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Abstract
Objective Immune complexes (IC) are generated and deposit in the glomeruli in systemic lupus erythematosus (SLE) patients with lupus nephritis (LN), thereby contributing to the pathogenetic process. We here evaluated anti-dsDNA in circulating IC as a biomarker for kidney activity and response to immunosuppressive therapy.
Methods We included 112 SLE patients. Seventy patients had active LN confirmed by a recent kidney biopsy; 42 with class III/IV proliferative LN (PN), and 28 class V membranous LN (MN). Forty-two patients with active non-renal SLE (NR) were comparators (table 1). Twenty-nine patients underwent repeat biopsies evaluated for histological response to immunosuppressive therapy, in MN defined by resorption of immune deposits.1
SLE activity was estimated by SLE Disease Activity Index 2000 (SLEDAI-2K). All biopsies were graded for activity index. IC were purified and dissolved as previously described.2 Four biomarkers were compared: anti-dsDNA in serum and in IC were measured with bead array, and anti-C1q and C1q-binding IC in serum with ELISA.
Results Levels of all four biomarkers distinguished NR from LN patients. Levels of anti-dsDNA in IC discriminated best between MN and PN (P=2*10e-6). At optimal cut-offs, anti-dsDNA in IC and anti-C1q discriminated best between MN and PN (OR 19 for both).
In all SLE patients together, all four biomarkers correlated strongly with SLEDAI. Only levels of anti-dsDNA in IC correlated with SLEDAI among NR (rho:0.38, p=0.02) and MN (rho 0.47 p=0.02) patients, no associations among PN patients were seen.
Among all 70 LN patients, anti-dsDNA in IC correlated most strongly with activity index (rho=0.61, p<0.0001). Among PN patients, anti-C1q in serum and especially anti-dsDNA in IC (rho=0.46, p=0.0027) correlated with renal activity index. No correlations were found among MN patients.
At optimal thresholds, low anti-dsDNA distinguished PN patients with histopathological response to treatment; OR 51 CI 1.7–1526; p=0.007 for serum levels and OR 55 CI 1.9–1623;p=0.004 for IC. Among MN patients, only anti-dsDNA in IC prognosticated histological treatment response: OR 42 CI 2.24–826; p= 0.01.
Conclusions Content of anti-dsDNA in IC is a new biomarker which discriminate MN from PN, mirror renal histological activity, and prognosticate response to treatment in LN.
Acknowledgements The study was supported by ALF funding from the Swedish Research Council, the Stockholm County Council, the Karolinska Institutets Foundation, the King Gustaf V 80th-year foundation, the Swedish Rheumatism Association, and the Swedish Kidney Foundation.
References
Zickert A, et al. Rheumatology 2021;60:3443–50.
Sohrabian A, et al. ARD 2018;77:1345–5
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