Anti-C1q antibodies in IgG4-related disease are common and associated with renal involvement and cutaneous small-vessel vasculitis

Abstract Objectives To evaluate the prevalence and clinical associations of anti-C1q antibodies in IgG4-related disease (IgG4-RD), focusing on renal involvement and cutaneous small-vessel vasculitis (CSVV). Methods We enrolled patients who met the revised 2020 Comprehensive Diagnostic Criteria and/or the 2019 ACR/EULAR Classification Criteria for IgG4-RD. Variables included demographics, organ involvement, clinical phenotypes, disease activity, serum biomarkers, follow-up duration, remission and relapses. Anti-C1q antibodies were measured using a quantitative enzyme-linked immunosorbent assay (cut-off <10 U/ml). Results Seventy patients with a mean age of 52.1 years were included. Thirty-four patients (48.6%) were male. Anti-C1q antibodies were positive in 74.3%, with a median level of 19.8 U/ml. Patients with active disease had higher anti-C1q antibody levels than inactive patients (P = 0.03). Renal involvement was more frequent in anti-C1q positive patients (P = 0.01). Six patients (8.6%) had CSVV, and all had positive anti-C1q levels. All exhibited palpable purpura and one patient had urticarial-like lesions. These patients had multi-organ involvement, and most had high IgG, IgG1, IgG4 and hypocomplementemia. Skin biopsies in three patients showed leukocytoclastic vasculitis with lymphocytic and eosinophilic infiltrates. Anti-C1q antibody levels correlated negatively with levels of C3 and C4, and positively with levels of IgG1, IgG4, and serum free light chains. Anti-C1q positivity did not predict relapse-free survival. Conclusions This study is the first to evaluate anti-C1q antibodies in IgG4-RD, finding a high prevalence, particularly in patients with renal involvement and CSVV. The results support the hypothesis that immune complex-mediated complement activation contributes to IgG4-RD pathogenesis.