Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: In anti-neutrophil cytoplasmic antibodies associated vasculitis (AAV), several clues suggest that the efficacy of B cell depletion therapy lies beyond the suppression of ANCA-producing cells and may involve the suppression of B-T cell crosstalk. However, little if any data are available regarding the impact of rituximab on CD4, regulatory T and CD8 T cells in this setting.
Methods: Using polychromatic flow cytometry we performed a thorough immunophenotypic analysis of CD4, regulatory T and CD8 cells of 53 patients with AAV in order to compare the effect of conventional immunosuppressants (CIS) and rituximab (RTX) on these 3 T cells compartments. Cytokine/chemokine production of in vitro stimulated CD8 T cells was assessed using a multiplex Luminex immunoassay
Results: Among CD4 T cells, we found that frequency of naïve and memory subsets and the expression of CCR5, CCR4 and CD161 were not influenced by maintenance treatment type. Similarly, total Treg frequency and Treg subsets including CD161+, Helios+, resting (CD45RA+) and memory (CD45RA–FoxP3hi) Tregs were comparable among RTX and CIS treated patients. By contrast, the type of maintenance treatment markedly influenced the CD8+ T cell compartment. Indeed, RTX inhibited late differentiated effector memory (TEMRA; CD45RA+CCR7–) CD8 cell expansion whereas CIS had the opposite effect, particularly in CMV positive individuals. Furthermore, we found that unlike CIS, B cell depletion therapy effectively inhibited the pro-inflammatory cytokine/chemokine production of in vitro stimulated CD8 T cells.
Conclusion: B cell depletion therapy has a profound impact on the CD8 T cell compartment. This observation raises the question whether the disruption of B cell help to CD8 T cells could contribute to the dramatic efficacy of RTX. Whether B cell depletion therapy promotes CD8 T cell exhaustion and/or inhibits immunosenescence deserves further investigations.
To cite this abstract in AMA style:Néel A, Bucchia M, Caristan A, Néel M, Rimbert M, Agard C, Hourmant M, Tilly G, Yap M, Perrin F, Godmer P, Graveleau J, Brouard S, Bressollette C, Fakhouri F, Hamidou M, Degauque N. B Cell Depletion Therapy Impact CD8 T Cells in ANCA-Associated Vasculitis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/b-cell-depletion-therapy-impact-cd8-t-cells-in-anca-associated-vasculitis/. Accessed November 23, 2020.
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