HLA-DRB1 allele impact on pediatric multiple sclerosis in a Hellenic cohort

Maria Gontika; Charalampos Skarlis; Artemios Artemiadis; Roser Pons; Sotiria Mastroyianni; George Vartzelis; Virginia Theodorou; Konstantinos Kilindireas; Leonidas Stefanis; Marinos Dalakas; George Chrousos; Maria Anagnostouli

doi:10.1177/2055217320908046

HLA-DRB1 allele impact on pediatric multiple sclerosis in a Hellenic cohort

Mult Scler J Exp Transl Clin. 2020 Feb 24;6(1):2055217320908046. doi: 10.1177/2055217320908046. eCollection 2020 Jan-Mar.

Affiliations

¹ Immunogenetics Laboratory, First Department of Neurology, Medical School,National and Kapodistrian University of Athens, NKUA, Aeginition Hospital, Athens, Greece.
² Immunogenetics Laboratory, First Department of Neurology, Medical School, National and Kapodistrian University of Athens, NKUA, Aeginition Hospital, Athens, Greece.
³ First Department of Pediatrics, National and Kapodistrian University of Athens, Medical School, Aghia Sophia Children's Hospital, Athens, Greece.
⁴ Department of Neurology, Children's Hospital of Athens "P. and A. Kyriakou", Athens, Greece.
⁵ Second Department of Pediatrics, National and Kapodistrian University of Athens, School of Medicine P. & A. Kyriakou Children's Hospital, Athens, Greece.
⁶ Department of Pediatric Neurology, "Aghia Sophia" Children's Hospital, Greece.
⁷ Demyelinating Diseases Unit, First Department of Neurology, Medical School, National and Kapodistrian University of Athens, NKUA, Aeginition Hospital, Athens, Greece.
⁸ First Department of Neurology, Medical School, National and Kapodistrian University of Athens, NKUA, Aeginition Hospital, Athens, Greece.
⁹ Neuroimmunology Unit, Department of Pathophysiology, National and Kapodistrian University of Athens Medical School, Athens, Greece.
¹⁰ University Research Institute of Maternal and Child Health & Precision Medicine, National and Kapodistrian University of Athens, Aghia Sophia Children's Hospital, Greece.
¹¹ Demyelinating Diseases Unit & Director of Immunogenetics Laboratory, First Department of Neurology, Medical School, National and Kapodistrian University of Athens, NKUA, Aeginition Hospital, Athens, Greece.

Abstract

Background: Pediatric-onset multiple sclerosis (POMS) is considered a complex disease entity with many genetic and environmental factors implicated in its pathogenesis. Linkage studies in Caucasian adult populations consistently demonstrate the major histocompatibility complex and its HLA (human leukocyte antigen) polymorphisms as the genetic locus most strongly linked to MS.

Objective: To investigate the frequencies and possible clinical and imaging correlations of HLA-DRB1 alleles in a Hellenic POMS sample.

Methods: Fifty POMS patients fulfilling the IPMSSG (International Pediatric Multiple Sclerosis Study Group) criteria were enrolled using 144 adult-onset MS (AOMS) patients and 246 healthy controls for comparisons. HLA genotyping was performed with standard low-resolution sequence-specific oligonucleotide (SSO) techniques. Clinical and imaging correlations with specific HLA-DRB1 alleles were also examined.

Results: The HLA-DRB1*03 genotype was significantly higher in POMS patients compared to both the AOMS population (26% vs. 12.5%, p = 0.042) and the general population (26% vs. 12.6%, p = 0.004). HLA-DRB1*03-positive POMS patients had significantly more relapses (6.9 ± 4.9 vs. 4.2 ± 4.4, p = 0.005) and more thoracic spinal cord lesions than HLA-DRB1*03-negative patients (61.5% vs. 27%, p = 0.043).

Conclusion: In our Hellenic population, HLA-DRB1*03 allele confers increased risk for POMS and it is also correlated with possibly increased disease activity, expanding the existing knowledge on HLA associations and POMS.

Keywords: Multiple sclerosis; clinical phenotype; human leukocyte antigens; magnetic resonance imaging; pediatric-onset multiple sclerosis; therapeutics.