title: Genetic variation in recipient B-cell activating factor modulates phenotype of GVHD.
abstract: 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.
authors.affiliation: Hematology and Stem Cell Transplantation Section, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: William B
authors.initials: WB
authors.lastname: Clark
authors.forename: Kristin D
authors.initials: KD
authors.lastname: Brown-Gentry
authors.forename: Dana C
authors.initials: DC
authors.lastname: Crawford
authors.forename: Kang-Hsien
authors.initials: KH
authors.lastname: Fan
authors.forename: Jennifer
authors.initials: J
authors.lastname: Snavely
authors.forename: Heidi
authors.initials: H
authors.lastname: Chen
authors.forename: Bipin N
authors.initials: BN
authors.lastname: Savani
authors.forename: Adetola
authors.initials: A
authors.lastname: Kassim
authors.forename: John P
authors.initials: JP
authors.lastname: Greer
authors.forename: Friedrich G
authors.initials: FG
authors.lastname: Schuening
authors.forename: Brian G
authors.initials: BG
authors.lastname: Engelhardt
authors.forename: Madan H
authors.initials: MH
authors.lastname: Jagasia
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D053264:B-Cell Activating Factor / Q000235:genetics*; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease / Q000235:genetics* / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D053264:B-Cell Activating Factor; C505719:TNFSF13B protein, human