自身免疫性疾病的机制研究已确认循环性T辅助细胞（cTfh）是自体免疫的推动因素。然而，由于缺乏年龄分层的正常范围以及对于该测试在自体免疫方面的敏感性和特异性的未知，cTfh细胞的定量尚未在临床实践中使用。我们纳入了238名健康参与者和130名患有常见和罕见的自体免疫性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细胞百分比的中值（范围4.8%-6.2%）在年龄组、性别、种族和族裔之间相当，除了1岁以下儿童的百分比明显较低（中值2.1%，CI：0.4%-6.8%，P < 0.0001）。在130名患有40多种免疫调节紊乱性疾病的患者中，超过12%的cTfh细胞百分比对于区别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。这个阈值对于活动性自身免疫具有86%的敏感性和100%的特异性，并在有效治疗后恢复正常。超过12%的cTfh细胞百分比可以区分自体免疫和自身炎症，从而区分具有重叠症状和不同治疗方法的两种免疫调节失常的内源型。版权所有 © 2023 Elsevier公司。保留所有权利。

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.Copyright © 2023 Elsevier Ltd. All rights reserved.