Goto Takeshi, Miyazaki Yusuke, Nakayamada Shingo, Shiraishi Naoki, Yoshinaga Takeshi, Tanaka Yoshiya, Nakamura Tadashi
Kumamoto University School of Medical Sciences, Kumamoto, Japan.
First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Mod Rheumatol Case Rep. 2023 Jan 3;7(1):237-242. doi: 10.1093/mrcr/rxac031.
Autoinflammatory diseases are innate immune-mediated inflammatory disorders, unlike autoimmune diseases, which are characterised by abnormalities in adoptive immunity, although autoimmune and autoinflammatory diseases have certain similar clinical features. Familial Mediterranean fever (FMF), the most common monogenic autoinflammatory disease, is associated with mutations in the MEFV gene that encodes pyrin, which results in inflammasome activation and uncontrolled production of interleukin (IL)-1β. Regular use of colchicine, the primary drug for FMF treatment, prevents febrile attacks and reduces the long-term risk of subsequent complications of amyloid A (AA) amyloidosis. However, a minority of FMF patients develop colchicine resistance, and anti-IL-1β treatment with canakinumab, which is a genetically modified human IgG subclass type 1 (IgG1) monoclonal antibody specific for human IL-1β, was beneficial in inhibiting inflammation in such patients. Here, we present a patient with FMF associated with AA amyloidosis, who was treated with canakinumab and demonstrated down-regulated Th17 cells and activated Th17 cells (from 21.4% to 12.8%, and from 1.45% to 0.83%, respectively) in peripheral blood, as shown by immunophenotyping via multicolour flow cytometry and by disease activity and improved laboratory inflammatory surrogate markers-C-reactive protein (CRP) and serum AA protein (SAA). CRP had values within normal limits, but SAA did not (Spearman's rank correlation coefficient; ρ = 0.133). We report that SAA and IL-1β may differentiate Th17 cells from CD4+-naïve T cells, and we discuss interactions between autoinflammation and autoimmunity as a model based on this case, through modes of action with IL-1β and SAA. This report is the first demonstrating that an IL-1β antagonist may reduce Th17 cells in FMF as a therapeutic option.
自身炎症性疾病是由先天免疫介导的炎症性疾病，与自身免疫性疾病不同，后者的特征是适应性免疫异常，尽管自身免疫性疾病和自身炎症性疾病有某些相似的临床特征。家族性地中海热（FMF）是最常见的单基因自身炎症性疾病，与编码 pyrin 的 MEFV 基因突变有关，这会导致炎性小体激活和白细胞介素（IL）-1β 的不受控制产生。定期使用秋水仙碱作为 FMF 治疗的主要药物，可预防发热发作并降低随后发生淀粉样蛋白 A（AA）淀粉样变性并发症的长期风险。然而，少数 FMF 患者会出现秋水仙碱耐药，而使用卡那单抗进行抗 IL-1β 治疗对抑制此类患者的炎症有益，卡那单抗是一种针对人 IL-1β 的基因改造人 IgG1 亚类单克隆抗体。在此，我们报告一例与 AA 淀粉样变性相关的 FMF 患者，其接受了卡那单抗治疗，通过多色流式细胞术免疫表型分析以及疾病活动情况和改善的实验室炎症替代标志物——C 反应蛋白（CRP）和血清 AA 蛋白（SAA）显示，外周血中 Th17 细胞下调且活化的 Th17 细胞减少（分别从 21.4%降至 12.8%，从 1.45%降至 0.83%）。CRP 值在正常范围内，但 SAA 不在（斯皮尔曼等级相关系数；ρ = 0.133）。我们报告 SAA 和 IL-1β 可能使 Th17 细胞与 CD4 + 初始 T 细胞区分开来，并且我们基于此病例通过与 IL-1β 和 SAA 的作用方式讨论自身炎症和自身免疫之间的相互作用作为一种模型。本报告首次证明 IL-1β 拮抗剂作为一种治疗选择可能会减少 FMF 中的 Th17 细胞。
