Impact of rituximab on Treg lymphocytes in MS patients
Author(s): ,
E. Maillart
Affiliations:
Neurology, Pitié Salpêtrière Hospital (AP-HP)
,
A. Ungureanu
Affiliations:
Neurology, Pitié Salpêtrière Hospital (AP-HP); Neurology, Saint Antoine Hospital (AP-HP)
,
D. Derai
Affiliations:
Immunology, Pitié Salpêtrière Hospital (AP-HP), Paris, France
,
G. Macaron
Affiliations:
Neurology, Pitié Salpêtrière Hospital (AP-HP); Mellen Center for Multiple Sclerosis, Neurological Institute, Cleveland Clinic Foundation, Cleveland, OH, United States
,
C. Lubetzki
Affiliations:
Neurology, Pitié Salpêtrière Hospital (AP-HP); Institut du Cerveau et de la Moelle épinière, Sorbonne Université, INSERM, UMR S 1127, CNRS UMR 7225
,
D. Sterlin
Affiliations:
Immunology, Pitié Salpêtrière Hospital (AP-HP), Paris, France; Centre d’Immunologie et des Maladies Infectieuses–Paris (CIMI-Paris), Sorbonne Université, INSERM, Paris, France
,
G. Gorochov
Affiliations:
Immunology, Pitié Salpêtrière Hospital (AP-HP), Paris, France; Centre d’Immunologie et des Maladies Infectieuses–Paris (CIMI-Paris), Sorbonne Université, INSERM, Paris, France
C. Papeix
Affiliations:
Neurology, Pitié Salpêtrière Hospital (AP-HP)
ECTRIMS Online Library. Maillart E. 10/10/18; 228398; P554
Elisabeth Maillart
Elisabeth Maillart
Contributions
Abstract

Abstract: P554

Type: Poster Sessions

Abstract Category: Therapy - Immunomodulation/Immunosuppression

Introduction: Rituximab (RTX), a chimeric anti-CD20 monoclonal antibody (Ab), shares similar mechanism of action with ocrelizumab, a humanized anti-CD20 monoclonal Ab, recently approved by the EMA and FDA for the treatment of multiple sclerosis (MS). RTX is sometimes used off-label in MS. RTX treatment results in circulating B cell, but also T cell depletion. Regulatory T cells (Treg) play an immune-regulatory role and were recently identified to promote oligodendrocyte differentiation and remyelination. Specific impact of RTX on Treg in MS remains unknown.
Objectives: To define the impact of RTX on T and B lymphocytes in MS patients.
Methods: RTX-treated MS patients from the Pitié-Salpêtrière center were consecutively included in a prospective observational study during RTX treatment: 1000 mg IV, followed by a maintenance dose of 1000 mg every 6 months. Main outcome was circulating lymphocytes kinetics (B CD19/B CD20/B CD27/T CD4/T CD8/Treg/NK cells) before the first infusion and 6 months later. Secondary outcomes were the annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) and MRI activity.
Results: 43 patients (55.8% women, 19 relapsing-remitting (RR) MS, 24 progressive MS) were analyzed after 6 months (M6) of follow-up. Mean (SD) EDSS at baseline was 5.2 (1.4) and 5.3 (1.5) at M6 respectively. ARR significantly decreased at M6 from a mean 1.18 (1.2) to 0.18 (0.6) (p=0.00094). MRI activity was reported in 11% of patients compared with 56% at baseline. Levels of CD19+ and CD27+ memory B cell lymphocytes were significantly depleted at M6 (both p< 0.0001). While CD8+ lymphocytes percentage remained unchanged, we found a significant increase in CD4+ lymphocytes levels at M6 (M0: 44,7% (10.8) to M6 52.6% (8.8); p=0.0008). Among CD4+ T cells, activated Treg percentage remained unchanged (M0: 2.24% (1.65) to M6: 1.9% (1.2); p=0.36), but quiescent Treg significantly increased (M0: 1.56% (1.36) to M6: 2.3% (2.2); p=0.036). No change in NK ant NKT cell populations was observed.
Conclusion: Our findings highlight that RTX treatment is associated with an unexpected up-regulation of circulating CD4+ lymphocytes and quiescent Treg levels in MS patients. We postulate that quiescent Treg increase could reflect their reduced conversion into activated Treg, in RTX responders. A larger cohort and a longer follow-up are requested in order to establish a potential link between RTX clinical efficacy and T cell parameters at the individual level.
Disclosure: Elisabeth Maillart has received consulting, lecturing fees and travel grants from Biogen Idec, Genzyme, Novartis, Merck Serono, Roche, Sanofi, and Teva Pharma, and research support from Novartis and Roche. Aurelian Ungureanu received travel grants form Biogen Idec and Genzyme and was supported by DuPré Grant Programme of MS International Federation. David Derai has nothing to disclose. Gabrielle Macaron is supported by Biogen Fellowship Grant # 6873-P-FEL. Catherine Lubetzki received research grants from Merck Serono and Biogen Idec, and consultation fees for advisory board participation from Roche. Delphine Sterlin has nothing to disclose. Guy Gorochov has nothing to disclose. Caroline Papeix has received consulting and lecturing fees from Merck Serono, Roche, Novartis, Biogen and Medday.

Abstract: P554

Type: Poster Sessions

Abstract Category: Therapy - Immunomodulation/Immunosuppression

Introduction: Rituximab (RTX), a chimeric anti-CD20 monoclonal antibody (Ab), shares similar mechanism of action with ocrelizumab, a humanized anti-CD20 monoclonal Ab, recently approved by the EMA and FDA for the treatment of multiple sclerosis (MS). RTX is sometimes used off-label in MS. RTX treatment results in circulating B cell, but also T cell depletion. Regulatory T cells (Treg) play an immune-regulatory role and were recently identified to promote oligodendrocyte differentiation and remyelination. Specific impact of RTX on Treg in MS remains unknown.
Objectives: To define the impact of RTX on T and B lymphocytes in MS patients.
Methods: RTX-treated MS patients from the Pitié-Salpêtrière center were consecutively included in a prospective observational study during RTX treatment: 1000 mg IV, followed by a maintenance dose of 1000 mg every 6 months. Main outcome was circulating lymphocytes kinetics (B CD19/B CD20/B CD27/T CD4/T CD8/Treg/NK cells) before the first infusion and 6 months later. Secondary outcomes were the annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) and MRI activity.
Results: 43 patients (55.8% women, 19 relapsing-remitting (RR) MS, 24 progressive MS) were analyzed after 6 months (M6) of follow-up. Mean (SD) EDSS at baseline was 5.2 (1.4) and 5.3 (1.5) at M6 respectively. ARR significantly decreased at M6 from a mean 1.18 (1.2) to 0.18 (0.6) (p=0.00094). MRI activity was reported in 11% of patients compared with 56% at baseline. Levels of CD19+ and CD27+ memory B cell lymphocytes were significantly depleted at M6 (both p< 0.0001). While CD8+ lymphocytes percentage remained unchanged, we found a significant increase in CD4+ lymphocytes levels at M6 (M0: 44,7% (10.8) to M6 52.6% (8.8); p=0.0008). Among CD4+ T cells, activated Treg percentage remained unchanged (M0: 2.24% (1.65) to M6: 1.9% (1.2); p=0.36), but quiescent Treg significantly increased (M0: 1.56% (1.36) to M6: 2.3% (2.2); p=0.036). No change in NK ant NKT cell populations was observed.
Conclusion: Our findings highlight that RTX treatment is associated with an unexpected up-regulation of circulating CD4+ lymphocytes and quiescent Treg levels in MS patients. We postulate that quiescent Treg increase could reflect their reduced conversion into activated Treg, in RTX responders. A larger cohort and a longer follow-up are requested in order to establish a potential link between RTX clinical efficacy and T cell parameters at the individual level.
Disclosure: Elisabeth Maillart has received consulting, lecturing fees and travel grants from Biogen Idec, Genzyme, Novartis, Merck Serono, Roche, Sanofi, and Teva Pharma, and research support from Novartis and Roche. Aurelian Ungureanu received travel grants form Biogen Idec and Genzyme and was supported by DuPré Grant Programme of MS International Federation. David Derai has nothing to disclose. Gabrielle Macaron is supported by Biogen Fellowship Grant # 6873-P-FEL. Catherine Lubetzki received research grants from Merck Serono and Biogen Idec, and consultation fees for advisory board participation from Roche. Delphine Sterlin has nothing to disclose. Guy Gorochov has nothing to disclose. Caroline Papeix has received consulting and lecturing fees from Merck Serono, Roche, Novartis, Biogen and Medday.

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