HLA Allele Frequencies in Pediatric and Adolescent Multiple Sclerosis Patients

Abstract

Early-onset (pediatric and adolescent) multiple sclerosis (MS) is a chronic autoimmune and neurodegenerative disorder of the central nervous system, which accounts for 3-5% of all MS cases. The major histocompatibility complex (MHC) with its polymorphisms has been the genetic locus with the most robust association with adult MS, since its first discovery in the 1970s. Nowadays, human leukocyte antigen (HLA) typing studies and genome-wide association studies (GWAS) have tried to provide insight into the genetics of early-onset MS and their role in disease diagnosis, prognosis, and therapeutic decisionmaking. Fundamental genetic similarities have emerged, supporting the assumption that MS shares similar genetic variants and biological processes in all age groups. In this chapter, we considered it useful to collect all the available data concerning the HLA distribution in early-onset MS, given the absence of a review paper with such an approach. We additionally aimed toward the summarization of the association of the HLA frequencies in early-onset MS and the main acquired demyelinating disorders that are considered in differential diagnosis of early-onset MS, like ADEM, NMO/NMOSD, and anti-MOG encephalopathy, for further understanding and current or future research in this promising field.

Clinical and transcriptional recovery profiles in pediatric and adult multiple sclerosis patients

“…The involvement of antigen presentation, in recovery mechanism is not surprising, since these processes are known to play a role in MS disease course and in MS susceptibility presented by polymorphism of HLA‐DQB1, 29‐31 IL4R, 32 and HSP970 33,34 genes. A review by Anagnostouli et al (2018) 35 concluded that while HLA‐DRB1*1501 is clearly a risk factor for both POMS and AOMS patients, the results regarding the association between HLA‐DRB1 variability and age of MS onset are conflicting: some studies describe HLA‐DRB1*1501 as being associated with an earlier onset age, whereas others claim that there is no correlation between HLA‐DRB1*1501 and age. Of note, the HLA‐DRB1*1501 allele, which is known to increase the risk for developing MS 36,37 , is associated with a high expression level of HLA‐DQB1 38 .…”