Complement and C1q, the first component of the classical pathway of activation of the complement system, are considered to be involved in the pathogenesis of systemic lupus erythematosus (SLE), a systemic autoimmune disease. In fact, C1q deficiency is the strongest disease susceptibility gene for human SLE. However, most SLE patients do not have primary C1q deficiency, but a substantial number of patients with SLE develop secondary hypocomplementemia with depletion of C1q and its deposition in affected tissues. Furthermore, autoantibodies against C1q (anti-C1q) are frequently found in SLE patients and they are strongly associated with the consumption of C1q as well as the occurrence of severe lupus nephritis. Anti-nucleosome antibodies as a marker of active proliferative lupus nephritis To date there is no gold standard to predict severe nephritis in patients with SLE. Like anti-C1q antibodies, anti-dsDNA antibodies and anti-nucleosome antibodies are also considered to be useful markers of severe lupus nephritis. Therefore we aimed to establish the true prevalence of anti-nucleosome and anti-dsDNA antibodies at the time of active proliferative lupus nephritis, and compared this to inactive SLE controls who either had or had not experienced nephritis in the past. Results were compared to anti- C1q that had previously been investigated in the same cohort of patients. In this study, anti-C1q autoantibodies had been shown to be an excellent marker of active proliferative lupus nephritis, which suggests a pathogenic role in SLE. In contrast, our data on antinucleosome antibodies and anti-dsDNA antibodies suggest that these autoantibodies are of limited use in distinguishing patients with active proliferative lupus nephritis from SLE patients without active renal disease. Autoantibodies against complement C1q specifically target C1q bound on early apoptotic cells To better understand the pathogenic mechanisms in SLE, we intended to analyze the conditions that lead to an autoimmune response against C1q. Since anti-C1q are known to recognize neoepitopes on bound C1q but not on fluid phase C1q, we aimed to clarify the origin of anti-C1q by determining the mechanism that renders C1q antigenic. We analyzed the binding characteristics of anti-C1q antibodies, such as their ability to recognise C1q bound on different classes of immunoglobulins, on immune complexes and on cells undergoing apoptosis. Interestingly, we did not observe the binding of anti- C1q to C1q bound on immunoglobulins or immune complexes. However, anti-C1q were found to specifically target C1q bound on early apoptotic cells. Our findings provide a direct link between human SLE, apoptosis and C1q. Due to the exceptional presentation of neoantigens by the C1q molecule, our data suggest that early apoptotic cells are a major target of the autoimmune response in SLE. Anti-C1q autoantibodies do not correlate with the occurrence of nephritis in lupusprone MRL/MpJ+/+ mice In SLE patients, a strong correlation between the occurrence of anti-C1q antibodies and lupus nephritis has been demonstrated. However, it is difficult to demonstrate in SLE patients whether anti-C1q titers are predictive for a renal flare. Therefore we conducted a follow-up study of lupus-prone MRL/MpJ+/+ mice with the aim to analyze the occurrence of anti-C1q autoantibodies and their correlation with the onset, type and severity of nephritis. Despite the abundant and early presence of anti-C1q, they did not correlate with survival and severity of glomerulonephritis, contradicting our initial hypothesis. However, different pathogenic mechanisms in glomerulonephritis in lupusprone MRL/MpJ+/+ mice and human proliferative lupus nephritis might account for the unexpected observation.