Shimada Masako, Onizuka Makoto, Machida Shinichiro, Suzuki Rikio, Kojima Minoru, Miyamura Koichi, Kodera Yoshihisa, Inoko Hidetoshi, Ando Kiyoshi
Department of Haematology and Oncology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Br J Haematol. 2007 Nov;139(3):458-63. doi: 10.1111/j.1365-2141.2007.06797.x. Epub 2007 Sep 14.
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.
慢性移植物抗宿主病（GVHD）是造血干细胞移植（HSCT）后预后不良的最常见原因，而慢性GVHD的病理生理学仍知之甚少。由于慢性GVHD和自身免疫性疾病具有共同的临床特征，我们推测自身免疫性疾病相关基因可能是慢性GVHD相关的候选基因。最近的大规模队列研究表明，Fc受体样3基因（FCRL3）单核苷酸多态性（SNP）和肽基精氨酸脱氨酶瓜氨酸化酶4基因（PADI4）单倍型与自身免疫性疾病有关。本研究调查了这两个基因的多态性与慢性GVHD发病率之间的关联。我们分析了123例接受HSCT的日本人类白细胞抗原匹配的同胞受者及其供者。虽然类风湿关节炎特异性相关基因PADI4与慢性GVHD的发生无关，但慢性GVHD患者中受者FCRL3 - 169C/C基因型的频率明显低于无慢性GVHD的患者（P = 0.0086）。FCRL3多态性与急性GVHD之间没有关系。由于FCRL3由B细胞表达，可能在免疫调节中起重要作用，这种显著的保护性遗传效应引发了一个问题，即FCRL3是否也可能参与慢性GVHD的发病机制。
