Anti-Ro52 Autoantibodies Are Related to Chronic Graft-vs.-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation
Anti-Ro52 Autoantibodies Are Related to Chronic Graft-vs.-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation
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抗Ro52自身抗体与异基因造血干细胞移植后慢性移植物抗宿主病有关
DOI：
10.3389/fimmu.2020.01505
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发表时间：
2020-07-28
影响因子：
7.3
通讯作者：
Jin, Hua
中科院分区：
文献类型：
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作者：
Yang, Kaibo;Chen, Yanqiu;Jin, Hua
慢性graft-vs。-宿主病（cGVHD）仍然是异基因造血干细胞移植（alloo - hsct）后发病和死亡的主要原因。先前的研究表明，自身抗体在cGVHD的发展中起重要作用。抗核自身抗体（Anti-nuclear autoantibodies， ANA）是cGVHD患者最常检测到的自身抗体，但抗ro52自身抗体（anti-Ro52）在cGVHD中的作用尚不清楚。在这项研究中，我们分析了84例同种异体造血干细胞移植后患者的自身抗体，包括42例活动性cGVHD患者和42例无cGVHD患者。36例（42.9%）患者发现自身抗体。在这些自身抗体阳性的患者中，28例（77.8%）患者有活动性cGVHD。活动性cGVHD患者中最常见的自身抗体是ANA（50.0%）、抗ro52（28.6%）和抗线粒体2型自身抗体（4.8%）。我们进一步探讨了抗ro52与cGVHD之间的关系。活动期cGVHD患者抗ro52水平高于无活动期cGVHD患者（P< 0.05）。中、重度cGVHD患者抗ro52水平升高明显高于无cGVHD患者（P< 0.05）。分层和多变量logistic回归分析显示，中度/重度cGVHD是影响抗ro52水平的独立危险因素（P< 0.01）。ROC分析证实抗ro52是皮肤cGVHD进展的危险因素。此外，抗ro52水平与B细胞活化因子（BAFF）和IgG1抗体水平高度相关。我们的研究表明抗ro52与cGVHD有关。抗ro52水平升高与BAFF和IgG1抗体水平升高相关，表明抗ro52水平升高与B细胞异常稳态之间存在机制联系。
Chronic graft-vs.-host disease (cGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have shown that autoantibodies play an important role in the development of cGVHD. Anti-nuclear autoantibodies (ANA) is the most frequently detected autoantibodies in patients with cGVHD, but the role of anti-Ro52 autoantibodies (anti-Ro52) in cGVHD remains largely unknown. In this study, we analyzed autoantibodies from 84 patients after allo-HSCT, including 42 with active cGVHD and 42 without cGVHD. Autoantibodies were found in 36 (42.9%) patients. Among these autoantibody-positive patients, 28 (77.8%) patients had active cGVHD. The most frequent autoantibodies in patients with active cGVHD were ANA (50.0%), anti-Ro52 (28.6%) and anti-mitochondrial autoantibodies type 2 (4.8%). We further explored the association between anti-Ro52 and cGVHD. Patients with active cGVHD had higher anti-Ro52 levels than patients without cGVHD (P< 0.05). The increases of anti-Ro52 levels were more significant in patients with moderate/severe cGVHD compared to those of patients without cGVHD (P< 0.05). Stratified and multivariable logistic regression analysis demonstrated that moderate/severe cGVHD was an independent risk factor for the levels of anti-Ro52 (P< 0.01). ROC analysis confirmed anti-Ro52 as a risk factor for progression of skin cGVHD. Moreover, the anti-Ro52 levels were highly correlated with the levels of B cell-activating factor (BAFF) and IgG1 antibodies. Our study demonstrates that anti-Ro52 is associated with cGVHD. The increased levels of anti-Ro52 were associated with higher levels of BAFF and IgG1 antibodies, suggesting a mechanistic link between elevated anti-Ro52 levels and aberrant B cell homeostasis.