooth brucellae.

    PubMed

    Diaz, R; Jones, L M; Leong, D; Wilson, J B

    1968-10-01

    Surface antigens of smooth brucellae were extracted by ether-water, phenol-water, trichloroacetic acid, and saline and examined by immunoelectrophoresis and gel diffusion with antisera from infected and immunized rabbits. Ether-water extracts of Brucella melitensis contained a lipopolysaccharide protein component, which was specific for the surface of smooth brucellae and was correlated with the M agglutinogen of Wilson and Miles, a polysaccharide protein component devoid of lipid which was not restricted to the surface of smooth brucellae and was not correlated with the smooth agglutinogen (component 1), and several protein components which were associated with internal antigens of rough and smooth brucellae. Immunoelectrophoretic analysis of ether-water extracts of B. abortus revealed only two components, a lipopolysaccharide protein component, which was correlated with the A agglutinogen, and component 1. Component 1 from B. melitensis and B. abortus showed identity in gel diffusion tests, whereas component M from B. melitensis and component A from B. abortus showed partial identity with unabsorbed antisera and no cross-reactions with monospecific sera. Attempts to prepare monospecific sera directly by immunization of rabbits with cell walls or ether-water extracts were unsuccessful. Absorption of antisera with heavy fraction of ether-water extracts did not always result in monospecific sera. It was concluded (as has been described before) that the A and M antigens are present on a single antigenic complex, in different proportions depending upon the species and biotype, and that this component is a lipopolysaccharide protein complex of high molecular weight that diffuses poorly through agar gel. Components 1, A, and M were also demonstrated in trichloroacetic acid and phenol-water extracts. With all extracts, B. melitensis antigen showed greater diffusibility in agar than B. abortus antigens. After mild acid hydrolysis, B. abortus ether-water extract was able

  17. Characterisation of Sarcoptes scabiei antigens.

    PubMed

    Hejduk, Gloria; Hofstätter, Katja; Löwenstein, Michael; Peschke, Roman; Miller, Ingrid; Joachim, Anja

    2011-02-01

    In pig herds, the status of Sarcoptes scabiei infections is routinely monitored by serodiagnosis. Crude antigen for ELISA is usually prepared from S. scabiei var. canis or other variations and may lead to variations in the outcome of different tests, making assay standardisation difficult. This study was performed to investigate the antigen profiles of S. scabiei, including differences between hydrophilic and more hydrophobic protein fractions, by Western blotting with sera from pigs with defined infection status. Potential cross-reactivity among S. scabiei (var. canis, suis and bovis), Dermatophagoides farinae and Tyrophagus putrescentiae was also analysed. Hydrophobic S. scabiei antigens were detectable in the range of 40-50 kDa, whilst the hydrophilic fraction showed no specific antigenicity. In the hydrophobic fractions of D. farinae and T. putrescentiae, two major protein fractions in a similar size range could be identified, but no cross-reactivity with Sarcoptes-positive sera was detectable. However, examination of the hydrophilic fractions revealed cross-reactivity between Sarcoptes-positive sera and both the house dust mite and the storage mite in the range of 115 and 28/38 kDa. Specific bands in the same range (42 and 48 kDa) could be detected in blots from hydrophobic fractions of all three tested variations of S. scabiei (var. canis, bovis and suis). These results show that there are considerable differences in mange antibody reactivity, including reactions with proteins from free-living mites, which may interfere with tests based on hydrophilic antigens. Further refinement of antigen and the use of specific hydrophobic proteins could improve ELISA performance and standardisation. PMID:20865427

  18. [Farmer's lung antigens in Germany].

    PubMed

    Sennekamp, J; Joest, M; Sander, I; Engelhart, S; Raulf-Heimsoth, M

    2012-05-01

    Recent studies suggest that besides the long-known farmer's lung antigen sources Saccharopolyspora rectivirgula (Micropolyspora faeni), Thermoactinomyces vulgaris, and Aspergillus fumigatus, additionally the mold Absidia (Lichtheimia) corymbifera as well as the bacteria Erwinia herbicola (Pantoea agglomerans) and Streptomyces albus may cause farmer's lung in Germany. In this study the sera of 64 farmers with a suspicion of farmer's lung were examined for the following further antigens: Wallemia sebi, Cladosporium herbarum, Aspergillus versicolor, and Eurotium amstelodami. Our results indicate that these molds are not frequent causes of farmer's lung in Germany. PMID:22477566

  19. Proteolysis, proteasomes and antigen presentation

    NASA Technical Reports Server (NTRS)

    Goldberg, A. L.; Rock, K. L.

    1992-01-01

    Proteins presented to the immune system must first be cleaved to small peptides by intracellular proteinases. Proteasomes are proteolytic complexes that degrade cytosolic and nuclear proteins. These particles have been implicated in ATP-ubiquitin-dependent proteolysis and in the processing of intracellular antigens for cytolytic immune responses.

  20. Detection of O antigens in Escherichia coli

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lipopolysaccharide on the surface of Escherichia coli constitute the O antigens, which are important virulence factors that are targets of both the innate and adaptive immune system and play a major role in host-pathogen interactions. O antigens that are responsible for antigenic specificity of the ...

  1. Antigenic determinants and functional domains in core antigen and e antigen from hepatitis B virus

    SciTech Connect

    Salfeld, J.; Pfaff, E.; Noah, M.; Schaller, H.

    1989-02-01

    The precore/core gene of hepatitis B virus directs the synthesis of two polypeptides, the 21-kilodalton subunit (p21c) forming the viral nucleocapsid (serologically defined as core antigen (HBcAg)) and a secreted processed protein (p17e, serologically defined as HBe antigen (HBeAg)). Although most of their primary amino acid sequences are identical, HBcAg and HBeAg display different antigenic properties that are widely used in hepatitis B virus diagnosis. To locate and to characterize the corresponding determinants, segments of the core gene were expressed in Escherichia coli and probed with a panel of polyclonal or monoclonal antibodies in radioimmunoassays or enzyme-linked immunosorbent assays, Western blots, and competition assays. Three distinct major determinants were characterized. It is postulated that HBcAg and HBeAg share common basic three-dimensional structure exposing the common linear determinant HBe1 but that they differ in the presentation of two conformational determinants that are either introduced (HBc) or masked (HBe2) in the assembled core. The simultaneous presentation of HBe1 and HBc, two distinctly different antigenic determinants with overlapping amino acid sequences, is interpreted to indicate the presence of slightly differently folded, stable conformational states of p21c in the hepatitis virus nucleocapsid.

  2. Antigen Export Reduces Antigen Presentation and Limits T Cell Control of M. tuberculosis.

    PubMed

    Srivastava, Smita; Grace, Patricia S; Ernst, Joel D

    2016-01-13

    Persistence of Mycobacterium tuberculosis results from bacterial strategies that manipulate host adaptive immune responses. Infected dendritic cells (DCs) transport M. tuberculosis to local lymph nodes but activate CD4 T cells poorly, suggesting bacterial manipulation of antigen presentation. However, M. tuberculosis antigens are also exported from infected DCs and taken up and presented by uninfected DCs, possibly overcoming this blockade of antigen presentation by infected cells. Here we show that the first stage of this antigen transfer, antigen export, benefits M. tuberculosis by diverting bacterial proteins from the antigen presentation pathway. Kinesin-2 is required for antigen export and depletion of this microtubule-based motor increases activation of antigen-specific CD4 T cells by infected cells and improves control of intracellular infection. Thus, although antigen transfer enables presentation by bystander cells, it does not compensate for reduced antigen presentation by infected cells and represents a bacterial strategy for CD4 T cell evasion. PMID:26764596

  3. [Polyagglutinability due to Hempas antigen].

    PubMed

    Rochant, H; Gerbal, A

    1976-03-01

    A new antigen has been recently discoverd in patients with congenital dyserythropoietic anemia type II. The acronyme Hempas was proposed for this disease as a remind of the main morphological feature of erythroblasts (hereditary erythroblastic multinuclearity) and the characteristic serological findings (positive acidified serum test). The patients red cells are agglutinated and lysed by an IgM cold reacting antibody present in the serum of most normal subjects and not previously recognized. This behaviour is thus reminding of cells carrying antigens such as T, Tn, Cad or acquired B. As for T and Tn cells, sialic acid and electrophoretic mobility are reduced, but in contrast, agglutinability of Hempas cells is enhanced by enzyme treatment. Agglutination by anti H and anti Pr specific reagents is reduced. I and mainly i activity are strongly increased. The relationship between the membrane abnormalities of Hempas red cells and the failure of normoblasts to divide their cytoplasm i still largely unknown. PMID:788106

  4. Common antigens between hydatid cyst and cancers

    PubMed Central

    Daneshpour, Shima; Bahadoran, Mehran; Hejazi, Seyed Hossein; Eskandarian, Abas Ali; Mahmoudzadeh, Mehdi; Darani, Hossein Yousofi

    2016-01-01

    Background: Different research groups reported a negative correlation between cancers and parasitical infections. As an example, the prevalence of a hydatid cyst among patients with cancer was significantly lower than its prevalence among normal population. Tn antigens exist both in cancer and hydatid cyst. This common antigen may be involved in the effect of parasite on cancer growth. So in this work, common antigens between hydatid cyst and cancers have been investigated. Materials and Methods: Different hydatid cyst antigens including hydatid fluid, laminated and germinal layer antigens, and excretory secretory antigens of protoscolices were run in SDS PAGE and transferred to NCP paper. In western immunoblotting, those antigens were probed with sera of patients with different cancer and also sera of non-cancer patients. Also, cross reaction among excretory secretory products of cancer cells and antisera raised against different hydatid cyst antigen was investigated. Results: In western immunoblotting, antisera raised against laminated and germinal layers of hydatid cyst reacted with excretory secretory products of cancer cells. Also, a reaction was detected between hydatid cyst antigens and sera of patients with some cancers. Conclusion: Results of this work emphasize existence of common antigens between hydatid cyst and cancers. More investigation about these common antigens is recommended. PMID:26962511

  5. A progressive pruritic rash with blisters.

    PubMed

    Overcash, Michael D; Ewald, Matt

    2016-05-01

    This article describes a patient with a progressive pruritic rash and fluid-filled blisters. A punch biopsy later confirmed the diagnosis of bullous pemphigoid, an inflammatory condition that most commonly occurs in older adults and is treated with corticosteroids. PMID:27124233

  6. Anti-early endosome antigen 1 autoantibodies were detected in a pemphigus-like patient but not in the majority of pemphigus diseases.

    PubMed

    Nishikawa, Ryuhei; Takahashi, Hitoshi; Matsuda, Mitsuhiro; Imaoka, Kaoru; Ogawa, Masahiro; Teye, Kwesi; Tsuchisaka, Atsunari; Koga, Hiroshi; Komorowski, Lars; Probst, Christian; Hachiya, Takahisa; Fritzler, Marvin J; Ishii, Norito; Ohata, Chika; Furumura, Minao; Krol, Rafal P; Muro, Yoshinao; Morita, Eishin; Hashimoto, Takashi

    2016-05-01

    Although the major autoantigens in classic pemphigus are desmogleins, sera from various types of pemphigus react with a number of other molecules, including desmocollins and plakin proteins. However, other novel pemphigus-related autoantigens remain to be identified. In this study, immunoblotting for serum from an atypical autoimmune bullous disease patient identified an unknown 175 kDa protein. Subsequent studies using two-dimensional gel electrophoresis, immunoblotting and mass-spectrometry identified the 175 kDa protein as early endosome antigen 1 (EEA1). This finding was confirmed by subsequent immunological studies, including indirect immunofluorescence of skin and cultured keratinocytes, two-dimensional gel electrophoresis and immunoblotting with anti-EEA1 polyclonal antibody, and preabsorption with EEA1 recombinant protein. Finally, we developed a novel BIOCHIP assay using full-length EEA1 recombinant protein to detect anti-EEA1 antibodies. However, none of 35 sera from various types of pemphigus showed anti-EEA1 antibodies in the BIOCHIP assay, with the exception of the serum from the index case. In addition, various findings in the index case did not suggest pathogenic role of anti-EEA1 autoantibodies. Therefore, although we successfully identified the 175 kDa protein reacted by a serum of an atypical pemphigus-like patient as EEA1, novel BIOCHIP study for other pemphigus sera indicated that EEA1 is not a common and pathogenic autoantigen in pemphigus. PMID:26909655

  7. Viruses, cytokines, antigens, and autoimmunity.

    PubMed Central

    Gianani, R; Sarvetnick, N

    1996-01-01

    To explain the pathogenesis of autoimmunity, we hypothesize that following an infection the immune response spreads to tissue-specific autoantigens in genetically predisposed individuals eventually determining progression to disease. Molecular mimicry between viral and self antigens could, in some instances, initiate autoimmunity. Local elicitation of inflammatory cytokines following infection probably plays a pivotal role in determining loss of functional tolerance to self autoantigens and the destructive activation of autoreactive cells. We also describe the potential role of interleukin 10, a powerful B-cell activator, in increasing the efficiency of epitope recognition, that could well be crucial to the progression toward disease. PMID:8637859

  8. Recombinant hepatitis B triple antigen vaccine: Hepacare.

    PubMed

    Zuckerman, Jane N; Zuckerman, Arie J

    2002-08-01

    Infection with hepatitis B virus is a public health problem throughout the world. Hepatitis B vaccines are now included in national immunization programmes of infants and/or adolescents in 129 countries. Current single antigen vaccines, that are plasma-derived or produced by recombinant DNA technology are highly effective, but between 5-10% or more of healthy immunocompetent subjects do not mount an antihepatitis B surface antibody protective response and others respond poorly (hyporesponders). The inclusion of pre-S1 and -S2 components of hepatitis B surface antigen in addition to the single antigen (triple antigen) in a novel vaccine, Hepacare, Medeva Pharma Plc, Speke, UK, overcomes nonresponsiveness and hyporesponsiveness in a significant number of individuals. The triple antigen is indicated for vaccination of nonresponders (and hyporesponders) to the current single antigen vaccines and for persons who require rapid protection against hepatitis B infection. PMID:12901552

  9. Antigen Recognition By Variable Lymphocyte Receptors

    SciTech Connect

    Han, B.W.; Herrin, B.R.; Cooper, M.D.; Wilson, I.A.

    2009-05-18

    Variable lymphocyte receptors (VLRs) rather than antibodies play the primary role in recognition of antigens in the adaptive immune system of jawless vertebrates. Combinatorial assembly of leucine-rich repeat (LRR) gene segments achieves the required repertoire for antigen recognition. We have determined a crystal structure for a VLR-antigen complex, VLR RBC36 in complex with the H-antigen trisaccharide from human blood type O erythrocytes, at 1.67 angstrom resolution. RBC36 binds the H-trisaccharide on the concave surface of the LRR modules of the solenoid structure where three key hydrophilic residues, multiple van der Waals interactions, and the highly variable insert of the carboxyl-terminal LRR module determine antigen recognition and specificity. The concave surface assembled from the most highly variable regions of the LRRs, along with diversity in the sequence and length of the highly variable insert, can account for the recognition of diverse antigens by VLRs.

  10. Persistence of antigen in nonarthritic joints.

    PubMed Central

    Fox, A; Glynn, L E

    1975-01-01

    The presence of antigen, IgG and C3 was shown by radioautography and immunofluorescence in the collagenous tissues of the joints of animals injected intra-articularly with antigen after having been previously immunized with that antigen in Freund's incomplete adjuvant. Since these joints were shown to be virtually free of inflammatory reactions, we suggest that the persistence of immune complexes activating complement cannot fully explain the chronicity of experimental allergic arthritis. Images PMID:769709

  11. HLA antigens in cardiomyopathic Chilean chagasics.

    PubMed Central

    Llop, E; Rothhammer, F; Acuña, M; Apt, W

    1988-01-01

    The distribution of HLA antigens in a sample of 124 Chagas serologically positive Chilean individuals was studied. The sample was subdivided according to the presence or absence of chagasic cardiomyopathy, in order to search for genetic differences associated with this pathological condition. The frequency of antigen B40 in the presence of antigen Cw3 was found to be significantly lower in subjects with cardiomyopathy. We tentatively suggest that the presence of these antigens among noncardiomyopathics is associated with a decreased susceptibility to develop chagasic cardiomyopathy in the Chilean population. PMID:3189340

  12. Integrating influenza antigenic dynamics with molecular evolution

    PubMed Central

    Bedford, Trevor; Suchard, Marc A; Lemey, Philippe; Dudas, Gytis; Gregory, Victoria; Hay, Alan J; McCauley, John W; Russell, Colin A; Smith, Derek J; Rambaut, Andrew

    2014-01-01

    Influenza viruses undergo continual antigenic evolution allowing mutant viruses to evade host immunity acquired to previous virus strains. Antigenic phenotype is often assessed through pairwise measurement of cross-reactivity between influenza strains using the hemagglutination inhibition (HI) assay. Here, we extend previous approaches to antigenic cartography, and simultaneously characterize antigenic and genetic evolution by modeling the diffusion of antigenic phenotype over a shared virus phylogeny. Using HI data from influenza lineages A/H3N2, A/H1N1, B/Victoria and B/Yamagata, we determine patterns of antigenic drift across viral lineages, showing that A/H3N2 evolves faster and in a more punctuated fashion than other influenza lineages. We also show that year-to-year antigenic drift appears to drive incidence patterns within each influenza lineage. This work makes possible substantial future advances in investigating the dynamics of influenza and other antigenically-variable pathogens by providing a model that intimately combines molecular and antigenic evolution. DOI: http://dx.doi.org/10.7554/eLife.01914.001 PMID:24497547

  13. Antigenic variation in African trypanosomes

    PubMed Central

    Horn, David

    2014-01-01

    Studies on Variant Surface Glycoproteins (VSGs) and antigenic variation in the African trypanosome, Trypanosoma brucei, have yielded a remarkable range of novel and important insights. The features first identified in T. brucei extend from unique to conserved-among-trypanosomatids to conserved-among-eukaryotes. Consequently, much of what we now know about trypanosomatid biology and much of the technology available has its origin in studies related to VSGs. T. brucei is now probably the most advanced early branched eukaryote in terms of experimental tractability and can be approached as a pathogen, as a model for studies on fundamental processes, as a model for studies on eukaryotic evolution or often all of the above. In terms of antigenic variation itself, substantial progress has been made in understanding the expression and switching of the VSG coat, while outstanding questions continue to stimulate innovative new approaches. There are large numbers of VSG genes in the genome but only one is expressed at a time, always immediately adjacent to a telomere. DNA repair processes allow a new VSG to be copied into the single transcribed locus. A coordinated transcriptional switch can also allow a new VSG gene to be activated without any detectable change in the DNA sequence, thereby maintaining singular expression, also known as allelic exclusion. I review the story behind VSGs; the genes, their expression and switching, their central role in T. brucei virulence, the discoveries that emerged along the way and the persistent questions relating to allelic exclusion in particular. PMID:24859277

  14. Pilomatricoma with a bullous appearance.

    PubMed

    Inui, S; Kanda, R; Hata, S

    1997-01-01

    A 15-year-old Japanese girl had an asymptomatic nodule on the right thigh of seven months' duration. The clinical appearance was similar to that of a bulla. There was a history of blunt trauma from dog scratch to the skin over the tumor shortly before tumor growth. Histopathological findings were consistent with pilomatricoma. In the overlying dermis, the collagen bundles were compressed to the tissue surrounding the tumor and the large space was seen. Around the tumor, some dilated endothelium-lined vascular channels were found, which were identified as lymphatic vessels. PMID:9046744

  15. Direct immunofluorescence on hair follicles--present and future perspectives.

    PubMed

    Alexandru, Adina; Zurac, Sabina; Salavastru, Carmen M; Andrei, Razvan; Tebeica, Tiberiu; Staniceanu, Florica; Tiplica, George S

    2013-06-01

    Direct immunofluorescence (DIF) is an important tool for evaluating bullous autoimmune and connective tissue disorders. We report 21 cases of pemphigus vulgaris, bullous pemphigoid and lupus erythematosus that were investigated by performing DIF on scalp hair follicles. The study was done using a simplified technique of preparing the hairs for DIF testing. The anagen hairs tested positive in pemphigus vulgaris patients while the telogen hairs were negative. In bullous pemphigoid and lupus erythematosus cases hair DIF presented negative results.Hair DIF has the potential of taking the place of skin or mucosal DIF in pemphigus patients if performed on anagen hair follicles. The technique used to perform hair DIF is important in obtaining reliable results and eliminating the possibility of generating false-negative testing. Larger studies are needed in order to validate this method. PMID:23689693

  16. Antigenically Modified Human Pluripotent Stem Cells Generate Antigen-Presenting Dendritic Cells

    PubMed Central

    Zeng, Jieming; Wu, Chunxiao; Wang, Shu

    2015-01-01

    Human pluripotent stem cells (hPSCs) provide a promising platform to produce dendritic cell (DC) vaccine. To streamline the production process, we investigated a unique antigen-loading strategy that suits this novel platform. Specifically, we stably modified hPSCs using tumour antigen genes in the form of a full-length tumour antigen gene or an artificial tumour antigen epitope-coding minigene. Such antigenically modified hPSCs were able to differentiate into tumour antigen-presenting DCs. Without conventional antigen-loading, DCs derived from the minigene-modified hPSCs were ready to prime a tumour antigen-specific T cell response and further expand these specific T cells in restimulation processes. These expanded tumour antigen-specific T cells were potent effectors with central memory or effector memory phenotype. Thus, we demonstrated that immunocompetent tumour antigen-loaded DCs can be directly generated from antigenically modified hPSCs. Using such strategy, we can completely eliminate the conventional antigen-loading step and significantly simplify the production of DC vaccine from hPSCs. PMID:26471005

  17. Evidence for horizontal gene transfer of two antigenically distinct O antigens in Bordetella bronchiseptica

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antigenic variation is one mechanism pathogens use to avoid immune-mediated competition between closely related strains. Here, we show that two Bordetella bronchiseptica strains, RB50 and 1289, express two antigenically distinct O-antigen serotypes (O1 and O2 respectively). When 18 additional B. b...

  18. Diagnotic value of some Fasciola gigantica antigens.

    PubMed

    Shalaby, Said; El-Bahy, Mohammad; Hassan, Ali; Shalaby, Hatem; Gupta, Neelima

    2015-09-01

    The present study was aimed to select the specificity of antigens for Fasciola gigantica depending on its diagnostic utility and field applications. The tested antigens were coproantigen, excretory-secretory (ES) antigen and egg antigen. Coproantigen and Copro Hyperimmune serum were able to reflect the lowest level of cross-reaction with other tested F. gigantica antigens. By using SDS-PAGE, a structural homology was observed in F. gigantica ES and egg antigens. Intense cross reaction was observed between ES and egg antigens by ELISA technique even when there was no cross-reaction with coproantigen. The 27.6 kDa band proved to be the most specific in F. gigantica coproantigen and was different from the band at the same molecular weight by ES antigen. The results conclude that coproantigens show specific diagnostic ability for Fasciola and have low numbers of cross-reaction proteins reflecting its high specificity. Moreover, detection of coproantigen in faeces offers a new potential for diagnostics as compared to serum samples. This fact holds promise for a more accurate diagnostic technique in the near future for suspected Fasciola infection. PMID:26345056

  19. Antigenic composition of Litomosoides carini.

    PubMed

    Enayat, M S

    1976-07-01

    Three different phosphate buffered saline extracts of Litomosoides carini were prepared and examined by gel diffusion, immunoelectrophoresis and disc polyacrylamide gel electrophoresis using sera from infected cotton rats and antisera from hyperimmunized rabbits. Using disc polyacrylamide gel electrophoresis, up to 22 protein, 6 lipoprotein and 4 glycoprotein bands were identified. A minimum of 8 precipitin lines were detected by gel diffusion and a maximum of 11 precipitin arcs by immunoelectrophoresis when pooled rabbit antiserum was used. Using infected cotton rat sera, fewer number of precipitin lines and arcs were detected. Two precipitin arcs did not have a counterpart on examination against pooled rabbit antiserum. The importance of these two specific antigenic components for use in immunodiagnosis of human filariasis has been discussed. PMID:823514

  20. Calcium-dependent antigen binding as a novel modality for antibody recycling by endosomal antigen dissociation

    PubMed Central

    Hironiwa, N; Ishii, S; Kadono, S; Iwayanagi, Y; Mimoto, F; Habu, K; Igawa, T; Hattori, K

    2016-01-01

    The pH-dependent antigen binding antibody, termed a recycling antibody, has recently been reported as an attractive type of second-generation engineered therapeutic antibody. A recycling antibody can dissociate antigen in the acidic endosome, and thus bind to its antigen multiple times. As a consequence, a recycling antibody can neutralize large amounts of antigen in plasma. Because this approach relies on histidine residues to achieve pH-dependent antigen binding, which could limit the epitopes that can be targeted and affect the rate of antigen dissociation in the endosome, we explored an alternative approach for generating recycling antibodies. Since calcium ion concentration is known to be lower in endosome than in plasma, we hypothesized that an antibody with antigen-binding properties that are calcium-dependent could be used as recycling antibody. Here, we report a novel anti-interleukin-6 receptor (IL-6R) antibody, identified from a phage library that binds to IL-6R only in the presence of a calcium ion. Thermal dynamics and a crystal structure study revealed that the calcium ion binds to the heavy chain CDR3 region (HCDR3), which changes and possibly stabilizes the structure of HCDR3 to make it bind to antigen calcium dependently (PDB 5AZE). In vitro and in vivo studies confirmed that this calcium-dependent antigen-binding antibody can dissociate its antigen in the endosome and accelerate antigen clearance from plasma, making it a novel approach for generating recycling antibody. PMID:26496237

  1. Antigen-induced suppression of the in vitro lymphocyte response to different antigens and mitogens

    PubMed Central

    Möller, Göran; Kashiwagi, Noboru

    1972-01-01

    Certain concentrations of antigen stimulated DNA synthesis in sensitized human lymphocytes cultivated in vitro, higher and lower concentrations being less stimulatory. The simultaneous addition of two antigens in low concentrations to the same cells caused an additive response. The decreased response to a high antigen dose did not affect the capacity of the cells to respond to the simultaneous addition of another antigen, as determined at the population level as well as at the cellular level by autoradiography. Presumably specific immunological paralysis was induced by high antigen doses. Addition of low antigen doses for 1–3 days to human sensitized lymphocytes cultivated in vitro resulted in decreased DNA synthesis as a response to the same antigen added in an optimal dose. Suppression of DNA synthesis was not caused by induction of tolerance or antibody suppression, because the cells also failed to respond to an unrelated antigen and to non-specific mitogens, such as PHA and ALS. Most likely the suppressed response after antigen pretreatment represents a phenomenon analogous to antigenic competition, although this term is not appropriate, since there need not be competition between antigens for a detectable effect. No soluble mediators of suppression could be demonstrated in the supernatant of suppressed cultures. PMID:5026855

  2. Tiny T antigen: an autonomous polyomavirus T antigen amino-terminal domain.

    PubMed Central

    Riley, M I; Yoo, W; Mda, N Y; Folk, W R

    1997-01-01

    Three mRNAs from the murine polyomavirus early region encode the three well-characterized tumor antigens. We report the existence of a fourth alternatively spliced mRNA which encodes a fourth tumor antigen, tiny T antigen, which comprises the amino-terminal domain common to all of the T antigens but is extended by six unique amino acid residues. The amount of tiny T antigen in infected cells is small because of its short half-life. Tiny T antigen stimulates the ATPase activity of Hsc70, most likely because of its DnaJ-like motif. The common amino-terminal domain may interface with chaperone complexes to assist the T antigens in carrying out their diverse functions of replication, transcription, and transformation in the appropriate cellular compartments. PMID:9223500

  3. Antigenic variation: Molecular and genetic mechanisms of relapsing disease

    SciTech Connect

    Cruse, J.M.; Lewis, R.E.

    1987-01-01

    This book contains 10 chapters. They are: Contemporary Concepts of Antigenic Variation; Antigenic Variation in the Influenza Viruses; Mechanisms of Escape of Visna Lentiviruses from Immunological Control; A Review of Antigenic Variation by the Equine Infectious Anemia Virus; Biologic and Molecular Variations in AIDS Retrovirus Isolates; Rabies Virus Infection: Genetic Mutations and the Impact on Viral Pathogenicity and Immunity; Immunobiology of Relapsing Fever; Antigenic Variation in African Trypanosomes; Antigenic Variation and Antigenic Diversity in Malaria; and Mechanisms of Immune Evasion in Schistosomiasis.

  4. Non-antigenic and antigenic interventions in type 1 diabetes

    PubMed Central

    Rydén, Anna KE; Wesley, Johnna D; Coppieters, Ken T; Von Herrath, Matthias G

    2014-01-01

    Type 1 diabetes (T1D) results from autoimmune destruction of the pancreatic β-cells. Current T1D therapies are exclusively focused on regulating glycemia rather than the underlying immune response. A handful of trials have sought to alter the clinical course of T1D using various broad immune-suppressors, e.g., cyclosporine A and azathioprine.1–3 The effect on β-cell preservation was significant, however, these therapies were associated with unacceptable side-effects. In contrast, more recent immunomodulators, such as anti-CD3 and antigenic therapies such as DiaPep277, provide a more targeted immunomodulation and have been generally well-tolerated and safe; however, as a monotherapy there appear to be limitations in terms of therapeutic benefit. Therefore, we argue that this new generation of immune-modifying agents will likely work best as part of a combination therapy. This review will summarize current immune-modulating therapies under investigation and discuss how to move the field of immunotherapy in T1D forward. PMID:24165565

  5. Further characterization of filarial antigens by SDS polyacrylamide gel electrophoresis

    PubMed Central

    Dissanayake, S.; Galahitiyawa, S. C.; Ismail, M. M.

    1983-01-01

    SDS (sodium dodecyl sulfate)-polyacrylamide gel electrophoresis of an antigen isolated from sera of Wuchereria bancrofti-infected patients and Setaria digitata antigen SD2-4 is reported. Both antigens showed carbohydrate (glycoprotein) staining. The W. bancrofti antigen had an apparent relative molecular mass of 35 000 while the S. digitata antigen SD2-4 migrated at the marker dye position on SDS-polyacrylamide gel electrophoresis. SDS treatment of these antigens did not abolish the precipitation reaction with antibody. In the case of W. bancrofti antigen, SDS treatment probably exposed hitherto hidden antigen epitopes. PMID:6354508

  6. Cyclosporine inhibits macrophage-mediated antigen presentation

    SciTech Connect

    Ziegler, H.K.; Palay, D.; Wentworth, P.; Cluff, C.

    1986-03-01

    The influence of cyclosporine on antigen-specific, macrophage-dependent T cell activation was analyzed in vitro. Murine T cell activation by antigens derived from Listeria monocytogenes was monitored by the production of interleukin-2. Pretreatment (2 hrs., 37/sup 0/C) of macrophages with cyclosporine resulted in a population of macrophages with a markedly diminished capacity to support the activation of T lymphocytes. When cyclosporine-pretreated macrophages were added to cultures of antigen and untreated T cells, the dose of cyclosporine which produced 50% inhibition was 1.5 ..mu..g/ml. Appropriate control experiments indicated that cyclosporine was indeed inhibiting at the macrophage level. The addition of interleukin-1 or indomethacin to the cultures did not alter the inhibitory effect of cyclosporine. Under conditions which produced >90% inhibition of antigen presentation, macrophage surface Ia expression was not altered, and the uptake and catabolism of radiolabelled antigen was normal. Thus, cyclosporine inhibits antigen presentation by a mechanism which appears unrelated to changes in Il-1 elaboration, prostaglandin production, Ia expression, or antigen uptake and catabolism.

  7. Meningococcal vaccine antigen diversity in global databases

    PubMed Central

    Brehony, C; Hill, DM; Lucidarme, J; Borrow, R; Maiden, MC

    2016-01-01

    The lack of an anti-capsular vaccine against serogroup B meningococcal disease has necessitated the exploration of alternative vaccine candidates, mostly proteins exhibiting varying degrees of antigenic variation. Analysis of variants of antigen-encoding genes is facilitated by publicly accessible online sequence repositories, such as the Neisseria PubMLST database and the associated Meningitis Research Foundation Meningococcus Genome Library (MRF-MGL). We investigated six proposed meningococcal vaccine formulations by deducing the prevalence of their components in the isolates represented in these repositories. Despite high diversity, a limited number of antigenic variants of each of the vaccine antigens were prevalent, with strong associations of particular variant combinations with given serogroups and genotypes. In the MRF-MGL and globally, the highest levels of identical sequences were observed with multicomponent/multivariant vaccines. Our analyses further demonstrated that certain combinations of antigen variants were prevalent over periods of decades in widely differing locations, indicating that vaccine formulations containing a judicious choice of antigen variants have potential for long-term protection across geographic regions. The data further indicated that formulations with multiple variants would be especially relevant at times of low disease incidence, as relative diversity was higher. Continued surveillance is required to monitor the changing prevalence of these vaccine antigens. PMID:26676305

  8. Antigen clasping by two antigen-binding sites of an exceptionally specific antibody for histone methylation

    PubMed Central

    Hattori, Takamitsu; Lai, Darson; Dementieva, Irina S.; Montaño, Sherwin P.; Kurosawa, Kohei; Zheng, Yupeng; Akin, Louesa R.; Świst-Rosowska, Kalina M.; Grzybowski, Adrian T.; Koide, Akiko; Krajewski, Krzysztof; Strahl, Brian D.; Kelleher, Neil L.; Ruthenburg, Alexander J.; Koide, Shohei

    2016-01-01

    Antibodies have a well-established modular architecture wherein the antigen-binding site residing in the antigen-binding fragment (Fab or Fv) is an autonomous and complete unit for antigen recognition. Here, we describe antibodies departing from this paradigm. We developed recombinant antibodies to trimethylated lysine residues on histone H3, important epigenetic marks and challenging targets for molecular recognition. Quantitative characterization demonstrated their exquisite specificity and high affinity, and they performed well in common epigenetics applications. Surprisingly, crystal structures and biophysical analyses revealed that two antigen-binding sites of these antibodies form a head-to-head dimer and cooperatively recognize the antigen in the dimer interface. This “antigen clasping” produced an expansive interface where trimethylated Lys bound to an unusually extensive aromatic cage in one Fab and the histone N terminus to a pocket in the other, thereby rationalizing the high specificity. A long-neck antibody format with a long linker between the antigen-binding module and the Fc region facilitated antigen clasping and achieved both high specificity and high potency. Antigen clasping substantially expands the paradigm of antibody–antigen recognition and suggests a strategy for developing extremely specific antibodies. PMID:26862167

  9. Human immune response to Mycobacterium tuberculosis antigens.

    PubMed Central

    Havlir, D V; Wallis, R S; Boom, W H; Daniel, T M; Chervenak, K; Ellner, J J

    1991-01-01

    Little is known about the immunodominant or protective antigens of Mycobacterium tuberculosis in humans. Cell-mediated immunity is necessary for protection, and healthy tuberculin-positive individuals are relatively resistant to exogenous reinfection. We compared the targets of the cell-mediated immune response in healthy tuberculin-positive individuals to those of tuberculosis patients and tuberculin-negative persons. By using T-cell Western blotting (immunoblotting) of nitrocellulose-bound M. tuberculosis culture filtrate, peaks of T-cell blastogenic activity were identified in the healthy tuberculin reactors at 30, 37, 44, 57, 64, 71 and 88 kDa. Three of these fractions (30, 64, and 71 kDa) coincided with previously characterized proteins: antigen 6/alpha antigen, HSP60, and HSP70, respectively. The blastogenic responses to purified M. tuberculosis antigen 6/alpha antigen and BCG HSP60 were assessed. When cultured with purified antigen 6/alpha antigen, lymphocytes of healthy tuberculin reactors demonstrated greater [3H]thymidine incorporation than either healthy tuberculin-negative controls or tuberculous patients (8,113 +/- 1,939 delta cpm versus 645 +/- 425 delta cpm and 1,019 +/- 710 delta cpm, respectively; P less than 0.01). Healthy reactors also responded to HSP60, although to a lesser degree than antigen 6/alpha antigen (4,276 +/- 1,095 delta cpm; P less than 0.05). Partially purified HSP70 bound to nitrocellulose paper elicited a significant lymphocyte blastogenic response in two of six of the tuberculous patients but in none of the eight healthy tuberculin reactors. Lymphocytes of none of five tuberculin-negative controls responded to recombinant antigens at 14 or 19 kDa or to HSP70. Antibody reactivity generally was inversely correlated with blastogenic response: tuberculous sera had high titer antibody to M. tuberculosis culture filtrate in a range from 35 to 180 kDa. This is the first systematic evaluation of the human response to a panel of native

  10. Overexpressed oncogenic tumor-self antigens

    PubMed Central

    Bright, Robert K; Bright, Jennifer D; Byrne, Jennifer A

    2014-01-01

    Overexpressed tumor-self antigens represent the largest group of candidate vaccine targets. Those exhibiting a role in oncogenesis may be some of the least studied but perhaps most promising. This review considers this subset of self antigens by highlighting vaccine efforts for some of the better known members and focusing on TPD52, a new promising vaccine target. We shed light on the importance of both preclinical and clinical vaccine studies demonstrating that tolerance and autoimmunity (presumed to preclude this class of antigens from vaccine development) can be overcome and do not present the obstacle that might have been expected. The potential of this class of antigens for broad application is considered, possibly in the context of low tumor burden or adjuvant therapy, as is the need to understand mechanisms of tolerance that are relatively understudied. PMID:25483660

  11. Mapping Epitopes on a Protein Antigen by the Proteolysis of Antigen-Antibody Complexes

    NASA Astrophysics Data System (ADS)

    Jemmerson, Ronald; Paterson, Yvonne

    1986-05-01

    A monoclonal antibody bound to a protein antigen decreases the rate of proteolytic cleavage of the antigen, having the greatest effect on those regions involved in antibody contact. Thus, an epitope can be identified by the ability of the antibody to protect one region of the antigen more than others from proteolysis. By means of this approach, two distinct epitopes, both conformationally well-ordered, were characterized on horse cytochrome c.

  12. Tales of Antigen Evasion from CAR Therapy.

    PubMed

    Sadelain, Michel

    2016-06-01

    Both T cells bearing chimeric antigen receptors and tumor-specific antibodies can successfully target some malignancies, but antigen escape can lead to relapse. Two articles in this issue of Cancer Immunology Research explore what effective countermeasures may prevent it. Cancer Immunol Res; 4(6); 473-473. ©2016 AACRSee articles by Zah et al., p. 498, and Rufener et al., p. 509. PMID:27252092

  13. Vertebrate Cells Express Protozoan Antigen after Hybridization

    NASA Astrophysics Data System (ADS)

    Crane, Mark St. J.; Dvorak, James A.

    1980-04-01

    Epimastigotes, the invertebrate host stage of Trypanosoma cruzi, the protozoan parasite causing Chagas' disease in man, were fused with vertebrate cells by using polyethylene glycol. Hybrid cells were selected on the basis of T. cruzi DNA complementation of biochemical deficiencies in the vertebrate cells. Some clones of the hybrid cells expressed T. cruzi-specific antigen. It might be possible to use selected antigens obtained from the hybrids as vaccines for immunodiagnosis or for elucidation of the pathogenesis of Chagas' disease.

  14. Safety of targeting tumor endothelial cell antigens.

    PubMed

    Wagner, Samuel C; Riordan, Neil H; Ichim, Thomas E; Szymanski, Julia; Ma, Hong; Perez, Jesus A; Lopez, Javier; Plata-Munoz, Juan J; Silva, Francisco; Patel, Amit N; Kesari, Santosh

    2016-01-01

    The mechanisms underlying discrimination between "self" and "non-self", a central immunological principle, require careful consideration in immune oncology therapeutics where eliciting anti-cancer immunity must be weighed against the risk of autoimmunity due to the self origin of tumors. Whole cell vaccines are one promising immunotherapeutic avenue whereby a myriad of tumor antigens are introduced in an immunogenic context with the aim of eliciting tumor rejection. Despite the possibility collateral damage to healthy tissues, cancer immunotherapy can be designed such that off target autoimmunity remains limited in scope and severity or completely non-existent. Here we provide an immunological basis for reconciling the safety of cancer vaccines, focusing on tumor endothelial cell vaccines, by discussing the following topics: (a) Antigenic differences between neoplastic and healthy tissues that can be leveraged in cancer vaccine design; (b) The layers of tolerance that control T cell responses directed against antigens expressed in healthy tissues and tumors; and, (c) The hierarchy of antigenic epitope selection and display in response to whole cell vaccines, and how antigen processing and presentation can afford a degree of selectivity against tumors. We conclude with an example of early clinical data utilizing ValloVax™, an immunogenic placental endothelial cell vaccine that is being advanced to target the tumor endothelium of diverse cancers, and we report on the safety and efficacy of ValloVax™ for inducing immunity against tumor endothelial antigens. PMID:27071457

  15. The 65-kilodalton antigen of Mycobacterium tuberculosis.

    PubMed Central

    Shinnick, T M

    1987-01-01

    The immune response of the host to the antigens of Mycobacterium tuberculosis plays the key role in determining immunity from infection with as well as the pathogenicity of this organism. A 65-kilodalton (kDa) protein has been identified as one of the medically important antigens of M. tuberculosis. The gene encoding this antigen was isolated from a lambda gt11-M. tuberculosis recombinant DNA library using monoclonal antibodies directed against the 65-kDa antigen as the specific probes. The nucleotide sequence of this gene was determined, and a 540-amino-acid sequence was deduced. This sequence was shown to correspond to that of the 65-kDa antigen by constructing a plasmid in which this open reading frame was fused to the lacZ gene. The resulting fusion protein reacted specifically with the anti-65-kDa protein antibodies. A second long open reading frame was found downstream of the 65-kDa antigen gene which could encode a protein of 517 amino acids. This putative protein contained 29 tandemly arranged partial or complete matches to a pentapeptide sequence. Images PMID:3029018

  16. Do lymphocytes from Chagasic patients respond to heart antigens?

    PubMed Central

    Todd, C W; Todd, N R; Guimaraes, A C

    1983-01-01

    Lymphocyte transformation studies of nonadherent lymphocytes from chronic Chagasic and uninfected persons demonstrated that responses of all individuals to a mouse heart homogenate showed a correlation with responses to streptococcal antigens. Considering the known cross-reactions between streptococcal and cardiac antigens and the high reactivity of Chagasic patients to streptococcal antigens, it is possible that positive lymphocyte transformation to unfractionated heart antigen preparations may not represent specific reactivity to heart antigens. PMID:6404836

  17. Serological response to in vitro-shed antigen(s) of Tritrichomonas foetus in cattle.

    PubMed Central

    Bondurant, R H; van Hoosear, K A; Corbeil, L B; Bernoco, D

    1996-01-01

    We developed a serological assay for detection of (l) an erythrocyte-adhering molecule(s) shed by the bovine venereal pathogen Tritrichomonas foetus and (II) serum antibodies to this antigen(s) in exposed cattle. Sera from exposed and unexposed cattle were tested for their ability to induce complement-mediated lysis of bovine erythrocytes that had been previously incubated overnight at room temperature in pH-adjusted supernatants of T. foetus culture media. Eight of 180 serum specimens from six groups of presumably unexposed cows or heifers showed a positive (> or = 1:2) hemolytic titer (specificity = 95.6%). Thirteen of 14 females in two experimentally infected groups showed a positive hemolytic titer following infection (sensitivity = 94%). In experimentally infected heifers, there was little correlation (r2 = 0.33) between serum hemolytic titers with respect to shed antigen and titers obtained in serum enzyme-linked immunosorbent assays in which whole T. foetus served as the antigen. Serum hemolytic titers rose 3 to 4 weeks sooner than did previously described vaginal mucus immunoglobulin G1 or immunoglobulin A titers with respect to whole-cell antigen or TF1.17 subunit antigen, respectively. Among 14 chronically infected bulls, only 6 (43%) showed a positive hemolytic titer. This study is the first, to our knowledge, to show a specific serological response in the host to an in vitro-shed antigen(s) of T. foetus and suggests a useful diagnostic test for potentially exposed herds. PMID:8807209

  18. Tresyl-Based Conjugation of Protein Antigen to Lipid Nanoparticles Increases Antigen Immunogencity

    PubMed Central

    Jain, Anekant; Yan, Weili; Miller, Keith R.; O'Carra, Ronan; Woodward, Jerold G.; Mumper, Russell J.

    2010-01-01

    The present studies were aimed at investigating the engineering of NPs with protein-conjugated-surfactant at their surface. In order to increase the immunogenicity of a protein antigen, Brij 78 was functionalized by tresyl chloride and then further reacted with the primary amine of the model proteins ovalbumin (OVA) or horseradish peroxide (HRP). The reaction yielded Brij 78-OVA and Brij 78-HRP conjugates which were then used directly to form NP-OVA or NP-HRP using a one-step warm oil-in-water microemulsion precursor method with emulsifying wax as the oil phase, and Brij 78 and the Brij 78-OVA or Brij 78-HRP conjugate as surfactants. Similarly, Brij 700 was conjugated to HIV p24 antigen to yield Brij 700-p24 conjugate. The utility of these NPs for enhancing the immune responses to protein-based vaccines was evaluated in vivo using ovalbumin (OVA) as model protein and p24 as a relevant HIV antigen. In separate in vivo studies, female BALB/c mice were immunized by subcutaneous (s.c.) injection with NP-OVA and NP-p24 formulations along with several control formulations. These results suggested that with multiple antigens, covalent attachment of the antigen to the NP significantly enhanced antigen-specific immune responses. This facile covalent conjugation and incorporation method may be utilized to further incorporate other protein antigens, even multiple antigens, into an enhanced vaccine delivery system. PMID:20837122

  19. Beyond antigens and adjuvants: formulating future vaccines.

    PubMed

    Moyer, Tyson J; Zmolek, Andrew C; Irvine, Darrell J

    2016-03-01

    The need to optimize vaccine potency while minimizing toxicity in healthy recipients has motivated studies of the formulation of vaccines to control how, when, and where antigens and adjuvants encounter immune cells and other cells/tissues following administration. An effective subunit vaccine must traffic to lymph nodes (LNs), activate both the innate and adaptive arms of the immune system, and persist for a sufficient time to promote a mature immune response. Here, we review approaches to tailor these three aspects of vaccine function through optimized formulations. Traditional vaccine adjuvants activate innate immune cells, promote cell-mediated transport of antigen to lymphoid tissues, and promote antigen retention in LNs. Recent studies using nanoparticles and other lymphatic-targeting strategies suggest that direct targeting of antigens and adjuvant compounds to LNs can also enhance vaccine potency without sacrificing safety. The use of formulations to regulate biodistribution and promote antigen and inflammatory cue co-uptake in immune cells may be important for next-generation molecular adjuvants. Finally, strategies to program vaccine kinetics through novel formulation and delivery strategies provide another means to enhance immune responses independent of the choice of adjuvant. These technologies offer the prospect of enhanced efficacy while maintaining high safety profiles necessary for successful vaccines. PMID:26928033

  20. Genetic and antigenic changes in porcine rubulavirus

    PubMed Central

    Sánchez-Betancourt, José I.; Trujillo, María E.; Mendoza, Susana E.; Reyes-Leyva, Julio; Alonso, Rogelio A.

    2012-01-01

    Blue eye disease, caused by a porcine rubulavirus (PoRV), is an emergent viral swine disease that has been endemic in Mexico since 1980. Atypical outbreaks were detected in 1990 and 2003. Growing and adult pigs presented neurological signs, mild neurological signs were observed in piglets, and severe reproductive problems were observed in adults. Amino acid sequence comparisons and phylogenetic analysis of the hemagglutinin-neuraminidase (HN) protein revealed genetically different lineages. We used cross-neutralization assays, with homologous and heterologous antisera, to determine the antigenic relatedness values for the PoRV isolates. We found antigenic changes among several strains and identified a highly divergent one, making up a new serogroup. It seems that genetically and antigenically different PoRV strains are circulating simultaneously in the swine population in the geographical region studied. The cross neutralization studies suggest that the HN is not the only antigenic determinant participating in the antigenic changes among the different PoRV strains. PMID:22754092

  1. Antigen-specific vaccines for cancer treatment

    PubMed Central

    Tagliamonte, Maria; Petrizzo, Annacarmen; Tornesello, Maria Lina; Buonaguro, Franco M; Buonaguro, Luigi

    2014-01-01

    Vaccines targeting pathogens are generally effective and protective because based on foreign non-self antigens which are extremely potent in eliciting an immune response. On the contrary, efficacy of therapeutic cancer vaccines is still disappointing. One of the major reasons for such poor outcome, among others, is the difficulty of identifying tumor-specific target antigens which should be unique to the tumors or, at least, overexpressed on the tumors as compared to normal cells. Indeed, this is the only option to overcome the peripheral immune tolerance and elicit a non toxic immune response. New and more potent strategies are now available to identify specific tumor-associated antigens for development of cancer vaccine approaches aiming at eliciting targeted anti-tumor cellular responses. In the last years this aspect has been addressed and many therapeutic vaccination strategies based on either whole tumor cells or specific antigens have been and are being currently evaluated in clinical trials. This review summarizes the current state of cancer vaccines, mainly focusing on antigen-specific approaches. PMID:25483639

  2. Antigenic Properties of N Protein of Hantavirus

    PubMed Central

    Yoshimatsu, Kumiko; Arikawa, Jiro

    2014-01-01

    Hantavirus causes two important rodent-borne viral zoonoses, hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome (HPS) in North and South America. Twenty-four species that represent sero- and genotypes have been registered within the genus Hantavirus by the International Committee on Taxonomy of Viruses (ICTV). Among the viral proteins, nucleocapsid (N) protein possesses an immunodominant antigen. The antigenicitiy of N protein is conserved compared with that of envelope glycoproteins. Therefore, N protein has been used for serological diagnoses and seroepidemiological studies. An understanding of the antigenic properties of N protein is important for the interpretation of results from serological tests using N antigen. N protein consists of about 430 amino acids and possesses various epitopes. The N-terminal quarter of N protein bears linear and immunodominant epitopes. However, a serotype-specific and multimerization-dependent antigenic site was found in the C-terminal half of N protein. In this paper, the structure, function, and antigenicity of N protein are reviewed. PMID:25123683

  3. Genetic and antigenic changes in porcine rubulavirus.

    PubMed

    Sánchez-Betancourt, José I; Trujillo, María E; Mendoza, Susana E; Reyes-Leyva, Julio; Alonso, Rogelio A

    2012-01-01

    Blue eye disease, caused by a porcine rubulavirus (PoRV), is an emergent viral swine disease that has been endemic in Mexico since 1980. Atypical outbreaks were detected in 1990 and 2003. Growing and adult pigs presented neurological signs, mild neurological signs were observed in piglets, and severe reproductive problems were observed in adults. Amino acid sequence comparisons and phylogenetic analysis of the hemagglutinin-neuraminidase (HN) protein revealed genetically different lineages. We used cross-neutralization assays, with homologous and heterologous antisera, to determine the antigenic relatedness values for the PoRV isolates. We found antigenic changes among several strains and identified a highly divergent one, making up a new serogroup. It seems that genetically and antigenically different PoRV strains are circulating simultaneously in the swine population in the geographical region studied. The cross neutralization studies suggest that the HN is not the only antigenic determinant participating in the antigenic changes among the different PoRV strains. PMID:22754092

  4. Separation of soluble Brucella antigens by gel-filtration chromatography.

    PubMed

    McGhee, J R; Freeman, B A

    1970-07-01

    Soluble precipitating antigens of Brucella suis have been, in various degrees, purified by filtration on Sephadex gels. The most useful gels employed were Sephadex G-150, Sephadex G-200, and Sepharose 4B. Although not all fractions proved to be immunologically pure, some crude molecular-size estimates of most of the 13 soluble antigens of the Brucella cell could be given. In addition, monospecific antisera to three purified Brucella antigens have been prepared. By using purified preparations, physical and chemical data were obtained on two major antigens, E and 1, and a minor antigen, f. Antigen E is not an agglutinogen and may be toxic. Antigen 1 is of low molecular weight and is neither toxic nor agglutinogenic. The minor antigen f is an agglutinogen as well as a precipitinogen and is found on the cell surface. Both major antigens, when purified, were immunogenic in rabbits. PMID:16557798

  5. Immunochemical characterization of Ancylostoma caninum antigens.

    PubMed

    Schnieder, T; Kohlmetz, C; Epe, C; Stoye, M

    1996-06-01

    Adult worms of Ancylostoma caninum were dissected and manually separated into cephalic glands, cervical glands, intestine, esophagus and cuticula. These fractions as well as third stage larvae were fractionated with Triton X-114 into water soluble (hydrophilic), Triton soluble (hydrophobic) and unsoluble proteins. These fractions were characterized by immunoblotting with serum from rabbits immunized either with a pool of cervical, cephalic glands and intestine, or the esophagus fraction as well as with sera from percutaneously infected dogs and rabbits. Immunodominant antigens were found that reacted with dog or rabbit post infection sera and could be suited as antigens in serodiagnostic tests. Hidden antigens were found in the several fractions. Those from esophagus and intestine could be vaccine candidates that will be tested in immunization trials. PMID:8688863

  6. Antigen sampling in the fish intestine.

    PubMed

    Løkka, Guro; Koppang, Erling Olaf

    2016-11-01

    Antigen uptake in the gastrointestinal tract may induce tolerance, lead to an immune response and also to infection. In mammals, most pathogens gain access to the host though the gastrointestinal tract, and in fish as well, this route seems to be of significant importance. The epithelial surface faces a considerable challenge, functioning both as a barrier towards the external milieu but simultaneously being the site of absorption of nutrients and fluids. The mechanisms allowing antigen uptake over the epithelial barrier play a central role for maintaining the intestinal homeostasis and regulate appropriate immune responses. Such uptake has been widely studied in mammals, but also in fish, a number of experiments have been reported, seeking to reveal cells and mechanisms involved in antigen sampling. In this paper, we review these studies in addition to addressing our current knowledge of the intestinal barrier in fish and its anatomical construction. PMID:26872546

  7. Podosomes of dendritic cells facilitate antigen sampling

    PubMed Central

    Reinieren-Beeren, Inge; Cambi, Alessandra; Figdor, Carl G.; van den Bogaart, Geert

    2014-01-01

    Summary Dendritic cells sample the environment for antigens and play an important role in establishing the link between innate and acquired immunity. Dendritic cells contain mechanosensitive adhesive structures called podosomes that consist of an actin-rich core surrounded by integrins, adaptor proteins and actin network filaments. They facilitate cell migration via localized degradation of extracellular matrix. Here we show that podosomes of human dendritic cells locate to spots of low physical resistance in the substrate (soft spots) where they can evolve into protrusive structures. Pathogen recognition receptors locate to these protrusive structures where they can trigger localized antigen uptake, processing and presentation to activate T-cells. Our data demonstrate a novel role in antigen sampling for podosomes of dendritic cells. PMID:24424029

  8. Polyomavirus T Antigens Activate an Antiviral State

    PubMed Central

    Giacobbi, Nicholas S.; Gupta, Tushar; Coxon, Andrew; Pipas, James M.

    2014-01-01

    Ectopic expression of Simian Virus 40 (SV40) large T antigen (LT) in mouse embryonic fibroblasts (MEFs) increased levels of mRNAs encoding interferon stimulated genes (ISGs). The mechanism by which T antigen increases levels of ISGs in MEFs remains unclear. We present evidence that expression of T antigen from SV40, Human Polyomaviruses BK (BKV) or JC (JCV) upregulate production of ISGs in MEFs, and subsequently result in an antiviral state, as determined by inhibition of VSV or EMCV growth. The first 136 amino acids of LT are sufficient for these activities. Furthermore, increased ISG expression and induction of the antiviral state requires STAT1. Finally, the RB binding motif of LT is necessary for activation of STAT1. We conclude that the induction of the STAT1 mediated innate immune response in MEFs is a common feature shared by SV40, BKV and JCV. PMID:25589241

  9. Human Tumor Antigens and Cancer Immunotherapy

    PubMed Central

    Vigneron, Nathalie

    2015-01-01

    With the recent developments of adoptive T cell therapies and the use of new monoclonal antibodies against the immune checkpoints, immunotherapy is at a turning point. Key players for the success of these therapies are the cytolytic T lymphocytes, which are a subset of T cells able to recognize and kill tumor cells. Here, I review the nature of the antigenic peptides recognized by these T cells and the processes involved in their presentation. I discuss the importance of understanding how each antigenic peptide is processed in the context of immunotherapy and vaccine delivery. PMID:26161423

  10. Carbohydrate-functionalized nanovaccines preserve HIV-1 antigen stability and activate antigen presenting cells

    PubMed Central

    Vela Ramirez, J.E.; Roychoudhury, R.; Habte, H.H.; Cho, M. W.; Pohl, N. L. B.; Narasimhan, B.

    2015-01-01

    The functionalization of polymeric nanoparticles with ligands that target specific receptors on immune cells offers the opportunity to tailor adjuvant properties by conferring pathogen mimicking attributes to the particles. Polyanhydride nanoparticles are promising vaccine adjuvants with desirable characteristics such as immunomodulation, sustained antigen release, activation of antigen presenting cells, and stabilization of protein antigens. These capabilities can be exploited to design nanovaccines against viral pathogens, such as HIV-1, due to the important role of dendritic cells and macrophages in viral spread. In this work, an optimized process was developed for carbohydrate functionalization of HIV-1 antigen-loaded polyanhydride nanoparticles. The carbohydrate-functionalized nanoparticles preserved antigenic properties upon release and also enabled sustained antigen release kinetics. Particle internalization was observed to be chemistry-dependent with positively charged nanoparticles being taken up more efficiently by dendritic cells. Up-regulation of the activation makers CD40 and CD206 was demonstrated with carboxymethyl-α-d-mannopyranosyl-(1,2)-d-mannopyranoside functionalized nanoparticles. The secretion of the cytokines IL-6 and TNF-α was shown to be chemistry-dependent upon stimulation with carbohydrate-functionalized nanoparticles. These results offer important new insights upon the interactions between carbohydrate-functionalized nanoparticles and antigen presenting cells and provide foundational information for the rational design of targeted nanovaccines against HIV-1. PMID:25068589