Sachinidis Athanasios, Trachana Maria, Taparkou Anna, Gavriilidis George, Verginis Panayotis, Psomopoulos Fotis, Adamichou Christina, Boumpas Dimitrios, Garyfallos Alexandros
4 Department of Internal Medicine, Hippokration General Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Paediatric Immunology and Rheumatology Referral Centre, 1 Paediatric Department, Hippokration General Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Mediterr J Rheumatol. 2023 Mar 31;34(1):117-120. doi: 10.31138/mjr.34.1.117. eCollection 2023 Mar.
Age-associated B cells (ABCs) constitute a B cell subset, defined as CD19CD21CD11c, that expands continuously with age and accumulates strongly in individuals with autoimmune and/or infectious diseases. In humans, ABCs are principally IgDCD27 double-negative (DN) B cells. Data from murine models of autoimmunity, implicate ABCs/DN in the development of autoimmune disorders. T-bet, a transcription factor which is highly expressed in these cells, is considered to play a major role in various aspects of autoimmunity, such as the production of autoantibodies and the formation of spontaneous germinal centres.
Despite the available data, the functional features of ABCs/DN and their exact role in the pathogenesis of autoimmunity remain elusive. This project focuses on the investigation of the role of ABCs/DN in the pathogenesis of systemic lupus erythematosus (SLE) in humans, as well as the effects that various pharmacological agents may have on these cells.
Samples from patients with active SLE will be used to enumerate and immunophenotype - via flow cytometry - the ABCs/DN found in the peripheral blood of the patients. Transcriptomic analysis and functional assays for the cells, both before and after in vitro pharmacological treatments, will also be performed.
The results of the study are expected to allow characterization of the pathogenetic role of ABCs/DN in SLE and could probably contribute, following careful association with the clinical state of the patients, towards the discovery and validation of novel prognostic and diagnostic markers of disease.
年龄相关B细胞（ABCs）构成一个B细胞亚群，定义为CD19⁺CD21⁻CD11c⁺，其随年龄持续扩增，并在自身免疫性疾病和/或感染性疾病患者中大量积聚。在人类中，ABCs主要是IgD⁻CD27双阴性（DN）B细胞。自身免疫性小鼠模型的数据表明ABCs/DN参与自身免疫性疾病的发生发展。T-bet是一种在这些细胞中高表达的转录因子，被认为在自身免疫的各个方面发挥主要作用，如自身抗体的产生和自发生发中心的形成。
尽管已有相关数据，但ABCs/DN的功能特征及其在自身免疫发病机制中的确切作用仍不明确。本项目聚焦于研究ABCs/DN在人类系统性红斑狼疮（SLE）发病机制中的作用，以及各种药物制剂对这些细胞可能产生的影响。
将使用活动性SLE患者的样本，通过流式细胞术对患者外周血中的ABCs/DN进行计数和免疫表型分析。还将对细胞在体外药物处理前后进行转录组分析和功能测定。
该研究结果有望明确ABCs/DN在SLE发病机制中的作用，并且在与患者临床状态仔细关联后，可能有助于发现和验证疾病的新型预后和诊断标志物。
