Neppelenbroek Sam, Blomberg Nienke J, Kampstra Arieke S B, van der Hem Joost G K, Huizinga Tom W J, Toes René E M, Scherer Hans U
Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands.
Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands.
J Autoimmun. 2024 Dec;149:103320. doi: 10.1016/j.jaut.2024.103320. Epub 2024 Sep 28.
Autoimmune diseases (AIDs) are frequently hallmarked by the presence of autoreactive B cell responses which are involved in disease pathogenesis. However, the dynamics of such responses and their relation to clinical disease activity in humans is poorly understood. Rheumatoid arthritis (RA), a prototypic chronic AID, is hallmarked by B cell responses directed against citrullinated proteins.
To determine the relation between the activity of the anti-citrullinated protein antibody (ACPA) B cell response and clinical disease activity in ACPA patients with RA.
Expression of B cell activation markers by ACPA, tetanus toxoid (TT) and ACPA memory B cells (MBCs) from peripheral blood of ACPA RA patients receiving different treatments was analyzed by flow cytometry. Results were correlated to clinical disease activity.
Compared to TT and ACPA MBCs, ACPA MBCs displayed a highly activated phenotype as evidenced by increased expression of Ki-67, CD86, CD80, CD19 and CD20 and reduced expression of CD32. The activated phenotype of ACPA MBCs did not associate with clinical disease activity in a cross-sectional analysis of RA patients treated with various therapeutic agents. Also, in a longitudinal analysis of patients treated with Janus kinase (JAK) inhibitors, ACPA MBCs retained their activated phenotype despite effective control of inflammation and clinical disease.
ACPA MBCs remain active despite clinical disease control in patients with RA across a range of interventions. This persistent activity indicates the absence of immunological remission and might explain why ACPA patients rarely reach sustained drug-free remission and frequently flare upon drug tapering.
自身免疫性疾病（AIDs）通常以自身反应性B细胞反应的存在为特征，这些反应参与疾病的发病机制。然而，人们对这种反应的动态变化及其与人类临床疾病活动的关系了解甚少。类风湿性关节炎（RA）是一种典型的慢性自身免疫性疾病，其特征是针对瓜氨酸化蛋白的B细胞反应。
确定抗瓜氨酸化蛋白抗体（ACPA）B细胞反应活性与ACPA阳性RA患者临床疾病活动之间的关系。
通过流式细胞术分析接受不同治疗的ACPA阳性RA患者外周血中ACPA、破伤风类毒素（TT）和ACPA记忆B细胞（MBCs）的B细胞活化标志物表达。结果与临床疾病活动相关。
与TT和ACPA MBCs相比，ACPA MBCs表现出高度活化的表型，表现为Ki-67、CD86、CD80、CD19和CD20表达增加以及CD32表达降低。在对接受各种治疗药物治疗的RA患者进行的横断面分析中，ACPA MBCs的活化表型与临床疾病活动无关。此外，在接受Janus激酶（JAK）抑制剂治疗的患者的纵向分析中，尽管炎症和临床疾病得到有效控制，ACPA MBCs仍保持其活化表型。
在一系列干预措施中，RA患者的ACPA MBCs尽管临床疾病得到控制，但仍保持活跃。这种持续的活性表明不存在免疫缓解，这可能解释了为什么ACPA阳性患者很少达到持续的无药缓解，并且在药物减量时经常复发。
