Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is characterized by a wide range of dermatological and musculoskeletal manifestations, and its outcome has recently been improved greatly by optimizing management. However, the treatment strategies are not standardized and require further refinement. Secukinumab, a fully human monoclonal antibody targeting IL-17A, is approved for the treatment of autoimmune psoriasis, psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Here, a 53-year-old man was diagnosed with AS, and he presented scattered pustulosis in both hands and feet with a 5-year history of recurrent lumbosacral area pain and abnormal pain in the neck and front chest area. Secukinumab improved the patient’s cutaneous lesion and prevented musculoskeletal pain by substituting adalimumab. Although only a few cases have been reported that secukinumab can effectively treat SAPHO syndrome complicated with AS, the efficacy remains controversial. Therefore, we hope to provide a novel valuable therapeutic strategy for SAPHO syndrome management, particularly in patients with skin lesions.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by immune dysregulation, heterogeneous clinical phenotypes, and a complex interplay of pathogenic mechanisms. RNA-binding proteins (RBPs), which orchestrate post-transcriptional gene regulation through dynamic interactions with target transcripts, are increasingly implicated in autoimmune pathogenesis. However, the cell-type-specific heterogeneity of RBPs expression and their regulatory networks in SLE remain poorly characterized. To delineate RBPs dynamics in SLE skin microenvironment, we conducted a comprehensive single-cell transcriptomic analysis of publicly accessible single cell RNA sequencing (scRNA-seq) datasets from lesional skin biopsies of SLE patients and healthy controls (HC). Cell-type-specific RBPs expression patterns were systematically profiled across epidermal keratinocytes, dermal endothelial cells, and T cells. Complementary bulk RNA-Seq analyses employing Splicing Site Usage Variation Analysis (SUVA) were performed to identify immune gene-associated regulatory alternative splicing (RAS) events. Integrative co-expression networks linking RBPs, RAS events, and immune pathways were subsequently constructed. Single-cell resolution revealed marked heterogeneity in RBPs expression across keratinocyte, endothelial cell, and T cell in SLE compared to HC. Notably, disease-specific RBPs were enriched in pathways governing interferon response, cytokine signaling, and leukocyte activation. Cross-analysis with bulk transcriptomic data highlighted JUN and HLA-A as hub regulators exhibiting elevated expression in SLE T cells. Network modeling further uncovered coordinated interactions between JUN, HLA-A, and RAS events in immune genes, implicating their synergistic roles in modulating T cell effector functions. Our multi-omics integration identifies JUN and HLA-A as central coordinators of alternative splicing programs in SLE T cells. These molecular hubs, embedded within immune regulatory networks, may drive pathogenic rewiring of T cell responses in SLE.

Background /Objectives: Autophagy plays a role in systemic lupus erythematosus (SLE) pathogenesis. Nevertheless, the specific genetic determinants underpinning this process remain poorly characterized. Summary data-based Mendelian randomization (SMR) analysis was therefore utilized to pinpoint autophagy-related genes associated with SLE risk. Methods: We analyzed 700 autophagy-related genes, integrating methylation quantitative trait loci (mQTL), expression QTL (eQTL) from blood and relevant tissue, and protein QTL (pQTL) data with genome-wide association studies (GWAS) data on SLE from the IEU dataset (discovery). GWAS data from FinnGen and the GWAS Catalog were used as replication datasets. Colocalization analysis identified shared genetic variants. Blood samples from 10 healthy control and 20 SLE patients were collected and analyzed for the expression of candidate genes. Results: Our SMR analysis identified suggestive associations between NLRP6 expression (OR = 0.528, 95%CI = 0.291–0.96) and p27Kip1 protein abundance (OR = 0.269, 95%CI = 0.08–0.904) with SLE susceptibility in the discovery cohort, supported by colocalization evidence. Additionally, we found that the methylation of the NLRP6 promoter (cg06432119) was significantly increased, while NLRP6 expression and p27Kip1 level were significantly decreased in SLE patients compared to controls. Furthermore, NLRP6 mRNA expression was significantly negatively correlated with the SLE severity (SLEDAI-2000). Conclusions: These findings not only prioritized candidate genes via SMR analysis but also provided evidence of epigenetic dysregulation of NLRP6 and its correlation with disease activity in SLE, thereby offering novel insights into the underlying mechanisms.