Effect of Fc-? Receptor Polymorphism on Rituximab-Mediated B Cell Depletion in ABO-Incompatible Adult Living Donor Liver Transplantation.

ABSTRACT: BACKGROUND:The affinity of IgG Fc receptor (Fc?R) for rituximab, an anti-CD20 IgG1, differs based on single-nucleotide polymorphisms (SNPs) in Fc?Rs. This study aimed to explore the effect of such SNPs on clinical response to rituximab and outcomes in patients of ABO-incompatible (ABOi) living donor liver transplantation (LDLT). METHODS:SNPs of FCGR2A[131H/R] and FCGR3A[158F/V], alleles encoding Fc?R, were identified in 20 patients desensitized with rituximab before ABOi LDLT. The effect of these SNPs on B cell elimination and outcomes was analyzed in the patients. RESULTS:The isoform encoded by FCGR2A[131H/H] had a higher affinity for IgG1, and accordingly, the effects of rituximab on B cells were more profound in individuals with FCGR2A[131H/H] than in individuals with FCGR2A[131H/R or R/R]. Specifically, the time to B-cell reappearance in the peripheral blood was significantly delayed, and total serum IgM levels were significantly lower early after LDLT in individuals with FCGR2A[131H/H], even though these SNPs did not significantly affect the reduction of antiblood group A/B antibodies. The incidence of blood stream infection was also significantly higher in individuals with FCGR2A[131H/H], and this SNP was associated with poor prognosis. Despite no significant effect of FCGR3A[158F/V] on survival after ABOi liver grafts, the incidence of infection was significantly higher in individuals with FCGR3A[158F/V or F/F] than in individuals with FCGR3A[158V/V]. CONCLUSIONS:Our findings indicate FCGR SNPs influence the effect of rituximab on B-cell depletion and are possibly predisposing factors for infectious complications after ABOi LDLT. This study will be a good foundation for further studies on larger cohorts.

SUBMITTER: Sakai H 

PROVIDER: S-EPMC5464783 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature