University of Munster, Munster, Germany.
Alder Hey Children's Hospital and University of Liverpool, Liverpool, UK.
Arthritis Rheumatol. 2020 Feb;72(2):210-219. doi: 10.1002/art.41107. Epub 2020 Jan 2.
Systemic juvenile idiopathic arthritis (JIA) is a form of arthritis in childhood that is initially dominated by innate immunity-driven systemic inflammation and is thus considered a polygenic autoinflammatory disease. However, systemic JIA can progress toward an adaptive immunity-driven afebrile arthritis. Based on this observation of biphasic disease progression, a "window of opportunity" for optimal, individualized and target-directed treatment has been proposed. This hypothesis requires testing, and in this review we summarize current evidence regarding molecular factors that may contribute to the progression from an initially predominantly autoinflammatory disease phenotype to autoimmune arthritis. We consider the involvement of innately adaptive γδ T cells and natural killer T cells that express γδ or αβ T cell receptors but cannot be classified as either purely innate or adaptive cells, versus classic B and T lymphocytes in this continuum. Finally, we discuss our understanding of how and why some primarily autoinflammatory conditions can progress toward autoimmune-mediated disorders over the disease course while others do not and how this knowledge may be used to offer individualized treatment.
全身型幼年特发性关节炎（systemic juvenile idiopathic arthritis，sJIA）是一种儿童期关节炎，最初以先天免疫驱动的全身炎症为主，因此被认为是一种多基因自身炎症性疾病。然而，全身型 JIA 可进展为适应性免疫驱动的无热关节炎。基于这种双相疾病进展的观察，提出了一个“治疗机会窗”，以实现最佳、个体化和靶向治疗。这一假说需要验证，在这篇综述中，我们总结了目前关于可能导致从最初主要是自身炎症性疾病表型向自身免疫性关节炎进展的分子因素的证据。我们考虑了固有适应性 γδ T 细胞和自然杀伤 T 细胞的参与，这些细胞表达 γδ 或 αβ T 细胞受体，但不能被归类为纯粹的先天或适应性细胞，与该连续体中的经典 B 和 T 淋巴细胞相对。最后，我们讨论了我们对一些主要自身炎症性疾病如何以及为何在疾病过程中会向自身免疫介导的疾病进展，而其他疾病则不会，以及如何利用这些知识为患者提供个体化治疗。
