Abstract
BACKGROUND: Anti-C1q autoantibodies can disrupt normal complement function, contributing to the formation of pathogenic immune complexes and end-organ damage. Although their role in SLE is well-established, their detection rate and clinical relevance across a broader spectrum of diseases remain insufficiently characterised. This study aimed to investigate the distribution of abnormal anti-C1q levels in the population and examine their associations with age, sex and specific clinical subtypes. METHODS: This retrospective study included patients who underwent anti-C1q testing at our hospital between September 2020 and September 2023. The primary outcome was the detection rate of abnormal anti-C1q levels (>10 U/mL) categorised by patient sex, age and disease diagnosis. One-way and two-way fixed-effect models were used to assess associations between odds of abnormal antibody levels and demographic factors. Multivariate logistic regression was performed to identify disease-specific correlates. RESULTS: Among 15 363 patients (median (IQR) age, 38 (28-53) years; 79.02% female; 52.19% aged <40 years) representing 67 distinct diagnoses, 7.88% showed abnormal anti-C1q levels. Female sex and younger age showed higher median anti-C1q levels and a greater proportion of abnormal results. SLE subtypes showed the highest detection rate of abnormal anti-C1q levels, with SLE without severe complications (853 of 3760, 22.69%) and lupus nephritis (88 of 294, 29.93%) being the most obvious. Lupus haematological and encephalopathic manifestations were associated with elevated antibody levels. Additionally, autoimmune cirrhosis (7 of 59, 11.86%) and systemic sclerosis (19 of 165, 11.52%) also showed high detection rates of abnormal anti-C1q levels. Both univariate and multivariate analyses indicated that male sex and younger age were significantly associated with increased odds of abnormal anti-C1q levels. CONCLUSION: Elevations in anti-C1q levels extend beyond SLE and are influenced by both demographic factors and specific disease phenotypes. Male sex and younger age emerged as significant predictors of abnormal anti-C1q status. Our findings underscore the potential utility of anti-C1q testing for improving diagnostic precision and risk stratification across a wide range of clinical conditions.