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C. blood CD19+ B lymphocytes before the third dose of vaccination in pwMS treated with fingolimod predict the subsequent increase of anti-SARS-CoV2 Mouse monoclonal to CD21.transduction complex containing CD19, CD81and other molecules as regulator of complement activation antibodies. Conclusion This work suggests that evaluating the percentage of CD19+ B cells may be important to identify patients at risk of not producing SARS-CoV-2 antibodies, with possible reduced protection from COVID-19. Keywords: Multiple sclerosis, Fingolimod, COVID-19 vaccination, B lymphocytes, anti-SARS-CoV2 antibodies 1.?Introduction Coronavirus disease 2019 (COVID-19) vaccination is less effective in patients with multiple sclerosis (MS) treated with fingolimod, as evaluated through antibody response, T-cell specific responses and risk of developing breakthrough COVID-19. Even GnRH Associated Peptide (GAP) (1-13), human after the third dose of COVID-19 vaccine, only a fraction of patients treated with fingolimod develop an antibody response, whose mean levels are lower compared to untreated subjects (Achiron?et?al., 2022). The reason of the lower response to COVID-19 vaccine is only partially explained by the mechanism of action of fingolimod, a functional antagonist of the sphingosine-1-phospgate receptors, which causes a decrease of circulating T- and B- lymphocytes due to impaired recirculation. Total lymphopenia is the only factor which has been associated to impaired humoral response to COVID-19 vaccination in patients treated with fingolimod (Achiron?et?al., 2022). The objective of the present study was to ascertain whether the numbers and proportion of circulating main lymphocyte subsets predict the antibody response to COVID-19 vaccination in MS patients treated with fingolimod. 2.?Methods 2.1. Patients This is a prospective single-center observational exploratory study including a subgroup of adult GnRH Associated Peptide (GAP) (1-13), human patients with MS (pwMS) in treatment with fingolimod just enrolled for COVID-19 vaccine in MS (CovaXiMS) study. All of them underwent COVID-19 vaccination and were willing to provide blood samples for assessment of antibody levels and for the evaluation of immunological status before and after the three vaccination doses. Additional details about inclusion?criteria are available elsewhere (Sormani?et?al., 2021). All participants signed written informed consent before starting any study procedures. The study was conducted in accordance with all national regulations and?with principles of the Declaration of Helsinki and the protocol was approved by the regional ethic committee (CER Liguria: 5/2021 – DB id 11,169- 21/01/2021) and at national level by AIFA/Spallanzani (Parere n 351, 2020/21). 2.2. SARS CoV2 antibodies Levels of anti-SARS-CoV-2 antibodies were measured within one month before the first dose of vaccine, one month after the second GnRH Associated Peptide (GAP) (1-13), human dose and within one month before and one month after the third dose, by a centralized laboratory with a double-antigen sandwich-based electrochemiluminescence immunoassay (ECLIA), using a commercial kit (Elecsys, Anti-SARS-CoV-2 S, Roche Diagnostics). 2.3. Lymphocyte subsets Total GnRH Associated Peptide (GAP) (1-13), human number and percentage of CD3+ T lymphocytes and CD19+ B lymphocytes were measured through clinical immune profiling at the IRCCS Ospedale Policlinico San Martino before the third dose of COVID-19 vaccination. 2.4. Statistical analysis According to previous literature, the distribution of antibody levels was normalized by a Log10 transformation. A linear regression model was used to identify the association between antibody levels and lymphocytes (total number and percentage of CD3+ GnRH Associated Peptide (GAP) (1-13), human T and CD19+ B), after having adjusted for age and sex. The effect on the antibody levels and of all the relevant covariates was reported as a geometric mean, that represents the multiplicative factor for the reference level of the considered covariate. Differences in antibody levels between two group was assessed by Mann-Whitney U Test. 3.?Results From January 2021 until April 2021, 20 adult pwMS on fingolimod?(15 females/5 males) with a mean age of 49.3??10.41 years were enrolled for the study. Fourteen (70.0%) had relapsing-remitting MS, median EDSS was 3.5 (IQR: 1.8 C 4.8), mean disease duration was 15.2??11.38 years, and 75.0% had already been treated with different DMTs before fingolimod. The factors associated to antibody levels after the third vaccination dose were the age (with a 2.46-fold decrease every 10 years of age, p?=?0.003) and CD19+ lymphocytes (with a 1.21-fold increase every percentage point increase, p?=?0.010).