The role of immunosenescence in autoimmune/autoinflammatory pathogenesis of Behçet's disease

Abstract

Background and objectives: Behçet’s disease (BD) is a chronic inflammatory disease characterized by recurrent mucocutaneous ulceration and complications such as blindness and large vessel inflammation. Immunosenescence, aging of immune system, is related to increased susceptibility to infectious diseases, vaccine failure, and chronic low grade systemic inflammation. The role of immunosenescence in BD is not well understood. Therefore, the aim of this study was to investigate the differences in the frequencies of immunosenescent cells in the peripheral blood mononulclear cells in BD patients and controls.

Material and methods: Peripheral blood mononulclear cells (PBMCs) were extracted from age-matched active BD patients (n=19), inactive BD patients (n=20), disease controls (DCs, n=15) and healthy controls (HCs, n=15). Using flow cytometry, the frequencies of senescent CD4+ T cells (CD3+ CD4+ CD27- CD28- cells), CD8+ T cells (CD3+ CD8+ CD27- CD28- cells), and B cells (CD19+ CD27- IgD- cells) were analyzed. The differences among the groups, the correlation with chronological age in HC group, and whether the clinical indicators of disease severity, ongoing steroid treatment, or specific organ involvement affected the frequencies of senescent immune cells were investigated. In addition, senescence-associated β galactosidase (SA-β-Gal) activity was investigated in CD8+ T cells, using flow cytometry with 5-dodecanoylaminofluorescein di-β-D-galactopyranoside (C12FDG).

Results: In active BD patients, the frequency of CD3+ CD8+ CD27- CD28- cells was significantly higher than in DCs and in HCs, respectively. Also, the frequency of CD3+ CD8+ CD27- CD28- cells increased significantly with the age in HCs, in accordance with the previous literature. Other senescent immune cells did not show significant differences. The levels of both C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) which indicate disease activity did not correlate with increased frequencies of senescent immune cells. Neither the steroid treatment nor specific organ involvement had significant influence on frequencies of senescent immune cells. Frequencies of SA-β-Gal+ cells among CD8+ T cells were significantly higher in active BD and in inactive BD compared to those in DCs and HCs, respectively.

Conclusion: CD3+ CD8+ CD27- CD28- cells, or senescent CD8+ T cells, were increased in the peripheral blood of patients with BD. Functional study or senescence-inducing study are needed to further elucidate the role of immunosenescence in the pathogenesis of BD.