Uncovering the Underworld of Axial Spondyloarthritis.
Uncovering the Underworld of Axial Spondyloarthritis.
复制标题
DOI：
10.3390/ijms24076463
复制
发表时间：
2023-03-30
影响因子：
5.6
通讯作者：
Lopalco, Giuseppe
中科院分区：
文献类型：
--
作者：
Del Vescovo, Sergio;Venerito, Vincenzo;Iannone, Claudia;Lopalco, Giuseppe
中轴型脊柱关节炎（Axis-SpA）是一种多因素疾病，其特征是骶髂关节和脊柱炎症、骨重吸收和异常骨沉积，可能导致强直。疾病发病机制取决于遗传、免疫、机械和生物环境因素。 HLA-B27 代表最重要的遗传因素，尽管该疾病在缺乏遗传因素的情况下也可能发生。这种MHC I类分子已经从分子角度进行了深入研究。已经提出了不同的理论来解释其作用，包括致关节炎肽、未折叠蛋白反应和 HLA-B27 同二聚体形成。从免疫学的角度来看，先天免疫系统和适应性免疫系统之间复杂的相互作用与疾病的发生有关。与其他系统性自身免疫性疾病不同，中轴型 SpA 中的先天免疫系统发挥着至关重要的作用，其特点是先天免疫细胞（包括 γδ T 细胞、3 型先天淋巴细胞、中性粒细胞和粘膜相关不变 T 细胞）在易患该疾病的组织特异性部位异常活动。另一方面，T 细胞适应性反应似乎与轴向 SpA 发病机制有关，正如几项关注 TCR 低克隆异质性和克隆扩张以及个体间共享 CD4/8 T 细胞受体的研究所强调的那样。由于这种免疫失调，参与中轴型 SpA 病理机制的细胞内缠结通路激活后会产生多种促炎分子。本综述旨在扩大目前对中轴型 SpA 发病机制的认识，指出导致疾病发展的新分子机制，并进一步研究潜在的治疗靶点。
Axial spondyloarthritis (axial-SpA) is a multifactorial disease characterized by inflammation in sacroiliac joints and spine, bone reabsorption, and aberrant bone deposition, which may lead to ankylosis. Disease pathogenesis depends on genetic, immunological, mechanical, and bioenvironmental factors. HLA-B27 represents the most important genetic factor, although the disease may also develop in its absence. This MHC class I molecule has been deeply studied from a molecular point of view. Different theories, including the arthritogenic peptide, the unfolded protein response, and HLA-B27 homodimers formation, have been proposed to explain its role. From an immunological point of view, a complex interplay between the innate and adaptive immune system is involved in disease onset. Unlike other systemic autoimmune diseases, the innate immune system in axial-SpA has a crucial role marked by abnormal activity of innate immune cells, including γδ T cells, type 3 innate lymphoid cells, neutrophils, and mucosal-associated invariant T cells, at tissue-specific sites prone to the disease. On the other hand, a T cell adaptive response would seem involved in axial-SpA pathogenesis as emphasized by several studies focusing on TCR low clonal heterogeneity and clonal expansions as well as an interindividual sharing of CD4/8 T cell receptors. As a result of this immune dysregulation, several proinflammatory molecules are produced following the activation of tangled intracellular pathways involved in pathomechanisms of axial-SpA. This review aims to expand the current understanding of axial-SpA pathogenesis, pointing out novel molecular mechanisms leading to disease development and to further investigate potential therapeutic targets.
登录
查看更多内容
影响因子：
27.4
作者：
Baeten D;Østergaard M;Wei JC;Sieper J;Järvinen P;Tam LS;Salvarani C;Kim TH;Solinger A;Datsenko Y;Pamulapati C;Visvanathan S;Hall DB;Aslanyan S;Scholl P;Padula SJ
通讯作者：
Padula SJ
影响因子：
158.5
作者：
Baeten, Dominique;Sieper, Joachim;Richards, Hanno B.
通讯作者：
Richards, Hanno B.
影响因子：
7.3
作者：
van Tok MN;Mandour M;Wahle J;Labadia ME;van de Sande MGH;Nabozny G;Baeten DL;van Duivenvoorde LM
通讯作者：
van Duivenvoorde LM
影响因子：
7.3
作者：
Adams, Ralph;Maroof, Asher;Griffiths, Meryn
通讯作者：
Griffiths, Meryn
影响因子：
6.2
作者：
Baraliakos, Xenofon;Braun, Juergen;Fierlinger, Anke
通讯作者：
Fierlinger, Anke