Verjans G M, Messer G, Weiss E H, van der Linden S M, Kijlstra A
Department of Ophthalmo-Immunology, The Netherlands Ophthalmic Research Institute, Amsterdam.
Rheum Dis Clin North Am. 1992 Feb;18(1):177-86.
HLA antigens have been shown to be associated with several immunoinflammatory diseases. The mechanisms by which these antigens confer susceptibility to disease continue to be of major interest. Rapid progress has been made in the elucidation of the structure and function of class I and II MHC molecules, and several genes located within the HLA complex have been identified which are potentially involved in immunologic processes. Because of the HLA localization of the TNF-alpha and -beta genes and the biologic activities of the gene products, recent investigation has focused on a possible role of polymorphic TNF genes in the pathogenesis of HLA-associated diseases. Allelic variations have only been detected in the TNF-beta gene. No evidence has been found so far that a particular TNF-beta allele contributes significantly in the susceptibility to the diseases studied. Although it has been postulated that the TNF beta*2 allele contributes to susceptibility to IDDM in HLA-DR3, 4 heterozygous individuals, a larger group of HLA-typed patients and controls is needed to provide more conclusive evidence for this hypothesis. The increasing number of genes of unknown function encoded by the class III region leaves the possibility that the observed HLA associations in some diseases may be related to the presence of these genes. In AS, the lack of association with the TNF-beta alleles furthermore supports the function of the HLA-B27 molecule in the disease and underlines the improbability that HLA-B27 is merely a marker for a closely linked susceptibility gene.
人类白细胞抗原（HLA）抗原已被证明与多种免疫炎症性疾病相关。这些抗原赋予疾病易感性的机制一直是人们主要关注的问题。在阐明I类和II类主要组织相容性复合体（MHC）分子的结构和功能方面已取得迅速进展，并且已鉴定出位于HLA复合体中的几个基因，它们可能参与免疫过程。由于肿瘤坏死因子（TNF）-α和-β基因的HLA定位以及基因产物的生物学活性，最近的研究集中在多态性TNF基因在HLA相关疾病发病机制中的可能作用。仅在TNF-β基因中检测到等位基因变异。到目前为止，尚未发现证据表明特定的TNF-β等位基因对所研究疾病的易感性有显著贡献。尽管有人推测TNF beta*2等位基因在HLA-DR3、4杂合个体中导致胰岛素依赖型糖尿病（IDDM）的易感性增加，但需要更多的HLA分型患者和对照来为这一假说提供更确凿的证据。由III类区域编码的功能未知基因数量不断增加，这使得在某些疾病中观察到的HLA关联可能与这些基因的存在有关。在强直性脊柱炎（AS）中，与TNF-β等位基因缺乏关联进一步支持了HLA-B27分子在该疾病中的作用，并强调了HLA-B27仅仅是紧密连锁的易感基因标记的可能性不大。
