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The landscape and diagnostic potential of T and B cell repertoire in Immunoglobulin A Nephropathy

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单位: [1]Department of Nephrology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China [2]BGI-Shenzhen, Shenzhen 518083, China [3]China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China [4]Tianjin Medical Laboratory, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China [5]Department of Nephrology, China-Japan Friendship Hospital, Beijing 100029, China [6]James D. Watson Institute of Genome Sciences, Hangzhou 310058, China [7]Department of Vascular and Endocrine Surgery, Xijing Hospital, Forth Military Medical University, Xi'an 710032, China
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关键词: Immunoglobulin A Nephropathy (IgAN) TCRB repertoire IGH repertoire Non-invasive Biomarkers

摘要:
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.

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出版当年[2018]版:
大类 | 1 区 医学
小类 | 2 区 免疫学
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 免疫学
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出版当年[2017]版:
Q1 IMMUNOLOGY
最新[2024]版:
Q1 IMMUNOLOGY

影响因子: 最新[2024版] 最新五年平均[2021-2025] 出版当年[2017版] 出版当年五年平均[2013-2017] 出版前一年[2016版] 出版后一年[2018版]

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第一作者单位: [1]Department of Nephrology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China
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通讯机构: [2]BGI-Shenzhen, Shenzhen 518083, China [3]China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China [*1]BGI-Shenzhen, Shenzhen 518083, China
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