Clinical and Immunological Changes Following Dupilumab Treatment in Patients with IgG4-related Disease

Background IgG4-related disease is a rare, immune-mediated fibroinflammatory condition that affects multiple organs. Despite concerns over long-term side effects and relapse, glucocorticoids and immunosuppressants remain the standard treatment. This study assesses the efficacy of dupilumab, a monoclonal antibody targeting IL-4Rα that blocks type 2 helper T cell-mediated inflammation, in patients with IgG4-related disease. Case presentation: Five individuals diagnosed based on the 2019 ACR/EULAR classification criteria received dupilumab (600 mg initially, followed by 300 mg biweekly) and were monitored for up to 64 weeks. Clinical evaluations included organ/site scores, IgG4 scores, and the IgG4-related disease responder index. Laboratory analyses measured serum immunoglobulin levels, IgG subclasses, and IgG4-RD-related biomarkers. Four of the five patients showed clinical improvement and reduced IgG4 levels following dupilumab treatment. However, one patient (Patient 4) had an atypical response, with increased IgG4 levels despite therapy. Organ/site scores declined in four patients but remained high in Patient 4. Serum IgG4 levels significantly decreased in four patients, normalizing in 3. A notable inverse correlation was found between cumulative oral corticosteroid dosage and dupilumab treatment duration ( r  = − 0.5455, P  < 0.0001). Among the biomarkers, galectin-3 levels showed a significant decline at 32 weeks ( P  < 0.05). Conclusions Dupilumab may offer therapeutic benefit in IgG4-related disease, although individual responses vary, underscoring the need for personalized treatment strategies.