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This study aimed to investigate the associations of anti-C1q antibodies with systemic lupus erythematosus (SLE) disease activity and lupus nephritis (LN) in northeast of China. Ninety patients with SLE, 37 patients with other autoimmune diseases, and 40 healthy donors in northeast of China were enrolled. Serum anti-C1q antibodies were measured by ELISA with 20 RU/ml as the threshold of positive results. The prevalence and levels of anti-C1q antibodies in SLE group (50%, 20.54 ± 34.67 RU/ml) were significantly higher than those in autoimmune disease and healthy control groups ( P < 0.05), yet no significant difference between LN patients and non-LN lupus patients (57.14% vs 41.46%, P > 0.05; 25.92 ± 39.94 vs 13.07 ± 27.39 RU/ml, P > 0.05). Anti-C1q antibody levels were positively correlated with levels of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, anti-dsDNA, and anti-cardiolipin and negatively correlated with serum C3 and C4 ( P < 0.05). The prevalence of anti-Sm and anti-nucleosome increased in anti-C1q-positive lupus patients ( P < 0.05). Compared with anti-C1q-negative lupus patients, patients with 20-40 RU/ml anti-C1q antibodies had comparable disease activity ( P > 0.05); patients with 40-80 RU/ml anti-C1q antibodies had significantly lower levels of serum complement ( P < 0.05); patients with above 80 RU/ml anti-C1q antibodies had much more severe hypocomplementemia, increased SLEDAI scores, and higher incidence of hematuria and proteinuria ( P < 0.05). Furthermore, the specificity and positive predictive value of 80 RU/ml anti-C1q antibodies for LN was 97.56% and 87.50%, respectively. In conclusion, anti-C1q antibodies are associated with SLE and LN disease activity, and the contribution hinges on the titers. Moreover, high-level anti-C1q antibodies are valuable for diagnosing LN. [ABSTRACT FROM AUTHOR]