Granzyme B producing regulatory B-cells in patients with giant cell arteritis.

Abstract

Objectives: Giant cell arteritis (GCA) is a serious inflammatory rheumatic disease driven by T-cells which are regulated by B-cells with anti-inflammatory activity. However, the role of these regulatory B-cells has not been studied in detail. The aim of this study is to investigate the anti-inflammatory B-cell compartment in patients with GCA.

Methods: Peripheral blood mononuclear cells (PBMC) of GCA Patients (n=47) and healthy controls (HC) (n=49) were isolated to assess the granzyme B (GrB) and Interleukin- 10 (IL-10) production of regulatory B-cells (Breg) after in vitro stimulation.

Results: The fraction of GrB producing Breg in GCA patients was diminished as compared to HC, and this was independent of current disease activity. In contrast, there were no significant differences between patients and HC with regard to IL-10 producing Breg. In GCA patients with active disease, CD4+ T-cells produced less IFNγ than HC. Regarding other T-cell derived pro-inflammatory cytokines, a trend towards a lower expression as compared to HC was seen.

Conclusions: Regulatory B-cells were differentially altered in patients with GCA. While GrB producing Breg were persistently diminished, IL-10 producing Breg showed no differences between patients and controls. This may indicate a lack of B-cell based suppressive capacity which has influence on the T-cell compartment.