Expansion of the immature B lymphocyte compartment in Graves' disease
Expansion of the immature B lymphocyte compartment in Graves' disease
复制标题
格雷夫斯病中未成熟 B 淋巴细胞区室的扩张
DOI：
10.1093/ejendo/lvad107
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发表时间：
2023
影响因子：
5.8
通讯作者：
Lane L
中科院分区：
文献类型：
--
作者：
Lane L
Graves病（GD）中驱动自身免疫的具体机制在很大程度上仍然未知。κ缺失重组切除环（KREC）是骨髓中B细胞成熟期间产生的环状DNA分子，其提供B细胞产生和增殖的量度。我们的目的是调查之间的关联KREC和B细胞亚群，甲状腺状态和临床结果在GD patients. MethodsKappa删除重组切除环采用三重插入质粒对照在132例GD患者和140名健康对照定量实时PCR测定。此外，根据1年时的临床结局，分析了GD患者停用抗甲状腺药物（ATD）和6-10周后的KREC。对分离的CD 19 +B细胞进行流式细胞术，以定量7 B淋巴细胞亚群在65 GD patients.ResultsCirculating KREC是较高的GD vs. control（P= 1.5 × 10−9），并表现出正相关性甲状腺激素和自身抗体（游离甲状腺素：P= 2.14 × 10−5，rho = 0.30;游离三碘甲状腺原氨酸：P= 1.99 × 10−7，rho = 0.37;促甲状腺激素受体自身抗体：P= 1.36 × 10−5，rho = 0.23）。GD患者ATD停药后6-10周KREC升高与1年时甲亢复发相关（P= 0.04）。KREC与CD 19 +B细胞总数呈正相关（P= 3.2 × 10−7）。结论本研究报告了KREC与GD之间的强相关性，强调了B细胞在GD发病机制中的重要性以及甲状腺状态对B细胞活性的影响。这些发现表明KREC作为GD疾病活动和结果的标志物的潜在作用。
ObjectiveThe specific mechanisms driving autoimmunity in Graves' disease (GD) remain largely unknown. Kappa-deleting recombination excision circles (KRECs) are circular DNA molecules generated during B cell maturation in the bone marrow which provide a measure of B cell production and proliferation. We aimed to investigate the association between KRECs and B cell subpopulations, with thyroid status and clinical outcome in GD patients.MethodsKappa-deleting recombination excision circles were measured by quantitative real-time PCR using a triple-insert plasmid control in 132 GD patients and 140 healthy controls. In addition, KRECs in GD patients on withdrawal of antithyroid drug (ATD) and 6-10 weeks later were analysed according to a clinical outcome at 1 year. Flow cytometry was performed on isolated CD19+B cells to quantitate 7 B lymphocyte subpopulations in 65 GD patients.ResultsCirculating KRECs were higher in GD vs. controls (P= 1.5 × 10−9) and demonstrated a positive correlation to thyroid hormones and autoantibodies (free thyroxine:P= 2.14 × 10−5, rho = .30; free triiodothyronine:P= 1.99 × 10−7, rho = .37; thyroid stimulating hormone receptor autoantibodies:P= 1.36 × 10−5, rho = .23). Higher KRECs in GD patients 6-10 weeks after ATD withdrawal were associated with relapse of hyperthyroidism at 1 year (P= .04). The KRECs were positively correlated to the total CD19+B cell count (P= 3.2 × 10−7).ConclusionsThis study reports a robust association between KRECs and GD, highlighting the importance of B cells in the pathogenesis of GD and the influence of thyroid status on B cell activity. The findings indicate a potential role for KRECs as a marker of disease activity and outcome in GD.