Association of Fc Receptor-Like Protein Family with Chronic Graft-Versus-Host Disease.

Chronic graft versus host disease (cGVHD) is the most common cause of poor outcomes after hematopoietic stem cell transplantation (HSCT), while the pathophysiology of cGVHD remains poorly understood. We have revealed the association Fc receptor-like protein 3 (FCRL3) gene -169C/T single nucleotide polymorphism (SNP) and developing cGVHD. This gene is a member of Fc receptor-like protein gene family which contains 5 genes and well known as autoimmune disease associated gene. These 5 genes make cluster lesion on chromosome 1q21 to 23. In this current study, to investigate the relationship with another Fc receptor-like protein genes and cGVHD, we used 4 microsatellite polymorphisms belong to FCRL1, 2, 3 and 4 as a linkage analysis genetic marker. And we also investigated FCRL3 -169C/T SNP and another 3 SNPs to explore haplotype and the incidence of cGVHD. We analyzed 123 case of Japanese HLA-matched sibling recipients and their donor who underwent HSCT in the Japanese Red-Cross Nagoya First hospital. Before day 100, 11 patients died from severe acute GVHD, infection, thrombotic microangiopathy or disease relapse. Therefore, we analyzed 112 recipients and 108 donors for the relationship between gene polymorphisms and chronic GVHD. We analyzed microsatellite polymorphisms and SNPs by using TaqMan® assay. Chronic GVHD occurred in 54 out of 112 (48.2%) patients in this cohort. The nearest microsatellite marker from FCRL3 gene had significant different allele frequency between cGVHD and non-GVHD recipient (p=0.0034). There were no association with another microsatellites allele and developing cGVHD. FCRL3 gene haplotypes with frequency >0.01 were -TGGG-, -CACA- and -CGCA-. Chronic GVHD patients significantly less the frequency of -CACA- or -CGCA- allele than non GVHD patients (p=0.0040). There were no significant difference in donor allele frequency and incidence of cGVHD. In conclusion, our studies show FCRL3, which is autoimmune disease associated gene, is also the candidate of cGVHD associated gene and its protective haplotype may prevent from occurring cGVHD but not homologous another FCRL proteins.