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Immunogenetics: Open Access

Immunogenetics: Open Access
Open Access

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Abstract

HLA-Genotype in Multiple Sclerosis: The Role in Disease Onset, Clinical Course, Cognitive Status and Response to Treatment: A Clear Step Towards Personalized Therapeutics

Petros Stamatelos and Maria Anagnostouli

Multiple Sclerosis (MS) is probably the best studied chronic inflammatory and demyelinating disease of the Central Nervous System (CNS), with a clear impact on patients’ quality of life. Many factors have been described to play a role in the initiation and clinical course of the disease, as well as in the response to medication. These factors include age at onset, gender, viral infections, Human Leucocyte Antigen (HLA)-genotype, non-HLA genes, Vitamin D levels and smoking. HLA genetic profile is the most important one, as it not only influences every aspect of the disease, but it also modifies the effect of the other factors.

In this review article we summarize the decisive effect of HLA-genotype on MS initiation, clinical course, cognitive impairment and therapeutically outcome, as well as on other demyelinating diseases of the CNS (including Neuromyelitis Optica and Acute Disseminated Encephalomyelitis). HLA-DRB1*15:01 is the best established allele, both increasing the risk of MS 2-3 times and influencing response to first line medication (including Interferon-beta and Glatiramer Acetate), but neutralizing antibodies’ formation against natalizumab, as well. Other Class I and Class II HLA alleles have either a detrimental (DRB1*08:01, 03:01, 13:03, 15:03, 04:05) or a protective (DRB1*14:01, *07, *11, A*02:01) effect on MS. Taking into account their epistatic interactions, we conclude that HLA-genotyping may lead to an individualized approach of MS patients, in different ethnic groups.

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