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1.
Neurol Clin Pract ; 14(1): e200241, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38204588

ABSTRACT

Background: Anti-CD20 therapies have proven to be highly effective and safe therapies for multiple sclerosis (MS) and have had rapid uptake in the MS community. However, no clear consensus has arisen regarding an approach to screening or surveillance lab monitoring. Recent Findings: Based on current evidence, for screening labs before anti-CD20 initiation, we propose checking liver function test (LFT), complete blood count with differential (CBC), absolute B-cell count, quantitative immunoglobulins, hepatitis B virus serologies, varicella zoster virus IgG, John Cunningham virus (JCV) status, and age-appropriate vaccination history. For surveillance monitoring in an otherwise asymptomatic individual, we propose biannual LFTs and CBC, quantitative immunoglobulins annually after year 3, absolute B-cell count at month 6 and in the setting of relapse, and JCV only if clinical or radiographic features of progressive multifocal leukoencephalopathy arise. For ublituximab, pregnancy testing is additionally recommended before each infusion. Implications for Practice: We propose evidence-based screening and safety surveillance labs which take into account likelihood of changing management in an otherwise stable or asymptomatic individual.

2.
Nat Med ; 27(11): 1990-2001, 2021 11.
Article in English | MEDLINE | ID: mdl-34522051

ABSTRACT

SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared with healthy controls (n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (TFH) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (TH1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating TFH responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20.


Subject(s)
COVID-19 Vaccines/therapeutic use , Multiple Sclerosis/immunology , Multiple Sclerosis/therapy , SARS-CoV-2/immunology , Animals , Antibodies, Monoclonal/therapeutic use , Antibodies, Viral/analysis , Antibodies, Viral/blood , Antigens, CD20/immunology , COVID-19/prevention & control , Case-Control Studies , Chlorocebus aethiops , HEK293 Cells , Humans , Immunity, Cellular , Immunity, Humoral/drug effects , Immunity, Humoral/physiology , Immunotherapy/methods , Longitudinal Studies , Multiple Sclerosis/blood , RNA, Messenger/immunology , RNA, Viral/immunology , Rituximab/pharmacology , Rituximab/therapeutic use , SARS-CoV-2/genetics , Vaccination , Vero Cells
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