Objectives <p>This study aimed to explore the clinical characteristics, treatment, and prognosis of IgG4-related disease (IgG4-RD) patients with comorbid autoimmune diseases (AIDs).</p> Method <p>A total of 879 IgG4-RD patients treatment-naïve at baseline from Peking Union Medical College Hospital were retrospectively included in this study. IgG4-RD patients with comorbid AIDs were classified into the AID-positive (AID-Pos) group, while those without AIDs were classified into the AID-negative (AID-Neg) group. Additionally, AIDs were classified as systemic or organ-specific subgroups. The clinical features, laboratory findings, treatment regimens, and long-term prognosis were compared among the AID-Pos and AID-Neg groups, and the characteristics of AIDs were also explored.</p> Results <p>AID prevalence in IgG4-RD was 9.67% (85/879), with systemic (<i>n</i> = 47; 55.3%) and organ-specific (<i>n</i> = 38; 44.7%) subtypes. Common AIDs included vitiligo (<i>n</i> = 15; 17.6%), systemic vasculitis (<i>n</i> = 12; 14.1%), psoriasis (<i>n</i> = 12; 14.1%), Hashimoto’s thyroiditis (<i>n</i> = 11; 12.9%), and rheumatoid arthritis (<i>n</i> = 10; 11.8%). Most preceded/synchronized with IgG4-RD; 88.2% had a single AID. All groups showed a median of 3 involved organs, but AID-Neg had more multi-organ involvement. AID-Pos had lower IgG4 levels, while systemic AIDs showed higher ESR and IgG1. Treatment and prognosis did not differ between groups.</p> Conclusions <p>IgG4-RD patients can complicate with other AIDs. Compared with the AID-Neg group, IgG4-RD patients with comorbid AIDs contained a lower proportion of patients with multi-organ involvement, and their patients have lower serum IgG4 levels. The treatment and prognosis were similar between the two groups.</p> <p><Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry align="left" nameend="c2" namest="c1"> <p>Key Points</p> <p>• IgG4-related disease (IgG4-RD) can complicate with autoimmune diseases (AIDs). The relationship between IgG4-RD and AID is yet to be fully elucidated.</p> <p>• 9.67% of IgG4-RD patients (85/879) had comorbid AIDs. AID-positive patients showed lower IgG4, and patients with systemic AIDs showed higher ESR and IgG1.</p> <p>• IgG4-RD and AIDs are not entirely contrary in the diagnosis of IgG4-RD.</p> </entry> </row> </tbody> </tgroup> </Table></p>