Polymorphism in the Interleukin-7 Receptor-alpha and Outcome after Allogeneic Hematopoietic Cell Transplantation with Matched Unrelated Donor

被引:18
|
作者
Shamim, Z. [1 ,2 ]
Spellman, S. [3 ]
Haagenson, M. [3 ]
Wang, T. [4 ]
Lee, S. J. [5 ]
Ryder, L. P. [6 ]
Muller, K. [7 ,8 ]
机构
[1] Rigshosp, Univ Hosp, Dept Clin Immunol, Sect 7631, DK-2100 Copenhagen, Denmark
[2] Rigshosp, Univ Hosp, Inst Inflammat Res, Sect 7541, DK-2100 Copenhagen, Denmark
[3] CIBMTR, Dept Immunobiol Res, Minneapolis, MN USA
[4] Med Coll Wisconsin, Milwaukee, WI 53226 USA
[5] Fred Hutchinson Canc Res Ctr, Clin Transplant Res, Seattle, WA 98104 USA
[6] Rigshosp, Univ Hosp, Dept Clin Immunol, Sect 7631, DK-2100 Copenhagen, Denmark
[7] Rigshosp, Univ Hosp, Dept Rheumatol, Paediat Clin 2 4064, DK-2100 Copenhagen, Denmark
[8] Rigshosp, Univ Hosp, Inst Inflammat Res 7541, DK-2100 Copenhagen, Denmark
关键词
SINGLE NUCLEOTIDE POLYMORPHISMS; MULTIPLE-SCLEROSIS; T-CELLS; MARROW-TRANSPLANTATION; ALLERGIC INFLAMMATION; GENETIC POLYMORPHISMS; HOST-DISEASE; IL-7; GRAFT; RECONSTITUTION;
D O I
10.1111/sji.12077
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Interleukin-7 (IL-7) is essential for T cell development in the thymus and maintenance of peripheral T cells. The -chain of the IL-7R is polymorphic with the existence of SNPs that give rise to non-synonymous amino acid substitutions. We previously found an association between donor genotypes and increased treatment-related mortality (TRM) (rs1494555G) and acute graft versus host disease (aGvHD) (rs1494555G and rs1494558T) after hematopoietic cell transplantation (HCT). Some studies have confirmed an association between rs6897932C and multiple sclerosis. In this study, we evaluated the prognostic significance of IL-7R SNP genotypes in 590-recipient/donor pairs that received HLA-matched unrelated donor HCT for haematological malignancies. Consistent with the primary studies, the rs1494555GG and rs1494558TT genotypes of the donor were associated with aGvHD and chronic GvHD in the univariate analysis. The Tallele of rs6897932 was suggestive of an association with increased frequency of relapse by univariate analysis (P=0.017) and multivariate analysis (P=0.015). In conclusion, this study provides further evidence of a role of the IL-7 pathway and IL-7R SNPs in HCT.
引用
收藏
页码:214 / 220
页数:7
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