HLA-DPB1*03 as Risk Allele and HLA-DPB1*04 as Protective Allele for Both Early- and Adult-Onset Multiple Sclerosis in a Hellenic Cohort

Abstract

Background: Human Leucocyte Antigens (HLA) represent the genetic loci most strongly linked to Multiple Sclerosis (MS). Apart from HLA-DR and HLA–DQ, HLA-DP alleles have been previously studied regarding their role in MS pathogenesis, but to a much lesser extent. Our objective was to investigate the risk/resistance influence of HLA-DPB1 alleles in Hellenic patients with early- and adult-onset MS (EOMS/AOMS), and possible associations with the HLA-DRB1*15:01 risk allele. Methods: One hundred MS-patients (28 EOMS, 72 AOMS) fulfilling the McDonald-2010 criteria were enrolled. HLA genotyping was performed with standard low-resolution Sequence-Specific Oligonucleotide techniques. Demographics, clinical and laboratory data were statistically processed using well-defined parametric and nonparametric methods and the SPSSv22.0 software. Results: No significant HLA-DPB1 differences were found between EOMS and AOMS patients for 23 distinct HLA-DPB1 and 12 HLA-DRB1 alleles. The HLA-DPB1*03 allele frequency was found to be significantly increased, and the HLA-DPB1*02 allele frequency significantly decreased, in AOMS patients compared to controls. The HLA-DPB1*04 allele was to be found significantly decreased in AOMS and EOMS patients compared to controls. Conclusions: Our study supports the previously reported risk susceptibility role of the HLA-DPB1*03 allele in AOMS among Caucasians. Additionally, we report for the first time a protective role of the HLA-DPB1*04 allele among Hellenic patients with both EOMS and AOMS.

Human Leukocyte Antigen Association Study Reveals DRB1*04:02 Effects Additional to DRB1*07:01 in Anti-LGI1 Encephalitis

“…A notable finding was a strong independent protective effect of DPA1*01:02∼DPB1*03:01, a finding distinct from previously reported DPA1*02:01∼DPB1*11:01 predisposing effects. 16 Of interest, DPB1*03:01 is a high-expression allele 35 and has been involved in susceptibility (not protection) to a number of other autoimmune diseases, such as multiple sclerosis, 36-38 severe aplastic anemia, 39 primary biliary cholangitis, 40 and B27 negative ankylosing spondylitis. 41 By contrast, although HLA class I alleles known to be associated with DRB1*07:01, such as B*57:01, B*44:03, C*06:02, and C*16:01, were increased in the sample uncorrected for DRB1*07:01 (data not shown) as previously reported, 16 all HLA class I association disappeared after controlling for the main DR7 association (data not shown).…”

Advances in Multiple Sclerosis Research–Series I

“…In addition, MS patients with early relapses compared to those with a longer, stable disease expressed lower levels of tetraspanin-32 on their PBMC [4]. Hence, tetraspanin-32 is involved in immune responses underlying the pathophysiology of MS, and could be a viable diagnostic marker or therapeutic target against MS. [7]. No significant differences were noted between early onset MS compared to adult onset MS for 23 distinct HLA-DPB1 and 12 HLA-DRB1 alleles.…”

Novel Approaches in the Immunotherapy of Multiple Sclerosis: Cyclization of Myelin Epitope Peptides and Conjugation with Mannan

“…Major Effects MBP 83-99 and PLP 139-151 [10][11][12][13][14][15][16][17][18] These agonist peptides are involved in the pathophysiology of MS and also induce EAE in animal models.…”

“…The pathogenesis of MS has been extensively studied over the last years, which shows a complex immunological involvement. Myelin epitopes have been identified as a target for autoimmune CD4+ T cells and antibodies, and much focus has been around the modulation of Th1 pro-inflammatory autoreactive CD4+ T cells against myelin epitopes, namely myelin basic protein (MBP), proteolipid protein (PLP), and myelin oligodendrocyte glycoprotein (MOG) [10][11][12][13][14][15][16][17][18]. Herein, we summarize the efforts utilized to develop novel approaches to manage MS, which are primarily efforts of immune modulation via the synthesis of selective peptide epitopes of MBP, PLP, and MOG with or without conjugation to mannan.…”

“…The pathogenesis of MS has been extensively studied over the last years, which shows a complex immunological involvement. Myelin epitopes have been identified as a target for autoimmune CD4+ T cells and antibodies, and much focus has been around the modulation of Th1 pro-inflammatory autoreactive CD4+ T cells against myelin epitopes, namely myelin basic protein (MBP), proteolipid protein (PLP), and myelin oligodendrocyte glycoprotein (MOG) [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”