Session Type: ACR Concurrent Abstract Session
Session Time: 9:00AM-10:30AM
The current study is aimed to assess the effect of B-cell depletion on the distribution of effector T-cell subsets in AAV-patients. Alterations in CD4+ Th effector cell (Th1/Th2/Th17/TFH) homeostasis may contribute to the therapeutic effect of rituximab (RTX) as Th-effector imbalances are involved in the emergence of autoimmune diseases.
Patients with active AAV were treated in a randomized, controlled trial with corticosteroids combined with RTX 375 mg/m2 weekly x 4 or oral cyclophosphamide (CYC) 2m/kg/d for 6 months as induction therapy. Blood samples from 69 of these AAV-patients were obtained at baseline, 2 months, and 6 months (primary endpoint), and time of assessment for clinical remission. The frequency of circulating Th1 (producing IFNγ), Th2 (producing IL-4), Th17 (producing IL-17), and TFH (producing IL-21) cells were assessed at all time-points using flow cytometry upon in vitro stimulation with PMA and Calcium Ionophore.
At baseline, the four circulating effector Th-cell subsets were comparable in frequency between the RTX-group and the CYC-group. Among the RTX-treated patients, the frequency of Th2 cells decreased steadily, whereas, no significant changes were seen in frequencies of Th1, Th17, and TFH cells. The frequencies of Th2 and TFH cells in CYC-treated patients remained unchanged during the follow-up compared to baseline; whereas, a significant increase was observed in Th17 and Th1 cells at 2 and 6 months, respectively. Interestingly, the decrease in the percentage of Th2 cells among the RTX-treated patients at 6 months was restricted to patients who achieved complete and sustained remission up to 18 months (n=24); whereas, no such changes were observed in patients who relapsed after the achievement of complete remission at 6 months (n=9). Moreover, among the CYC treated patients, the increases in Th17 cells at 2 and 6 months were restricted to patients who achieved complete and sustained remission (n=15) in comparison to those who experienced relapses (n=7).
In patients with active AAV, B-cell depletion therapy, as well as treatment with oral CYC influences blood Th cell homeostasis. Changes in Th cell during induction therapy with RTX or CYC may contribute to long-term clinical outcome.
To cite this abstract in AMA style:Abdulahad WH, Specks U, Bijma T, Phippard DJ, Karnell F, Lim N, Stone JH, Kallenberg CGM. B-Cell Depletion By Rituximab Affects the Distribution of Effector Th-Cell Subsets in Patients with ANCA Associated Vasculitis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/b-cell-depletion-by-rituximab-affects-the-distribution-of-effector-th-cell-subsets-in-patients-with-anca-associated-vasculitis/. Accessed October 20, 2020.
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