HLA B*44: protective effects in MS susceptibility and MRI outcome measures.
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).


CONCLUSIONS
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.
Healy
B C
BC
Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, NRB 168c, Boston, MA 02115, USA.
Liguori
M
M
Tran
D
D
Chitnis
T
T
Glanz
B
B
Wolfish
C
C
Gauthier
S
S
Buckle
G
G
Houtchens
M
M
Stazzone
L
L
Khoury
S
S
Hartzmann
R
R
Fernandez-Vina
M
M
Hafler
D A
DA
Weiner
H L
HL
Guttmann
C R G
CR
De Jager
P L
PL
D000328:Adult; D016009:Chi-Square Distribution; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics*; D059948:HLA-B44 Antigen; D015236:HLA-C Antigens / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics*; D017063:Outcome Assessment, Health Care; D011859:Radiography; D012720:Severity of Illness Index
D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D059948:HLA-B44 Antigen; D015236:HLA-C Antigens