Holoshitz Joseph
Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Discov Med. 2013 Sep;16(87):93-101.
Dozens of human diseases and health traits are significantly more common among individuals carrying particular human leukocyte antigens (HLA) alleles. The underlying mechanism of this phenomenon, commonly referred to as "HLA-disease association," has been the subject of a decades-long debate. The prevailing hypotheses implicate an auto-aggressive immune response due to aberrant presentation of self-, self-mimicking-, or altered self-antigens by HLA molecules. However, the identity of such putative antigens remains elusive in the vast majority of HLA-associated diseases. Moreover, antigen presentation-based hypotheses are difficult to reconcile with epidemiologic data and functional characteristics of HLA molecules. To provide better answers to these inconsistencies an alternative theory involving allele-based, antigen presentation-independent mechanism is proposed here. Recent research findings in rheumatoid arthritis, an emblematic HLA-associated disease, lend support to the proposed theory.
数十种人类疾病和健康特征在携带特定人类白细胞抗原（HLA）等位基因的个体中显著更为常见。这种现象的潜在机制，通常被称为“HLA与疾病的关联”，一直是长达数十年争论的主题。主流假说是由于HLA分子异常呈递自身、自身模拟或改变的自身抗原而引发自身攻击性免疫反应。然而，在绝大多数HLA相关疾病中，此类假定抗原的身份仍然难以捉摸。此外，基于抗原呈递的假说难以与HLA分子的流行病学数据和功能特征相协调。为了更好地解答这些矛盾之处，本文提出了一种涉及基于等位基因、不依赖抗原呈递的机制的替代理论。类风湿关节炎是一种典型的HLA相关疾病，近期的研究结果为该理论提供了支持。
