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 (FcγRs) that are expressed on most immune cells, including neutrophils, natural killer cells, and B cells. Most FcγRs are activating and controlled by a single inhibitory receptor, FcγRIIB (CD32B), which also regulates some aspects of B-cell activation and antibody production. FcγRIIB-deficient mice develop severe chronic arteriopathy in a murine cardiac allograft model. A single nucleotide polymorphism in human FcγRIIB (rs1050501) results in profound receptor dysfunction and is associated with systemic lupus erythematosus. The frequency of this FcγRIIB-I/T232 polymorphism also shows significant racial variation. METHODS: In the present study, we sought to determine whether the FcγRIIB-I/T232 single nucleotide polymorphism rs1050501 affected susceptibility to renal allograft rejection or loss and transplant recipient survival. FcγRIIB-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 FcγRIIB-I/T232 genotype. CONCLUSION: This negative result is surprising, given the importance of this receptor in modulating antibody effector function.
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 (FcγRs) that are expressed on most immune cells, including neutrophils, natural killer cells, and B cells. Most FcγRs are activating and controlled by a single inhibitory receptor, FcγRIIB (CD32B), which also regulates some aspects of B-cell activation and antibody production. FcγRIIB-deficient mice develop severe chronic arteriopathy in a murine cardiac allograft model. A single nucleotide polymorphism in human FcγRIIB (rs1050501) results in profound receptor dysfunction and is associated with systemic lupus erythematosus. The frequency of this FcγRIIB-I/T232 polymorphism also shows significant racial variation. METHODS: In the present study, we sought to determine whether the FcγRIIB-I/T232 single nucleotide polymorphism rs1050501 affected susceptibility to renal allograft rejection or loss and transplant recipient survival. FcγRIIB-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 FcγRIIB-I/T232 genotype. CONCLUSION: This negative result is surprising, given the importance of this receptor in modulating antibody effector function.
Authors: T Hirohashi; C M Chase; P Della Pelle; D Sebastian; A Alessandrini; J C Madsen; P S Russell; R B Colvin Journal: Am J Transplant Date: 2011-11-09 Impact factor: 8.086
Authors: K Solez; R B Colvin; L C Racusen; M Haas; B Sis; M Mengel; P F Halloran; W Baldwin; G Banfi; A B Collins; F Cosio; D S R David; C Drachenberg; G Einecke; A B Fogo; I W Gibson; D Glotz; S S Iskandar; E Kraus; E Lerut; R B Mannon; M Mihatsch; B J Nankivell; V Nickeleit; J C Papadimitriou; P Randhawa; H Regele; K Renaudin; I Roberts; D Seron; R N Smith; M Valente Journal: Am J Transplant Date: 2008-02-19 Impact factor: 8.086
Authors: Lisa C Willcocks; Edward J Carr; Heather A Niederer; Tim F Rayner; Thomas N Williams; Wanling Yang; J Anthony G Scott; Britta C Urban; Norbert Peshu; Timothy J Vyse; Yu Lung Lau; Paul A Lyons; Kenneth G C Smith Journal: Proc Natl Acad Sci U S A Date: 2010-04-12 Impact factor: 11.205
Authors: L G Hidalgo; B Sis; J Sellares; P M Campbell; M Mengel; G Einecke; J Chang; P F Halloran Journal: Am J Transplant Date: 2010-08 Impact factor: 8.086
Authors: Chris J Callaghan; Thet Su Win; Reza Motallebzadeh; Thomas M Conlon; Manu Chhabra; Inês Harper; Siva Sivaganesh; Eleanor M Bolton; J Andrew Bradley; Rebecca J Brownlie; Kenneth G C Smith; Gavin J Pettigrew Journal: J Immunol Date: 2012-11-12 Impact factor: 5.422
Authors: Davide Scozzi; Mohsen Ibrahim; Cecilia Menna; Alexander S Krupnick; Daniel Kreisel; Andrew E Gelman Journal: Am J Transplant Date: 2016-07-25 Impact factor: 8.086