B-Cell Depletion By Rituximab Affects the Distribution of Effector Th-Cell Subsets in Patients with ANCA Associated Vasculitis

Wayel H. Abdulahad¹, Ulrich Specks², Theo Bijma³, Deborah J. Phippard⁴, Fredrick Karnell⁵, Noha Lim⁵, John H. Stone⁶ and Cees G.M. Kallenberg¹, ¹Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands, ²Mayo Clinic College of Medicine, Rochester, MN, ³UMCG, Groningen, Netherlands, ⁴3 Bethesda Metro Center,, Suite 400, Bethesda, MD, ⁵Immune Tolerance Network, Bethesda, MD, ⁶Rheumatology Unit, Massachusetts General Hospital, Boston, MA

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: ANCA, rituximab and vasculitis, T cells

Session Information

Date: Wednesday, November 8, 2017

Title: Vasculitis III: Pathogenesis

Session Type: ACR Concurrent Abstract Session

Session Time: 9:00AM-10:30AM

Background/Purpose:

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/T_FH) homeostasis may contribute to the therapeutic effect of rituximab (RTX) as Th-effector imbalances are involved in the emergence of autoimmune diseases.

Methods:

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 T_FH (producing IL-21) cells were assessed at all time-points using flow cytometry upon in vitro stimulation with PMA and Calcium Ionophore.

Results:

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 T_FH cells. The frequencies of Th2 and T_FH 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).

Conclusion:

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.

Disclosure: W. H. Abdulahad, None; U. Specks, None; T. Bijma, None; D. J. Phippard, None; F. Karnell, None; N. Lim, None; J. H. Stone, None; C. G. M. Kallenberg, None.

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 .

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