den Uyl Debby, van der Horst-Bruinsma Irene E, van Agtmael Michiel
Department of Rheumatology, VU University Medical Centre Amsterdam, The Netherlands.
AIDS Rev. 2004 Apr-Jun;6(2):89-96.
HLA-B27 is known for its strong association with inflammatory spondyloarthropathies (SpA), a group of rheumatic diseases. Apart from playing its role in the onset of these inflammatory diseases, HLA-827 is so ubiquitous in the world that the carrying of this gene must have also have an advantage. There are some indications that a beneficial effect can be found as a less severe course of viral infections among B27-carriers. The literature on this subject was reviewed and revealed a favorable course of infection with influenza virus, herpes simplex type 2 virus, Epstein-Barr virus and, even more interesting, a protective effect of HLA-B27 in the progression of HIV infections. The course of HIV infection differs among individuals and is thought to be partly related to host-factor variability, reflecting broad genetic heterogeneity. The polymorphic human leukocyte antigens (HLA) are herein analyzed intensively with respect to this relationship. Cytotoxic T lymphocyte (CTL) responses, activated by HLA antigen presentation, are implicated in the control of HIV replication. An immunological explanation for the protective role for HLA B27 in HIV disease is that B27+ patients have a specific and strong CTL response against the p24 epitope, a conservative HIV protein that does not easily mutate. Some HLA genes seen in long-term non-progressors (LTNP) (>10 years disease free) are associated with a favorable prognosis. One of the alleles found predominantly in LTNPs is HLA-B27. More genetic factors seem to influence disease progression in HIV infections. Therefore, it would be interesting to further explore the influence of the genetic make up of these HIV-infected individuals. Knowledge of the immunogenetic profile might give clues for the individual course of the HIV infection, may influence the development of drug-resistant viruses and will possibly lead to a tailored therapeutic strategy in HIV-infected persons.
HLA - B27因与炎症性脊柱关节病(SpA,一组风湿性疾病)密切相关而闻名。除了在这些炎症性疾病的发病过程中发挥作用外,HLA - B27在世界范围内极为普遍,携带该基因必定也有其优势。有迹象表明,在携带B27的人群中,病毒感染的病程较轻,存在有益影响。对该主题的文献进行综述后发现,感染流感病毒、单纯疱疹病毒2型、爱泼斯坦 - 巴尔病毒时病程呈良性,更有趣的是,HLA - B27在HIV感染进展过程中具有保护作用。HIV感染在个体间的病程有所不同,被认为部分与宿主因素的变异性有关,这反映了广泛的基因异质性。本文针对这种关系深入分析了多态性人类白细胞抗原(HLA)。由HLA抗原呈递激活的细胞毒性T淋巴细胞(CTL)反应与HIV复制的控制有关。对HLA B27在HIV疾病中保护作用的一种免疫学解释是,携带B27的患者对p24表位有特异性且强烈的CTL反应,p24是一种不易突变的保守HIV蛋白。在长期不进展者(LTNP,疾病无进展超过10年)中发现的一些HLA基因与良好预后相关。在LTNP中主要发现的等位基因之一是HLA - B27。似乎有更多遗传因素影响HIV感染的疾病进展。因此,进一步探究这些HIV感染者的基因构成所产生的影响将很有意思。了解免疫遗传特征可能为HIV感染的个体病程提供线索,可能影响耐药病毒的产生,并可能为HIV感染者带来量身定制的治疗策略。