TY - JOUR
T1 - 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
AU - Verstegen, Niels J.M.
AU - Hagen, Ruth R.
AU - Kreher, Christine
AU - Kuijper, Lisan H.
AU - van den Dijssel, Jet
AU - Ashhurst, Thomas
AU - Kummer, Laura Y.L.
AU - Cabeza, Virginia Palomares
AU - Steenhuis, Maurice
AU - Duurland, Mariël C.
AU - de Jongh, Rivka
AU - van der Schoot, C. Ellen
AU - Konijn, Veronique A.L.
AU - Mul, Erik
AU - Kedzierska, Katherine
AU - van Dam, Koos P.J.
AU - Stalman, Eileen W.
AU - Boekel, Laura
AU - Wolbink, Gertjan
AU - Tas, Sander W.
AU - Killestein, Joep
AU - Rispens, Theo
AU - Wieske, Luuk
AU - Kuijpers, Taco W.
AU - Eftimov, Filip
AU - van Kempen, Zoé L.E.
AU - van Ham, S. Marieke
AU - ten Brinke, Anja
AU - van de Sandt, Carolien E.
AU - vd Kooi, A. J.
AU - Raaphorst, J.
AU - Zwinderman, A. H.Koos
AU - Löwenberg, M.
AU - Volkers, A. G.
AU - D'Haens, G. R.A.M.
AU - Takkenberg, R. B.
AU - Spuls, P. I.
AU - Bekkenk, M. W.
AU - Musters, A. H.
AU - Post, N. F.
AU - Bosma, A. L.
AU - Hilhorst, M. L.
AU - Ruiter, A. M.
AU - van der Woude, D.
AU - Baars, M. A.E.
AU - Hijnen, D. J.
AU - Schreurs, C. R.G.
AU - van der Pol, W. L.
AU - Goedee, H. S.
AU - de Wit, J.
N1 - Publisher Copyright:
© Author(s) (or their employer(s)) 2024.
PY - 2024/8/16
Y1 - 2024/8/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85190647857&partnerID=8YFLogxK
U2 - 10.1136/jnnp-2023-332224
DO - 10.1136/jnnp-2023-332224
M3 - Article
C2 - 38548324
AN - SCOPUS:85190647857
SN - 0022-3050
VL - 95
SP - 855
EP - 864
JO - Journal of Neurology, Neurosurgery and Psychiatry
JF - Journal of Neurology, Neurosurgery and Psychiatry
IS - 9
M1 - jnnp-2023-332224
ER -