POS0263 PHENOTYPIC AND FUNCTIONAL ALTERATION OF UNCONVENTIONAL T CELLS IN ADULT IGA VASCULITIS
Authors: A. Hankard, E. Barsac, L. Gonzalez, C. Paget, A. Audemard Verger
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> IgA vasculitis (IgAV) affects small vessels and often occurs after a mucosal infection. Patients with IgAV present with purpura associated with joint, gastrointestinal and renal involvement. Diagnosis is based on invasive procedures such as biopsies of the tissue injured. Unconventional T cells (UTC) represent a heterogeneous family of T cells characterised by hybrid properties of both innate and adaptive immunity. They comprise three main lineages including mucosal-associated invariant T cells (MAIT), invariant Natural Killer T cells (iNKT), and certain subsets of γδ T cells (γδT). The role of UTC in the field of autoimmune diseases has already been supported by numerous experimental and clinical studies. However, their involvement in the pathophysiology of vasculitis, and more specifically in IgA vasculitis has been poorly studied. <h3>Objectives:</h3> In this context, we believe it is important to reassess the pathophysiology of IgA vasculitis through the prism of UTC. To this end, we will study the phenotypic and functional characteristics of UTC in IgAV. <h3>Methods:</h3> To investigate a potential involvement of these cells, we studied peripheral blood mononuclear cells (PBMCs) of adult patients from the University Tours Hospital (France) with histologically proven IgA vasculitis prior any corticosteroid treatment. Control patients with ANCA-associated vasculitis (AAV) and giant cell arteritis (GCA), as well as healthy donors (HC), were also enrolled. <h3>Results:</h3> Ten patients with IgAV have been included (Figure 1A), half of them were women (57%) with a median age of 62 years. Regarding the frequencies of circulating UTC, no differences were observed in iNKT cells while the frequency of γδT and MAIT cells were both significantly decreased in IgAV patients (Figure 1B). Interesting, MAIT cells from IgAV patients displayed a clear phenotype of activated cells as demonstrated by increased CD69 and PD-1 expression (Figure 1C). A decreasing trend in MAIT cells during the course of two others vasculitis, ACG and ANCA associated vasculitis has was also observed. In addition, a higher proportion of CD4<sup>+</sup> MAIT in IgAV patients compared with HC was founded (Figure 1D). Among a large panel of integrins and/or chemokine receptors potentially expressed by MAIT, a decrease of the expression of CCR6 on the circulating MAIT in patients with IgAV compared to HC was observed. MAIT cells of IgAV patients were also more prone to produce interferon-γ compared to HC. In parallel, no difference was noted regarding IL-17A secretion (Figure 1.E). Finally, we observed, one month after the vasculitis diagnosis, a trend towards an increase in the percentage of circulating MAIT cells (Figure 1F). <h3>Conclusion:</h3> We described for the first time a numerical and phenotypic alteration in circulating UTC MAIT cells in IgAV patients. This latter phenomenon is also observed in others vasculitis such as ACG and ANCA associated vasculitis. The next step is to localise MAITs in the tissues affected by vasculitis in order to support their role in IgA vasculitis. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>