Antibody response to common viruses and human leukocyte antigen-DRB1 in pediatric multiple sclerosis

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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Antibody response to myelin oligodendrocyte glycoprotein and myelin basic protein depend on familial background and are partially associated with human leukocyte antigen alleles in multiplex families and sporadic multiple sclerosis

Journal of Neuroimmunology ◽

10.1016/s0165-5728(02)00271-0 ◽

2002 ◽

Vol 131 (1-2) ◽

pp. 201-207 ◽

Cited By ~ 12

Author(s):

Andreas Lutterotti ◽

Markus Reindl ◽

Christoph Gassner ◽

Katharina Poustka ◽

Kathrin Schanda ◽

...

Keyword(s):

Multiple Sclerosis ◽

Antibody Response ◽

Human Leukocyte Antigen ◽

Myelin Basic Protein ◽

Basic Protein ◽

Human Leukocyte ◽

Myelin Oligodendrocyte Glycoprotein ◽

Leukocyte Antigen ◽

Multiplex Families

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Faculty Opinions recommendation of Smoking and two human leukocyte antigen genes interact to increase the risk for multiple sclerosis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.8488956.8960054 ◽

2011 ◽

Author(s):

Sreeram Ramagopalan ◽

Adam Handel

Keyword(s):

Multiple Sclerosis ◽

Human Leukocyte Antigen ◽

Human Leukocyte ◽

Leukocyte Antigen

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Multiple sclerosis: disease modifying therapy and the human leukocyte antigen

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20180103 ◽

2018 ◽

Vol 76 (10) ◽

pp. 697-704 ◽

Cited By ~ 2

Author(s):

Lineu Cesar Werneck ◽

Paulo José Lorenzoni ◽

Cláudia Suemi Kamoi Kay ◽

Rosana Herminia Scola

Keyword(s):

Multiple Sclerosis ◽

Human Leukocyte Antigen ◽

Human Leukocyte ◽

Hla Class I ◽

Class I ◽

Interferon Β ◽

Leukocyte Antigen ◽

Specific Subset ◽

Hla Type ◽

Disease Modifying

ABSTRACT Objective: To investigate the potential relationship between the human leukocyte antigen (HLA) type (class I and II) and the response to several disease-modifying therapies (DMTs) in patients with multiple sclerosis (MS). Methods: We analyzed clinical data of 87 patients with MS at the beginning and end of each type of DMT including the disease duration, Expanded Disability Status Scale and Multiple Sclerosis Severity Score (MSSS). Genotyping of HLA-DRB1, HLA-DPB1, HLA-DQB1, HLA-A, HLA-B and HLA-C alleles were identified using high-resolution techniques. Statistical correlation between the HLA type and response to DMTs was done using the initial and final MSSS. Results: Statistical relationships (p < 0.05) were found for only 15 of 245 alleles tested. There was a reduction in the MSSS for patients treated with corticosteroids (DRB1*15:01, DPB1*04:01, DQB1*02:01 and DQB1*03:01), azathioprine (DRB1*03:01, DPB1*04:01, DQB1*03:02, DQB1*06:02, HLA-C*07:02), interferon β-1a 22 mcg (DRB1*11:04, DQB1*03:01 and DQB1*03:02), interferon β-1a 30 mcg (DPB1*02:01, HLA-C*05:01) and interferon β-1b (DQB1*02:01). Conclusion: These findings suggest a few relationships between the HLA and response to DMTs in the disability for some types of HLA class I and II alleles in a specific subset of MS patients.

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Smoking and two human leukocyte antigen genes interact to increase the risk for multiple sclerosis

Brain ◽

10.1093/brain/awq371 ◽

2011 ◽

Vol 134 (3) ◽

pp. 653-664 ◽

Cited By ~ 154

Author(s):

Anna Karin Hedström ◽

Emilie Sundqvist ◽

Maria Bäärnhielm ◽

Nina Nordin ◽

Jan Hillert ◽

...

Keyword(s):

Multiple Sclerosis ◽

Human Leukocyte Antigen ◽

Human Leukocyte ◽

Leukocyte Antigen

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Multiple sclerosis: The elevated antibody response to Epstein–Barr virus primarily targets, but is not confined to, the glycine–alanine repeat of Epstein–Barr nuclear antigen-1

Journal of Neuroimmunology ◽

10.1016/j.jneuroim.2014.04.005 ◽

2014 ◽

Vol 272 (1-2) ◽

pp. 56-61 ◽

Cited By ~ 17

Author(s):

Klemens Ruprecht ◽

Benjamin Wunderlich ◽

René Gieß ◽

Petra Meyer ◽

Madlen Loebel ◽

...

Keyword(s):

Multiple Sclerosis ◽

Antibody Response ◽

Epstein Barr Virus ◽

Nuclear Antigen ◽

Barr Virus ◽

Epstein Barr ◽

Epstein Barr Nuclear Antigen

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Multiple sclerosis and human leukocyte antigen genotypes: Focus on the Middle East and North Africa region

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217319881775 ◽

2020 ◽

Vol 6 (1) ◽

pp. 205521731988177

Author(s):

Zhila Maghbooli ◽

Mohammad Ali Sahraian ◽

Abdorreza Naser Moghadasi

Keyword(s):

Multiple Sclerosis ◽

Middle East ◽

Human Leukocyte Antigen ◽

North Africa ◽

Human Leukocyte ◽

Genetic Studies ◽

Leukocyte Antigen ◽

Genetic Components ◽

Control Designs

Recent reports have demonstrated that the prevalence of multiple sclerosis (MS) is increasing in the Middle East and North Africa region. There is also emerging evidence regarding the genetic components of MS risk. This review provides an overview of the role of genetic factors in MS susceptibility by examining human leukocyte antigen loci in patients within the Middle East and North Africa region. Most of the genetic studies conducted in the Middle East and North Africa region have been based on case–control designs, which cannot confirm direct causality of genetic variants on MS susceptibility. Moreover, there are very limited and inconsistent studies on human leukocyte antigen class I and II (DQA and DQB) in MS patients of the Middle East and North Africa region. To identify common risk haplotypes in the Middle East and North Africa region or its sub-populations, further longitudinal studies will be required.

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Human Leukocyte Antigen Genotype as a Marker of Multiple Sclerosis Prognosis

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2019.329 ◽

2019 ◽

Vol 47 (2) ◽

pp. 189-196 ◽

Cited By ~ 1

Author(s):

Andreas P. Lysandropoulos ◽

Gaetano Perrotta ◽

Thibo Billiet ◽

Annemie Ribbens ◽

Renaud Du Pasquier ◽

...

Keyword(s):

Multiple Sclerosis ◽

Human Leukocyte Antigen ◽

Visual Memory ◽

Verbal Learning ◽

Human Leukocyte ◽

Hla Typing ◽

Lesion Volume ◽

Leukocyte Antigen ◽

Hla Genotype

ABSTRACT:Objective:In a previous pilot monocentric study, we investigated the relation between human leukocyte antigen (HLA) genotype and multiple sclerosis (MS) disease progression over 2 years. HLA-A*02 allele was correlated with better outcomes, whereas HLA-B*07 and HLA-B*44 were correlated with worse outcomes. The objective of this extension study was to further investigate the possible association of HLA genotype with disease status and progression in MS as measured by sensitive and complex clinical and imaging parameters.Methods:Hundred and forty-six MS patients underwent HLA typing. Over a 4-year period of follow-up, we performed three clinical and magnetic resonance imaging (MRI) assessments per patient, which respectively included Expanded Disability Status Scale, Multiple Sclerosis Severity Scale, Timed-25-Foot-Walk, 9-Hole Peg Test, Symbol Digit Modalities Test, Brief Visual Memory Test, California Verbal Learning Test-II, and whole-brain atrophy, fluid-attenuated inversion recovery (FLAIR) lesion volume change and number of new FLAIR lesions using icobrain. We then compared the clinical and MRI outcomes between predefined HLA patient groups.Results:Results of this larger study with a longer follow-up are in line with what we have previously shown. HLA-A*02 allele is associated with potentially better MS outcomes, whereas HLA-B*07, HLA-B*44, HLA-B*08, and HLA-DQB1*06 with a potential negative effect. Results for HLA-DRB1*15 are inconclusive.Conclusion:In the era of MS treatment abundance, HLA genotype might serve as an early biomarker for MS outcomes to inform individualized treatment decisions.

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