Simultaneous detection of anti-C1q and anti-double stranded DNA autoantibodies in lupus nephritis: predictive value for renal flares

Abstract

Clinical difficulties in predicting systemic lupus erythematosus (SLE) renal flares are still encountered. Biological markers such as autoantibodies (aAbs) may be of major interest for clinicians in the follow-up of SLE patients. The aim of our study was to investigate the clinical utility of one of these biological markers, anti-C1q aAbs, in predicting renal flares of SLE nephritis in comparison with the 'gold standard' anti-double stranded DNA (anti-dsDNA) aAbs. Anti-C1q aAbs and anti-dsDNA aAbs were analysed through a longitudinal retrospective study of 23 SLE patients presenting with one or more renal flares. Anti-C1q and/or anti-dsDNA aAbs were found in 20 (87%) of 23 patients, of whom 16 (69%) displayed both. Thirty-three renal flares occurred during the course of the study, and anti-C1q aAbs and anti-dsDNA aAbs were positive in 25 (76%) and 24 (73%) of these flares respectively. The sensitivity of anti-C1q and/or anti-dsDNA aAbs in predicting renal flares reached 85%. The specificity of anti-C1q aAbs was 84%, of anti-dsDNA aAbs 77% and of both aAbs 97%. Positive and negative predictive values were as follows: 56% and 70% for anti-C1q aAbs, 53% and 72% for anti-dsDNA aAbs. The combination of both aAbs had the highest positive predictive value (69%), whereas absence of both aAbs was associated with the highest negative predictive value (74%). In conclusion, our results confirm that anti-C1q aAbs are present in a significant percentage of SLE patients with active renal involvement, suggesting that these aAbs could be a useful additional marker. The presence of anti-C1q and anti-dsDNA aAbs was associated with a high risk of renal flare, whereas the absence of both aAbs excluded such an event. These data confirm that systematic detection of anti-C1q and anti-dsDNA aAbs is of interest for the follow-up in SLE patients with renal involvement.

Elevated Subclinical Double-Stranded DNA Antibodies and Future Proliferative Lupus Nephritis

“…The study cohort had an average SLEDAI score, average NIH Activity and Chronicity indices, and a prevalence of elevated anti-dsDNA antibody at diagnosis that were similar to those noted in previous reports (11,17,20,21). Anti-dsDNA antibody was elevated months to years before 78% of patients with PLN but in only one control with SLE without LN.…”

“…Anti-dsDNA antibody was elevated months to years before 78% of patients with PLN but in only one control with SLE without LN. A similar percentage of known patients with SLE manifest elevated anti-dsDNA antibody before LN flare (21)(22)(23)(24). In addition, the one control who had anti-dsDNA antibody-positive SLE without LN developed a positive titer less than a year before diagnosis and could conceivably develop PLN in the future.…”

“…Defining the prediagnostic trajectory and temporal relationship of all LN-associated autoantibodies may establish a more comprehensive predictive autoantibody profile for PLN risk. Data already suggest that dual-positive anti-dsDNA antibody and anti-C1q antibody are more sensitive and specific for LN flare and portend a worse renal prognosis than either autoantibody individually (20,21). Even a comprehensive autoantibody profile will probably not predict development of PLN in all cases.…”

Biomarkers in systemic lupus erythematosus: challenges and prospects for the future

“…For example, Moroni and colleagues followed 228 patients with lupus nephritis for 6 years and found that elevation of anti-C1q levels predicted renal flares in patients with proliferative lupus nephritis, with a sensitivity of 81% and a specificity of 71% ]. Some investigators suggested that the prediction value would be further enhanced when both anti-C1q and anti-dsDNA were measured [Matrat et al 2011]. Moreover, it has been reported that levels of anti-C1q antibodies decreased after successful treatment of lupus nephritis [Trendelenburg et al 2006].…”

C-reactive protein, immunoglobulin G and complement co-localize in renal immune deposits of proliferative lupus nephritis

“…Although changing levels of ANA directed against double-stranded (ds) DNA has been found useful to monitor lupus nephritis (LN) disease activity, antibodies to complement protein 1q (anti-C1q) have been reported to be somewhat more specifically associated with renal disease [2,3]. Matrat et al recommended that anti-dsDNA and anti-C1q antibodies should be used in combination to monitor LN disease activity [4]. In European SLE patients, renal involvement occurs over time in approximately one third of the cases, and LN remains a major cause of morbidity and mortality worldwide [5].…”