Department of Orthopedics, Changhai Hospital, The Second Military Medical University, 200433 Shanghai, PR China.
Med Hypotheses. 2013 Jan;80(1):36-8. doi: 10.1016/j.mehy.2012.10.003. Epub 2012 Nov 1.
Ankylosing spondylitis (AS) is a form of seronegative inflammatory arthritis whose strong genetic association with the human leucocyte antigen (HLA)-B27 has been known for almost 4 decades. However, its mechanism remains poorly understood. Recently, with the development of genetics, further more genes have been robustly associated with the disease. Genome-wide association studies identified the association between AS and ERAP1 (endoplasmic reticulum associated aminopeptidase 1). And ERAP1 has shown the potential in trimming antigenic peptides to optimal length for binding to HLA-B27 in the ER (endoplasmic reticulum). However, the length of the peptides are strictly restricted in the process of peptide transporting, processing and presentation. A hypothesis is proposed that the abnormal mechanism of AS may related to the trimming of N-terminal sequences from antigenic precursors in the ER and the length of the antigenic peptides that are presented to the T-cell receptors.
强直性脊柱炎（AS）是一种血清阴性炎症性关节炎，其与人类白细胞抗原（HLA）-B27 的强遗传关联已近 40 年。然而，其发病机制仍不清楚。最近，随着遗传学的发展，越来越多的基因与该疾病有明显的相关性。全基因组关联研究确定了 AS 与 ERAP1（内质网相关氨肽酶 1）之间的关联。ERAP1 已显示出在 ER（内质网）中将抗原肽修剪成与 HLA-B27 结合的最佳长度的潜力。然而，在肽转运、加工和呈递过程中，肽的长度受到严格限制。提出了一个假设，即 AS 的异常机制可能与 ER 中抗原前体的 N 末端序列的修剪以及呈递给 T 细胞受体的抗原肽的长度有关。
