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OP0079 Increased Frequencies of IL-23R Positive T Cells and IL-22 and IL-17 Producing Mait Cells in The Peripheral Blood of Patients with Ankylosing Spondylitis: Preliminary Results
  1. E. Toussirot1,
  2. C. Laheurte2,
  3. B. Gaugler3,
  4. P. Saas3
  1. 1Clinical Investigation Center Biotherapy, University Hospital
  2. 2Clinical Investigation Center Biotherapy, EFS B/FC, Plateforme de BioMonitoring
  3. 3INSERM UMR1098, EFS BFC, Besançon, France

Abstract

Background Ankylosing spondylitis (AS) is the prototypic and most common form of spondyloarthritis (SpA). It was recently suggested that IL-23 could play a pivotal role in the pathophysiology of SpA. Indeed, there is a strong genetic association of SpA with polymorphisms of the IL-23 receptor (IL-23R) gene. In experimental models, IL-23 is produced during the misfolding phenomenon of HLA-B27 heavy chain in the endoplasmic reticulum. Furthermore, in animal models, IL-23 overexpression induced a SpA-like disease via IL-23+ resident T cells infiltrating entheseal structures and producing IL-17 and IL-22. In addition, there is an increased number of circulating cells producing IL-17 in patients with AS. Recent data also suggested that IL-17A is a potential target in the treatment of patients with AS.

Objectives Cells that expressed IL-23R as well as those producing IL-17 and/or IL-22 have been poorly characterized in AS and/or SpA. Thus, we aimed to better delineate the peripheral blood T cells that expressed IL-23R and the IL-17 and IL-22 producing cell subsets, notably conventional T cells as well as mucosal associated invariant T cells (MAIT) in patients with AS.

Methods 36 patients with AS (modified NY criteria; 27 M; age: 44.7 ± 2.6, disease duration: 12.7 ± 1.6; all under NSAIDs or traditional DMARDs) and 31 healthy controls (HC) (8 M; age: 46 ± 2.3) were evaluated. For each subject, peripheral blood T cell subsets were assessed using multi-color flow cytometry. Intracellular cytokine IL-17A, IL-22 and IFN-γ were evaluated after phorbol myristate acetate and ionomycine activation and permeabilization and analysed by flow cytometry. MAIT cells were identified by using TCRVα7.2 specific monoclonal antibodies. IL-22 serum levels were determined by ELISA using commercially available kit.

Results the number and percentage of CD3+ T cells, CD3+CD4+ and CD3+CD8+ T cells were comparable between patients and HC. Circulating IL-22 levels did not differ between patients and HC (22.6 ± 8.4 vs 15.1 ± 4.4 pg/ml, p=0.7). IFN-γ producing CD4+ and CD8+ T cells were decreased in AS compared to HC (4.6 ± 1.7 vs 11.4 ± 2.5% and 23.3 ± 1.9 vs 34.3 ± 2.3%, respectively, p=0.005 and p=0.002). CD8+ T cells expressing IL-23R were significantly increased in AS: 72.8 ± 1.5 vs 65.2 ± 2% (p=0.009). The percentage of MAIT T cells did not differ between patients and HC but we found an increased percentage of MAIT cells that produced IL-17 and IL-22: MAIT IFN-γ IL-17+: 0.43 ± 0.1 vs 0.12 ± 0.008%, p=0.006; MAIT IFN-γ IL-22+: 0.83 ± 0.1 vs 0.3 ± 0.1%, p=0.004. No correlation was found between the percentage of CD8+ IL-23R+ T cells and measurements of disease activity as well as between IL-17+ or IL-22+ MAIT cells and disease activity.

Conclusions These preliminary results suggest that the peripheral blood of patients with AS is enriched in CD8+ IL-23R+ T cells as well as IL-17 and IL-22 producing MAIT cells. Since MAIT cells are involved in antibacterial immunity and bacterial agents are potentially involved in SpA, our preliminary data suggest that this T cell subset could potentially play a role in AS via IL-17 and IL22 production. This remains to be clarified by future and complementary studies.

Disclosure of Interest None declared

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