This study demonstrates for the first time that plasma exosomal miRNA profiles are significantly altered in bullous pemphigoid (BP). We identified let-7i-5p as a promising biomarker, whose expression inversely correlates with disease activity and independently predicts higher risks of relapse and infection. Exosomal let-7i-5p may serve as an objective tool for disease monitoring and risk stratification in BP.

Purpose:Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disorder. Although mucosal involvement is uncommon, it may indicate a more severe clinical phenotype. This study evaluated the prevalence and clinical features associated with mucosal involvement in BP. Patients and Methods:This retrospective cohort study included 265 patients with BP diagnosed at Peking Union Medical College Hospital between January 2013 and May 2022. Clinical, laboratory, immunological, and treatment-related characteristics were compared between patients with and without mucosal involvement. Logistic regression analyses were performed to identify factors associated with mucosal involvement, and model performance was assessed using receiver operating characteristic analysis. Results:Seventy-one patients (26.8%) had mucosal involvement, most commonly affecting the oral mucosa, followed by genital and ocular sites. Compared with patients without mucosal lesions, those with mucosal involvement were younger at disease onset, more frequently had a history of malignancy, and showed a more severe clinical phenotype, including higher hospitalization rates, more infections within 1 year, higher corticosteroid requirements, higher BPDAI scores, and more frequent head/neck and hands/feet involvement. Indirect immunofluorescence seropositivity and peripheral eosinophilia were less frequent in patients with mucosal involvement. In multivariate analysis, head/neck involvement (adjusted OR 8.276, 95% CI 2.211-30.977), hands/feet involvement (adjusted OR 34.559, 95% CI 8.191-145.805), and higher BPDAI score (adjusted OR 1.055, 95% CI 1.020-1.091) were independently associated with mucosal involvement, whereas peripheral eosinophilia was inversely associated (adjusted OR 0.027, 95% CI 0.005-0.148). The model demonstrated excellent apparent discrimination (AUC 0.937). Conclusion:Mucosal involvement in BP is associated with a more severe clinical phenotype. Head/neck and acral involvement, higher BPDAI scores, and a lower frequency of peripheral eosinophilia may serve as practical clinical indicators for identifying patients who require closer mucosal assessment and more intensive monitoring.

Bullous pemphigoid (BP) is an acquired autoimmune bullous disease that often occurs in elderly patients. Some BP patients with early age of disease onset were observed to have difficulty in receiving applicable disease control. It remains challenging for clinicians to choose the appropriate treatment for these patients. This study aimed to analyze the differences between patients of different ages at disease onset and further explore the possible mechanism of these differences between patients of different ages. A total of 215 BP patients seen at the dermatology department of Peking Union Medical College Hospital between January 2009 and September 2020 were included. The patients were allocated to five groups according to the age at disease onset. Clinical data were collected through medical records and telephone follow-up interviews. Analyses of anti-BP180 antibody subclasses, anti-BP230 antibodies, complement fixation, serum cytokine levels, and single nucleotide polymorphisms (SNPs) were conducted. Nearly 52% of patients under 60 were misdiagnosed on their first visit, often presenting with oral mucosal involvement. The anti-BP180 immunoglobulin (Ig) E titers and C3 deposition increased in patients under 60 (p = 0.044 and p = 0.014, respectively), while the anti-BP230 IgG titers decreased (p = 0.043). The hospitalization rate of patients under 50 was significantly higher than that of patients aged 80 and older (p < 0.001). The patients under 60 had a significantly higher serum concentration of interleukin (IL)-13, tumor necrosis factor (TNF)-α, and interferon gamma (IFN-γ) (p < 0.005, respectively). We observed significant differences in the distribution of genotypes or alleles of TNF-α rs1799964, TNF-α rs1800630, and IFN-γ rs2069705. Approximately one-third of the elderly patients suffered from neurological diseases. Elderly patients usually presented with peripheral eosinophilia (p = 0.013). No significant difference was identified in the recurrence rate and complement-activating capacity among the age groups. In conclusion, the early age of BP onset was associated with a more severe clinical presentation, higher titers of anti-BP180 IgE, lower titers of anti-BP230 IgG, and significantly higher serum concentrations of IL-13, TNF-α, and IFN-γ. It may also be associated with the presence of SNPs of cytokines, including TNF-α rs1799964, TNF-α rs1800630, and IFN-γ rs2069705 variants.

Steroid resistance is a common phenomenon observed in the treatment of bullous pemphigoid (BP). Previous studies addressing steroid resistance in BP were limited and were mainly case reports or case series. This retrospective study aims to compare the clinical and laboratory characteristics of steroid-resistant bullous pemphigoid (SRBP) patients and steroid-sensitive bullous pemphigoid (SSBP) patients and to identify potential risk factors associated with SRBP at diagnosis. We retrospectively reviewed the medical records of patients with BP who were diagnosed between January 2010 and June 2024 at Peking Union Medical College Hospital. This study analyzed 126 BP patients with moderate-to-severe disease severity, including 27 SRBP patients and 99 SSBP patients. Compared to SSBP patients, SRBP patients were of younger age [59 (47-65) vs. 71 (59-78), p < 0.001], higher female proportion [20 (74.1%) vs. 37 (37.4%), p < 0.001], higher anti-BP180 autoantibodies levels [130.6 ± 43.4 U/mL vs. 84.3 ± 59.5 U/mL, p < 0.001], lower hemoglobin [128 (106-142) g/L vs. 140 (127-150) g/L, p = 0.011], and lower serum albumin levels [31.5 (25.0-38.0) g/L vs. 38.0 (34.0-43.0) g/L, p < 0.001]. Multivariate logistic regression analysis confirmed that younger age (OR, 0.921; 95% CI, 0.876-0.968; p = 0.001), female sex (OR, 0.189; 95% CI, 0.048-0.739; p = 0.017), and lower albumin levels (OR, 0.777; 95% CI, 0.677-0.892; p < 0.001) are independent risk factors for steroid resistance in BP patients. This study showed that younger age, female sex, and low levels of serum albumin were independent risk factors of steroid resistance in BP patients. Correcting low serum albumin levels may be a crucial strategy to reduce steroid resistance.

BACKGROUND:Bullous pemphigoid (BP) is a severe autoimmune sub-epidermal bullous disease. Exosomes are small extracellular vesicles secreted by most cell types. The exosomal membrane proteins are implicated in various biological and pathological pathways. This study aims to explore the potential roles of exosomes in BP pathomechanism. RESEARCH DESIGN:We collected plasma samples from 30 BP patients and 31 healthy controls. Nanoparticle tracking analysis (NTA) was used to analyze the size and concentration of exosomes. The immunogold labelling experiment and extracellular vesicle (EV) array were performed to detect the content and distribution of exosomes. RESULTS:The exosomes from both the BP and control groups' plasma were successfully extracted. EV Array showed that CD63 and CD9 levels were significantly higher in the BP group than in the control group (p < 0.05). Expression levels of the BP180 NC16A and intracellular domain (ICD) were higher in the anti-BP180 positive group versus the controls (p < 0.05). The active BP group exhibits higher CD63 and BP180 ICD protein concentrations than the control or inactive BP groups (p < 0.05). CONCLUSION:BP180 autoantigen fragments were expressed on the exosomal membrane in BP patients. The BP180 ICD and CD63 on exosomes could potentially be novel biomarkers for monitoring disease activity.

Background: Previous studies have revealed the factors associated with the relapse of bullous pemphigoid (BP). This study aims to assess the characteristics of BP patients at the time of initial diagnosis and a potential association with subsequent relapse occurrences. Methods: A retrospective cohort study was conducted on 205 BP patients from January 2009 to May 2022 at the Peking Union Medical College Hospital in Beijing, China. The median follow-up duration was 2.7 years. We conducted univariate and multivariate analyses on various clinical indicators (e.g., lesional involvements and medical history) and laboratory test results. Results: Among the 205 patients, 118 (57.6 %) relapsed during the follow-up period. Univariate analysis revealed several factors associated with relapse, which were greater age [Hazard Ratio (HR)1.018, 95 % confidence interval (CI) 1.004-1.032] (p = 0.010), a past medical history of thyroid diseases [HR 3.674, 95 % CI 1.472-9.167] (p = 0.005), hematological disease complications [HR 4.123, 95 % CI 1.301-13.061] (p = 0.016), negative C3 deposition in direct immunofluorescence [HR 0.574, 95 % CI 0.374-0.883] (p = 0.011) and prealbumin level less than 200 mg/L[HR 0.580, 95 % CI 0.351-0.957] (p = 0.033). Multivariate analysis demonstrated that patients with negative C3 deposition in direct immunofluorescence [HR 0.524, 95 % CI 0.296-0.927] (p = 0.026) and prealbumin levels below 200 mg/L [HR 0.541, 95 % CI 0.301-0.974] (p = 0.041) were associated with further relapses of BP. Conclusions: Negative C3 deposition in direct immunofluorescence and a prealbumin level below 200 mg/L at initial diagnosis served as predictive markers for future relapses of BP. Systemic evaluation of BP patients at initial diagnosis could be essential in helping prevent recurrences and achieve more effective disease management.

Background Bullous pemphigoid (BP) is a senile chronic autoimmune bullous skin disease with a high relapse rate, which significantly impairs patients’ quality of life and contributes to disease mortality. This observational case-control study explores the gene polymorphisms of cytokines and their clinical significance in Chinese patients with BP. Methods IL-1α (rs1800587), IL-1β (rs16944, rs1143627, rs1143634), IL-4 (rs2243250), IL-6 (rs1800795), IL-10 (rs1800896, rs1800871, rs1800872), IL-13 (rs1800925, rs20541), TNF-α (rs1799964, rs1800630, rs1799724, rs361525), IFN-γ (rs1799964, rs1800630, rs361525, rs1800629, rs4248160, rs1800750), and TGF-β1 (rs2317130, rs1800469, rs4803457) genes were genotyped in the healthy controls and BP patients, respectively. Expression of these cytokines in serum was measured. Medical profiles of patients, including baseline characteristics and prognosis, were statistically analyzed. Results We found that IL-1 β and IL-13 concentrations were higher in the BP patients’ sera compared to those in the controls. For IL-13, significant differences were found in the nucleotide ratio/genotype/haploid frequency/haplotype, respectively. IL-13 (rs20541, rs1800925) is related to gender, and the IL-13 genotype was significantly associated with recurrence. Conclusions BP is associated with IL-13 gene polymorphism and IL-13 concentration is elevated in blood circulation in patients with BP. Our results support that IL-13 is relevant in the pathogenesis of BP, suggesting that IL-13 could potentially represent a promising target for BP therapy and a prognostic marker.

Background: Hypertension, diabetes, dyslipidemia, and obesity are prevalent in patients with bullous pemphigoid (BP) and are all components of metabolic syndrome (MS). However, the prevalence of MS in patients with BP is unknown. We aimed to evaluate the relationship between MS and BP and to define the clinical and laboratory characteristics of patients with both conditions. Methods: This retrospective case–control study was conducted for 12 years at Peking Union Medical College (162 with BP and 162 age and sex-matched controls). The components of MS were analyzed and logistic regression was used to identify independent risk factors for BP. In addition, the clinical and laboratory characteristics of patients with BP ± MS were compared. Results: The prevalence of MS in patients with BP was 35.2% and that in controls was 14.8% ( p < 0.001). After adjustment for sex and age, multivariate analysis demonstrated a positive correlation between BP and MS [odds ratio (OR) 2.490, 95% confidence interval (CI) 1.040–5.963], diabetes (OR 1.870, 95% CI 1.029–3.396), and overweight or obesity (OR 1.807, 95% CI 1.026–3.182). In the BP group, participants with MS were older ( p = 0.006), were less likely to present erythema ( p = 0.028), and had higher serum C3 ( p = 0.007) and incidence of infection within 1 year of their diagnosis ( p = 0.035) than participants without MS. Conclusion: MS and its components hyperglycemia and overweight were found to be independently associated with BP. Therefore, clinicians should screen for MS in patients with BP, especially if they are older, present less erythema, or have a high serum C3.

Skin is the largest organ of human, which can reflect host's health condition. Dermatovenereology is an important clinical discipline which focus on the profile of morphology. The challenge of learning is too much content but limited teaching hours. As to medical students, they may often feel dull and lose learning interest. How to arouse the enthusiasm and autonomy of medical students, and improve teaching effectiveness is one of difficulties in clinical teaching of dermatovenereology so draw attention by faculty as a potential orientation of education remodeling This paper aims for exploring a new teaching method, ‘diagnosis-initiated mode’, which may stimulate their interest in the learning of dermatovenereology.

Abstract Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering disease. It usually affects people older than 70 years of age. The two main autoantigens are BP180 and BP230, both of which are components of hemidesmosomes. Immunoglobulin (Ig)G and IgE autoantibodies to BP180 detected by the enzyme-linked immunoassay (ELISA) show close associations with the activity and severity of BP. In addition, inflammatory cells (eosinophils, neutrophils and mast cells) and cytokines (e.g. interleukins and CC chemokine ligands) play an important part in the pathogenesis, activity and severity of BP. We summarized the potential contribution of each factor postulated to be associated with the activity and severity of BP, and provide guidance for clinicians to pay timely and close attention to such parameters. This review may also promote the development of novel therapies for BP. Key Messages Bullous Pemphigoid Disease Area Index (BPDAI) is a scoring system which can reflect the extent of clinical involvement of BP patients. The titres of IgE autoantibodies and IgG autoantibodies against the NC16A domain of BP180 are closely correlated with the activity and severity of BP. Many inflammatory cells and molecules, such as eosinophils and interleukins, can also reflect the activity and severity of BP.

Bullous pemphigoid (BP) is a senile autoimmune blistering disease with autoantibodies against the basement membrane. Less than 20 cases of localized BP in young adults have been reported and the understanding of localized BP is very limited. An unusual location of localized BP is here described. A 30-year-old woman presented with a 4-month history of itchy erythema on her trunk. The lesion, well-demarcated erythema and maculopapules in bra’s shape, had been misdiagnosed as contact dermatitis. Laboratory finding was notable for serum autoantibodies to BP antigen 180 (BP180). Histopathological examination revealed a subepidermal blister with eosinophils and neutrophils infiltration. Salt-split indirect immunofluorescence revealed linear deposition of IgG at the dermoepidermal junction. After treating her with minocycline 200 mg and nicotinamide 1,500 mg per day, all lesions resolved within 1 month. Localized BP is usually misdiagnosed. It starts from various triggers and has a more benign disease course. It should be emphasized that a long-term follow-up of patients with localized BP may be important for management of the chronic disease, given a relatively high risk of developing generalized BP.

Naevus flammeus, also called port-wine stains (PWS), is congenital capillary malformation which usually involves the head and neck area. It occurs in approximately 0.3% of newborns. Over time, the lesions become darker red or purple in colour and the involved skin may get thicker. We report the PWS case with a very negative cosmetic consequence, to raise the clinicians’ concern about such a condition. A 40-year-old man presented to the dermatology department in July 2019, with a 3-year history of a progressively growing purple-red nodular mass on the left side of his scalp, accompanied with intermittent purulent secretion, but with no systemic symptoms. The patient had naevus flammeus on his left head, face and neck since birth. Over the preceding 3 years, the lesions on the head gradually turned purple in colour and thickened. In addition, multiple nodules appeared and purulent secretion was observed at times. In order to prevent infection, the patient had taken minocycline 200mg/d for 2 years irregularly. The purulent secretion and the number of nodules increased rapidly in the last 3 months. Physical examination revealed a significant purple-red mass with multiple nodules on his left scalp, covered with purulent secretion. Sporadic purple-red patches were also present on his left face and neck (Fig. 1). A skin biopsy revealed atrophy of the prickle cell layer, hyperpigmentation of the basal cell layer, and multiple enlarged vessel lumens and lymphoid structures in the dermis. Enlarged vessel lumens were filled with blood, and partial blood vessel wall was thick. Cell heteromorphism was not obvious. Immunohistochemical tests showed CD31 (+), CD34 (+) and D2-40 ( ). Laboratory evaluation revealed a white cell count of 8000 cells/mm with 79% neutrophils. Culture of the pyogenic sample was positive for Pseudomonas aeruginosa and methicillin-sensitive Staphylococcus aureus. Ultrasonic examination revealed multiple enlarged lymph nodes in the left neck. Magnetic resonance angiography of the patient’s head revealed no abnormalities. The clinical findings were consistent with nodular changes due to naevus flammeus. Hypertrophy is an important feature in the development of PWS and usually affects people over 50 years of age. Increasing age is significantly associated with hypertrophy. Hypertrophy is more common on the face than elsewhere on the body; red PWS are also at a significantly higher risk for hypertrophy compared with pink PWS. The pathogenesis of PWS remains unknown. Treatment of PWS has improved since the application of the pulsed dye laser (PDL), but hypertrophic PWS do not response well to treatment with PDL. There had been studies proving that both PKCa and PI3K signalling pathways play essential roles in the development of PWS hypertrophy and

Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering disease. It usually affects people older than 70 years of age. The two main autoantigens are BP180 and BP230, both of which are components of hemidesmosomes. Immunoglobulin (Ig)G and IgE autoantibodies to BP180 detected by the enzyme-linked immunoassay (ELISA) show close associations with the activity and severity of BP. In addition, inflammatory cells (eosinophils, neutrophils and mast cells) and cytokines (e.g. interleukins and CC chemokine ligands) play an important part in the pathogenesis, activity and severity of BP. We summarized the potential contribution of each factor postulated to be associated with the activity and severity of BP, and provide guidance for clinicians to pay timely and close attention to such parameters. This review may also promote the development of novel therapies for BP.Key Messages Bullous Pemphigoid Disease Area Index (BPDAI) is a scoring system which can reflect the extent of clinical involvement of BP patients. The titres of IgE autoantibodies and IgG autoantibodies against the NC16A domain of BP180 are closely correlated with the activity and severity of BP. Many inflammatory cells and molecules, such as eosinophils and interleukins, can also reflect the activity and severity of BP.

GENERAL COMMENTARY article Front. Immunol., 16 July 2020Sec. Autoimmune and Autoinflammatory Disorders Volume 11 - 2020 | https://doi.org/10.3389/fimmu.2020.01506

嵌合抗原受体T(chimeric antigen receptor-T,CAR-T)细胞是一种通过基因编辑表达跨膜嵌合抗原受体并具有特异性导向的T细胞.CAR-T作为一种新兴的免疫治疗,已在肿瘤治疗方面取得较大突破.近年来,基于当前自身免疫性疾病治疗的局限性,研究者们正在不断探索CAR-T及其衍生疗法在自身免疫性疾病中的潜在治疗价值.本文重点阐述CAR-T在自身免疫性疾病领域的研究进展及现阶段所面临的挑战,为自身免疫性疾病的精准治疗提供理论依据.

Bullous pemphigoid (BP) is the most common subepidermal bullous disease and involves an immune response directed against two hemidesmosome components in basal keratinocytes: BP antigen 180 (BP180) and BP antigen 230. The major epitope in patients with BP is the noncollagenous 16A (NC16A) domain of BP180. BP most commonly occurs in people of advanced age, especially those aged >70 years. The worldwide incidence of BP ranges from 12 to 66 cases per million people per year, and the disease prevalence increases with age. Degenerative neurological diseases, psychiatric disorders, and the chronic use of neuroleptics or spironolactone are known independent risk factors for the development of BP. Dipeptidyl peptidase 4 (DPP-4) inhibitors are a drug class that was first introduced into the market in 2006 to treat type 2 diabetes mellitus. In recent years, an increasing body of evidence has suggested that DPP-4 inhibitors may be implicated in the development of BP. Current knowledge regarding the association between DPP-4 inhibitor intake and BP is based mainly on case reports.We herein report the first case of DPP-4 inhibitorassociated BP in China, and the DDP-4 inhibitor in this case was linagliptin.

类天疱疮群是一组由自身抗体攻击基底膜带抗原蛋白,导致真表皮分离、表皮下水疱的自身免疫性疱病。该群组包含大疱性类天疱疮、黏膜类天疱疮等多个疾病,其中大疱性类天疱疮最为常见。不同国家和地区的类天疱疮发病特点不同,有些类天疱疮的病因和发病机制尚不明确。本文对几种较常见类天疱疮的流行病学特征及可能致病因素进行综述,为疾病的干预提供新视角。