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Updated: Jun 10, 2026
Magnetic Resonance Imaging of Multiple Sclerosis at 7.0 Tesla
Published on: February 19, 2021
HLA B*44: protective effects in MS susceptibility and MRI outcome measures
1Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, NRB 168c, Boston, MA 02115, USA.
Objective:
In addition to the main multiple sclerosis (MS) major histocompatibility complex (MHC) risk allele (HLA DRB1*1501), investigations of the MHC have implicated several class I MHC loci (HLA A, HLA B, and HLA C) as potential independent MS susceptibility loci. Here, we evaluate the role of 3 putative protective alleles in MS: HLA A*02, HLA B*44, and HLA C*05.
Methods:
Subjects include a clinic-based patient sample with a diagnosis of either MS or a clinically isolated syndrome (n = 532), compared to subjects in a bone marrow donor registry (n = 776). All subjects have 2-digit HLA data. Logistic regression was used to determine the independence of each allele's effect. We used linear regression and an additive model to test for correlation between an allele and MRI and clinical measures of disease course.
Results:
After accounting for the effect of HLA DRB1*1501, both HLA A*02 and HLA B*44 are validated as susceptibility alleles (p(A*02) 0.00039 and p(B*44) 0.00092) and remain significantly associated with MS susceptibility in the presence of the other allele. Although A*02 is not associated with MS outcome measures, HLA B*44 demonstrates association with a better radiologic outcome both in terms of brain parenchymal fraction and T2 hyperintense lesion volume (p = 0.03 for each outcome).
Conclusion:
The MHC class I alleles HLA A*02 and HLA B*44 independently reduce susceptibility to MS, but only HLA B*44 appears to influence disease course, preserving brain volume and reducing the burden of T2 hyperintense lesions in subjects with MS.
Insights
Two major histocompatibility complex (MHC) class I alleles, HLA A*02 and HLA B*44, were found to reduce multiple sclerosis (MS) susceptibility. Only HLA B*44 influences disease progression, preserving brain volume and reducing lesions.
Area of Science:
- Immunogenetics
- Neuroimmunology
- Human Genetics
Background:
- The major histocompatibility complex (MHC) plays a crucial role in immune regulation and is strongly associated with multiple sclerosis (MS) susceptibility, primarily through the HLA DRB1*1501 allele.
- Investigations have suggested that MHC class I loci, including HLA A, HLA B, and HLA C, may also contribute independently to MS risk.
Purpose of the Study:
- To investigate the potential protective roles of three specific MHC class I alleles (HLA A*02, HLA B*44, and HLA C*05) in multiple sclerosis (MS).
- To determine if these alleles independently influence MS susceptibility and disease course.
Main Methods:
- A cohort of 532 individuals diagnosed with MS or clinically isolated syndrome was compared with 776 healthy bone marrow donors, all possessing 2-digit HLA data.
- Logistic regression analysis was employed to assess the independence of each allele's effect on MS susceptibility.
- Linear regression and an additive model were used to correlate allele presence with MRI and clinical measures of disease progression.
Main Results:
- HLA A*02 and HLA B*44 were validated as independent susceptibility alleles for MS, even after accounting for the known risk associated with HLA DRB1*1501.
- While HLA A*02 did not show an association with MS outcome measures, HLA B*44 was significantly associated with better radiologic outcomes.
- Specifically, HLA B*44 correlated with a higher brain parenchymal fraction and a reduced volume of T2 hyperintense lesions (p = 0.03 for both).
Conclusions:
- The MHC class I alleles HLA A*02 and HLA B*44 confer an independent reduction in susceptibility to multiple sclerosis (MS).
- The HLA B*44 allele demonstrates a significant role in influencing MS disease course, contributing to the preservation of brain volume and a decreased burden of white matter lesions.
