Mathieu Alessandro, Paladini Fabiana, Vacca Alessandra, Cauli Alberto, Fiorillo Maria Teresa, Sorrentino Rosa
Department of Medical Sciences, University of Cagliari, University Clinic, Monserrato - Cagliari, Italy.
Autoimmun Rev. 2009 Mar;8(5):420-5. doi: 10.1016/j.autrev.2009.01.003. Epub 2009 Feb 26.
Due to its strong association with Ankylosing Spondylitis and the other Spondyloarthropathies, the HLA-B27 family of alleles and, in particular, the ancestral HLA-B2705, has been the object of numerous studies. More recently, some novel interesting features have emerged such as the ability of HLA-B27 to confer resistance to the progression of HIV infection and to promote a spontaneous CD8+ T cell-mediated viral clearance of HCV. The co-occurrence of these protective and pathogenic features suggests a common ground, i.e. to promote a more pronounced immune/inflammatory response leading to an effective clearance of some pathogens on one side and to autoimmunity on the other. This might be due to the antigen presenting properties and/or to the co-inheritance of gene variants that contribute to an altered homeostasis in case of microbial infections or tissue injury. The existence of conserved HLA haplotypes have since long been thought to result from a selective pressure by some pathogens that have edited the immune response genes. The peculiar distribution of the ancestor HLA-B2705 along a latitude-dependent gradient and the opposite distribution of their variants have suggested a correlation with endemic malaria. In this respect, Sardinia, a small Mediterranean island plagued by malaria, represents an interesting laboratory since its population is enriched in conserved HLA haplotypes and several genetic studies have disclosed their correlation with infectious and autoimmune diseases.
由于其与强直性脊柱炎及其他脊柱关节病密切相关，HLA - B27等位基因家族，尤其是原始的HLA - B2705，一直是众多研究的对象。最近，一些新的有趣特征出现了，比如HLA - B27赋予抵抗HIV感染进展的能力以及促进HCV自发的CD8 + T细胞介导的病毒清除。这些保护性和致病性特征的共同出现提示了一个共同点，即促进更显著的免疫/炎症反应，一方面导致某些病原体的有效清除，另一方面导致自身免疫。这可能是由于抗原呈递特性和/或基因变异的共同遗传，在微生物感染或组织损伤时这些变异会导致内环境稳态改变。长期以来，人们一直认为保守的HLA单倍型的存在是某些编辑免疫反应基因的病原体施加选择压力的结果。原始HLA - B2705沿纬度依赖性梯度的特殊分布及其变异体的相反分布提示与地方性疟疾有关。在这方面，撒丁岛，一个饱受疟疾困扰的地中海小岛，是一个有趣的研究场所，因为其人群中保守的HLA单倍型丰富，并且多项遗传学研究揭示了它们与感染性和自身免疫性疾病的相关性。
