T cell activation markers CD38 and HLA-DR indicative of non-seroconversion in anti-CD20-treated patients with multiple sclerosis following SARS-CoV-2 mRNA vaccination

Niels J M Verstegen; Ruth R Hagen; Christine Kreher; Lisan H Kuijper; Jet van den Dijssel; Thomas Ashhurst; Laura Y L Kummer; Virginia Palomares Cabeza; Maurice Steenhuis; Mariël C Duurland; Rivka de Jongh; C Ellen van der Schoot; Veronique A L Konijn; Erik Mul; Katherine Kedzierska; Koos P J van Dam; Eileen W Stalman; Laura Boekel; Gertjan Wolbink; Sander W Tas; Joep Killestein; Theo Rispens; Luuk Wieske; Taco W Kuijpers; Filip Eftimov; Zoé L E van Kempen; S Marieke van Ham; Anja Ten Brinke; Carolien E van de Sandt; T2B! immunity against SARS-CoV-2 study group

doi:10.1136/jnnp-2023-332224

T cell activation markers CD38 and HLA-DR indicative of non-seroconversion in anti-CD20-treated patients with multiple sclerosis following SARS-CoV-2 mRNA vaccination

J Neurol Neurosurg Psychiatry. 2024 Mar 28:jnnp-2023-332224. doi: 10.1136/jnnp-2023-332224. Online ahead of print.

Authors

Niels J M Verstegen¹, Ruth R Hagen^#^{2

3}, Christine Kreher^#¹, Lisan H Kuijper^#¹, Jet van den Dijssel^#^{2

3}, Thomas Ashhurst^{4

5}, Laura Y L Kummer^{1

6}, Virginia Palomares Cabeza¹, Maurice Steenhuis¹, Mariël C Duurland¹, Rivka de Jongh¹, C Ellen van der Schoot³, Veronique A L Konijn¹, Erik Mul⁷, Katherine Kedzierska^{8

9}, Koos P J van Dam⁶, Eileen W Stalman⁶, Laura Boekel¹⁰, Gertjan Wolbink¹⁰, Sander W Tas¹¹, Joep Killestein¹², Theo Rispens¹, Luuk Wieske^{6

13}, Taco W Kuijpers¹⁴, Filip Eftimov⁶, Zoé L E van Kempen¹², S Marieke van Ham^{1

15}, Anja Ten Brinke¹⁶, Carolien E van de Sandt^{17

8}; T2B! immunity against SARS-CoV-2 study group

Collaborators

T2B! immunity against SARS-CoV-2 study group:
A J Vd Kooi, J Raaphorst, A H Koos Zwinderman, M Löwenberg, A G Volkers, Gram D'Haens, R B Takkenberg, P I Spuls, M W Bekkenk, A H Musters, N F Post, A L Bosma, M L Hilhorst, Y Vegting, F J Bemelman, L Fernandez, S Keijzer, Jbd Keijser, O Cristianawati, A E Voskuyl, B Broens, A P Sanchez, S Nejentsev, E S Mirfazeli, B A Rutgers, K de Leeuw, B Horváth, Jjgm Verschuuren, A M Ruiter, L van Ouwerkerk, D van der Woude, Rcf Allaart, Yko Teng, P A Pieter van Paassen, M H Busch, E Brusse, P A van Doorn, Mae Baars, D J Hijnen, Crg Schreurs, W L van der Pol, H S Goedee, Cacm van Els, J de Wit

Affiliations

¹ Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
² Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
³ Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
⁴ Sydney Cytometry Core Research Facility, Charles Perkins Centre, Centenary Institute, and The University of Sydney, Sydney, NSW, Australia.
⁵ School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
⁶ Department of Neurology and Neurophysiology, Amsterdam Neuroscience, Amsterdam UMC, location AMC, University of Amsterdam, Amsterdam, The Netherlands.
⁷ Research Facilities, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
⁸ Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
⁹ Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan.
¹⁰ Department of Rheumatology, Amsterdam Rheumatology and Immunology Center location Reade, Amsterdam, The Netherlands.
¹¹ Department of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
¹² Department of Neurology, Amsterdam UMC, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.
¹³ Department of Clinical Neurophysiology, St Antonius Hospital, Nieuwegein, The Netherlands.
¹⁴ Department of Pediatric Immunology, Rheumatology and Infectious Disease, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, The Netherlands.
¹⁵ Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
¹⁶ Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands cvandesandt@unimelb.edu.au a.tenbrinke@sanquin.nl.
¹⁷ Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands cvandesandt@unimelb.edu.au a.tenbrinke@sanquin.nl.

^# Contributed equally.

PMID: 38548324
DOI: 10.1136/jnnp-2023-332224

Abstract

Background: Messenger RNA (mRNA) vaccines provide robust protection against SARS-CoV-2 in healthy individuals. However, immunity after vaccination of patients with multiple sclerosis (MS) treated with ocrelizumab (OCR), a B cell-depleting anti-CD20 monoclonal antibody, is not yet fully understood.

Methods: In this study, deep immune profiling techniques were employed to investigate the immune response induced by SARS-CoV-2 mRNA vaccines in untreated patients with MS (n=21), OCR-treated patients with MS (n=57) and healthy individuals (n=30).

Results: Among OCR-treated patients with MS, 63% did not produce detectable levels of antibodies (non-seroconverted), and those who did have lower spike receptor-binding domain-specific IgG responses compared with healthy individuals and untreated patients with MS. Before vaccination, no discernible immunological differences were observed between non-seroconverted and seroconverted OCR-treated patients with MS. However, non-seroconverted patients received overall more OCR infusions, had shorter intervals since their last OCR infusion and displayed higher OCR serum concentrations at the time of their initial vaccination. Following two vaccinations, non-seroconverted patients displayed smaller B cell compartments but instead exhibited more robust activation of general CD4⁺ and CD8⁺ T cell compartments, as indicated by upregulation of CD38 and HLA-DR surface expression, when compared with seroconverted patients.

Conclusion: These findings highlight the importance of optimising treatment regimens when scheduling SARS-CoV-2 vaccination for OCR-treated patients with MS to maximise their humoral and cellular immune responses. This study provides valuable insights for optimising vaccination strategies in OCR-treated patients with MS, including the identification of CD38 and HLA-DR as potential markers to explore vaccine efficacy in non-seroconverting OCR-treated patients with MS.

Keywords: COVID-19; MULTIPLE SCLEROSIS.