The Landscape and Prognosis Potential of the T-Cell Repertoire in Membranous Nephropathy. Zhang Yu,Jin Yabin,Guan Zhanwen,Li Huishi,Su Zuhui,Xie Chao,Chen Xiangping,Liu Xiaofen,Pan Yingming,Ye Peiyi,Zhang Lifang,Kong Yaozhong,Luo Wei Frontiers in immunology Membranous nephropathy (MN), a common pathological type of adult nephrotic syndrome, is an antibody-mediated kidney disease. It is widely accepted now that MN is an immune-related disease that involves the whole immune system. In this study, we analyzed the T-cell receptor beta chain (TCRβ) repertoire of the circulating T lymphocytes of MN patients and healthy controls using high-throughput sequencing. We compared multiple aspects of the TCRβ repertoire, including diversity and the Vβ and Jβ genes between MN patients and healthy controls, and we found that the diversities within the VJ cassette combination in the peripheral blood of MN patients were lower than in the healthy controls. We also found the TCRβ repertoire similarity between pre- and post-therapy could reflect the clinical outcome, and two Vβ genes in pre-therapy had the potential to predict the therapeutic effect. These findings indicated the potential of the TCRβ repertoire as non-invasive biomarkers for the prognosis prediction of MN. The characteristics of circulating T-lymphocyte repertoires shed light on MN detection, treatment, and surveillance. 10.3389/fimmu.2020.00387

Assessment of variation in B-cell receptor heavy chain repertoire in patients with end-stage renal disease by high-throughput sequencing. Wang Lei,Dai Yong,Liu Song,Lai Liusheng,Yan Qiang,Chen Huaizhou,Zhang Jiaxing,Sui Weiguo Renal failure End-stage renal disease (ESRD), characterized by progressive loss of rental function during the disease course, has been reported to be correlated with immune dysregulation. To date, a majority of previous studies on immune response to ESRD have been focused on the T-cell response. This prospective study was to assess the B-cell receptor (BCR) heavy chain repertoire in ESRD patients. A total of 10 ESRD patients and six healthy controls were prospectively enrolled in this study. BCR immunoglobulin heavy chain (IGH) repertoire in the peripheral blood from ESRD patients and healthy individuals were analyzed by means of next generation sequencing (NGS) in combination with multiplex PCR, Illumina sequencing, and the international ImMunoGeneTics database (IMGT). Abnormal BCR complementary-determining region 3 (CDR3) sequences were identified in relation to ESRD. We also found that the degree of the B-cell clonal expansion in the ESRD group was significantly greater than that in the control group ( < .05), whereas the distributions of BCR CDR3, V, D, J, and V-J gene segments were comparable between the ESRD and control groups. T-test for analysis of the distribution ratio of the V, D, J, and V-J genes revealed five up-regulated genes and nine down-regulated genes associated with ESRD, and there were significant differences between the ESRD and control groups ( < .05). We have provided a successful approach to analyzing peripheral B-cell repertoire in ESRD patients, and the results suggest a direct correlation between the BCR repertoire and ESRD. The ESRD-specific BCR CDR3 sequences may hold promise for potentially therapeutic benefit. 10.1080/0886022X.2018.1487862

The landscape and diagnostic potential of T and B cell repertoire in Immunoglobulin A Nephropathy. Huang Chen,Li Xuemei,Wu Jinghua,Zhang Wei,Sun Shiren,Lin Liya,Wang Xie,Li Hongmei,Wu Xiaolei,Zhang Peng,Xu Guoshuang,Wang Hanmin,Liu Hongbao,Liu Yuzhen,Chen Dapeng,Zhuo Li,Li Wenge,Yang Huanming,Wang Jian,Wang Ling,Liu Xiao Journal of autoimmunity Immunoglobulin A Nephropathy (IgAN) is the most common glomerulonephritis worldwide. The pathologic hallmark of IgAN is immune complex deposited in glomerular mesangium, which induces inflammation and affects the kidney's normal functions. The exact pathogenesis of IgAN, however, remains obscure. Further, in current clinical practice, the diagnosis relies on needle biopsy of renal tissue. Therefore, a non-invasive method for diagnosis and prognosis surveillance of the disease is highly desirable. To this end, we investigated the T cell receptor beta chain (TCRB) and immunoglobulin heavy chain (IGH) repertoire in circulating lymphocytes and compared them with kidney infiltrating lymphocytes using immune repertoire high throughput sequencing. We found that some features of TCRB and IGH in renal tissues were remarkably different from that in the blood, including decreased repertoire diversity, increased IgA and IgG frequency, and more antigen-experienced B cells. The complementarity-determining region 3 (CDR3) length of circulating TCRB and IGH in IgAN patients was significantly shorter than that in healthy controls, which is the result of both VDJ rearrangement and clonal selection. The IgA1 frequency in the blood of IgAN patients is significantly higher than that in other Nephropathy (NIgAN) patients and healthy control. Importantly we identified a set of TCRB and IGH clones, which can be used to distinguish IgAN from NIgAN and healthy controls with high accuracy. These results indicated that the TCRB and IGH repertoire can potentially serve as non-invasive biomarkers for the diagnosis of IgAN. The characteristics of the kidney infiltrating and circulating lymphocytes repertoires shed light on IgAN detection, treatment and surveillance. 10.1016/j.jaut.2018.10.018