Autoantibodies against C1q as a Diagnostic Measure of Lupus Nephritis: Systematic Review and Meta-analysis

Abstract

ObjectivesTo evaluate the diagnostic accuracy of C1q autoantibodies in identifying lupus nephritis (LN) in patients with systemic lupus erythematosus (SLE).Data sources and methodsCitation indexes were searched and 370 articles published from 1977 to 2013 were evaluated. The 31 selected studies included in the meta-analysis were cross-sectional in design. Among the 31 studies, 28 compared anti-C1q antibodies in 2769 SLE patients with (n=1442) and without a history of LN (n=1327). Nine studies examined anti-C1q in 517 SLE patients with active (n=249) and inactive LN (n=268). Hierarchical summary receiver operating characteristic (HSROC) random effects models were fitted to pool estimates of accuracy across the studies.ResultsAnti-C1q antibodies discriminated between patients with and without a history of LN, with a median specificity of 73.5%. The HSROC model estimated the corresponding sensitivity to be 70.4%. A hypothetical patient with a 55% prior probability of having a history of LN as opposed to no history (the median prevalence across 28 eligible studies) would have a post-test probability of 76.4% following a positive test result (positive predictive value) or 33.0% following a negative test result (negative predictive value). For discriminating active from inactive LN the median specificity of anti-C1q antibodies was 80%, with a corresponding estimated sensitivity value 75.7% based on the HSROC model. A hypothetical patient with a 56% prior probability of active as opposed to inactive LN (the median prevalence across the 9 eligible studies) would have a post-test probability of 82.8% following a positive test result or 27.9% following a negative test result.ConclusionsAlthough C1q antibodies are associated with lupus nephritis the post-test probabilities are not sufficiently convincing to provide reasonable certainty of the presence or absence of history of disease/active disease.

Pediatric lupus nephritis

“…(25,34) Patients cannot be diagnosed with LN based solely on anti-C1q antibodies. (35) However, when anti-C1q antibodies are associated with high levels of anti-dsDNA antibodies and low C3 and C4 levels in adults with SLE, the chances or renal involvement increase 15-fold. (36)…”

Urinary soluble CD163 is useful as “liquid biopsy” marker in lupus nephritis at both diagnosis and follow-up to predict impending flares

“…Indeed, the strongest genetic factor associated with SLE is noted to be C1q (93 % in homozygous) and an increased genetic risk is also reported with the other components of the classical pathway (C1r, C1s, C4, C2 and C3) [ 37 ]. Genetic defects are rare events and more often SLE patients develop a secondary C1q deficiency due to the presence of anti-C1q Abs with a prevalence ranging from 30 to 70 % and in this case an association with proliferative LN is reported [ 38 ], as well as an association with hypocomplementemic urticarial vasculitis (HUV) with 3 cases encountered in this study [ 39 ]. In patients from our cohort with LN, anti-C1q Ab and anti-dsDNA Ab detection performances were close in predicting LN-A, for suspecting a proliferative class III/IV ± V LN-A, and during follow-up to evaluate the therapeutic response and flares in agreement with previous studies [ 38 , 40 ].…”

“…Genetic defects are rare events and more often SLE patients develop a secondary C1q deficiency due to the presence of anti-C1q Abs with a prevalence ranging from 30 to 70 % and in this case an association with proliferative LN is reported [ 38 ], as well as an association with hypocomplementemic urticarial vasculitis (HUV) with 3 cases encountered in this study [ 39 ]. In patients from our cohort with LN, anti-C1q Ab and anti-dsDNA Ab detection performances were close in predicting LN-A, for suspecting a proliferative class III/IV ± V LN-A, and during follow-up to evaluate the therapeutic response and flares in agreement with previous studies [ 38 , 40 ]. Anti-C1q Abs are expressed in arbitrary units (AU) and the assigned positive cut-off fixed by Werfen's laboratory using healthy controls as reference (20 AU/mL) ought to have good capacity to discriminate LN-A from LN-IR and non-LN patients (69–79 % specificity, respectively, and 60 % sensitivity both).…”

Anti-C1q antibodies: a biomarker for diagnosis and management of lupus nephritis. A narrative review

“…evaluated the diagnostic accuracy of anti-C1q in 2769 patients with SLE and suggested that anti-C1qAb, when used as a stand-alone biomarker, may have variable sensitivity and specificity values across studies. The authors concluded that while anti-C1qAb may have potential as a diagnostic test for monitoring and detecting LN in SLE patients, it would be better to consider them as part of a panel of autoantibodies ( 62 ). Regarding autoantibodies panel, the authors refer to the study of Isenberg et al, in which LN monitoring relies on anti-DNA antibodies ( 60 ).…”