期刊
TRANSPLANTATION DIRECT
卷 3, 期 6, 页码 -出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/TXD.0000000000000683
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资金
- Japan Agency for Medical Research and development, AMED [15fk0210016h003]
- Grants-in-Aid for Scientific Research [15K10166] Funding Source: KAKEN
Background. The affinity of IgG Fc receptor (Fc gamma R) for rituximab, an anti-CD20 IgG1, differs based on single-nucleotide polymorphisms (SNPs) in Fc gamma 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 gamma 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.
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