Abstract
Membranous nephropathy (MN), an autoimmune glomerular disease, is one of the most common causes of nephrotic syndrome in adults. In current clinical practice, the diagnosis is dependent on renal tissue biopsy. A new method for diagnosis and prognosis surveillance is urgently needed for patients. In the present study, we recruited 66 MN patients before any treatment and 11 healthy control (HC) and analyzed multiple aspects of the immunoglobulin heavy chain (IGH) repertoire of these samples using high-throughput sequencing. We found that the abnormalities of CDR-H3 length, hydrophobicity, somatic hypermutation (SHM), and germ line index were progressively more prominent in patients with MN, and the frequency of IGHV3-66 in post-therapy patients was significantly lower than that in pre-therapy patients. Moreover, we found that the IGHV3-38 gene was significantly related to PLA2R, which is the most commonly used biomarker. The most important discovery was that several IGHV, IGHD transcripts, CDR-H3 length, and SHM rate in pre-therapy patients had the potential to predict the therapeutic effect. Our study further demonstrated that the IGH repertoire could be a potential biomarker for prognosis prediction of MN. The landscape of circulating B-lymphocyte repertoires sheds new light on the detection and surveillance of MN.
Highlights
Membranous nephropathy (MN) is the most common cause of idiopathic nephrotic syndrome in non-diabetic adults worldwide, representing between 20 and 37% in most series and rising to as high as 40% in adults over 60 [1, 2]
We found that six IGHC, one IGHD, and 24 IGHV genes were significantly different between MN patients and healthy control (HC)
We found that the frequency of IGHM, IGHD, and IGHE in Peripheral blood mononuclear cells (PBMCs) was significantly higher than those in MN patients
Summary
Membranous nephropathy (MN) is the most common cause of idiopathic nephrotic syndrome in non-diabetic adults worldwide, representing between 20 and 37% in most series and rising to as high as 40% in adults over 60 [1, 2]. It is widely accepted that MN is an autoimmune reaction to inherent podocyte antigens. The antigenic targets of these antibodies are most often PLA2R and THSD7A [4, 5]. Renal biopsy is an invasive procedure, and it could increase the potential for kidney infection. During pre- and post-treatments, repeating kidney biopsies to monitor disease progression is inconvenient. Patients badly need a dependable and minimally invasive biomarker to diagnose MN, assess disease stage, and evaluate treatment effect.
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