Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
J Autoimmun. 2023 Nov;140:103088. doi: 10.1016/j.jaut.2023.103088. Epub 2023 Aug 5.
Mechanistic studies of autoimmune disorders have identified circulating T follicular helper (cTfh) cells as drivers of autoimmunity. However, the quantification of cTfh cells is not yet used in clinical practice due to the lack of age-stratified normal ranges and the unknown sensitivity and specificity of this test for autoimmunity. We enrolled 238 healthy participants and 130 patients with common and rare disorders of autoimmunity or autoinflammation. Patients with infections, active malignancy, or any history of transplantation were excluded. In 238 healthy controls, median cTfh percentages (range 4.8%-6.2%) were comparable among age groups, sexes, races, and ethnicities, apart from a significantly lower percentages in children less than 1 year of age (median 2.1%, CI: 0.4%-6.8, p < 0.0001). Among 130 patients with over 40 immune regulatory disorders, a cTfh percentage exceeding 12% had 88% sensitivity and 94% specificity for differentiating disorders with adaptive immune cell dysregulation from those with predominantly innate cell defects. This threshold had a sensitivity of 86% and specificity of 100% for active autoimmunity and normalized with effective treatment. cTfh percentages exceeding 12% distinguish autoimmunity from autoinflammation, thereby differentiating two endotypes of immune dysregulation with overlapping symptoms and different therapies.
自身免疫性疾病的发病机制研究表明，循环滤泡辅助性 T 细胞（cTfh）是自身免疫的驱动因素。然而，由于缺乏年龄分层的正常范围，以及该检测对自身免疫的敏感性和特异性未知，cTfh 细胞的定量检测尚未在临床实践中应用。我们纳入了 238 名健康参与者和 130 名患有常见和罕见自身免疫或自身炎症性疾病的患者。排除了感染、活动性恶性肿瘤或任何移植史的患者。在 238 名健康对照者中，cTfh 细胞百分比（范围 4.8%-6.2%）在年龄组、性别、种族和民族之间相似，但 1 岁以下儿童的百分比明显较低（中位数 2.1%，CI：0.4%-6.8%，p<0.0001）。在 130 名患有 40 多种免疫调节障碍的患者中，cTfh 细胞百分比超过 12%，对区分具有适应性免疫细胞失调的疾病与主要具有固有细胞缺陷的疾病具有 88%的敏感性和 94%的特异性。该阈值对活动性自身免疫的敏感性为 86%，特异性为 100%，且随着有效治疗而正常化。cTfh 细胞百分比超过 12%可将自身免疫与自身炎症区分开来，从而区分具有重叠症状和不同治疗方法的两种免疫失调表型。
