Defunctioning Polymorphism in the Immunoglobulin G Inhibitory Receptor (FcγRIIB-T/T232) Does not Impact on Kidney Transplant or Recipient Survival

被引:14
作者
Clatworthy, Menna R. [1 ]
Matthews, Rebeccah J. [1 ]
Doehler, Bernd [2 ]
Willcocks, Lisa C. [1 ]
Opelz, Gerhard [2 ]
Smith, Kenneth G. C. [1 ]
机构
[1] Univ Cambridge, Dept Med, Sch Clin Med, Cambridge CB2 0QH, England
[2] Heidelberg Univ, Dept Transplantat Immunol, Heidelberg, Germany
基金
英国惠康基金;
关键词
Antibodies; IgG; Fc gamma receptors; Fc gamma RIIB; CD32B; Renal transplantation; Chronic antibody-mediated rejection; FC-GAMMA-RIIB; SYSTEMIC-LUPUS-ERYTHEMATOSUS; ANTIBODY-MEDIATED REJECTION; NK CELLS; DEFICIENT MICE; LIPID RAFTS; IN-VIVO; SUSCEPTIBILITY; INFECTION; PATHOLOGY;
D O I
10.1097/TP.0000000000000287
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. There is an increasing appreciation of the deleterious effects of antibody and B cells on acute and chronic transplant outcomes. Many effector functions of antibody are mediated by a family of receptors (Fc gamma Rs) that are expressed on most immune cells, including neutrophils, natural killer cells, and B cells. Most Fc gamma Rs are activating and controlled by a single inhibitory receptor, Fc gamma RIIB (CD32B), which also regulates some aspects of B-cell activation and antibody production. Fc gamma RIIB-deficient mice develop severe chronic arteriopathy in a murine cardiac allograft model. A single nucleotide polymorphism in human Fc gamma RIIB (rs1050501) results in profound receptor dysfunction and is associated with systemic lupus erythematosus. The frequency of this Fc gamma RIIB-I/T232 polymorphism also shows significant racial variation. Methods. In the present study, we sought to determine whether the Fc gamma RIIB-I/T232 single nucleotide polymorphism rs1050501 affected susceptibility to renal allograft rejection or loss and transplant recipient survival. Fc gamma RIIB-I/T232 genotype was determined in 2,851 Caucasian and 570 Afro-Caribbean renal transplant recipients, and in 236 transplant recipients with a primary diagnosis of systemic lupus erythematosus, all of whom were enrolled into the Collaborative Transplant Study. Results. We found no significant difference in pretransplant panel reactive antibodies, acute rejection at 1-year nor in 10-year transplant or patient survival in individuals with differing Fc gamma RIIB-I/T232 genotype. Conclusion. This negative result is surprising, given the importance of this receptor in modulating antibody effector function.
引用
收藏
页码:285 / 291
页数:7
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