Investigating the Role of T-bet+ B Cells (ABCs/DN) in the Immunopathogenesis of Systemic Lupus Erythematosus

Athanasios Sachinidis; Maria Trachana; Anna Taparkou; George Gavriilidis; Panayotis Verginis; Fotis Psomopoulos; Christina Adamichou; Dimitrios Boumpas; Alexandros Garyfallos

doi:10.31138/mjr.34.1.117

Investigating the Role of T-bet⁺ B Cells (ABCs/DN) in the Immunopathogenesis of Systemic Lupus Erythematosus

Mediterr J Rheumatol. 2023 Mar 31;34(1):117-120. doi: 10.31138/mjr.34.1.117. eCollection 2023 Mar.

Authors

Athanasios Sachinidis¹, Maria Trachana², Anna Taparkou², George Gavriilidis³, Panayotis Verginis⁴, Fotis Psomopoulos³, Christina Adamichou¹, Dimitrios Boumpas⁵, Alexandros Garyfallos¹

Affiliations

¹ 4 Department of Internal Medicine, Hippokration General Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
² Paediatric Immunology and Rheumatology Referral Centre, 1 Paediatric Department, Hippokration General Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
³ Institute of Applied Biosciences, Centre for Research and Technology Hellas, Thermi, Thessaloniki, Greece.
⁴ Laboratory of Immune Regulation and Tolerance, Division of Basic Sciences, Medical School, University of Crete, Heraklion, Greece.
⁵ 4 Department of Internal Medicine, "Attikon" University Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Abstract

Background: Age-associated B cells (ABCs) constitute a B cell subset, defined as CD19⁺CD21^-CD11c⁺, that expands continuously with age and accumulates strongly in individuals with autoimmune and/or infectious diseases. In humans, ABCs are principally IgD^-CD27^- 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.

Aims of the study: 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.

Methods: 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.

Anticipated benefits: 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.

Keywords: ABCs; DN; SLE; T-bet; age-associated B cells; autoimmunity.