A large single-center study of 15,363 adults found that anti-C1q antibodies—classically linked to lupus—were elevated across a broader range of autoimmune and inflammatory diseases. Abnormal levels (≥10 U/mL) appeared in 7.9% of patients, with the highest rates in systemic lupus erythematosus without severe complications (22.7%) and lupus nephritis (29.9%). Hematologic and encephalopathic lupus manifestations showed striking elevations of 71.4% and 50%. Anti-C1q positivity also occurred in autoimmune cirrhosis, systemic sclerosis, and Sjögren syndrome. After full adjustment, younger age and male sex predicted abnormal results, suggesting disease activity rather than diagnosis drove elevations. Findings were published in Lupus Science & Medicine.