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

BACKGROUND: The affinity of IgG Fc receptor (FcγR) for rituximab, an anti-CD20 IgG1, differs based on single-nucleotide polymorphisms (SNPs) in FcγRs. This study aimed to explore the effect of such SNPs on clinical response to rituximab and outcomes in patients of ABO-incompatible (ABOi) living dono...

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Detalles Bibliográficos
Autores principales: Sakai, Hiroshi, Tanaka, Yuka, Tazawa, Hirofumi, Shimizu, Seiichi, Verma, Sapana, Ohira, Masahiro, Tahara, Hiroyuki, Ide, Kentaro, Ishiyama, Kohei, Kobayashi, Tsuyoshi, Onoe, Takashi, Ohdan, Hideki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464783/
https://www.ncbi.nlm.nih.gov/pubmed/28620648
http://dx.doi.org/10.1097/TXD.0000000000000683
Descripción
Sumario:BACKGROUND: The affinity of IgG Fc receptor (FcγR) for rituximab, an anti-CD20 IgG1, differs based on single-nucleotide polymorphisms (SNPs) in FcγRs. 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 FcγR, 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.