Relationship between B cell signatures and disease flare in lupus nephritis patients

Abstract

Background: Nephritic flares in patients with lupus nephritis (LN) reduce renal survival but factors contributing to flares remain elusive. Perturbations of B cell subsets have been implicated in the pathogenesis of LN, but the relationship between B cell signatures and relapse has not been investigated. Methods: We compared circulating B cell subsets and signatures (miRNA148a, BACH1, BACH2 and PAX5) in the serum and plasma cells during disease quiescence between Class III/IV±V LN patients who are multiple relapsers (MR, defined as ≥3 relapses within 36 months unrelated to non-compliance) or non-relapsers (NR, defined as no relapse after the presenting episode). Results: 33 patients were included (MR n=20; NR n=13). MR showed lower percentage of circulating naïve and memory B cells (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) and higher plasma cell-to-naïve B cell ratio (1.52±2.19 vs. 0.21±0.33, p=0.011) compared with NR. MR had higher miRNA148a in serum and plasma cells compared with NR [relative expression (RQ) 4.25±2.86 vs. 0.71±0.55 and 3.53±1.56 vs. 1.38±1.17, p=0.002 and 0.128] (Figure 1A). MR also showed lower BACH2 expression in circulating plasma cells [RQ 12.86±3.10 vs. 28.10±11.87, p=0.036)], but no difference in BACH1 and PAX5 (p>0.05 for both) (Figure 1B). Conclusions: Elevated serum and plasma cell miRNA148a might be related to BACH2 downregulation in plasma cells and altered circulating B cell subsets, thereby increasing risk of LN relapse.