Absence of Anti-C1q Antibodies in C1q Nephropathy: Evidence for a Distinct Pathogenic Mechanism from Lupus Nephritis

Background: C1q nephropathy (C1qN) and lupus nephritis (LN) both feature C1q deposition in glomeruli, yet there remains great debate regarding the pathogenesis and clinicopathologic distinctions between these two glomerular diseases, particularly with mesangioproliferative LN. Anti-C1q antibodies have been implicated in the pathophysiology and disease activity of systemic lupus erythematosus (SLE), particularly high activity lupus nephritis. Whether these antibodies are also present in C1qN, a condition defined by C1q deposition in the absence of systemic lupus, remains unclear. Methods: We conducted an analysis of serum anti-C1q antibody levels in biopsy-proven C1qN (n = 11) and class IV LN (n = 9) patients, identified from the University of North Carolina-Chapel Hill nephropathology biorepository. Anti-C1q antibody levels were measured using a standardized ELISA method, with positivity defined per manufacturer’s thresholds. Internal controls with known negative SLE samples and known positive SLE samples were used. Clinical and histopathologic data were reviewed to confirm diagnosis and exclude overlap with SLE in C1qN cases. Results: None of the patients with C1q nephropathy (n = 11) demonstrated detectable anti-C1q antibodies. In contrast, eight patients with class IV lupus nephritis (n = 9) tested positive for anti-C1q antibodies. The internal controls were in agreement with the manufacturer control samples. This stark contrast persisted despite histologic similarity in glomerular C1q deposition, and all C1qN patients met clinical and serologic criteria excluding SLE. Conclusion: This is the first study to our knowledge to evaluate anti-C1q antibodies in C1qN patients. Though these were small sample sizes, our findings demonstrate that anti-C1q antibodies are consistently absent in C1q nephropathy, while predominantly present in class IV lupus nephritis. This suggests a distinct immunopathologic mechanism in C1qN, despite the shared immunophenotypic hallmark of glomerular C1q deposition. The absence of anti-C1q antibodies may serve as a useful biomarker to help distinguish C1q nephropathy from lupus nephritis in diagnostically challenging cases.