Elevated anti-C1q antibody levels were detected across multiple autoimmune and inflammatory diseases, extending beyond systemic lupus erythematosus, according to findings published in Lupus Science & Medicine.
Siwei Xie, MD, of the Third Affiliated Hospital of Sun Yat-sen University in Guangzhou, Guangdong, China, and colleagues analyzed 15,363 adults who were tested for anti-C1q between September 2020 and 2023 to determine demographic and disease-specific associations. They identified abnormal anti-C1q levels (greater than 10 U/mL) in 7.9% of patients. Detection rates were highest in systemic lupus erythematosus (SLE) without severe complications (22.7%) and in lupus nephritis (29.9%). Lupus-related hematologic and encephalopathic manifestations showed the strongest elevations—71.4% and 50%, respectively. Anti-C1q elevations were also observed in autoimmune cirrhosis (11.9%), systemic sclerosis (11.5%), and Sjögren syndrome (4.4%), suggesting the antibody’s diagnostic relevance may extend beyond SLE. While the proportion was relatively low, the researchers also detected the presence of anti-C1q in patients with hepatitis B virus infection and pneumonia, consistent with reports of elevated anti-C1q in infectious diseases.
To account for variability by disease type and clinical department, the investigators used fixed-effect logistic regression models, treating both diagnosis and department as fixed effects to control for systematic differences in testing across clinical settings. In the crude data, females had higher mean test results and a greater proportion of abnormal findings than males overall (8.5% vs 5.6%). After adjustment, this association reversed because females were over-represented in high-prevalence diagnoses and younger age groups, illustrating case-mix confounding. Female patients younger than 18 years and those aged 18 to 39 years also had higher crude abnormal proportions than males in those same age strata (22.5% vs 8.7% for those younger than 18 years; 10.1% vs 7.4% for those aged 18 to 39 years).
After full adjustment for diagnosis and department, younger age and male sex emerged as independent predictors of abnormal anti-C1q results. Among the overall cohort (median age 38 years; 79% female), the highest abnormal rates were observed in those younger than 18 years (19.4%) and in those aged 18 to 39 years (9.6%), suggesting that elevated anti-C1q levels may reflect underlying disease activity or immune dysregulation rather than disease prevalence.
The researchers suggested that anti-C1q testing may serve as a valuable biomarker for risk stratification, particularly in lupus nephritis and other severe autoimmune phenotypes, potentially aiding earlier diagnosis and disease monitoring. The retrospective, single-center design and lack of treatment or activity data were cited as study limitations, and the results reflect antibody positivity within tested populations rather than population-wide prevalence.
The study was supported by the National Natural Science Foundation of China and affiliated institutional programs.
Source: Lupus Science & Medicine