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  • Title: Association of autoimmune disease-related gene polymorphisms with chronic graft-versus-host disease.
    Author: Shimada M, Onizuka M, Machida S, Suzuki R, Kojima M, Miyamura K, Kodera Y, Inoko H, Ando K.
    Journal: Br J Haematol; 2007 Nov; 139(3):458-63. PubMed ID: 17868046.
    Abstract:
    Chronic graft-versus-host disease (GVHD) is the most common cause of poor outcomes after haematopoietic stem cell transplantation (HSCT), while the pathophysiology of chronic GVHD remains poorly understood. As both chronic GVHD and autoimmune disease share clinical features, we speculated that autoimmune disease-related genes might be candidate chronic GVHD-related genes. Recent large-scale cohort studies showed that Fc receptor-like 3 gene (FCRL3) single nucleotide polymorphism (SNP) and peptidylarginine deiminases citrullinating enzymes 4 gene (PADI4) haplotype were associated with autoimmune disease. The present study investigated the association between polymorphisms of these two genes and the incidence of chronic GVHD. We analysed 123 cases of Japanese human leucocyte antigen-matched sibling recipients and their donors who underwent HSCT. Although PADI4, which is the rheumatoid arthritis-specific related gene, was not associated with the occurrence of chronic GVHD, the recipient FCRL3-169C/C genotype was significantly less frequent in chronic GVHD patients than in those without chronic GVHD (P = 0.0086). There was no relationship between FCRL3 polymorphism and acute GVHD. As FCRL3 is expressed by B cells and might have an important role in immunoregulation, this significant protective genetic effect raises the question of whether FCRL3 might also be involved in the pathogenesis of chronic GVHD.
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