Genetic variation in recipient B-cell activating factor modulates phenotype of GVHD
Genetic variation in recipient B-cell activating factor modulates phenotype of GVHD
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DOI：
10.1182/blood-2010-09-310011
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发表时间：
2011-07-28
期刊：
影响因子：
20.3
通讯作者：
Jagasia, Madan H.
中科院分区：
文献类型：
--
作者：
Clark, William B.;Brown-Gentry, Kristin D.;Jagasia, Madan H.
B细胞激活因子(BAFF)单核苷酸多态性(SNPs)与自身免疫性疾病相关。由于经典重叠慢性移植物抗宿主病(CGVHD)患者具有自身免疫性疾病的特点，我们研究了异基因干细胞移植后受体和/或供者BAFF单核苷酸多态与GVHD表型的关系。对164对受者/供者对BAFF基因的20个tag SNPs进行了基因分型。急性移植物抗宿主病(AGVHD)23例，重叠移植物抗宿主病(GVHD)29例，典型移植物抗宿主病(CGVHD)72例。在SNP分析中，在20个标签SNP中，有9个标签SNP在经典/重叠cGVHD与aGVHD亚型/无GVHD之间有显著差异。在多变量分析中，4个受体BAFF SNPs(rs16972217[优势比=2.72，P=0.004]、rs7993590[优势比=2.35，P=.011]、rs12428930[优势比2.53，P=.008]和rs2893321[优势比=2.48，P=.009])是移植物抗宿主病亚型的独立预测因素。本研究表明，BAFF的遗传变异对异基因干细胞移植后的GVHD表型有调节作用。(血。2011；118(4)：1140-1144)
B-cell activating factor (BAFF) single nucleotide polymorphisms (SNPs) are associated with autoimmune diseases. Because patients with classic and overlap chronic GVHD (cGVHD) have features of autoimmune diseases, we studied the association of recipient and/or donor BAFF SNPs with the phenotype of GVHD after allogeneic stem cell transplantation. Twenty tagSNPs of the BAFF gene were genotyped in 164 recipient/donor pairs. GVHD after day 100 occurred in 124 (76%) patients: acute GVHD (aGVHD) subtypes (n = 23), overlap GVHD (n = 29), and classic cGVHD (n = 72). In SNP analyses, 9 of the 20 tag SNPs were significant comparing classic/overlap cGVHD versus aGVHD subtypes/no GVHD. In multivariate analyses, 4 recipient BAFF SNPs (rs16972217 [odds ratio = 2.72, P = .004], rs7993590 [odds ratio = 2.35, P = .011], rs12428930 [odds ratio2.53, P = .008], and rs2893321 [odds ratio = 2.48, P = .009]) were independent predictors of GVHD subtypes, adjusted for conventional predictors of cGVHD. This study shows that genetic variation of BAFF modulates GVHD phenotype after allogeneic stem cell transplantation. (Blood. 2011; 118(4):1140-1144)