Both the HLA‐DPB1 and ‐DRB1 alleles correlate with risk for multiple sclerosis in Japanese: clinical phenotypes and gender as important factors

Abstract

The purpose of this study was to clarify the association of HLA-DRB1 and -DPB1 alleles with multiple sclerosis (MS) in Japanese, to determine whether optico-spinal MS (OS-MS) and conventional MS are immunogenetically distinct, and to verify the role of gender difference in HLA associations of MS. We studied HLA-DRB1 and -DPB1 polymorphisms in 166 Japanese patients with MS. Forty-seven patients were classified as having the optico-spinal MS (OS-MS) and 119 as having conventional MS. A lack of DPB1*0301 and a higher frequency of DPB1*0501 compared with controls (corrected P<0.0074; odds ratio=9.48) were found in OS-MS. By contrast, we found for the first time an association of DPB1*0301 with conventional MS in Japanese (corrected P=0.0444; odds ratio=3.28). Logistic analysis, adjusted for sex and age, revealed independent associations of DPB1*0301 (P=0.0004, adjusted odds ratio (aOR)=4.70), DPB1*0501 (P=0.0081, aOR= 2.50) and DRB1*1501 (P=0.0252, aOR=2.21) with conventional MS. However, the frequencies of DRB1*1501 and DPB1*0501 in male patients with conventional MS were equal to those in male controls while the DPB1*0301 frequency was increased in both male and female patients. We did not find any association of these HLA alleles with disease course and severity. In conclusion, OS-MS is a DPB1*0501-associated distinct subtype of MS, and DPB1*0301 is the most strongly associated allele with conventional MS in Japanese. In addition, gender plays an important role in HLA association with MS.

DPB1 disparities contribute to severe GVHD and reduced patient survival after unrelated donor bone marrow transplantation

“…[26][27][28][29][30] These observations suggest that the DP molecule could act as a transplantation antigen.…”

Multiple sclerosis patients show sexual dimorphism in cytokine responses to myelin antigens

“…Thus, the key to observing sex differences among cytokines that distinguish between Th1 responses and Th2 responses in MS is the use of myelin-specific antigens. It is important to note that several studies have reported an association between HLA DR2 (DRB1*1502 and *0501) and female gender in MS (Al-Shammri et al, 2004;Duquette et al, 1992;Fukazawa et al, 2000;Van et al, 1986), highlighting the importance of studying male and female patients separately. We were not trying to repeat these studies, but rather to assess whether our genderskewed cytokine responses can be explained by a disproportionate representation of HLA alleles in our MS patient cohort.…”

B7-H1 shapes T-cell–mediated brain endothelial cell dysfunction and regional encephalitogenicity in spontaneous CNS autoimmunity

“…First, the density of antigen expression in different target (CNS) areas, in conjunction with the antigen specificity of CNS-autoreactive T cells, has been suggested to influence lesion topography (3)(4)(5). However, in light of the particular animal model used in our study, we can exclude variations of antigen density or T-cell antigen specificity contributing to the observed changes in lesion topography.…”

“…The reasons underlying distinct lesion development at different anatomical sites still remain however largely elusive: Some authors have proposed that the nature and expression pattern of the target autoantigen might play a role (3,4). Others have observed an influence of the HLA complex and its role in shaping antigen presentation, thus suggesting that T-cell antigen specificity might impact the location of inflammation (5). Additionally, T-cell polarization into distinct T helper subtypes, as well as their expression pattern of chemokine receptors and adhesion molecules, has been implicated in determining the localization of inflammatory lesions within the CNS (6-8).…”