Background: Systemic lupus erythematosus (SLE) is an autoimmune disease driven by B cell dysfunction, leading to autoantibody production and systemic inflammation. GPR56, a regulator of immune cell function, has been studied in T and NK cells but remains understudied in B cells. Exploring GPR56 expression in B cells may uncover its role in SLE pathogenesis and its potential as a diagnostic biomarker.

Objectives: This study aims to investigate the role of GPR56 in peripheral blood B cells and its alterations in systemic lupus erythematosus (SLE) patients, emphasizing its potential as a clinical diagnostic marker.

Methods: Peripheral blood samples were obtained from 30 SLE patients and 21 healthy controls. GPR56 expression in B cells was analyzed using flow cytometry. CD19+GPR56+ and CD19+GPR56- B cells were isolated and subjected to RNA sequencing to identify differentially expressed genes and pathways. In vitro experiments examined GPR56 expression and its associated molecules (CD28, CD226, CD2, GZMB, GNLY, IL-1β) in both resting and LPS-stimulated PBMCs. The relationship between GPR56+ B cell subsets and clinical indicators was assessed, and the diagnostic value of these subsets was evaluated using ROC curve analysis.

Results: GPR56 expression was significantly elevated in SLE patients compared to healthy controls, particularly in plasmablasts. RNA sequencing revealed substantial upregulation of immune-related molecules,such as CD28 and CD226, along with cytotoxic effectors (GZMB, GNLY, IL-1β) in GPR56+ B cells, indicating enhanced immune activity. Flow cytometry confirmed elevated levels of CD28, CD226, and CD2 in GPR56+ B cells. Moreover, the proportion of GPR56+ B cells demonstrated strong correlations with clinical indicators, including anti-U1RNP antibodies and IgM levels. ROC curve analysis highlighted the diagnostic potential of GPR56+ B cells and related subsets, with area under the curve (AUC) values ranging from 0.6754 to 0.8377.

Conclusion: GPR56+ B cells play a pivotal role in immune regulation and are likely contributors to the autoimmune dysregulation observed in SLE. Their increased prevalence in SLE patients highlights their potential utility as a diagnostic biomarker.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.