HUMORAL RESPONSE TO SARS-CoV-2 AND COVID-19 VACCINES IN PATIENTS WITH MULTIPLE SCLEROSIS TREATED WITH IMMUNE RECONSTITUTION THERAPIES

Background: As remote infections with common herpes viruses are associated with modulation of the risk of multiple sclerosis (MS), we hypothesized that antibody concentrations against these viruses may further modify risk. As many common viruses are first encountered during childhood, pediatric MS offer a unique opportunity to investigate more closely their influence on susceptibility. Our aim was to determine if MS patients who were positive for these viruses had higher levels of antibodies to these viruses. We also assessed whether human leukocyte antigen (HLA)-DRB1*1501 genotype influenced viral antibody levels. Methods: Antibody response levels toward Epstein Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV)-1, and HLA-DRB1*1501 status were determined in pediatric MS patients ( n=189) and controls ( n=38). Multivariate analyses were used, adjusted for age, gender, race, ethnicity and use of disease-modifying therapies. Results: The antibody concentrations against EBV (Epstein-Barr nuclear antigen 1 (EBNA-1), viral capsid antigen (VCA) and early antigen (EA)), CMV and HSV-1 were similar between pediatric MS patients and controls positive for seroconversion against the virus of interest. EBNA-1 humoral responses were higher in HLA-DRB1 positive individuals ( p=0.005) whereas other viral humoral responses were similar in HLA-DRB1 positive and negative individuals. Conclusion: Among those positive for EBNA-1, MS patients did not have higher levels of antibody response to EBNA-1: however, titers for EBNA-1 were higher in those who were HLA-DRB1 positive. This suggests that genotype might influence the humoral response to EBV. Whether other genotypes influence antibody response to other viruses remains to be determined.

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Pregnancy in multiple sclerosis: from scientific aspects to practical

The Moldovan Medical Journal ◽

10.52418/moldovan-med-j.64-3.21.14 ◽

2021 ◽

Vol 64 (3) ◽

pp. 78-84

Author(s):

Anna Belenciuc ◽

◽

Ana-Maria Bubuioc ◽

Olesea Odainic ◽

Marina Sangheli ◽

...

Keyword(s):

Multiple Sclerosis ◽

Family Planning ◽

Immune Reconstitution ◽

Interferon Beta ◽

Reproductive Age ◽

Childbearing Age ◽

Disease Modifying Drugs ◽

Choice Of Treatment ◽

Key Issues ◽

Disease Modifying

Background: Multiple sclerosis (MS) is a disease that affects young people of reproductive age (20-40 years old), predominantly women. Therefore, almost every patient has questions about pregnancy and breastfeeding. Family planning is one of the key issues in the choice of treatment tactics. Despite the growing number of therapeutic options for individualized treatment, it is still a question how to manage women with MS who become pregnant while taking disease-modifying drugs or want to become pregnant after starting this treatment. Conclusions: Women with MS should not be discouraged from pregnancy due to their illness. It is necessary to proactively discuss pregnancy planning with all women with MS of childbearing age. Based on available data, interferon beta and glatiramer acetate appear to be most suitable for use up until the time of confirmed pregnancy. A large amount of data (more than 1000 cases) obtained from registries shows that use of interferon beta before conception and during pregnancy suggests no evidence of increase in the rate of congenital anomalies or spontaneous abortions. For women with persistent high disease activity, pulsed immune reconstitution therapy gives additional opportunity for family planning after the last dose. The choice between available options for pulsed immune reconstitution therapy should be based on efficacy balanced against the risks.

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Vaccination opportunities in multiple sclerosis patients treated with cladribine tablets

Current Neuropharmacology ◽

10.2174/1570159x20666211217160451 ◽

2021 ◽

Vol 20 ◽

Author(s):

Lucia Moiola ◽

Agostino Riva ◽

Ferdinando Nicoletti ◽

Antonio Uccelli ◽

Marco Salvetti ◽

...

Keyword(s):

Multiple Sclerosis ◽

Immune System ◽

Mechanism Of Action ◽

Vaccination Campaign ◽

Humoral Response ◽

Focused Attention ◽

Vulnerable Patients ◽

Mass Vaccination Campaign ◽

Multiple Sclerosis Patients ◽

Vaccination Campaigns

: The COVID-19 pandemic and the mass vaccination campaign highlighted the situation of the most vulnerable patients. In this work, we focused attention on patients who have Multiple Sclerosis (MS), particularly in treatment with cladribine tablets, trying to understand if and when it is possible to administer the vaccine successfully. Considering the innovative topic, we reviewed the existing literature with an analysis of the experiences also related to other vaccinations, including influenza and VZV, and very recent data from countries with vaccination campaigns already advanced. Overall, we have taken into account the mechanism of action, the pharmacokinetic/pharmacodynamic of cladribine and the changes in the immune system after its administration, together with the preliminary data about the humoral response to influenza, VZV and SARS-CoV-2 vaccinations in cladribine treated patients. In conclusion, data showed that the use of cladribine tablets seems to permit flexibility regarding vaccination timing and we suggest that vaccination in those patients should be safe and effective.

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Immune Reconstitution Inflammatory Syndrome and Rebound Syndrome on Withdrawal of Immunomodulatory Drugs for Multiple Sclerosis: Current Understanding and a Case Report

Neuroscience and Behavioral Physiology ◽

10.1007/s11055-018-0619-z ◽

2018 ◽

Vol 48 (6) ◽

pp. 693-702 ◽

Cited By ~ 1

Author(s):

A. N. Belova ◽

M. V. Rasteryaeva ◽

N. I. Zhulina ◽

E. M. Belova ◽

A. N. Boiko

Keyword(s):

Multiple Sclerosis ◽

Case Report ◽

Immune Reconstitution Inflammatory Syndrome ◽

Immune Reconstitution ◽

Current Understanding ◽

Immunomodulatory Drugs ◽

Inflammatory Syndrome ◽

Rebound Syndrome

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The Meaning of Immune Reconstitution after Alemtuzumab Therapy in Multiple Sclerosis

Cells ◽

10.3390/cells9061396 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1396 ◽

Cited By ~ 3

Author(s):

Simona Rolla ◽

Alessandro Maglione ◽

Stefania Federica De Mercanti ◽

Marinella Clerico

Keyword(s):

Multiple Sclerosis ◽

Monoclonal Antibody ◽

Immune Reconstitution ◽

Current Knowledge ◽

Intermittent Infusion ◽

B Cell Depletion ◽

Relapsing Remitting ◽

Temporary Suspension ◽

Relapsing Remitting Multiple Sclerosis

Alemtuzumab is a monoclonal antibody that binds to CD52, a protein present on the surface of mature lymphocytes, but not on the stem cells from which these lymphocytes are derived. It is currently used as an immune reconstitution therapy in patients with relapsing–remitting multiple sclerosis. Alemtuzumab treatment is an intermittent infusion that induces long-term remission of Multiple Sclerosis also in the treatment-free period. After the robust T and B cell depletion induced by alemtuzumab, the immune system undergoes radical changes during its reconstitution. In this review, we will discuss the current knowledge on the reconstitution of the lymphocyte repertoire after alemtuzumab treatment and how it could affect the development of side effects, which led to its temporary suspension by the European Medical Agency.

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Natalizumab modulates the humoral response against HERV-Wenv73–88 in a follow-up study of Multiple Sclerosis patients

Journal of the Neurological Sciences ◽

10.1016/j.jns.2015.07.007 ◽

2015 ◽

Vol 357 (1-2) ◽

pp. 106-108 ◽

Cited By ~ 7

Author(s):

Giannina Arru ◽

Elisa Caggiu ◽

Stefania Leoni ◽

Giuseppe Mameli ◽

Maura Pugliatti ◽

...

Keyword(s):

Multiple Sclerosis ◽

Humoral Response ◽

Follow Up Study ◽

Multiple Sclerosis Patients

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Association of Mycobacterium avium subsp. paratuberculosis and SLC11A1 polymorphisms in Sardinian multiple sclerosis patients

The Journal of Infection in Developing Countries ◽

10.3855/jidc.2737 ◽

2013 ◽

Vol 7 (03) ◽

pp. 203-207 ◽

Cited By ~ 13

Author(s):

Davide Cossu ◽

Speranza Masala ◽

Eleonora Cocco ◽

Daniela Paccagnini ◽

Stefania Tranquilli ◽

...

Keyword(s):

Multiple Sclerosis ◽

Autoimmune Disease ◽

Mycobacterium Avium ◽

Humoral Response ◽

Mycobacterium Avium Subsp ◽

Nucleotide Polymorphisms ◽

Specific Pcr ◽

Pcr Rflp ◽

Mycobacterium Avium Subsp Paratuberculosis ◽

Multiple Sclerosis Patients

Introduction: Recent findings propose that Mycobacterium avium subsp. paratuberculosis (MAP) infection could act as risk factor in favoring multiple sclerosis (MS) progression. SLC11A1 is a gene associated with mycobacterial survival in the host and it may be involved in the induction and maintenance of autoimmune disease. Methodology: In this preliminary study, 100 MS patients and 100 healthy controls (HCs) from Sardinia were enrolled. Eight single nucleotide polymorphisms (SNPs) in the SLC11A gene were searched by PCR RFLP-genotyping. IS900 specie specific PCR was undertaken to search for MAP presence. Indirect ELISA was performed to asses if MS patients displayed a stronger humoral response against MAP2694 protein compared to the HCs. Results: Only rs2276631 SNP was associated with MS. MAP DNA was detected in 23 out of 100 MS patients (23%) and in 7 out of 100 HCs (7%). A strong humoral response against MAP2694 protein was detected in 36% of MS patients and only in 3% of HCs. A correlation between ELISA sero-positivity and the rs2276631 SNP was also found. Conclusion: Our preliminary results suggest that the Sardinian population might be prone to develop autoimmune disease due to polymorphisms in immunomodulating the SLC11A1 gene, which is important in the immune response against intracellular bacteria such as MAP.

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