AUTHOR=Yap Desmond Y. H. , Yung Susan , Lee Paul , Yam Irene Y. L. , Tam Cheryl , Tang Colin , Chan Tak Mao 

TITLE=B Cell Subsets and Cellular Signatures and Disease Relapse in Lupus Nephritis

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.01732

DOI=10.3389/fimmu.2020.01732

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>Renal relapses adversely affect the long-term outcomes of patients with lupus nephritis (LN), but the pathogenic mechanisms remain elusive. B cell signatures of miR-148a, BACH1, BACH2, and PAX5 expression are relevant to the regulation of B lymphocyte homeostasis. It is unknown whether B cell signature is related to the relapse of LN.</p></sec><sec><title>Methods</title><p>We compared B lymphocyte subsets and cellular signatures during disease quiescence between LN patients with multiple relapses (MR, ≥3 LN relapses within 36 months) and those with no relapse (NR). Also, circulating B lymphocytes were isolated from treatment-naïve patients with active LN and treated with antagomir-148a <italic>in vitro</italic> to investigate the relationship between miR-148a, BACH1, BACH2, and PAX5.</p></sec><sec><title>Results</title><p>MR patients (<italic>n</italic> = 19), when compared with NR (<italic>n</italic> = 14), showed significantly lower percentage of circulating naïve B cells and higher memory B cell-to-naïve B cell ratio. MR patients also showed higher miR-148a levels in sera and B cells, and lower BACH1, BACH2, and PAX5 expression in naïve and memory B cells. Antagomir-148a upregulated BACH1, BACH2, and PAX5 expression, and reduced B cell proliferation upon stimulation, in naïve and memory B cells isolated from treatment-naïve active LN patients.</p></sec><sec><title>Conclusion</title><p>Altered B cell subsets and cellular signatures of miR-148a, BACH1, BACH2, and PAX5 may be associated with distinct patient phenotypes related to the risk of LN relapse.</p></sec>