Circulating lymphocyte subsets and disease relapse in lupus nephritis

Abstract

Background: Repeated renal flares herald adverse long-term outcomes in lupus nephritis (LN) but the mechanisms pertaining to relapse remain poorly understood. Lymphocyte subset abnormalities have been implicated in the pathogenesis of LN, but their relationship to LN relapse has not been investigated. Methods: We compared circulating lymphocyte subsets and serum cytokine profiles during disease quiescence between patients with Class III/IV±V LN who are multiple relapsers (MR, defined as >=3 relapses within 36 months unrelated to non-compliance) and non-relapsers (NR, defined as no relapse after the presenting episode). Results: 37 patients were included (MR n=24; NR n=13). MR showed lower percentage of circulating naïve B and memory B cells compared with NR (0.48%, IQR 0.24%-3.15% vs. 4.52%, IQR 3.18%-8.25%; and 0.51%, IQR 0.26%-0.67% vs. 0.96%, IQR 0.86%-1.91%; p=0.014 and 0.014 respectively), while the two groups had similar percentage of circulating plasma cells (0.61%, IQR 0.31%-0.77% vs. 0.38%, IQR 0.33%-0.79%, p=0.883). The plasma cell-to-naïve B cell ratio was higher in MR (1.52±2.19 vs.0.21±0.33, p=0.011). MR and NR did not differ in the percentage of circulating Th1, Th2, Th17 and Treg cells, nor the level of IL-6, IL-18, IL-21, IL-23, BAFF, IFN-α, IFN-γ or IP-10 (p>0.05 for all). Conclusions: Our results suggest that altered prevalence of distinct circulating B cell subsets might be related to the pathogenesis of disease flares in LN patients.