新的基因预测因子可用于 HLA-B*57:01 阳性个体中对阿巴卡韦的耐受性。
New genetic predictors for abacavir tolerance in HLA-B*57:01 positive individuals.
机构信息
Institute for Immunology and Infectious Diseases, Murdoch University, Western Australia, Australia; Telethon Kids Institute, Western Australia, Australia.
Institute for Immunology and Infectious Diseases, Murdoch University, Western Australia, Australia; School of Human Sciences, University of Western Australia, Western Australia, Australia.
出版信息
Hum Immunol. 2020 Jun;81(6):300-304. doi: 10.1016/j.humimm.2020.02.011. Epub 2020 Mar 12.
Abacavir hypersensitivity syndrome (ABC HSS) is strongly associated with carriage of human leukocyte antigen (HLA)-B57:01, which has a 100% negative predictive value for the development of ABC HSS. However, 45% of individuals who carry HLA-B57:01 can tolerate ABC. We investigated immune and non-immune related genes in ABC HSS (n = 95) and ABC tolerant (n = 43) HLA-B*57:01 + patients to determine other factors required for the development of ABC HSS. Assignment of phenotype showed that ABC HSS subjects were significantly less likely than tolerants to carry only ERAP1 hypoactive trimming allotypes (p = 0.02). An altered self-peptide repertoire model by which abacavir activates T cells is in keeping with observation that endoplasmic reticulum aminopeptidase 1 (ERAP1) allotypes that favour efficient peptide trimming are more common in ABC HSS patients compared to patients who tolerate ABC. Independently, non-specific immune activation via soluble cluster of differentiation antigen 14 (sCD14) may also influence susceptibility to ABC HSS.
阿巴卡韦超敏综合征（ABC HSS）与人类白细胞抗原（HLA）-B57:01 的携带密切相关，其对 ABC HSS 发展的阴性预测值为 100%。然而，携带 HLA-B57:01 的 45%个体可以耐受 ABC。我们研究了 ABC HSS（n=95）和 ABC 耐受（n=43）HLA-B*57:01+患者中与免疫和非免疫相关的基因，以确定 ABC HSS 发展所需的其他因素。表型分配表明，ABC HSS 患者与耐受者相比，携带仅 ERAP1 低活性修剪同种型的可能性显著降低（p=0.02）。阿巴卡韦激活 T 细胞的改变自身肽库模型与内质网氨肽酶 1（ERAP1）同种型更常见于 ABC HSS 患者而非耐受 ABC 的患者的观察结果一致，因为 ERAP1 同种型有利于有效的肽修剪。独立地，通过可溶性分化抗原 14（sCD14）的非特异性免疫激活也可能影响对 ABC HSS 的易感性。
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