Service of Immunology, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
Immunol Lett. 2011 Dec 30;141(1):140-4. doi: 10.1016/j.imlet.2011.09.005. Epub 2011 Sep 24.
B cell responses to minor histocompatibility antigens (mHags) have not been extensively studied after allogeneic hematopoietic stem cell transplantation (HSCT). Glutathione S-transferase T1 (GSTT1) is a drug metabolizing enzyme encoded by a single gene that is highly expressed in liver and kidney. Anti-GSTT1 antibodies have been described in the context of antibody-mediated rejection in kidney and liver transplantation, due to a mismatch between donor and recipient. The aim of the present study was to investigate the specific immune response against GSTT1 in HSCT with production of antibodies and their influence in the development of hepatic graft-versus-host-disease (GVHD). Forty patients and their respective donors were included in the study. The median follow-up time was 35.6 months (range 0.6-76 months) and a total of 349 serum samples were tested for the presence of anti-GSTT1 antibodies by ELISA test. Statistical analysis was performed by defining the GSTT1 null donor/positive recipient as mismatch compared with the other three genetic combinations regarded as GSTT1-matched. Antibodies were found in three patients within the group of null donor/positive recipient and one within the null/null group. Development of liver GVHD, particularly its acute form, was highly associated with the GSTT1-mismatch (P=0.0178) and with the presence of post-transplant anti-GSTT1 antibodies (P=0.0076). We conclude that GSTT1 could be considered as a new mHag in hepatic GVHD. The fact that three donors were parous females and the rapid production of antibodies after HSCT suggests the existence in the graft of memory B-cells specific for the GSTT1 antigen.
B 细胞对次要组织相容性抗原（mHags）的反应在异基因造血干细胞移植（HSCT）后尚未得到广泛研究。谷胱甘肽 S-转移酶 T1（GSTT1）是一种由单个基因编码的药物代谢酶，在肝脏和肾脏中高度表达。由于供体和受者之间存在不匹配，抗-GSTT1 抗体已在肾和肝移植中的抗体介导排斥反应中被描述。本研究旨在调查 HSCT 中针对 GSTT1 的特异性免疫反应，产生抗体及其对肝移植物抗宿主病（GVHD）发展的影响。研究纳入了 40 名患者及其各自的供体。中位随访时间为 35.6 个月（范围 0.6-76 个月），共检测了 349 份血清样本，通过 ELISA 试验检测抗-GSTT1 抗体的存在。通过将 GSTT1 缺失供体/阳性受者定义为与其他三种遗传组合（视为 GSTT1 匹配）相比的不匹配，进行统计分析。在缺失供体/阳性受者组中有 3 名患者和在缺失/缺失组中有 1 名患者发现了抗体。肝 GVHD 的发展，特别是其急性形式，与 GSTT1 不匹配高度相关（P=0.0178），与移植后抗-GSTT1 抗体的存在相关（P=0.0076）。我们得出结论，GSTT1 可被视为肝 GVHD 的新 mHag。三个供体都是多产妇女性，以及 HSCT 后抗体的快速产生，提示移植物中存在针对 GSTT1 抗原的记忆 B 细胞。
