Autoimmune Blistering Disorder Research Articles

Characterization of Disparities, Diagnoses and Treatment Outcomes with Pemphigus Vulgaris

Pemphigus vulgaris (PV) and foliaceus (PF) are classified as rare autoimmune blistering disorders in which IgG antibodies destroy desmosome proteins desmoglein 1 and desmoglein 3 within the stratum spinosum of the epithelial layer of the skin. These disorders once used to be a fatal condition, but the advent of steroids and immunosuppressants has made these diseases manageable. Such treatments, however, only alleviate symptoms and have not been viable in allowing patients to achieve prolonged steroid-free remission. In 2018, the US Food and Drug Administration (FDA) approved the anti-CD20 monoclonal antibody rituximab as the first-line treatment for moderate to severe cases of pemphigus. While rituximab has been generally successful in treating this disease and has led to prolonged steroid-free remission in many patients, treatment disparities and differences in patient outcomes due to social determinants of health have not yet been studied in the context of PV and PF. Such studies have already been conducted with more common dermatological disorders such as hidradenitis suppurativa (HS), which show significant evidence of outcome disparities due to social factors such as race, ethnicity and socioeconomic status. However, such studies have yet to be conducted with pemphigus likely because of how rare the disease is and because the current first-line treatment was FDA approved recently in 2018. The aim of this study is to conduct a retrospective multivariable analysis of 100 patients with pemphigus from UT Southwestern Medical Center and Parkland County Hopital to determine which social factors are the most responsible for any discovered pemphigus treatment outcome disparities. The impacts of this study are far-reaching as any discovered disparities can alert dermatologists to place a special emphasis to address any social factors that may play a role in leading to treatment outcome differences for patients with pemphigus.

Pemphigoid diseases in patients with end-stage kidney diseases: pathogenesis and treatment.

Pemphigoid diseases constitute a group of autoimmune blistering disorders characterized by subepithelial blistering. The association between pemphigoid diseases and both end-stage kidney disease (ESKD) and its treatment is notable. However, there is limited evidence about the management of pemphigoid diseases in patients with ESKD. This systematic review compiled case reports and relevant studies, summarized the underlying mechanisms of pemphigoid diseases in patients with ESKD, and summarized the efficacy of various therapies. A systematic search of PubMed and Embase was performed for articles published between 1982 to June 2, 2024. Fifty-three case reports and eight relevant studies were included. Triggers for pemphigoids in patients with ESKD included materials used to treat ESKD, immune dysregulation of patients with ESKD, and rejection of renal allograft. Treatment for these patients included removing triggers, as well as administering of corticosteroids, mycophenolate mofetil (MMF), tetracyclines, rituximab, methotrexate, dapsone, azathioprine, cyclosporine, intravenous immunoglobin (IVIG), plasmapheresis, and Janus kinase inhibitors. Removing triggers is the most effective strategy. Despite their suboptimal efficacy, corticosteroids remain the most commonly used agents in this patient population. MMF, tetracyclines, and rituximab are less used but with benefits. There are significant adverse effects associated with methotrexate treatment. Other treatment may also be beneficial and require further investigation. These findings may enable clinicians to optimize the therapeutic approach for these patients.

Case series of cutaneous myiasis in neglected cases of autoimmune bullous disorders.

Myiasis is an infestation of the tissues and organs of living vertebrates and humans by fly larvae, usually those belonging to the Calliphoridae family. The larvae feed on the host's necrotic or living tissue. Preexisting dermatological conditions and poor hygiene have been described as predisposing factors for myiasis, and it is especially common among neglected, dependent patients. Based on our literature search, we could find only a few case reports reported on cutaneous myiasis in autoimmune bullous disorders. It is especially more common in the South Indian Tamil Nadu population due to the false belief that autoimmune blistering disorders like pemphigus and bullous pemphigoid are considered chicken pox and treated with neem and turmeric preparation with poor hygiene. Herein we report a series of eight autoimmune blistering disorders with cutaneous myiasis.

Clinical and demographic characteristics of mucous membrane pemphigoid in India: A retrospective analysis.

Background Mucous membrane pemphigoid (MMP) is a rare subepidermal autoimmune blistering disorder. The clinical and demographic parameters of this disease in Indian patients have not yet been elucidated in detail. Objective We aimed to study the clinical and demographic characteristics, disease course, and treatment aspects of MMP patients. Methods The data for this study were obtained by reviewing the case record forms of patients registered in the Autoimmune Bullous Disease (AIBD) Clinic of the Department of Dermatology, Venereology & Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, a tertiary care centre in India. The diagnosis of MMP was established on the basis of clinical and immune-histopathological features which are consistent with standard diagnostic criteria for the disease. Results A total of 52 patients with MMP registered in the AIBD clinic were included. The mean age at disease onset was 50 years and the average age at presentation was 56 years. Females outnumbered males in the study with a ratio of 1.36:1. The oral and ocular mucosae were the most commonly affected sites (82.6% and 63.4% respectively). Visual difficulty was reported by half the patients (26 of 52 patients). IgG, C3, and IgA deposits were detected on direct immunofluorescence (DIF) in 29, 21, and 11 patients, respectively. Serologic analysis was performed in only 7 of the patients and of these, just 1 exhibited a positive result on multivariant ELISA and epidermal pattern of binding on salt split skin indirect immunofluorescence. Most patients were treated with prednisolone (44 of 52). Steroid-sparing adjuvants were used in combination including cyclophosphamide, azathioprine, methotrexate, dapsone, and colchicine. Rituximab was administered in 7 patients with severe or refractory disease. Limitations This is a retrospective analysis of data available from a clinic registry. In patients with negative direct immunofluorescence on biopsy, the diagnosis was based on clinico-pathologic consensus. Conclusion MMP is not as uncommon in India as the paucity of reports suggest. Visual complications are frequent in Indian MMP patients. A high index of suspicion is required for early diagnosis and appropriate treatment to prevent ocular complications.

State-of-the-art diagnosis of autoimmune blistering diseases.

Autoimmune blistering disorders (AIBDs) are a heterogeneous group of approximately a dozen entities comprising pemphigus and pemphigoid disorders and dermatitis herpetiformis. The exact diagnosis of AIBDs is critical for both prognosis and treatment and is based on the clinical appearance combined with the detection of tissue-bound and circulating autoantibodies. While blisters and erosions on the skin and/or inspectable mucosal surfaces are typical, lesions may be highly variable with erythematous, urticarial, prurigo-like, or eczematous manifestations. While direct immunofluorescence microscopy (IFM) of a perilesional biopsy is still the diagnostic gold standard, the molecular identification of the major target antigens opened novel therapeutic avenues. At present, most AIBDs can be diagnosed by the detection of autoantigen-specific serum antibodies by enzyme-linked immunosorbent assay (ELISA) or indirect IFM when the clinical picture is known. This is achieved by easily available and highly specific and sensitive assays employing recombinant immunodominant fragments of the major target antigens, i.e., desmoglein 1 (for pemphigus foliaceus), desmoglein 3 (for pemphigus vulgaris), envoplakin (for paraneoplastic pemphigus), BP180/type XVII collagen (for bullous pemphigoid, pemphigoid gestationis, and mucous membrane pemphigoid), laminin 332 (for mucous membrane pemphigoid), laminin β4 (for anti-p200 pemphigoid), type VII collagen (for epidermolysis bullosa acquisita and mucous membrane pemphigoid), and transglutaminase 3 (for dermatitis herpetiformis). Indirect IFM on tissue substrates and in-house ELISA and immunoblot tests are required to detect autoantibodies in some AIBD patients including those with linear IgA disease. Here, a straightforward modern approach to diagnosing AIBDs is presented including diagnostic criteria according to national and international guidelines supplemented by long-term in-house expertise.

Exploring the Potential Advantages of Traditional Therapies in Autoimmune Blistering Illnesses: A Comprehensive Review and Analysis, Research

Autoimmune blistering diseases, such as Linear IgA Bullous Dermatosis (LABD) and Chronic Bullous Disease of Childhood (CBDC), provide considerable therapeutic treatment issues. Samana Aushadhis are regularly prescribed by Ayurvedic practitioners as part of therapy regimens for dermatological diseases including LABD and CBDC. Although anecdotal data and clinical observations point to the potential usefulness of traditional medicines in promoting long-term remission and alleviating symptoms, the precise mechanisms by which they exert their therapeutic benefits in LABD/CBD remain incompletely known in contemporary science. The potential advantages of traditional therapies in autoimmune blistering illnesses are being investigated through clinical trials, observational research, and mechanistic investigations. The therapeutic potential of these herbal remedies in LABD and CBDC is being investigated through clinical trials, observational research, and mechanistic investigations. Clinical trials, observational studies, and mechanistic investigations are being conducted in an effort to better understand the therapeutic potential of conventional medications in autoimmune blistering disorders. The effectiveness of these herbal treatments in causing remission and easing symptoms in LABD and CBDC is being closely examined. Overall, while traditional therapies hold promise in the management of autoimmune blistering diseases like LABD and CBDC, more research is necessary to fully understand their mechanisms of action and therapeutic potential. Through rigorous scientific inquiry, the integration of traditional and contemporary medicine may offer new avenues for managing these difficult conditions. Clinical trials, observational research, and mechanistic investigations are all contributing to the exploration of the therapeutic potential of these herbal remedies in LABD and CBDC.

Mild cognitive impairment in pemphigus.

Pemphigus is a group of autoimmune blistering disorders that have been associated with dementia in previous studies. Mild cognitive impairment (MCI) can be the first stage of progression into dementia. The objective of the present study was to evaluate the frequency of MCI in pemphigus patients compared to a control group. This case-control study included 80 patients with pemphigus referred to the dermatology clinics of Shohadaye Tajrish and Loghman Hakim hospitals, Tehran, Iran, in 2021. A group of 80 individuals without pemphigus who visited the same clinics for cosmetic consultation or interventions were regarded as controls. Age, sex, marital status, and education were recorded for all participants. Disease duration, medications, and severity were noted for pemphigus patients. The Persian version of the Montreal Cognitive Assessment (MoCA) test was used to assess cognitive function. MCI was significantly more frequent in pemphigus patients than in controls (55% vs. 37.5%, P = 0.026). Furthermore, the total MoCA score was significantly lower in pemphigus patients compared to controls (23.98 ± 3.77 vs. 25.21 ± 3.45, P = 0.032); however, among MoCA's different domains, only the executive functions score was significantly lower in pemphigus patients (P = 0.010). After adjustment, multivariable logistic regression analysis revealed that every 1-year higher education in patients decreased the odds of MCI by 52% (adjusted odds ratio = 0.483, 95% confidence interval 0.326; 0.715, P < 0.001). The frequency of MCI was found to be significantly higher, and overall scores of the MoCA test, as well as its executive function domain, were significantly lower among pemphigus patients in this study compared to the control group. Additionally, a higher level of education was associated with decreased odds of MCI in pemphigus patients. Identifying pemphigus patients with MCI through the use of the MoCA test can facilitate early intervention, enabling them to seek help and support.

Childhood Bullous Pemphigoid with Atypical Immunopathology: A Case Series

Bullous pemphigoid (BP) is a rare autoimmune blistering disorder primarily affecting older adults, with limited occurrences in children. BP in children typically manifests as large, tense blisters on the skin, often on flexural areas. It also more often affects the oromucosal areas and the face in children than in adults. Diagnosis involves histopathological examination revealing eosinophilic spongiosis or subepidermal split, immunofluorescence tests highlighting immunoglobulin G (IgG) and C3 depositions, and immunological assays detecting BP180 and BP230 IgG autoantibodies. This report presents two cases of childhood BP (CBP) with atypical immunopathological findings. Clinically, the two cases had generalized plaques and bullae, including the face. The first case exhibited the characteristic linear deposits of IgG and C3 on the basement membrane through direct immunofluorescence (DIF) and revealed negative anti-BP180 antibodies on enzyme-linked immunosorbent assay (ELISA). In contrast, the second case showed negative DIF results, despite clinical suspicion, but had positive anti-BP180 IgG antibodies on ELISA. It is, therefore, crucial to consider the complete clinical presentation of the patient, in conjunction with the histological findings and immunopathologic assessments to diagnose CBP.

A Comprehensive Review on the Efficacy of Anti-CD20 Therapies in Pemphigus Treatment.

Pemphigus, an autoimmune blistering disorder, poses significant therapeutic challenges due to dysregulated B cells and the involvement of CD20. This review assesses the efficacy of anti-CD20 therapies, including rituximab, ofatumumab, ocrelizumab, and obinutuzumab, in pemphigus treatment. Mechanisms of action, clinical studies, and safety profiles were analyzed, revealing diverse impacts on disease severity. B cell depletion emerged as a pivotal factor, disrupting the autoimmune process and reducing pathogenic antibodies. Varied efficacy and safety profiles among agents underscore the need for personalized treatment strategies guided by biomarkers. Challenges such as resistance and long-term safety concerns necessitate continued research and vigilance. In clinical practice, insights from this review inform nuanced, tailored approaches for improved pemphigus management. The dynamic landscape of emerging therapies and personalized medicine emphasizes the need for ongoing research and strategic clinical decision-making. This review is a foundation for future investigations, providing insights for clinicians and researchers in optimizing pemphigus treatment.

Rituximab in Childhood and Juvenile Pemphigus Vulgaris: A Systematic Review.

Pemphigus vulgaris (PV) is a chronic autoimmune blistering disorder characterized by the loss of intraepithelial adhesion, affecting the skin and mucous membranes. Both males and females are affected, although it predominantly affects females in their fifth and sixth decades of life. Approximately 1.4 to 3.7% of PV cases occur in the pediatric population (≤18 years of age), and may be classified into childhood/pediatric PV, which affects individuals under 12 years old, and juvenile/adolescent PV, affecting those between 12 and 18 years old. Due to its rare occurrence in children and adolescents, there is often a delay in diagnosis and treatment in this age group. A systematic literature search was conducted on MEDLINE/PubMed, Web of Science, EMBASE, SCOPUS, and Cochrane Library databases to evaluate the efficacy of rituximab (RTX) in childhood and juvenile PV patients. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist was employed to assess the risk of bias in case reports and series, while the Cochrane ROBINS-I tool was utilized for evaluating observational studies or non-randomized intervention studies. A total of 18 studies encompassing 46 juvenile or childhood PV patients in the pediatric and adolescent age groups were included for qualitative synthesis. The studies included nine case reports, two case series, five retrospective studies, one prospective study, and one open-label pilot study. Almost all cases of childhood and juvenile PV achieved either complete or partial remission after undergoing RTX treatment during the final follow-up periods. Furthermore, most cases reported no relapse, and only minor adverse events were noted in the RTX treatment group. Despite its potential benefits, the utilization of RTX in pediatric patients raises concerns due to the scarcity of evidence and the absence of controlled studies specific to this age group. Further exploration is necessary to establish a standardized treatment regimen for RTX in pediatric PV, which involves identifying the optimal dosage, frequency, treatment cycle duration, and maintenance therapy duration.

Immunopathogenesis and Therapeutic Insights into Cicatricial Pemphigoid: A Comprehensive Review

Cicatricial Pemphigoid (CP), also known as mucous membrane pemphigoid, is a rare autoimmune blistering disorder characterized by subepithelial blistering and scarring of mucous membranes. The hallmark of CP is the formation of autoantibodies against structural proteins within the basement membrane zone, leading to an array of clinical manifestations affecting oral, ocular, and other mucosal surfaces. This review aims to elucidate the complex immunopathogenic mechanisms underlying CP, exploring the role of autoantigens such as BP180 and BP230, as well as the involvement of inflammatory mediators and immune cells. Additionally, the article provides a comprehensive overview of current diagnostic modalities and therapeutic approaches, ranging from systemic corticosteroids to novel immunomodulatory agents and biological therapies. The challenges in managing CP, including potential side effects of immunosuppressive treatments, are discussed alongside emerging strategies to enhance treatment efficacy and minimize adverse effects. A deeper understanding of the molecular pathways involved in CP pathogenesis is crucial for the development of targeted therapies, fostering improved patient outcomes and quality of life

Autoimmune blistering disorders and cardiovascular risks: A population-based cohort study

BackgroundAutoimmune blistering disorders (ABDs) might elevate cardiovascular risk, but studies are lacking. ObjectiveTo examine if ABDs elevate the risk of atherosclerotic cardiovascular disease (ASCVD), heart failure, arrhythmia, venous thromboembolism, and cardiovascular death. MethodsA population-based cohort of Danish patients with ABD (≥18 years of age) diagnosed during 1996–2021 (n=3,322) was compared with an age and sex-matched comparison cohort from the general population (n=33,195). ResultsCompared with the general population, patients with ABDs had higher one-year risks of ASCVD (3.4% vs. 1.6%), heart failure (1.9% vs. 0.7%), arrhythmia (3.8% vs. 1.3%), venous thromboembolism (1.9% vs. 0.3%), and cardiovascular death (3.3% vs. 0.9%). The elevated risk persisted after 10 years for all outcomes but arrhythmia. The hazard ratios associating ABD with the outcomes during the entire follow-up were 1.24 (1.09–1.40) for ASCVD, 1.48 (1.24–1.77) for heart failure, 1.16 (1.02–1.32) for arrhythmia, 1.87 (1.50–2.34) for VTE, and 2.01 (1.76–2.29) for cardiovascular death. The elevated cardiovascular risk was observed for both pemphigus and pemphigoid. LimitationsOur findings might only generalize to patients with ABDs without prevalent cardiovascular diseases. ConclusionPatients with ABDs had an elevated cardiovascular risk compared with age and sex-matched controls.

Linear IgA bullous dermatosis of childhood: Retrospective single-center cohort.

Linear IgA bullous dermatosis (LABD) is a rare autoimmune blistering disorder impacting children and adults. In this single-center retrospective chart review of pediatric patients with LABD at a large tertiary referral center, we report the unifying and unique clinical features of 10 pediatric patients. Patients typically presented with the "cluster of jewels" sign (n = 6; 60%), mucous membrane involvement (n = 5; 50%) and had a mean disease duration of 38 months; six patients (60%) required inpatient admission for management of their skin disease, including all five patients who had mucous membrane involvement. Our findings suggest that pediatric LABD may be a disease with high morbidity and may be associated with severe complications when mucous membranes are involved.

Adult-onset linear IgA bullous dermatosis: a retrospective single-center cohort study of 81 patients and literature review.

Linear IgA bullous dermatosis (LABD) is a rare autoimmune blistering disorder that may be drug-induced or paraneoplastic. We aim to characterize features of LABD and determine differentiating factors among idiopathic, drug-induced, or malignancy-associated diseases. We conducted a single-center retrospective chart review of adult patients with linear IgA bullous dermatosis at a large tertiary referral center and a literature review of adult linear IgA bullous dermatosis. Eighty-one patients were included in the study. Ten patients (12.3%) had comorbid malignancy and nine (11.1%) had inflammatory bowel disease. Median disease duration was significantly shorter in both drug-induced (1.2 vs. 48.8 months; P < 0.001) and malignancy-associated (1.7 vs. 48.8 months; P < 0.001) LABD compared with idiopathic LABD. Recurrent episodes occurred significantly more often in idiopathic LABD compared to those with drug-induced (76.1 vs. 11.5%; P < 0.001) or malignancy-associated disease (76.1 vs. 33.3%; P = 0.019). Time to diagnosis was significantly shorter in the drug-induced (0.2 vs. 5.4 months; P < 0.001) and malignancy-associated groups (0.7 vs. 5.4 months; P = 0.049) compared with idiopathic; similarly, time to improvement was significantly shorter in both drug-induced (0.4 vs. 3.0 months; P < 0.001) and malignancy-associated disease (1.1 vs. 3.0 months; P = 0.016). Clinical morphology was indistinguishable between groups. Limitations included retrospective data collection, data from tertiary referral centers, and limited racial and ethnic diversity. Screening for underlying malignancy, as well as for a predisposing medication or possibly inflammatory bowel disease, may be advisable in patients with LABD, particularly when it is newly diagnosed.

Development of De Novo Pemphigus Vulgaris Following COVID-19 Vaccination

The vaccines manufactured by Pfizer, Moderna, and AstraZeneca to prevent the spread of SARS-CoV-2 have been reported to cause a wide range of adverse cutaneous reactions. The most common of these include delayed large local reactions, injection site reactions, urticaria, and morbilliform eruptions. The rarest and severe cutaneous reactions include the development of autoimmune blistering diseases such as pemphigus vulgaris and bullous pemphigoid. In this case report, we present a 73-year-old female patient who developed de novo pemphigus vulgaris two weeks after receiving the Pfizer-BioNTech COVID-19 vaccine. To the best of our knowledge, ours is the first case of new-onset pemphigus vulgaris following the Pfizer COVID-19 vaccine in the United States and only the third worldwide. This report confirms a suspected association between COVID-19 vaccination and the onset of pemphigus vulgaris, although it is exceedingly rare. It also highlights the importance of considering the COVID-19 mRNA vaccines as etiologies for new-onset pemphigus vulgaris and potentially other autoimmune blistering disorders. This knowledge may be important for medical providers when considering a differential diagnosis of new-onset blistering disease to expedite accurate diagnosis and initiation of treatment.

Profile of Teleconsultation in Dermatology at a Tertiary Care Hospital in South India during the First Wave of COVID-19 Pandemic

Abstract Background: There was a rapid expansion of teledermatology around the world with the onset of COVID-19 pandemic. This helped to reduce hospital visits with better adherence to medication and overall costs, especially in chronic dermatoses. Methodology: A retrospective study of teleconsultations during the first wave of COVID-19 pandemic at the dermatology department of a tertiary care hospital in South India was done from May to October 2020. Real-time video teleconsultations were done using the hospital’s teleconsultation portal. Demography, clinical profile of patients, and outcome of teleconsultation were studied. Results: During the study period, 476 teleconsultation sessions in 265 patients were carried out. The mean age of patients was 40.65 ± 16.79 years; geriatric population constituted 38 (14.3%) patients. Urban to rural population ratio was 1:1.3. Median disease duration was 2.5 years (interquartile range 4.75 years). Papulosquamous disorders and infectious diseases were the most common disorders constituting 52 (19.6%) and 51 (19.2%) cases, respectively. Patients with chronic dermatoses on systemic therapy constituted 268 (56.42%) teleconsultation sessions in 119 (44.9%) patients; common diseases being autoimmune blistering disorders (38; 31.9%), psoriasis (23; 19.3%), and leprosy (17; 14.3%). Optimization of therapy was done in 117 (44.2%) patients, initiation of new medication in 89 (33.6%), and continuation of therapy in 75 (28.3%) patients. An in-person review was advised in 46 (9.7%) sessions in 36 (13.6%) patients. Six (2.3%) patients were advised to have an urgent review. Conclusion: Teledermatology was an effective tool during the pandemic to extend hospital services. Optimization of therapy was the outcome in nearly half the sessions. This service can benefit patients from remote areas and geriatric population, especially with chronic dermatoses.

The nuclear receptor Nurr1 is preferentially expressed in human pro-inflammatory macrophages and limits their inflammatory profile.

Nurr1 is a member of the orphan nuclear receptor family NR4A (nuclear receptor subfamily 4 group A) that modulates inflammation in several cell lineages, both positively and negatively. Macrophages are key regulators of inflammatory responses, yet information about the role of Nurr1 in human macrophages is scarce. Here we examined Nurr1 expression and activity in steady state and activated human macrophages. Pro- and anti-inflammatory macrophages were generated in vitro by culture of blood monocytes with granulocyte/macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF), respectively. Nurr1 expression was predominant in macrophages with the pro-inflammatory phenotype. Nurr1 activation with the agonists 1,1-bis(3'-indolyl)-1-(p-chlorophenyl) methane (C-DIM12) or isoxazolo-pyridinone 7e (IP7e) did not globally modify the polarization status of pro-inflammatory macrophages, but they decreased their production of TNF, IL-1β, IL-6, IL-8, IL-12 p40, CCL2, IFN-β, and reactive oxygen species, with variable potencies. Conversely, Nurr1 deficient macrophages increased the expression of transcripts encoding inflammatory mediators, particularly that of IL6, IFNB1, and CCL2. Mechanistically, endogenous Nurr1 interacted with NF-κB p65 in basal conditions and upon lipopolysaccharide (LPS)-mediated activation. C-DIM12 stabilized those complexes in cells exposed to LPS and concurrently decreased NF-κB transcriptional activity and p65 nuclear translocation. Expression of high levels of Nurr1 was associated with a subset of dermal macrophages that display enhanced levels of TNF and lower expression of the anti-inflammatory marker CD163L1 in skin lesions from patients with bullous pemphigoid (BP), a chronic inflammatory autoimmune blistering disorder. These results suggest that Nurr1 expression is linked with the pro-inflammatory phenotype of human macrophages, both in vivo and in vitro, where it may constitute a brake to attenuate the synthesis of inflammatory mediators.

Role of Human Leukocyte Antigen Class II in Antibody-Mediated Skin Disorders.

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.

The Diagnosis and Treatment Methods of the Autoimmune Blistering Diseases

Background: Autoimmune blistering disorders are a group of rare skin diseases. They develop when your body's mucous membranes the lining of your mouth, nose, and other cavities and skin are attacked by your immune system. Blisters grow as a result of this. Objective: The main goal of this study is to determine the diagnosis and treatment methods of the autoimmune blistering diseases in Bangladesh. Methods: A cross sectional study was conducted in a total of 260 patients from January 2021 to December 2021 in 250 Bedded General hospital, Jamalpur, Bangladesh. Results: In our study, 55% patients were male and 45% patients were female. Maximum patients (19.6%) were between 30 to 39 years of age group. Minimum number of patients (13.2%) were between 20 to 29 of age group. Maximum patients (75) had pemphigus vulggaris and minimum number of patients (15) had pemphigus foliaceus. Maximum patients were treated with steroids (51) and azathioprine (53). Minimum number of patients (10) were treated with cyclosporine. Side effects like (Cushing syndrome, Growth retardation, Osteoporosis) were observed in patients treated with steroids (6), Neutropenic sepsis (4) in Rituximab, Hemolytic anemia (3) in Dapsone and Nausea (4) in Azathioprine. 141 patients had complete remission off therapy and 119 patients had partial remission on therapy. Conclusion: As the population ages, more people will eventually require treatment for autoimmune skin illnesses that cause blistering. Rituximab, infliximab, etanercept, leflunomide, doxycycline, omalizumab, and immunoadsorption are currently being explored in controlled prospective trials since there is an urgent need for specific and well-tolerated medicines. Prospective, controlled trials are still needed to verify the effectiveness of the present treatments.

Type 2 T-Cell Responses against Distinct Epitopes of the Desmoglein 3 Ectodomain in Pemphigus Vulgaris

Pemphigus vulgaris (PV) is an autoimmune blistering disorder of the skin and/or mucous membranes caused by IgG autoantibodies that predominantly target two transmembrane desmosomal cadherins: desmoglein (DSG)1 and DSG3. DSG-specific T cells play a central role in PV pathogenesis because they provide help to autoreactive B cells for autoantibody production. In this study, we characterized DSG3-specific peripheral T cells in a cohort of 52 patients with PV and 41 healthy controls with regard to cytokine profile and epitope specificity. By ELISpot analysis, type 2 T cells reactive with the DSG3 ectodomain were significantly increased in patients with PV compared with those in healthy controls. By dextramer analysis, CD4+ T cells specific for an epitope within the extracellular domain of DSG3, DSG3(206-220), were found at significantly higher frequencies in patients with PV than in HLA-matched healthy controls. T-cell recognition of two distinct DSG3 epitopes, that is, DSG3(206-220) and DSG3(378-392), correlated significantly, suggesting a synergistic effect in B-cell help. Immunization of HLA-DRB1∗04:02-transgenic mice with PV with the same set of DSG3 peptides induced pathogenic DSG3-specific IgG antibodies, which induced loss of keratinocyte adhesion invitro. Thus, DSG3 peptide-specific T cells are of particular interest as surrogate markers of disease activity and potential therapeutic targets in PV.