Autoantibodies Against the Immunodominant Bullous Pemphigoid Epitopes Are Rare in Patients With Dermatitis Herpetiformis and Coeliac Disease
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ABSTRACT:
SUBMITTER: Natynki A
PROVIDER: S-EPMC7544946 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
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Project description:Dermatitis herpetiformis (DH) is a cutaneous manifestation of coeliac disease. Increased bone fracture risk is known to associate with coeliac disease, but this has been only scantly studied in DH. In this study, self-reported fractures and fracture-associated factors in DH were investigated and compared to coeliac disease. Altogether, 222 DH patients and 129 coeliac disease-suffering controls were enrolled in this study. The Disease Related Questionnaire and the Gastrointestinal Symptom Rating Scale and Psychological General Well-Being questionnaires were mailed to participants; 45 out of 222 (20%) DH patients and 35 out of 129 (27%) of the coeliac disease controls had experienced at least one fracture (p = 0.140). The cumulative lifetime fracture incidence did not differ between DH and coeliac disease patients, but the cumulative incidence of fractures after diagnosis was statistically significantly higher in females with coeliac disease compared to females with DH. The DH patients and the coeliac disease controls with fractures reported more severe reflux symptoms compared to those without, and they also more frequently used proton-pump inhibitor medication. To conclude, the self-reported lifetime bone fracture risk is equal for DH and coeliac disease. After diagnosis, females with coeliac disease have a higher fracture risk than females with DH.
| S-EPMC5872769 | biostudies-literature
Project description:Itch which is one of the major, subjective symptoms in a course of bullous pemphigoid and dermatitis herpetiformis makes those two diseases totally different than other autoimmune blistering diseases. Its pathogenesis is still not fully known. The aim of this research was to assess the role of IL-31 in development of itch as well as to measure its intensity. Obtained results, as well as literature data, show that lower concentration of IL-31 in patients' serum may be correlated with its role in JAK/STAT signaling pathway which is involved in development of autoimmune blistering disease. Intensity of itch is surprisingly huge problem for the patients and the obtained results are comparable with results presented by atopic patients.
| S-EPMC5541788 | biostudies-other
Project description:The reason why only few coeliac patients develop the cutaneous manifestation of the disease, named dermatitis herpetiformis (DH), is still unknown. Epidermal transglutaminase (TG3) has been described as the main autoantigen of humoral immunity in DH but the mechanisms leading to this autoimmune response remain obscure. Here we characterized T cells from skin, gut and peripheral blood of DH and coeliac disease (CD) patients, evaluated the impact of the gluten-free diet on circulating T lymphocytes' phenotype and investigated antigen specific T cell response toward epidermal and tissue transglutaminase (TG2). DH patients showed an increased frequency of skin-derived T cells producing TNFα when compared to CD patients. Moreover, circulating T cells producing TNFα and IL-17A positively correlated with clinical score of skin disease activity and decreased after gluten-free diet. Finally, TG2 and TG3-specific T cells resulted more reactive to antigens stimulation in DH patients and showed cross reactivity toward the two autoantigens in both the group of patients. Our data suggest a role of TNFα and IL-17A producing cells in the development of DH and, for the first time, show the existence of a crossed T cell response toward the two transglutaminases isoforms, thus suggesting new insights on T cells role in skin damage.
| S-EPMC8093623 | biostudies-literature
Project description:Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by autoantibodies targeting cellular adhesion molecules. While IgE autoantibodies are occasionally reported in other autoimmune blistering diseases, BP is unique in that most BP patients develop an IgE autoantibody response. It is not known why BP patients develop self-reactive IgE and the precise role of IgE in BP pathogenesis is not fully understood. However, clinical evidence suggests an association between elevated IgE antibodies and eosinophilia in BP patients. Since eosinophils are multipotent effector cells, capable cytotoxicity and immune modulation, the putative interaction between IgE and eosinophils is a primary focus in current studies aimed at understanding the key components of disease pathogenesis. In this review, we provide an overview of BP pathogenesis, highlighting clinical and experimental evidence supporting central roles for IgE and eosinophils as independent mediators of disease and via their interaction. Additionally, therapeutics targeting IgE, the Th2 axis, or eosinophils are also discussed.
| S-EPMC6787172 | biostudies-literature
Project description:IntroductionDermatitis herpetiformis (DH) is a cutaneous manifestation of coeliac disease. Increased cardiovascular morbidity has been reported in coeliac disease, but in DH only little is known about this. In this cohort study with a long-term follow-up, the risk for vascular diseases in patients with dermatitis herpetiformis (DH) and coeliac disease was assessed.MethodsThe study consisted of 368 DH and 1072 coeliac disease patients with biopsy-proven diagnosis performed between 1966 and 2000. For each DH and coeliac disease patient three matched reference individuals were obtained from the population register. Data regarding all outpatient and inpatient treatment periods between 1970 and 2015 were reviewed for diagnostic codes of vascular diseases from the Care Register for Health Care. Cox proportional hazard model was used to assess the risks for the diseases studied and the HRs were adjusted for diabetes mellitus (aHR).ResultsThe median follow-up time of DH and coeliac disease patients was 46 years. The risk for cardiovascular diseases did not differ between DH patients and their references (aHR 1.16, 95% CI 0.91-1.47), but among coeliac disease patients, the risk was increased (aHR 1.36, 95% CI 1.16-1.59). The risk for cerebrovascular diseases was found to be decreased in DH patients when compared with references (aHR 0.68, 95% CI 0.47-0.99) and increased in coeliac disease patients (aHR 1.33, 95% CI 1.07-1.66). The risk for venous thrombosis was increased in coeliac disease patients (aHR 1.62, 95% CI 1.22-2.16) but not in DH.ConclusionsThe risk for vascular complications appears to differ between DH and coeliac disease. In DH the risk for cerebrovascular diseases seems to be decreased, while in coeliac disease an elevated risk for cerebrovascular and cardiovascular diseases was observed. These differing vascular risk profiles between the two manifestations of the same disease merit further investigation.
| S-EPMC10308869 | biostudies-literature
Project description:BackgroundBullous pemphigoid (BP) is the most common autoimmune blistering disease in the West. Oral steroids are the standard treatment.This is an update of the review published in 2005.ObjectivesTo assess treatments for bullous pemphigoid.Search strategyIn August 2010 we updated our searches of the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (Clinical Trials), MEDLINE, EMBASE, and the Ongoing Trials registers.Selection criteriaRandomised controlled trials of treatments for participants with immunofluorescence-confirmed bullous pemphigoid.Data collection and analysisAt least two authors evaluated the studies for the inclusion criteria, and extracted data independently.Main resultsWe included 10 randomised controlled trials (with a total of 1049 participants) of moderate to high risk of bias. All studies involved different comparisons, none had a placebo group. In 1 trial plasma exchange plus prednisone gave significantly better disease control at 1 month (0.3 mg/kg: RR 18.78, 95% CI 1.20 to 293.70) than prednisone alone (1.0 mg/kg: RR 1.79, 95% CI 1.11 to 2.90), while another trial showed no difference in disease control at 6 months.No differences in disease control were seen for different doses or formulations of prednisolone (one trial each), for azathioprine plus prednisone compared with prednisone alone (one trial), for prednisolone plus azathioprine compared with prednisolone plus plasma exchange (one trial), for prednisolone plus mycophenolate mofetil or plus azathioprine (one trial), for tetracycline plus nicotinamide compared with prednisolone (one trial). Chinese traditional medicine plus prednisone was not effective in one trial.There were no significant differences in healing in a comparison of a standard regimen of topical steroids (clobetasol) with a milder regimen (RR 1.00, 95% 0.97 to 1.03) in one trial. In another trial, clobetasol showed significantly more disease control than oral prednisolone in people with extensive and moderate disease (RR 1.09, 95% CI 1.02 to 1.17), with significantly reduced mortality and adverse events (RR 1.06, 95% CI 1.00 to 1.12).Authors' conclusionsVery potent topical steroids are effective and safe treatments for BP, but their use in extensive disease may be limited by side-effects and practical factors. Milder regimens (using lower doses of steroids) are safe and effective in moderate BP. Starting doses of prednisolone greater than 0.75 mg/kg/day do not give additional benefit, lower doses may be adequate to control disease and reduce the incidence and severity of adverse reactions. The effectiveness of adding plasma exchange, azathioprine or mycophenolate mofetil to corticosteroids, and combination treatment with tetracycline and nicotinamide needs further investigation.
| S-EPMC7138251 | biostudies-literature
Project description:Background and objectives: Dermatitis herpetiformis (DH) is a blistering dermatosis, which shares common immunologic features with celiac disease (CD). The aim of the present study was to explore the performance of a panel of CD-related antibodies and IL-17A in Bulgarian patients with DH. Materials and Methods: Serum samples from 26 DH patients at mean age 53 ± 15 years and 20 healthy controls were assessed for anti-tissue transglutaminase (anti-tTG), anti-deamidated gliadin peptides (anti-DGP), anti-actin antibodies (AAA), and IL-17A by enzyme linked immuno-sorbent assay (ELISA), as well as anti-tTG, anti-gliadin (AGA), and anti-Saccharomyces cerevisiae antibodies (ASCA) using immunoblot. Results: The average serum levels of anti-tTG, anti-DGP, AGA, AAA, and the cytokine IL-17A were at significantly higher levels in patients with DH compared to the average levels in healthy persons which stayed below the cut-off value (p < 0.05). Anti-DGP and anti-tTG antibodies showed the highest diagnostic sensitivity and specificity, as well as acceptable positive and negative predictive value. None of the healthy individuals was found positive for the tested antibodies, as well as for ASCA within the DH group. All tests showed good to excellent correlations (r = 0.5 ÷ 0.9, p < 0.01). Conclusions: Although the diagnosis of DH relies on skin biopsy for histology and DIF, serologic testing of a panel of celiac-related antibodies could be employed with advantages in the diagnosing process of DH patients. Furthermore, DH patients who are positive for the investigated serologic parameters could have routine monitoring for gastrointestinal complications typical for the gluten-sensitive enteropathy.
| S-EPMC6572648 | biostudies-literature
Project description:Total knee arthroplasty is one of the safest and most routinely performed orthopedic procedures. As the volume of cases is expected to rise each year, so too will the incidence of uncommon complications. We describe a rare case of bullous pemphigoid, an autoimmune skin blistering disorder, that occurred after total knee arthroplasty in an otherwise healthy patient and led to hospital readmission. Early diagnosis and treatment of this condition may limit its spread and help to avoid comorbid sequelae.
| S-EPMC8141602 | biostudies-literature
Project description:Bullous pemphigoid (BP) is a common autoimmune blistering disease in which autoantibodies target the hemidesmosomal components BP180 and/or BP230 in basal keratinocytes. In BP, 80 to 90% of autoantibodies target the juxtamembranous extracellular non-collagenous 16th A (NC16A) domain of BP180. Recently, the administration of dipeptidyl peptidase-IV inhibitors (DPP4i), which are widely used as antihyperglycemic drugs, has been recognized to be a causative factor for BP. DPP4i-associated BP (DPP4i-BP) autoantibodies tend to target epitopes on non-NC16A regions of BP180, and the pathomechanism for the development of the unique autoantibodies remains unknown. To address the characteristics of DPP4i-BP autoantibodies in detail, we performed epitope analysis of 18 DPP4i-BP autoantibodies targeting the non-NC16A domains of BP180 using various domain-specific as well as plasmin-digested polypeptides derived from recombinant BP180. Firstly, Western blotting showed that only one DPP4i-BP serum reacted with the epitopes on the intracellular domain of BP180, and no sera reacted with the C-terminal domain of the molecule. In addition, only 2 DPP4i-BP sera reacted with BP230 as determined by enzyme-linked immunosorbent assay. Thus, DPP4i-BP autoantibodies were found to mainly target the non-NC16A mid-portion of the extracellular domain of BP. Interestingly, Western blotting using plasmin-digested BP180 as a substrate revealed that all of the DPP4i-BP sera reacted more intensively with the 97-kDa processed extracellular domain of BP180, which is known as the LABD97 autoantigen, than full-length BP180 did. All of the DPP4i-BP autoantibodies targeting the LABD97 autoantigen were IgG1, and IgG4 was observed to react with the molecule in only 7 cases (38.9%). In summary, the present study suggests that IgG1-class autoantibodies targeting epitopes on the processed extracellular domain of BP180, i.e., LABD97, are the major autoantibodies in DPP4i-BP.
| S-EPMC6549357 | biostudies-literature
Project description:Importance:Enzyme-linked immunosorbent assay (ELISA) and/or chemiluminescent enzyme immunoassay (CLEIA) for BP180 noncollagenous 16A (NC16A) extracellular domain is a sensitive diagnostic tool for bullous pemphigoid (BP). However, some patients with BP have negative results for these assays. Objective:To elucidate the clinical and immunological features of patients with BP without antibodies that react to BP180 NC16A. Design, Setting, and Participants:This retrospective case series study included 152 patients who were diagnosed with BP and followed up at the Kurume University Hospital in Japan from 2007 to 2016. The diagnosis was made using clinical, histological, and immunological findings. Main Outcomes and Measures:Clinical and immunological features of patients with BP who had negative results for BP180 NC16A using ELISA and/or CLEIA. Results:Of the 152 patients, 69 (45.4%) were men and 83 (54.6%) were women. The mean (SD) age of participants was 75.2 (14.4) years. Of the 152 patients with BP, 14 (9.2%) had negative results for BP180 NC16A on ELISA and/or CLEIA; most of these patients exhibited no erythema and had relatively mild phenotypes. Two (14%) of the 14 patients had positive results for intact BP180 in epidermal extracts, 10 (71%) had positive results for a 120-kD fragment of BP180 (LAD-1) and 3 (21%) had positive results for BP180 C-terminal domain. Seven (50%) patients tested positive in BP230 ELISA. Five (36%) patients did not require oral prednisolone treatment, whereas the others required a dose of prednisolone at less than 30 mg per day. Three (21%) patients were administered a dipeptidyl peptidase-4 inhibitor (DPP4i) before disease onset. This ratio was not significantly higher than that in patients with BP who tested positive for BP180 NC16A ELISA and/or CLEIA (19 [14%] of 138 patients). Our follow-up study (mean [SD], 31.9 [33.2] weeks; range, 0-108 weeks) revealed that patients with BP tested negative for BP180 NC16A ELISA and/or CLEIA during the later stages of the disease. Conclusions and Relevance:This study indicates that patients with BP negative for BP180 NC16A ELISA and/or CLEIA had milder phenotypes, fewer erythemas, and required less extensive treatments.
| S-EPMC5885813 | biostudies-literature