SAT0273 Increased IL-6 Production by Effector B Cells in GIANT Cell Arteritis and Polymyalgia Rheumatica
Authors: K. van der Geest, W. Abdulahad, P. Lorencetti, G. Horst, A. Boots, E. Brouwer
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The role of B cells in auto-immunity may extend beyond the production of auto-antibodies. B cells can influence T cell responses via antigen presentation and secretion of cytokines. Pathogenic T cell responses are critical in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). Cytokine-producing B cells with distinct effects on T cells have been described. B<sub>regulatory</sub> cells suppress T cell responses via IL-10, whereas B<sub>effector</sub> cells promote inflammation via secretion of TNF-α and/or IL-6. IL-6 is currently considered important in the pathogenesis of GCA and PMR. Little is known on the contribution of B<sub>effector</sub> and B<sub>regulatory</sub> cells to the immunopathology of GCA and PMR. <h3>Objectives</h3> To study the distribution of B<sub>effector</sub> cells and B<sub>regulatory</sub> cells in GCA and PMR patients before and after corticosteroid treatment. <h3>Methods</h3> Circulating B cells were analyzed in 34 newly-diagnosed, non-treated patients with GCA and PMR, and in 44 follow-up samples of GCA and PMR patients receiving corticosteroids for 2 weeks and 3 months. For comparison, 40 age-matched, healthy controls (HCs) were included. Serum BAFF levels were determined by ELISA and temporal arteries were studied by immunohistochemistry. Intracellular staining for TNF-α, IL-6 and IL-10 was performed after stimulating B cells with PMA and Ca2+ ionophore in the presence of Brefelin A for 4 hours. <h3>Results</h3> Newly-diagnosed GCA and PMR patients had decreased numbers of circulating CD19+ B cells when compared to HCs. B cell numbers recovered rapidly in treated GCA and PMR patients in remission. This recovery was not achieved by compensatory hyperproliferation or enhanced bone marrow production. The low B cell counts in newly-diagnosed GCA and PMR patients were associated with an increase in serum levels of the B cell growth factor BAFF. Serum BAFF levels diminished upon the return of B cells during remission. Functional characterization of the B cells showed that circulating numbers of IL-10 producing B<sub>regulatory</sub> cells remain normal in GCA and PMR patients, irrespective of disease activity and treatment. In contrast, circulating numbers of TNF-α producing B<sub>effector</sub> cells were profoundly decreased in newly-diagnosed GCA and PMR patients, but recovered during remission. Moreover, the returning B<sub>effector</sub> cells in GCA and PMR patients demonstrated an enhanced capacity to produce IL-6. Few B cells were found in temporal artery biopsies of GCA patients. <h3>Conclusions</h3> Our combined data indicate that B<sub>effector</sub> cells, but not B<sub>regulatory</sub> cells, are redistributed during active disease and quickly return upon remission. These B<sub>effector</sub> cells are characterized by an enhanced capacity to produce IL-6. The role of these IL-6 producing B<sub>effector</sub> cells in GCA and PMR warrants further investigation, as B cells and IL-6/IL-6R are potential targets for treatment. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2596