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HLA class II molecules are key factors determining susceptibility to autoimmune disorders, and their role in immune-mediated skin conditions such as psoriasis has been extensively investigated. However, there is currently little understanding of their role in antibody-mediated skin diseases such as autoimmune blistering disorders. We researched the available literature using PubMed to narratively review the current knowledge on HLA associations in antibody-mediated blistering skin pathologies. Our results summarized the risk alleles that are identified in the literature, together with certain known protective alleles: in the pemphigus group, alleles HLA-DQB1*0503 and HLA-DRB1*0402 are most commonly associated with disease; in the pemphigoid group, the most studied allele is HLA-DQB1*0301; in epidermolysis bullosa acquisita, few genetic studies are available; in dermatitis herpetiformis, the association with haplotypes HLA-DQ2 and HLA-DQ8 is strongly established; finally, in linear IgA bullous disease, specific HLA alleles may be responsible for pediatric presentations. Our current pathogenic understanding of this group of disorders assigns a key role to predisposing HLA class II alleles that are able to bind disease autoantigens and therefore stimulate antigen-specific autoreactive T cells. The latter engage B lymphocytes that will produce pathogenic autoantibodies. The distribution of HLA alleles and their disease associations are variable across demographics, and an in-depth pathogenetic understanding is needed to support associations between HLA alleles and disease phenotypes. Additionally, in a personalized medicine approach, the identification of HLA alleles associated with the risk of disease may become clinically relevant in identifying susceptible subjects that should avoid exposure to known triggers, such as medication, when possible. [ABSTRACT FROM AUTHOR] more...

Collagen XVII (COL17) is a hemidesmosomal transmembrane protein in the skin, which, in several autoimmune blistering skin diseases, may be targeted by autoantibodies. In addition, loss-of-function mutations in the COL17A1 gene induce a subtype of junctional epidermolysis bullosa. The extracellular domain of COL17 can be physiologically cleaved from the cell surface by ADAM family proteins in a process known as ectodomain shedding. COL17 ectodomain shedding is thought to be associated with the migration and proliferation of keratinocytes. Furthermore, the C-terminal cleavage of COL17 may be associated with basement membrane formation. COL17 can be targeted by various proteases, including MMP9, neutrophil elastase, plasmin and granzyme B, which may be associated with blister formation in pemphigoid diseases. Interestingly, cleavage of COL17 may induce neoepitopes on the proteolysed fragments, and such induction is associated with dynamic structural changes. This review summarizes the current understanding of cleavage of COL17, and how such cleavage relates to blistering skin diseases. more...

Linear IgA bullous dermatosis (LABD) is characterized by presence of multiple IgA autoantibodies, and a comparatively lesser number of IgG antibodies, directed against different hemidesmosomal antigens. The main autoantigens are LAD-1, LABD-97, BP180 and BP230, type VII collagen and laminin 332. We retrospectively studied the serology of 54 Italian patients with LABD using enzyme-linked immunosorbent assay (ELISA), immunoblotting assay, and indirect immunofluorescence on monkey oesophagus and salt-split skin. Among these, indirect immunofluorescence of salt-split skin elicits the greatest sensitivity. Sixty-three percent of the sera were observed to be positive, with a lamina lucida pattern observed in 48%, a sub-lamina densa pattern in 2% and a mixed pattern in 13% of the cases. IgA reactivity to LAD-1 on immunoblotting was found in 52% of sera, to BP180-NC16A by ELISA in 32% and to BP230 in 26%. Only 17% of patients possessed circulating IgG autoantibodies. LAD-1 was determined to be a major autoantigen of the lamina lucida subtype. Combined serological assays demonstrated a high sensitivity (82%), suggesting that this approach could support diagnosis when a biopsy is not feasible or direct immunofluorescence results are negative. more...

Collagen XVII (COL17) is a hemidesmosomal transmembrane protein in the skin, which, in several autoimmune blistering skin diseases, may be targeted by autoantibodies. In addition, lossoffunction mutations in the COL17A1 gene induce a subtype of junctional epidermolysis bullosa. The extracellular domain of COL17 can be physiologically cleaved from the cell surface by ADAM family proteins in a process known as ectodomain shedding. COL17 ectodomain shedding is thought to be associated with the migration and proliferation of keratinocytes. Furthermore, the Cterminal cleavage of COL17 may be associated with basement membrane formation. COL17 can be targeted by various proteases, including MMP9, neutrophil elastase, plasmin and granzyme B, which may be associated with blister formation in pemphigoid diseases. Interestingly, cleavage of COL17 may induce neoepitopes on the proteolysed fragments, and such induction is associated with dynamic structural changes. This review summarizes the current understanding of cleavage of COL17, and how such cleavage relates to blistering skin diseases. [ABSTRACT FROM AUTHOR] more...

Linear immunoglobulin A (IgA) bullous dermatosis (LABD) is characterized by the presence of multiple IgA autoantibodies, and a comparatively lesser number of IgG antibodies, directed against different hemidesmosomal antigens. The main autoantigens are LAD-1, LABD-97, BP180 and BP230, type VII collagen and laminin 332. The serology of 54 Italian patients with LABD was studied retrospectively using enzymelinked immunosorbent assay (ELISA), immunoblotting assay, and indirect immunofluorescence on monkey oesophagus and salt-split skin. Among these, indirect immunofluorescence of salt-split skin elicits the greatest sensitivity. Sixty-three percent of the sera were observed to be positive, with a lamina lucida pattern observed in 48%, a sub-lamina densa pattern in 2% and a mixed pattern in 13% of cases. IgA reactivity to LAD-1 on immunoblotting was found in 52% of sera, to BP180-NC16A by ELISA in 32% and to BP230 in 26%. Only 17% of patients had circulating IgG autoantibodies. LAD-1 was determined to be a major autoantigen of the lamina lucida subtype. Combined serological assays demonstrated a high sensitivity (82%), suggesting that this approach could support diagnosis when a biopsy is not feasible or direct immunofluorescence results are negative. [ABSTRACT FROM AUTHOR] more...

Introduction The follow-up of patients with autoimmune bullous diseases (AIBDs) was temporarily interrupted during the initial phase of the COVID-19 pandemic due to restrictions in healthcare services, given the high contagiousness and rapid spread of SARS-CoV-2. Our objective was to assess the impact of the initial phase of the COVID-19 pandemic on the treatments and disease activity of AIBD patients. Methods We conducted a telephone survey of patients with AIBDs who had been regularly followed up in our hospital prior to the onset of the pandemic. A structured questionnaire that we designed was used. This questionnaire comprised questions examining the following issues between March and June of 2020: patients' follow-up, treatment, COVID-19 infection status, and changes in disease activity. Results Thirty-nine patients were included in the study. Among those, 26 (66.7%) were immunosuppressed. The frequency of follow-up for 37 patients (94.9%) changed significantly (p<0.001): 28 patients (71.8%) did not visit the hospital, and 26 of them (92.9%) did not communicate at all. The treatment for 10 patients (25.6%) was altered, either by their physician or by themselves. Disease activity reactivated in patients who altered their own treatments. There was only one patient (2.6%) who contracted COVID-19. Conclusions Documenting this period revealed that some patients were negatively impacted by the pandemic initially. The most significant contributing factor was the interruption of patient-physician communication., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Örnek et al.) more...

Linear IgA bullous disease (LABD) has been reported in association with inflammatory bowel disease, in particular ulcerative colitis (UC). We reporting a 34-year-old female who developed LABD during a flare-up of UC. We administered infliximab, which has been approved for the treatment of UC; infliximab dramatically improved the cutaneous lesions and bowel symptoms. This is the first report showing a marked effect of infliximab on LABD. First, we hypothesize that infliximab works for UC and then calms down excessive production of inflammatory cytokines and autoantibodies, and so stricter control of UC by infliximab is beneficial against the skin condition of LABD. Second, we suggest that TNF-α production in the lesion of LABD is increased, so TNF-α plays an important role in developing cutaneous lesions. This case suggests that infliximab, a monoclonal antibody against TNF-α, is efficacious in the cutaneous symptoms of LABD. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR] more...

The article discusses skin disorders, papulosquamous and bullous which are common in older people. The clinical features of pemphigus vulgaris, a systemic autoimmune blistering disease of the skin and mucous membrane, is provided as well as the mean age of onset which is about 50 to 60 years. Also discussed are clinical features and treatments for dermatomyositis, cicatricial pemphigoid, coma bullae and linear imunoglobulin A (IgA) bullous disease. more...

Autoimmune mucocutaneous blistering diseases (AMBD) are a rare group of dermatoses that can be potentially fatal. There are many subtypes and their clinical presentation can vary from being localized to general involvement. It is crucial that a diagnosis be made as early as possible and appropriate treatments are implemented. This article will discuss the diagnosis and available treatments of the major AMBDs. There are very few case-controlled studies regarding the treatments of these diseases. Most of the treatments used for these diseases are based on anecdotal reports. Hence, a synopsis of the conventional treatments and some brief recommendations will also be discussed. A brief discussion regarding 'rescue' therapies that have been used for those patients with more recalcitrant cases of AMBD will also be presented. [ABSTRACT FROM AUTHOR] more...

The article presents a case study of a 3-year-old boy who was diagnosed with cytomegalovirus (CMV) infection followed by trimtheporim-sulfametoxazole (TMP-SMX)-induced linear IgA bullous disease (LABD). It states that the boy was treated with gancyclovir, TMP-SMX and penicillin V due to cutaneous blistering eruption. It mentions that the CMV infection was a result of adverse cutaneous drug reactions. It adds that the patient was healed within two week after the intake of TMP-SMX was stopped. more...

The article presents a case report involving a 13-month-old boy who has been diagnosed with untreated varicella. Dermatologic examination result reveals a tense bullae and crusts on the patient's face including the neck, legs and genitalia. Other examinations include biopsy specimens obtained from lesional and perilesional skin for histopathologic and immunoflorescence examinations. Moreover, the patient has been diagnosed with chronic bullous disease of childhood (CBDC) and has been treated with erythromycin instead of dapsone due to microcytic anemia. Furthermore, CBDC is said to be the most immunobullous disease frequently occurring in children. more...