Session Type: Abstract Submissions (ACR)
Background/Purpose: 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. Bregulatory cells suppress T cell responses via IL-10, whereas Beffector 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 Beffector and Bregulatory cells to the immunopathology of GCA and PMR. Here, we studied the distribution of Beffector cells and Bregulatory cells in GCA and PMR patients before and after corticosteroid treatment.
Methods: 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.
Results: 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 Bregulatory cells remain normal in GCA and PMR patients, irrespective of disease activity and treatment. In contrast, circulating numbers of TNF-α producing Beffector cells were profoundly decreased in newly-diagnosed GCA and PMR patients, but recovered during remission. Moreover, the returning Beffector 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.
Conclusion: Our combined data indicate that Beffector cells, but not Bregulatory cells, are redistributed during active disease and quickly return upon remission. These Beffector cells are characterized by an enhanced capacity to produce IL-6. The role of these IL-6 producing Beffector cells in GCA and PMR warrants further investigation, as B cells and IL-6/IL-6R are potential targets for treatment.
K. S. M. van der Geest,
W. H. Abdulahad,
A. M. H. Boots,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-il-6-production-by-effector-b-cells-in-giant-cell-arteritis-and-polymyalgia-rheumatica/