摘要
Immunodysregulation, Polyendocrinopathy, Enteropathy, and X-linked (IPEX) syndrome is a rare autoimmune disorder caused by mutations in the FOXP3 gene. Patients with IPEX frequently present with severe dermatitis, diabetes, and enteropathy. This study explores the efficacy of Dupilumab (an anti-IL-4Rα monoclonal antibody) in treating persistent, severe dermatitis in an IPEX patient refractory to conventional treatments like sirolimus.
We conducted a clinical case study of a 2-year-old IPEX patient with refractory dermatitis. Whole-exome sequencing (WES) confirmed the FOXP3 mutation. Skin biopsies were analyzed for inflammatory gene expression by RNA sequencing and immunohistochemistry to characterize inflammatory pathways. Immune cell phenotyping was performed using flow cytometry pre- and post-treatment in peripheral blood mononuclear cells (PBMCs). The patient was treated with Dupilumab alongside sirolimus and prednisone. Clinical improvements were evaluated using the Eczema Area and Severity Index (EASI) score.
Immunohistochemistry revealed elevated IL-13 expression. RNA sequencing of skin samples revealed upregulation of both Th1- and Th2-related genes, suggesting a dual inflammatory phenotype in IPEX dermatitis. The patient exhibited significant clinical improvement after 8 months of sustained Dupilumab therapy, with the EASI decreasing from 24.8 to 0.4. Flow cytometry demonstrated a reduction in Th1 and Th2 cell subsets post-treatment, accompanied by an increase in Treg and Th3 cell populations as well as enhanced expression of immunosuppressive markers such as CTLA-4 and CD39.
Dupilumab appears promising as a therapeutic option for managing refractory dermatitis in IPEX, particularly by attenuating Th1/Th2 inflammation and promoting regulatory responses mediated by Treg and Th3 cells.