Background Compelling evidence suggests that IL-17 and IL-17 producing T lymphocytes play a pivotal role in the pathogenesis of primary Sjögren's syndrome (pSS). In particular, IL-17 producing CD3+CD4-CD8- (double negative, DN) T cells are expanded in the peripheral blood (PB), infiltrate minor salivary glands (MSGs), and are associated with ectopic lymphoneogenesis (1, 2). It has been demonstrated that, besides its B-cell tropism, the anti-CD20 antibody rituximab (RTX) is also able to interfere with IL-17 axis in the PB and synovial tissue of patients with rheumatoid arthritis by depleting the CD20+ cell fraction of IL-17-producing T lymphocytes. Similarly, RTX is able to reduce glandular IL-17 in pSS (3) but, to date, no data are available about its possible role on IL-17-producing T-cell subsets in this disease.
Objectives Aim of the study was to investigate phenotypic and functional effects of RTX on circulating and glandular IL-17 producing T cells in pSS.
Methods MSGs and PB samples were obtained from patients with early and active pSS at different time-points during the treatment with either RTX (n. 22) or disease modifying anti-rheumatic drugs (DMARDs) (n. 16). These patients were part of a previously published trial (4). Flow cytometry was employed for phenotypic analysis of PB and MSG T cells. Hematoxilin-eosin and double immunofluorescence staining were employed on MSG tissue specimens to assess cellular infiltrate, T/B-cell compartmentalization, and lymphoid organization.
Results RTX was able to deplete IL-17-producing DN T, but not CD4+Th17 cells, in the PB at month 3 (T3). At month 6 (T6), both cell subsets were significantly increased in the PB compared to baseline. After 2 courses of RTX (month 12, T12), glandular DN T cells and CD4+ Th17 cells were markedly depleted. No modifications in IL-17+DN T and CD4+Th17 cells were observed in PB and MSGs of patients treated with DMARDs at T3, T6 and T12. A subset of IL-17-producing DN T cells and CD4+Th17 cells isolated from PB and MSGs co-expresses CD20 on the cell surface explaining the T-cell depleting activity of RTX. The exposure to RTX did not rescue the already characterized in vitro corticosteroid (CS)-resistance of circulating pSS IL-17+DN T cells (1). Similarly to PB, also glandular DN T cells did not reduce IL-17 production in presence of CS in vitro. Of interest, unlike circulating CD4+Th17 cells (1), those isolated from pSS-MSGs were resistant to CS in vitro.
Conclusions In this study, we provided evidence that RTX is able to affect IL-17-producing T cells also in pSS by depleting the CD20+ cell fraction. Taken the well-established pathogenic role of IL-17 axis in pSS, our results further support the therapeutic role of RTX that, despite its B-cell specificity, appears able to hamper also IL-17-producing pathogenic T cells in this disease.
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Ciccia F et al. Rheumatology (Oxford) 2014;53:1313-20
Carubbi F et al. Arthritis Res Ther 2013;15:R172
Disclosure of Interest None declared