Genetic variation in recipient B-cell activating factor modulates phenotype of GVHD.

Clark WB, Brown-Gentry KD, Crawford DC, Fan KH, Snavely J, Chen H, Savani BN, Kassim A, Greer JP, Schuening FG, Engelhardt BG, Jagasia MH
Blood. 2011 118 (4): 1140-4

PMID: 21628416 · DOI:10.1182/blood-2010-09-310011

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.

MeSH Terms (15)

Adolescent Adult Aged B-Cell Activating Factor Female Genotype Graft vs Host Disease Hematopoietic Stem Cell Transplantation Humans Male Middle Aged Phenotype Polymorphism, Single Nucleotide Transplantation, Homologous Young Adult

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