Background: Pemphigus is a group of potentially life-threatening autoimmune bullous diseases induced by pathogenic autoantibodies binding to the surface of epidermal cells. The role of the gut microbiota (GM) has been described in various autoimmune diseases. However, the impact of the GM on pemphigus is less understood. This study aimed to investigate whether there was alterations in the composition and function of the GM in pemphigus patients compared to healthy controls (HCs). Methods: Fecal samples were collected from 20 patients with active pemphigus (AP), 11 patients with remission pemphigus (PR), and 47 HCs. To sequence the fecal samples, 16S rRNA was applied, and bioinformatic analyses were performed. Results: We found differences in the abundance of certain bacterial taxa among the three groups. At the family level, the abundance of Prevotellaceae and Coriobacteriaceae positively correlated with pathogenic autoantibodies. At the genus level, the abundance of Klebsiella, Akkermansia, Bifidobacterium, Collinsella, Gemmiger, and Prevotella positively correlated with pathogenic autoantibodies. Meanwhile, the abundance of Veillonella and Clostridium_XlVa negatively correlated with pathogenic autoantibodies. A BugBase analysis revealed that the sum of potentially pathogenic bacteria was elevated in the AP group in comparison to the PR group. Additionally, the proportion of Gram-negative bacteria in the PR group was statistically significantly lower in comparison to the HC group. Conclusion: The differences in GM composition among the three groups, and the correlation between certain bacterial taxa and pathogenic autoantibodies of pemphigus, support a linkage between the GM and pemphigus.

Thymic stromal lymphopoietin (TSLP), long known to be involved in Th2 response, is also implicated in multiple inflammatory dermatoses and cancers. The purpose of this study was to improve our understanding of the expression of TSLP in the skin of those dermatoses. Lesional specimens of representative immune-related dermatoses, including lichen planus (LP), discoid lupus erythematosus (DLE), eczema, bullous pemphigoid (BP), psoriasis vulgaris (PsV), sarcoidosis, and mycosis fungoides (MF), were retrospectively collected and analyzed by immunohistochemistry. Morphologically, TSLP was extensively expressed in the epidermis of each dermatosis, but the expression was weak in specimens of DLE. In a semiquantitative analysis, TSLP was significantly expressed in the epidermis in LP, BP, eczema, PsV, sarcoidosis, and MF. TSLP expression was higher in the stratum spinosum in LP, eczema, BP, PsV, and MF and higher in the stratum basale in sarcoidosis and PsV. Moreover, we found positive TSLP staining in the dermal infiltrating inflammatory cells of BP, PsV, and sarcoidosis. Our observation of TSLP in different inflammatory dermatoses might provide a novel understanding of TSLP in the mechanism of diseases with distinctly different immune response patterns and suggest a potential novel therapeutic target of those diseases.

Autoimmune bullous diseases (AIBDs), including pemphigus and bullous pemphigoid, are chronic inflammatory skin disorders characterized by dysregulated immune responses mediated by autoantibodies that target adhesion molecules in the skin and mucous membranes. Emerging evidence highlights the pivotal role of host microbiota dysbiosis in AIBDs pathogenesis, offering novel insights into disease mechanisms and therapeutic strategies. This review systematically synthesizes the current findings on gut, skin, and oral microbiota alterations in AIBDs, emphasizing their contributions via the gut-skin axis, microbial metabolites, and pathogen-host interactions. Key innovations include uncovering how specific pathogenic and commensal microbiota influence disease progression through intriguing skin inflammation and direct barrier impairment. Notably, while some microbiota changes overlap with other dermatoses, AIBDs exhibit distinct microbial signatures associated with their unique autoimmune mechanisms targeting adhesion molecules. Furthermore, we explore microbiota-targeted therapies, such as antibiotics, probiotics, and fecal microbiota transplantation, and demonstrate their potential to restore microbial homeostasis and improve clinical outcomes. By integrating multi-omics evidence and clinical data, this review bridges mechanistic insights with translational applications, proposing microbiota modulation as a promising adjunctive therapy for AIBDs. Our analysis identifies critical research gaps, including the need for longitudinal studies and personalized microbial interventions, positioning this review at the forefront of microbiome-inflammation-autoimmunity research.

Background: Bullous pemphigoid (BP) affects older adults and treatment is often limited by corticosteroid toxicity. Evidence for stapokibart in BP is limited. Objectives: To describe the clinical outcomes and safety of stapokibart-based combination therapy in BP. Methods: We retrospectively reviewed consecutive patients with BP who received stapokibart-based combination therapy at Peking Union Medical College Hospital between October 2024 and October 2025, and had a follow-up period of ≥ 4 months. Stapokibart was administered as a 600-mg loading dose, followed by 300 mg every 2 weeks. Outcomes included time to disease control; time to Bullous Pemphigoid Disease Area Index (BPDAI) activity score of 0; time to complete remission (CR) on minimal therapy; adverse events; and changes in BPDAI activity, pruritus numerical rating scale (NRS), anti-BP180 titres, eosinophil counts and concomitant corticosteroid exposure throughout the follow-up period. Results: Twelve patients were enrolled, with a median age of 77.5 years and a median follow-up period of 217 days. All received concomitant Tripterygium glycosides, and 7 of 12 (58%) also received oral corticosteroids at stapokibart initiation. All patients achieved disease control within a median time of 14.5 days. Eleven of the 12 patients (92%) reached disease control within 4 weeks. A BPDAI activity score of 0 was reached in all patients (median 65.5 days). Seven patients (58%) achieved CR on minimal therapy (median 176 days among responders). During follow-up, BPDAI activity, pruritus NRS, eosinophil counts, anti-BP180 titres and prednisone doses all decreased. One patient reported temporary fatigue and later developed herpes zoster. No patients stopped treatment throughout the study. Conclusions: Stapokibart-based combination therapy was associated with rapid short-term disease control and clinical improvement in this small retrospective cohort of patients with BP. Given the limited sample size and frequent concomitant therapy, these preliminary findings require confirmation in larger controlled studies.

Telitacicept, a TACI-Fc fusion that neutralizes BAFF/APRIL, was administered weekly (160 mg) to two women with pemphigus foliaceus who declined systemic corticosteroids and conventional immunosuppressants. Rapid disease control ensued (Pemphigus Disease Area Index score of 0 by weeks 8–10) with normalized anti-Dsg1 titres and sustained remission over 6 months; treatment was well tolerated without interruption. These preliminary observations, which represent, to our knowledge, the first use of telitacicept in pemphigus foliaceus, support BAFF/APRIL blockade as a potential steroid-sparing strategy.