CD24 is a genetic modifier for risk and progression of multiple sclerosis.
Multiple sclerosis (MS) is a chronic neurological disease of unknown etiology, but a genetic basis for the disease is undisputed. We have reported that CD24 is required for the pathogenicity of autoreactive T cells in experimental autoimmune encephalomyelitis, the mouse model of MS. Here we investigate the contribution of CD24 to MS by studying single-nucleotide polymorphism in the ORF among 242 MS patients and 207 population controls. This single-nucleotide polymorphism results in replacement of alanine (CD24a) with valine (CD24v) in the mature protein. We found that the CD24v/v renders a >2-fold increase in the relative risk of MS in the general population (P = 0.023). Among familial MS, the CD24v allele is preferentially transmitted into affected individuals (P = 0.017). Furthermore, 50% of CD24v/v patients with expanded disability status scale 6.0 reached the milestone in 5 years, whereas the CD24a/v (P = 0.00037) and CD24a/a (P = 0.0016) patients did so in 16 and 13 years, respectively. Moreover, our data suggest that the CD24v/v patients expressed higher levels of CD24 on peripheral blood T cells than did the CD24a/a patients. Transfection with CD24a and CD24v cDNA demonstrated that the CD24v allele can be expressed at higher efficiency than the CD24a alleles. Thus, CD24 polymorphism is a genetic modifier for susceptibility and progression of MS in the central Ohio cohort that we studied, perhaps by affecting the efficiency of CD24 expression on the cell surface.
Zhou
Qunmin
Q
Division of Cancer Immunology and Department of Pathology, Ohio State University, Columbus, OH 43210, USA.
Rammohan
Kottil
K
Lin
Shili
S
Robinson
Nikki
N
Li
Ou
O
Liu
Xingluo
X
Bai
Xue-feng
XF
Yin
Lijie
L
Scarberry
Bruce
B
Du
Peishuang
P
You
Ming
M
Guan
Kunliang
K
Zheng
Pan
P
Liu
Yang
Y
D000409:Alanine / Q000737:chemistry; D000483:Alleles; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000502:physiology*; D051927:CD24 Antigen; D017252:CD3 Complex / Q000096:biosynthesis; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008562:Membrane Glycoproteins; D051379:Mice; D008957:Models, Genetic; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000235:genetics*; D016366:Open Reading Frames; D010375:Pedigree; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013997:Time Factors; D014162:Transfection; D014633:Valine / Q000737:chemistry
D015703:Antigens, CD; D051927:CD24 Antigen; C497889:CD24 protein, human; D017252:CD3 Complex; C497890:Cd24a protein, mouse; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D014633:Valine; D000409:Alanine