Journal
TRANSPLANTATION
Volume 98, Issue 3, Pages 285-291Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/TP.0000000000000287
Keywords
Antibodies; IgG; Fc gamma receptors; Fc gamma RIIB; CD32B; Renal transplantation; Chronic antibody-mediated rejection
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Funding
- Wellcome Trust [081020, 083650/Z/07/Z] Funding Source: Medline
- Wellcome Trust [083650/Z/07/Z] Funding Source: Wellcome Trust
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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.
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