Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Increased Frequency of Circulating Follicular Helper T-Cells (TFH) in Patients with Granulomatosis with Polyangiitis.
Abdulahad1, Wayel H., Lepse1, Nikola, Tadema1, Henko, Huitema1, Minke G., der Meer1, Berber Doornbos-van, Stegeman1, Coen, Limburg1, Pieter C.
Follicular helper T cells (TFH) are a newly distinguishable subset of Th cells characterized by IL-21 production that influences B-cell differentiation and antibody production. Recent studies support the concept that TFH cells are an important player in antibody-mediated autoimmune diseases. In the present study, we aimed to explore a possible role for TFH cells in the immunopathogenesis of granulomatosis with polyangiitis (GPA).
Peripheral blood from 33 GPA-patients in remission and 22 age-matched healthy controls (HCs) were stimulated in vitro with Phorbol-Myristate-Acetate and Calcium-Ionophore in the presence of Brefeldin-A. Intracellular IL-21 was used as a marker for TFH cells. Since Th-17 cells produce a low level of IL-21, IL-17 was also included in the analysis to discriminate between TFH cells (IL-17-IL-21+) and Th-17 cells (IL-17+IL-21+/-). The frequencies of TFH cells were determined by 4-color cytometric detection of CD4 (negatively gated as CD3+CD8- cells), and intracellular cytokine expression of IL-21 and IL-17. The mRNA expression level of transcription factors Bcl-6 (for TFH) and RoRgc (for Th17) were evaluated in lysed cell from GPA-patients and HCs. To investigate the effect of IL-21 on antibody-production, PBMCs from GPA-patients were stimulated in vitro with BAFF/IL-21 for 12 days and total IgG was measured in supernatants by ELISA. In addition, the expression level of IL-21-receptor on B-cells was analyzed in GPA-patients and HCs.
Percentages of circulating TFH cells were significantly elevated in GPA-patients compared to HCs (P= 0.001). The expression level of Bcl-6 was significantly higher in GPA-patients, whereas no difference was found in RoRgc between GPA-patients and HCs. The hallmark cytokine for TFH, IL-21, enhance the production of IgG in vitro in stimulated PBMCs from GPA-patients. Moreover, frequencies of TFH cells were significantly increased in ANCA-positive patients (n=21) in comparison to HCs (P= 0.0009), whereas no such difference was found between ANCA-negative patients (n=12) and HCs.
Increased frequencies of circulating TFH cells producing IL-21 suggest a role for these cells in the immunopathogenesis of GPA. Blockade of IL-21 could constitute a new therapeutic strategy for GPA.
To cite this abstract, please use the following information:
Abdulahad, Wayel H., Lepse, Nikola, Tadema, Henko, Huitema, Minke G., der Meer, Berber Doornbos-van, Stegeman, Coen, et al; Increased Frequency of Circulating Follicular Helper T-Cells (TFH) in Patients with Granulomatosis with Polyangiitis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :794