Serum Anti-C1q: A Proposed Role in Lupus Nephritis A

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease which can cause multisystem affection. Lupus nephritis (LN) occurs in up to 50% of SLE patients. It is one of the most serious SLE complications associated with significant morbidity and mortality and it is the major predictor of poor prognosis. Novel biomarkers that are able to discriminate lupus renal activity and its severity, predict renal flares, and monitor treatment response and disease progress are clearly necessary. C1qis a collagen-like protein which plays an important role in the clearance of apoptotic bodies and immune complexes through both innate and adaptive immunity. In SLE the accumulation of apoptotic waste stimulates an antigen­driven immune response to produce auto antibodies to C1qwhich were found to be deposited on renal glomeruli of LN patients. Anti-C1q antibodies were found to amplify glomerular injury when they are bound within the glomerulus to C1q that has been already brought to that site by other types of glomerular-reactive autoantibodies. A strong association was detected between the C1q Ab present in serum and the nephritis status in SLE patients. The present systematic review aimed to clarify the accuracy of anti-C1q in diagnosing lupus nephritis. A systematic comprehensive research was electronically conducted and the results was filtered to include primary studies that compared the index test (serum anti-C1q) with the reference standard test whether renal biopsy or clinical and laboratory manifestations that meet ACR criteria (persistent proteinuria>0.5 gm per day or greater than 3+ by dipstick, and/or cellular casts including red blood cells [RBCs], hemoglobin, granular, tubular, or mixed). Twenty two studies were found to meet our inclusion criteria and were included in the review; both data extraction and quality assessment were done to all the included studies. Our systematic review included studies from 1994 to 2013 with a total of (2257) SLE patients of whom (1128) had lupus nephritis, patients were from Europe, Asia, North and South America and Africa, both adults and children were included. All the included studies diagnosed SLE and LN according to the ACR criteria. ELISA was used to measure anti-C1q Ab in serum. Issues regarding the quality assessment of the included studies were concerned with patient selection, index test and time factor between index and reference tests. No applicability concerns was found except the different cut off values used for defining the positive cases of anti-C1q Ab. Diagnostic performance of serum anti-C1q in diagnosing LN was found to be as follows: pooled sensitivity0.592 (0.524–0.656, 95% CI), pooled specificity of 0.738 (0.643–0.815, 95%CI), PLR2.415(1.774–3.287, 95%CI), NLR 0.390 (0.238–0.638, 95% CI)and DOR 5.237 (2.945–9.314, 95% CI). The Chi-square test indicated significantheterogeneity for both of pooled sensitivity andspecificity among the studies (p<0.001).The Cochran-Q valuesof PLR, NLR and DOR were 100.403 (I^2 =83.068%,p < 0.001), 270.208 (I^2 =93.709%, p < 0.001)and 92.92 (I^2 =81.705%, p <0.001) respectively,which also indicated a significant heterogeneityamong the studies.Heterogeneity may originate from some factors like: QUADAS scores, ELISA method, and differences in age, sex or ethnic group.