Complement levels and anti-C1q autoantibodies in patients with neuropsychiatric systemic lupus erythematosus

Abstract

Objective: The objective of this paper is to analyse serum levels of anti-C1q, C1q circulating immune complexes (CIC), complement activation and complement components in systemic lupus erythematosus (SLE) patients during the first central nervous system neuropsychiatric (NP) event and to define the possible association between these results and clinical and laboratory characteristics. Methods: A total of 280 patients suspected of having NP involvement due to SLE were recruited in the Leiden NPSLE-clinic. All SLE patients were classified according to the ACR 1982 revised criteria for the classification of SLE. The clinical disease activity was measured by the SLE Disease Activity Index 2000 (SLEDAI-2K) and NP diagnoses were classified according to the 1999 ACR case definitions for NPSLE. We measured in serum of all patients anti-C1q and C1q CIC levels, the activation capacity of complement (CH50 and AP50) and different complement components (C1q, C3, C4). Results: In 92 patients the symptoms were attributed to SLE. NPSLE patients consisted of 63 patients with focal NPSLE and 34 patients with diffuse NPSLE. Anti-C1q antibodies were significantly higher and CH50, AP50 and C3 were significantly lower in NPSLE patients compared with SLE patients without NPSLE. This association was specially marked for diffuse NPSLE while no differences were found for focal NPSLE. After using potential predictors, decreased C4 remained significantly associated with focal NPSLE, but only when antiphospholipid antibodies (aPL) were included in the model. C3 and AP50 were independently associated with diffuse NPSLE. When SLEDAI-2K was included in the model these two associations were lost. When individual NPSLE syndromes were analysed, psychosis and cognitive dysfunction showed significantly lower values of complement activation capacity and all complement components. No significant associations were seen for other individual NPSLE syndromes. Conclusion: The associations between diffuse NPSLE and anti-C1q, C3/AP50 and focal NPSLE and C4 may be explained by disease activity and the presence of aPL, respectively. The role of complement activation and complement components in lupus psychosis and cognitive dysfunction merits further research. Lupus (2016) 25, 878-888.

Nervous System Disease in Systemic Lupus Erythematosus: Current Status and Future Directions

“…This acquired procoagulant state has traditionally been considered noninflammatory. However, recent evidence implicates complement activation in association with focal NPSLE, psychosis, and cognitive dysfunction, suggesting an added inflammatory pathogenic component. Mice deficient in C3 and C5 components of complement are resistant to aPL‐induced thrombosis and endothelial activation .…”

Serum complement levels in anti‐N‐methyl‐d‐aspartate receptor encephalitis

“…In previously published articles, abnormal serum complement components have been associated with a variety of autoimmune disorders, including multiple sclerosis [7], neuromyelitis optica [8,9], systemic lupus erythematosus [10], rheumatoid arthritis [11] and Crohn's disease [12]. Recently, Martinez-Hernandez et al [13] demonstrated the absence of complement components including C3, C9neo and C5b-9 in the brain of patients with anti-NMDAR encephalitis.…”

Neuropsychiatric Systemic Lupus Erythematosus Involvement: Towards a Tailored Approach to Our Patients?

“…Several complement components have been associated with NPSLE: complement C3 with diffuse manifestations and complement C4 with focal NPSLE, although only with the concomitant presence of aPL. 26 Specifically, complement C5a may contribute to BBB dysfunction by inducing the production of pro-inflammatory cytokines, promoting reactive oxygen species formation, and prompting actin reorganization. 20 …”