Establishing a clear role for HLA-B*27 in the pathogenesis of spondyloarthritis continues to be challenging. Aberrant properties of the heavy chain as well as a potential role presenting arthritogenic peptides continue to be pursued as plausible mechanisms. Recent studies implicate HLA-B*27 in aberrant bone formation. An unanticipated cell surface interaction between HLA-B*27 and the bone morphogenetic protein pathway receptor subunit ALK2 may augment TGFβ superfamily signaling pathways, increasing responsiveness to Activin A and TGFβ. This has the potential to increase bone formation as well as Th17 T cell development, presenting an attractive model to explain several aspects of axial and peripheral spondyloarthritis. In a separate study, intracellular effects of misfolded HLA-B*27 implicate this mechanism in increased osteoblast mineralization and bone formation. HLA-B*27 expression in early osteoblasts activates unfolded protein response-mediated X-box binding protein-1 mRNA splicing and induction of the retinoic acid receptor-β gene, with downstream increases in expression of tissue non-specific alkaline phosphatase. Increased TNAP expression in osteoblasts was linked to increased mineralization in vitro and bone formation in vivo. In the ongoing search for evidence of arthritogenic peptides, high-throughput TCR (T cell receptor) sequencing has provided evidence for reduced clonal expansion and increased TCR diversity in ankylosing spondylitis. In addition to two common CD8+ TCR sequences identified in one study, similar CD8 and CD4 TCR motifs were found in another study. Further work will be needed to shed light on the nature of the peptide-HLA class I complex recognized by these T cells and its role in disease.

确定 HLA-B*27 在脊柱关节炎发病机制中的明确作用仍然具有挑战性。重链的异常特性以及呈递致关节炎肽的潜在作用继续作为可能的机制进行研究。最近的研究表明 HLA-B*27 与异常骨形成有关。HLA-B*27 和骨形态发生蛋白通路受体亚基 ALK2 之间的意外细胞表面相互作用可能会增强 TGFβ 超家族信号通路，从而增加对 Activin A 和 TGFβ 的反应性。这有可能增加骨形成以及 Th17 T 细胞发育，提供了一个有吸引力的模型来解释中轴和外周脊柱关节炎的几个方面。在另一项研究中，错误折叠的 HLA-B*27 的细胞内效应暗示了这种机制在增加成骨细胞矿化和骨形成中的作用。早期成骨细胞中 HLA-B*27 的表达激活了未折叠蛋白反应介导的 X-box 结合蛋白-1 mRNA 剪接和视黄酸受体-β 基因的诱导，下游组织非特异性碱性磷酸酶的表达增加。成骨细胞中 TNAP 表达增加与体外矿化和体内骨形成增加有关。在持续寻找关节炎肽证据的过程中，高通量 TCR（T 细胞受体）测序为 随着组织非特异性碱性磷酸酶表达的下游增加。成骨细胞中 TNAP 表达增加与体外矿化和体内骨形成增加有关。在持续寻找关节炎肽证据的过程中，高通量 TCR（T 细胞受体）测序为 随着组织非特异性碱性磷酸酶表达的下游增加。成骨细胞中 TNAP 表达增加与体外矿化和体内骨形成增加有关。在持续寻找关节炎肽证据的过程中，高通量 TCR（T 细胞受体）测序为在强直性脊柱炎中减少克隆扩增并增加TCR 多样性。除了在一项研究中鉴定出两种常见的 CD8+ TCR 序列外，在另一项研究中还发现了类似的 CD8 和 CD4 TCR 基序。需要进一步的工作来阐明这些 T 细胞识别的肽-HLA I 类复合物的性质及其在疾病中的作用。