-
Scientific Reports Jun 2022Autoimmune diseases caused by pathogenic IgG4 subclass autoantibodies (IgG4-AID) include diseases like MuSK myasthenia gravis, pemphigus vulgaris or thrombotic... (Meta-Analysis)
Meta-Analysis
Autoimmune diseases caused by pathogenic IgG4 subclass autoantibodies (IgG4-AID) include diseases like MuSK myasthenia gravis, pemphigus vulgaris or thrombotic thrombocytopenic purpura. Their etiology is still unknown. Polymorphisms in the human leukocyte antigen (HLA) gene locus, particularly in HLA-DRB1, are known genetic susceptibility factors for autoimmune diseases. We hypothesized a similar role for HLA polymorphisms in IgG4-AID and conducted a systematic review and meta-analysis with case-control studies on IgG4-AID based on MOOSE/ HuGENet guidelines. Genotype (G) and allele (A) frequencies of HLA-DQB1*05 (G: OR 3.8; 95% CI 2.44-5.9; p < 0.00001; A: OR 2.54; 95% CI 1.82-3.55; p < 0.00001) and HLA-DRB1*14 (G: OR 4.31; 95% CI 2.82-6.59; p < 0.00001; A: OR 4.78; 95% CI 3.52-6.49; p < 0.00001) and the HLA-DRB1*14-DQB1*05 haplotype (OR 6.3; 95% CI 3.28-12.09; p < 0.00001/OR 4.98; 95% CI 3.8-6.53; p < 0.00001) were increased while HLA-DRB1*13 (G: OR 0.48; 95% CI 0.34-0.68; p < 0.0001; A: OR 0.46; 95% CI 0.34-0.62; p < 0.00001) was decreased in IgG4-AID patients. In conclusion, the HLA-DQB1*05, HLA-DRB1*14 alleles and the HLA-DQB1*05-DRB1*14 haplotype could be genetic risk factors that predispose for the production of pathogenic IgG4 autoantibodies and the HLA-DRB1*13 allele may protect from IgG4 autoimmunity.
Topics: Autoantibodies; Autoimmunity; Gene Frequency; HLA-DRB1 Chains; Humans; Immunoglobulin G; Pemphigus
PubMed: 35654912
DOI: 10.1038/s41598-022-13042-2 -
Biology Feb 2022Pemphigus vulgaris (PV) is an IgG-mediated autoimmune disease characterised by epithelial cell-cell detachment (acantholysis) resulting in mucocutaneous blistering. The... (Review)
Review
BACKGROUND
Pemphigus vulgaris (PV) is an IgG-mediated autoimmune disease characterised by epithelial cell-cell detachment (acantholysis) resulting in mucocutaneous blistering. The exact pathogenesis of blister formation is unknown and this has hampered the development of non-steroidal, mechanism-based treatments for this autoimmune disease. This systematic review aims to investigate the role of caspases in the pathogenesis of PV to inform the choice of more targeted therapeutic agents.
METHODS
A systematic search of MEDLINE/PubMed and Scopus databases was conducted to identify eligible studies. Multiple phases of inclusion and exclusion of the primary articles were conducted in pairs, and studies were recorded and analysed according to the latest version of the preferred reporting items for systematic reviews and meta-analyses (PRISMA). Risk of bias assessment was conducted for extracted in vivo animal intervention studies using SYRCLE's risk of bias tool.
RESULTS
Eight articles from a total of 2338 in vitro, in vivo, and human studies met the inclusion criteria, with a high degree of inter-rater reliability. By and large, the results show that caspase activation was pathogenic in experimental PV because pan-caspase inhibitors could block or reduce PV acantholysis and blistering in vitro and in vivo, respectively. The pathogenic pathways identified involved caspase-1 and caspase-3. One study failed to show any improvement in the PV model with a caspase inhibitor. The majority of animal studies had high or unclear risk of bias.
CONCLUSION
There are consistent data pointing towards a pathogenic role of caspase activation in PV acantholysis. However, high-quality evidence to confirm that caspase inhibition can prevent PV-induced blistering in vivo is limited. Therefore, further research is required to test the preclinical efficacy of caspase inhibitors in PV.
PubMed: 35205180
DOI: 10.3390/biology11020314 -
Journal Der Deutschen Dermatologischen... Jan 2023Dupilumab interferes with the signaling pathways of IL-4 and IL-13 and is effective in treating atopic dermatitis. Specific genodermatoses, including Netherton syndrome,... (Review)
Review
Dupilumab interferes with the signaling pathways of IL-4 and IL-13 and is effective in treating atopic dermatitis. Specific genodermatoses, including Netherton syndrome, epidermolysis bullosa pruriginosa, and hyper-IgE syndrome, are Th2 skewed diseases with activation of type 2 inflammation. We performed this systematic review to investigate the therapeutic role of dupilumab in the treatment of genodermatosis. A systematic search was conducted of the PubMed, Embase, Web of Science, and Cochrane databases from inception to December 13, 2021. The review included studies with relevant terms including "dupilumab," "genodermatosis", "Netherton syndrome", "ichthyosis", "epidermolysis bullosa" and "hyper-IgE syndrome". The initial search yielded 2,888 results, of which 28 studies and 37 patients with genodermatosis were enrolled. The assessed genodermatoses included Netherton syndrome, epidermolysis bullosa pruriginosa, hyper-IgE syndrome, Hailey-Hailey disease, and severe eczema associated with genetic disorders. Most of the reported cases showed significant clinical improvement after the initiation of dupilumab treatment without major adverse events. Decreased immunoglobulin E levels and cytokine normalization have also been documented. In conclusion, Dupilumab may have a potential therapeutic role in certain genodermatoses skewed towards T helper 2 (Th2) immunity, including Netherton syndrome, epidermolysis bullosa pruriginosa, hyper-IgE syndrome, Hailey-Hailey disease, and severe eczema associated with some genetic disorders.
Topics: Humans; Pemphigus, Benign Familial; Eczema; Immunoglobulin E
PubMed: 36657040
DOI: 10.1111/ddg.14924 -
The American Journal of Dermatopathology Oct 2021Immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded tissue has been proposed as a potential tool in the diagnosis of autoimmune bullous diseases (AIBDs) in... (Meta-Analysis)
Meta-Analysis
Immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded tissue has been proposed as a potential tool in the diagnosis of autoimmune bullous diseases (AIBDs) in lieu of standard direct immunofluorescence (DIF) microscopy. To comprehensively determine the diagnostic accuracy of immunoglobulin and complement IHC for diagnosis of AIBDs, we conducted a systematic review and multivariate Bayesian model-based meta-analysis of the literature. Quality and heterogeneity assessment of studies was performed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist and the I2 index, respectively. Electronic searches using PubMed from April 1964 to July 2020 identified 14 articles meeting predetermined inclusion and exclusion criteria. Median sensitivities with 95% credible intervals in pemphigus and pemphigoid were 0.24 (0.01-0.89) and 0.22 (0.02-0.77) with immunoglobulin G (IgG), 0.77 (0.39-0.95) and 0.25 (0.02-0.85) with IgG4, 0.11 (0.02-0.32) and 0.86 (0.56-0.98) with C3d, and 0.84 (0.56-0.97) and 0.75 (0.37-0.94) with C4d, respectively. Specificities were 1.00 (0.00-1.00) with IgG, 0.98 (0.89-1.00) with IgG4, 0.99 (0.97-1.00) with C3d, and 0.99 (0.97-1.00) with C4d. The risk of bias and heterogeneity among studies was a serious problem, decreasing the level of evidence. Our work suggests that, in selected cases, paraffin-based IHC may be a helpful procedure to screen for AIBDs, especially when specialized laboratories and/or biopsy specimens for DIF do not exist. Nevertheless, more studies with a refined quality design are needed to explore the true usefulness of this diagnostic method in AIBDs.
Topics: Autoimmune Diseases; Complement C3d; Complement C4b; Dermatitis Herpetiformis; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunohistochemistry; Paraffin Embedding; Pemphigoid, Bullous; Pemphigus; Peptide Fragments; Skin Diseases, Vesiculobullous
PubMed: 33055534
DOI: 10.1097/DAD.0000000000001817 -
Dermatologic Therapy Jun 2022With dermatologic side effects being fairly prevalent following vaccination against COVID-19, and the multitude of studies aiming to report and analyze these adverse... (Review)
Review
A systematic review on mucocutaneous presentations after COVID-19 vaccination and expert recommendations about vaccination of important immune-mediated dermatologic disorders.
With dermatologic side effects being fairly prevalent following vaccination against COVID-19, and the multitude of studies aiming to report and analyze these adverse events, the need for an extensive investigation on previous studies seemed urgent, in order to provide a thorough body of information about these post-COVID-19 immunization mucocutaneous reactions. To achieve this goal, a comprehensive electronic search was performed through the international databases including Medline (PubMed), Scopus, Cochrane, Web of science, and Google scholar on July 12, 2021, and all articles regarding mucocutaneous manifestations and considerations after COVID-19 vaccine administration were retrieved using the following keywords: COVID-19 vaccine, dermatology considerations and mucocutaneous manifestations. A total of 917 records were retrieved and a final number of 180 articles were included in data extraction. Mild, moderate, severe and potentially life-threatening adverse events have been reported following immunization with COVID vaccines, through case reports, case series, observational studies, randomized clinical trials, and further recommendations and consensus position papers regarding vaccination. In this systematic review, we categorized these results in detail into five elaborate tables, making what we believe to be an extensively informative, unprecedented set of data on this topic. Based on our findings, in the viewpoint of the pros and cons of vaccination, mucocutaneous adverse events were mostly non-significant, self-limiting reactions, and for the more uncommon moderate to severe reactions, guidelines and consensus position papers could be of great importance to provide those at higher risks and those with specific worries of flare-ups or inefficient immunization, with sufficient recommendations to safely schedule their vaccine doses, or avoid vaccination if they have the discussed contra-indications.
Topics: COVID-19; COVID-19 Vaccines; Humans; Mucous Membrane; Skin; Vaccination
PubMed: 35316551
DOI: 10.1111/dth.15461 -
Autoimmunity Reviews Mar 2021Regulatory T cells (Tregs) are a subset of T cells responsible for the regulation of immune responses, thereby maintaining immune homeostasis and providing immune... (Review)
Review
Regulatory T cells (Tregs) are a subset of T cells responsible for the regulation of immune responses, thereby maintaining immune homeostasis and providing immune tolerance to both self and non-self-antigens. An increasing number of studies revealed Treg numbers and functions in a variety of autoimmune diseases. Treg deficiency can cause the development of several autoimmune skin diseases including vitiligo, alopecia areata, pemphigoid and pemphigus, psoriasis, and systemic sclerosis. Many clinical trials have been performed for autoimmune conditions using polyclonal Tregs, but efficiency can be significantly improved using antigen-specific Tregs engineered using T cell receptor (TCR) or chimeric antigen receptor (CAR) constructs. In this review, we systematically reviewed altered frequencies, impaired functions, and phenotypic features of Tregs in autoimmune skin conditions. We also summarized new advances in TCR and CAR based antigen-specific Tregs tested both in animal models and in clinics. The advantages and limitations of each approach were carefully discussed emphasizing possible clinical relevance to patients with autoimmune skin diseases. Moreover, we have reviewed potential approaches for engineering antigen-specific Tregs, and strategies for overcoming possible hurdles in clinical applications. Thereby, antigen-specific Tregs can be infused using autologous adoptive cell transfer to restore Treg numbers and to provide local immune tolerance for autoimmune skin disorders.
Topics: Animals; Autoimmune Diseases; Humans; Immune Tolerance; Receptors, Antigen, T-Cell; Skin Diseases; T-Lymphocytes, Regulatory
PubMed: 33476816
DOI: 10.1016/j.autrev.2021.102761 -
Immunopharmacology and Immunotoxicology Oct 2021Rituximab is a FDA-approved monoclonal antibody for adults with moderate to severe potentially life-threatening pemphigus vulgaris. Recent studies have focused on...
BACKGROUND
Rituximab is a FDA-approved monoclonal antibody for adults with moderate to severe potentially life-threatening pemphigus vulgaris. Recent studies have focused on assessments of efficacy and safety of low-dose rituximab (<2 gram in each cycle).
METHOD
Databases were searched from 2010 to 2020 (last update: 1 June 2020).
RESULT
Nine studies were entered; including180 cases (92: women, 88: men, age range: 9-83 years). The dosages of each Rituximab cycle varied between ultra-low-dose (≤500 mg for a cycle, either multiple infusions or a single infusion), low-dose (2 × 375 mg/m or 2 × 500 mg) and modified-dose (3 × 375 mg/m or 3 × 500 mg). The efficacy and safety of Rituximab in the studies are known by the recovery time, relapse time, and side events. According to the studies, 2 × 500 can lead to complete remission in a broad range, from 35 to 82%. These differences might be explained by different end-points and variable cumulative corticosteroid dosage after RTX administration. Although the studies showed that low dose RTX is efficient, there are some controversies regarding the choosing low-dose for severe patients.
CONCLUSION
Considering the effectiveness of low-dose, intermediate dose, and ultra-low-dose protocols of Rituximab in inducing remission in pemphigus disease and considering factors such as cost of therapy, and the need to induce a minimum of immunosuppression for a minimum duration in the COVID-19 pandemic, suggested to use low-dose Rituximab protocol (2 infusions of 500 mg Rituximab: interval of 2 weeks) to induce the remission in mild-to-moderate pemphigus patients.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; COVID-19; Child; Female; Humans; Immunocompromised Host; Immunologic Factors; Male; Middle Aged; Pemphigus; Remission Induction; Risk Factors; Rituximab; SARS-CoV-2; Treatment Outcome; Young Adult
PubMed: 34287098
DOI: 10.1080/08923973.2021.1953063 -
The British Journal of Dermatology Feb 2022
Meta-Analysis
Topics: Cause of Death; Humans; Pemphigoid, Bullous; Pemphigus
PubMed: 34510412
DOI: 10.1111/bjd.20759 -
Journal of the European Academy of... Nov 2023
Topics: Humans; Causality; COVID-19; Pemphigus; Vaccination; Case Reports as Topic
PubMed: 37328927
DOI: 10.1111/jdv.19271 -
Oral Diseases Jun 2019To assess the evidence for treatment of oral involvement of pemphigus and pemphigoid with biologics.
OBJECTIVE
To assess the evidence for treatment of oral involvement of pemphigus and pemphigoid with biologics.
STUDY DESIGN
This systematic review used a comprehensive search strategy to identify literature describing oral involvement of pemphigus or pemphigoid treated with a biologic agent. The primary outcome measures were efficacy and safety of biologic therapy.
RESULTS
Inclusion criteria were met by 154 studies including over 1200 patients. Treatment of pemphigus with a total of 11 unique biologic agents and 3 unique combinations of agents is reported. Five randomized controlled trials (RCT) were included in the final analysis that investigated infliximab, IVIg, rituximab, and autologous platelet-rich plasma therapy for pemphigus vulgaris. Three non-RCT studies reported on successful rituximab or IVIg therapy for mucous membrane pemphigoid. Studies demonstrated considerable heterogeneity in agent, methods, and quality.
CONCLUSIONS
Evidence clearly describing oral tissue response to biologic therapy is sparse. Two RCTs support use of rituximab, one supports use of IVIg, and one pilot study suggests intralesional injection of autologous platelet-rich plasma aids healing of oral PV lesions. As oral lesions of pemphigus and pemphigoid can be refractory to systemic therapy, drug trials including biologic therapies should document details regarding response of the oral lesions to therapy.
Topics: Biological Factors; Congresses as Topic; Humans; Pemphigoid, Benign Mucous Membrane; Pemphigoid, Bullous; Pemphigus; Pilot Projects; Rituximab; Treatment Outcome
PubMed: 31140696
DOI: 10.1111/odi.13083