Session Title: Vasculitis II
Session Type: Abstract Submissions (ACR)
Giant cell arteritis (GCA) is a primary vasculitis affecting large to medium-sized arteries. Ample evidence suggests that dendritic cells, T cells and monocytes/macrophages contribute to the immunopathology of GCA. Previous reports showed that B cells are not predominant cells in temporal arteries of GCA patients (Cid et al. AR 1989). However, a high prevalence of various auto-antibodies in serum of GCA patients is suggestive of B cell activation in GCA (Baerlecken et al. ARD 2012; Regent et al. ART 2011; Schmits et al. Clin Exp Immunol 2002). Furthermore, emerging data indicate that B cells can modulate immune responses of T cells and monocytes by producing IL-10 and TNF-α (Lund et al. Nat Rev Immunol 2010). In the current study, we assessed the distribution of defined B cell subsets, including IL-10+ regulatory B cells and TNF-α+ effector B cells, in GCA patients before and after glucocorticoid (GC) treatment.
B cells were analyzed in peripheral blood of 15 newly-diagnosed GCA patients. In addition, we studied 40 age-matched, healthy controls (HCs) and 28 disease controls, including 17 polymyalgia rheumatica (PMR) patients and 11 rheumatoid arthritis (RA) patients. In a prospective, longitudinal study design, 39 samples were obtained from GCA and PMR patients who were in remission after 2 and 12 weeks of treatment with GCs. Serum levels of BAFF were determined. Flow cytometric staining of B cells for intracellular TNF-α and IL-10 was performed after 4 hours of stimulation with PMA and calcium ionophore in the presence of brefeldin A.
Circulating B cells were decreased in newly-diagnosed GCA and PMR patients, but not in RA patients, compared to HCs. Following 2 and 12 weeks of GC treatment, B cell numbers normalized in GCA and PMR patients. This normalization was neither attributable to repopulation by immature-transitional B cells from the bone marrow, nor to compensatory hyperproliferation in the blood. Instead, already existing mature B cell subsets seemed to be mobilised towards the circulation of treated GCA and PMR patients. In particular the circulating pool of unswitched and switched memory B cells was expanded after GC treatment. B cell numbers inversely correlated with ESR, CRP and serum levels of the B cell growth factor BAFF. In newly-diagnosed GCA patients, TNF-α+ effector B cells but not IL-10+ regulatory B cells were decreased. Following treatment, numbers of TNF-α+ effector B cells and IL-10+ regulatory B cells were normal in GCA patients.
Our data indicate that B cells, including TNF-α+ effector B cells, are redistributed during active GCA and PMR. Following treatment, mature B cells subsets, in particular memory B cells, are mobilized to the circulation. In accordance with the high prevalence of various auto-antibodies reported in GCA and PMR, our data further suggest that activation of B cells occurs during the active stages of both diseases. Additional studies on the pro-inflammatory and regulatory role of B cells in GCA and PMR are ongoing.
K. S. M. van der Geest,
W. H. Abdulahad,
A. M. H. Boots,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/b-cells-revisited-in-giant-cell-arteritis/