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Abstract
Objective To determine whether immune deposit (ID) resorption in per-protocol repeat kidney biopsies in patients with proliferative lupus nephritis (PLN) correlates with histological response and/or predicts renal relapse.
Methods Twenty-eight patients with PLN (class III/IV±V) who underwent a per-protocol repeat kidney biopsy after a median time of 18.4 [11.5–29.2] months (i.e., performed irrespectively of the clinical response) were included in this retrospective study. We assessed IgG, IgA, IgM, C3, and C1q IDs by direct immunofluorescence using a semi-quantitative scale (0–3) at three sites (mesangial, subendothelial, subepithelial). We computed a total Ig score (0–27; 3 Ig subclasses x 3 sites x score 0–3) and a total C score (0–18; 2 C molecules x 3 sites x score 0–3). Activity index (AI) was measured according to the NIH scoring system. Renal relapse was defined as the reappearance of a urinary protein/creatinine ratio (uPCR) >1 g/g, following a clinical response with uPCR <0.5 g/g, prompting a biopsy and/or therapy modification.
Results Total Ig and C scores substantially decreased from the diagnostic (median [IQR]: 7.25 [5.00–10.00] and 6.00 [5.00–9.25], respectively) to the repeat biopsy (3.50 [0.75–6.00] and 2.50 [0.00–4.62]; p<0.001), with significant reductions for IgG, IgA, C3, and C1q (table 1). Significant resorption was observed in the mesangial (from 3.25 [0.00–5.25] to 0.00 [0.00–2.00]; p=0.005 for Ig and from 4.75 [3.00–6.00] to 0.00 [0.00–2.00]; p<0.001 for C) and subendothelial (from 0.00 [0.00–4.62] to 0.00 [0.00–0.00]; p=0.006 for Ig and from 0.00 [0.00–4.25] to 0.00 [0.00–0.00]; p=0.027 for C) sites, but not in the subepithelial site. There was no significant correlation between the decrease in AI and total Ig and C. Of seven relapsing patients, none had achieved a decrease of ≥75% in the total Ig ID score (table 2).
Conclusions Resorption of mesangial and subendothelial Ig and C IDs is attainable upon treatment and does not necessarily correlate with AI score reductions. Assessment of ID scores could serve as a valuable tool for determining the early treatment response and informing subsequent treatment adjustments.
Conflicts of interest IP has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia, Bristol Myers Squibb, Elli Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Otsuka, and Roche. The other authors declare that they have no conflicts of interest related to this work. The funders had no role in the design of the study, the analyses or interpretation of data, or the writing of the manuscript.
Immune deposits at baseline and per-protocol repeat biopsies. All values represent the sum scores on a semi-quantitative scale, ranging from 0 to 3 (0 = absent, 1 = minimal, 2 = moderate, 3 = extensive), for the evaluation of immune deposits (IgA, IgG, IgM, C3, and C1q) at three distinct sites: mesangial, subendothelial, and subepithelial. IQR, Interquartile range; SD, Standard deviation
Contingency table for renal relapses versus total Ig decrease by ≥75% from baseline
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