title: Defunctioning polymorphism in the immunoglobulin G inhibitory receptor (FcγRIIB-T/T232) does not impact on kidney transplant or recipient survival.
abstract: 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.
  
  
  CONCLUSIONS
  This negative result is surprising, given the importance of this receptor in modulating antibody effector function.
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.
authors.forename: Menna R
authors.initials: MR
authors.lastname: Clatworthy
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.
authors.forename: Rebeccah J
authors.initials: RJ
authors.lastname: Matthews
authors.affiliation: Department of Transplantation Immunology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Doehler
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Willcocks
authors.affiliation: Department of Transplantation Immunology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Opelz
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.
authors.forename: Kenneth G C
authors.initials: KGC
authors.lastname: Smith
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044383:Black People; D005260:Female; D005838:Genotype; D006085:Graft Survival; D006801:Humans; D016030:Kidney Transplantation / Q000401:mortality*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017452:Receptors, IgG / Q000235:genetics*; D014184:Transplantation, Homologous; D044465:White People
chemical_list: C499173:FCGR2B protein, human; D017452:Receptors, IgG