Laboratoire d'Immunologie et d'Histocompatibilité, Centre d'Innovations Biomédicales-Hématologie/Oncologie/Greffe (CIB-HOG), Institut Universitaire d'Hématologie (IUH), and Inserm, UMRS, 940, Hôpital Saint-Louis, Paris, France.
Blood. 2009 Dec 10;114(25):5216-24. doi: 10.1182/blood-2009-04-217430.
The MHC class I-related chain A (MICA) molecules exist as membrane-bound and soluble isoforms and are encoded by a polymorphic gene. Their genetic and phenotype characteristics have been studied in various pathologic settings but not in the context of hematopoietic stem cell transplantation (HSCT). Here, we evaluated whether MICA-related features namely MICA-129 gene polymorphism, serum levels of soluble MICA (sMICA) and anti-MICA antibodies (MICA Abs) before and after HSCT could influence the incidence of chronic graft-versus-host disease (cGVHD) and relapse of their disease in 211 HLA-identical sibling pairs and in a subset of 116 recipients, respectively. Although the MICA-129 val/val genotype and elevated sMICA serum levels after HSCT are independently associated with the incidence of cGVHD (P = .002 and .001) regardless of history of acute GVHD, the presence of MICA Abs before transplantation confers protection against cGVHD (P = .04). There is an inverse relationship between MICA Abs and sMICA, suggesting an antibody-based neutralization of deleterious effects of sMICA. Similarly, these genetic and phenotype characteristics of MICA influence the incidence of relapse. Altogether, these data suggest that the studied MICA genotype and phenotype specificities could be used as relevant biomarkers for cGVHD monitoring.
MHC Ⅰ类相关链 A（MICA）分子存在于膜结合和可溶性同种型，由多态性基因编码。它们的遗传和表型特征已在各种病理情况下进行了研究，但在造血干细胞移植（HSCT）背景下尚未进行研究。在这里，我们评估了 MICA 相关特征，即 MICA-129 基因多态性、HSCT 前后血清可溶性 MICA（sMICA）和抗 MICA 抗体（MICA Abs）水平，是否会影响 211 对 HLA 相同的同胞对和 116 名受者中的亚组的慢性移植物抗宿主病（cGVHD）发生率和疾病复发。尽管 MICA-129 val/val 基因型和 HSCT 后 sMICA 血清水平升高与 cGVHD 的发生独立相关（P =.002 和.001），与急性移植物抗宿主病的病史无关，但移植前存在 MICA Abs 可预防 cGVHD（P =.04）。MICA Abs 与 sMICA 呈负相关，表明抗体可中和 sMICA 的有害作用。同样，MICA 的这些遗传和表型特征也会影响复发的发生。总之，这些数据表明，所研究的 MICA 基因型和表型特异性可用作 cGVHD 监测的相关生物标志物。
