Lippert L E, Fisher L M, Schook L B
Department of Clinical Investigation, Walter Reed Army Medical Center, Washington, DC 20307-5001.
Thromb Haemost. 1990 Dec 28;64(4):564-8.
Approximately 14% of transfused hemophiliacs develop an anti-factor VIII inhibitory antibody which specifically neutralizes factor VIII procoagulant activity. In this study an association of the major histocompatibility complex (MHC) with inhibitor antibody formation was evaluated by restriction fragment length polymorphism (RFLP) analysis using BamHI, EcoRI, HindIII, PstI, PvuII and TaqI digested genomic DNA probed with DP beta, DQ alpha, DQ beta and DR beta class II MHC gene probes. The RFLP patterns for 16 non-inhibitor and 11 inhibitor hemophiliac patients were analyzed. These 24 enzyme:probe combinations generated 231 fragments. Fifteen (15) fragments associated with the inhibitor phenotype; odds ratios ranged from 5.1 to 45 and lower bounds of 95% confidence intervals were greater than 1.000 for all 15 fragments. Five (5) fragments associated with non-inhibitors, with odds ratios ranging from 6.4 to 51.7. This report establishes a MHC related genetic basis for the inhibitor phenotype. No statistically significant differences in the distribution of serologically defined HLA-DR phenotypes were observed between the inhibitor and non-inhibitor groups.
大约14%接受输血的血友病患者会产生抗凝血因子VIII抑制性抗体，该抗体可特异性中和凝血因子VIII的促凝血活性。在本研究中，通过限制性片段长度多态性（RFLP）分析，使用经BamHI、EcoRI、HindIII、PstI、PvuII和TaqI消化的基因组DNA，并用II类主要组织相容性复合体（MHC）基因探针DPβ、DQα、DQβ和DRβ进行探测，评估MHC与抑制性抗体形成之间的关联。分析了16名非抑制性血友病患者和11名抑制性血友病患者的RFLP模式。这24种酶：探针组合产生了231个片段。15个片段与抑制性表型相关；优势比范围为5.1至45，所有15个片段的95%置信区间下限均大于1.000。5个片段与非抑制性患者相关，优势比范围为6.4至51.7。本报告确立了抑制性表型的MHC相关遗传基础。在抑制性和非抑制性组之间，未观察到血清学定义的HLA-DR表型分布存在统计学显著差异。
