Clinic of Internal Medicine III, Oncology, Hematology, Rheumatology and Clinical Immunology, University Hospital Bonn, Bonn, Germany.
Clinic of Internal Medicine III, Oncology, Hematology, Rheumatology and Clinical Immunology, University Hospital Bonn, Bonn, Germany.
Autoimmun Rev. 2023 Jun;22(6):103328. doi: 10.1016/j.autrev.2023.103328. Epub 2023 Mar 27.
Giant cell arteritis is the most common form of large vessel vasculitis and preferentially involves large and medium-sized arteries in patients over the age of 50. Aggressive wall inflammation, neoangiogenesis and consecutive remodeling processes are the hallmark of the disease. Though etiology is unknown, cellular and humoral immunopathological processes are well understood. Matrix metalloproteinase-9 mediated tissue infiltration occurs through lysis of basal membranes in adventitial vessels. CD4+ cells attain residency in immunoprotected niches, differentiate into vasculitogenic effector cells and enforce further leukotaxis. Signaling pathways involve the NOTCH1-Jagged1 pathway opening vessel infiltration, CD28 mediated T-cell overstimulation, lost PD-1/PD-L1 co-inhibition and JAK/STAT signaling in interferon dependent responses. From a humoral perspective, IL-6 represents a classical cytokine and potential Th-cell differentiator whereas interferon-γ (IFN- γ) has been shown to induce chemokine ligands. Current therapies involve glucocorticoids, tocilizumab and methotrexate application. However, new agents, most notably JAK/STAT inhibitors, PD-1 agonists and MMP-9 blocking substances, are being evaluated in ongoing clinical trials.
巨细胞动脉炎是大血管血管炎中最常见的形式，主要发生在 50 岁以上的患者的大中动脉。侵袭性的壁炎症、新生血管形成和连续的重塑过程是该疾病的标志。尽管病因不明，但细胞和体液免疫病理过程已得到很好的理解。基质金属蛋白酶-9 介导的组织浸润是通过在血管外膜中的基底膜溶解发生的。CD4+细胞在免疫保护的龛位中定居，分化为血管生成效应细胞，并促进进一步的白细胞趋化。信号通路涉及 NOTCH1-Jagged1 通路开放血管浸润、CD28 介导的 T 细胞过度刺激、PD-1/PD-L1 共抑制丧失和干扰素依赖反应中的 JAK/STAT 信号。从体液的角度来看，IL-6 代表一种经典的细胞因子和潜在的 Th 细胞分化因子，而干扰素-γ（IFN-γ）已被证明能诱导趋化因子配体。目前的治疗方法包括应用糖皮质激素、托珠单抗和甲氨蝶呤。然而，新的药物，特别是 JAK/STAT 抑制剂、PD-1 激动剂和 MMP-9 阻断物，正在进行中的临床试验中进行评估。
