B Cell Depletion Therapy Impact CD8 T Cells in ANCA-Associated Vasculitis

Antoine Néel^1,2, Marie Bucchia³, Aurelie Caristan¹, Mélanie Néel², Marie Rimbert⁴, Christian Agard¹, Maryvonne Hourmant⁵, Gaelle Tilly², Michelle Yap², François Perrin¹, Pascal Godmer⁶, Julie Graveleau¹, Sophie Brouard², Celine Bressollette⁷, Fadi Fakhouri⁸, Mohamed Hamidou⁹ and Nicolas Degauque², ¹Internal Medicine Department, Nantes University Hospital, Nantes, France, ²INSERM U1064, Nantes, France, ³Pediatrics, Nantes University Hospital, Nantes, France, ⁴Immunology Laboratory, Nantes University Hospital, Nantes, France, ⁵Nephrology, Nantes University Hospital, Nantes, France, ⁶CH Vannes, Vannes, France, ⁷Virology Laboratory, Nantes University Hospital, Nantes, France, ⁸Nephrology Department, Nantes University Hospital, Nantes, France, ⁹Internal Medicine Department, Internal Medicine Department, Nantes University Hospital, Nantes, France

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: CD8 cells, rituximab and vasculitis, T cells, T-Regulatory Cells

Session Information

Date: Monday, November 14, 2016

Title: T Cell Biology and Targets in Autoimmune Disease - Poster Session I

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^–FoxP3^hi) 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.

Disclosure: A. Néel, None; M. Bucchia, None; A. Caristan, None; M. Néel, None; M. Rimbert, None; C. Agard, None; M. Hourmant, None; G. Tilly, None; M. Yap, None; F. Perrin, None; P. Godmer, None; J. Graveleau, None; S. Brouard, None; C. Bressollette, None; F. Fakhouri, None; M. Hamidou, None; N. Degauque, None.

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 .

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