HLA-DRB1 and disease outcome in multiple sclerosis.
The association between susceptibility to multiple sclerosis (MS) and the class II MHC allele HLA-DRB1*15 is well established although a possible relationship between this allele and outcome in MS is less clear. HLA-DRB1 typing was performed on 375 unrelated white patients with clinically definite MS and on 367 healthy controls. Putative associations of the gene with outcome were examined by dividing patients into two groups: those with an EDSS of 0-5.5 (mild/moderate disease) and those with an EDSS of 6-10 (severe disease). In order to minimise the effects of disease variability patients with a disease duration of at least 10 years or 15 years were examined. As subsidiary HLA-DRB1*03 and HLA-DRB1*04 associations have been previously reported, the effect of these alleles was also examined. As expected, HLA-DRB1*15 was found more frequently in patients than in controls (P < 0.000001). HLA-DRB1*15 positive patients had a significantly earlier age at onset than HLA-DRB1*15 negative patients. No significant associations were noted between HLA-DRB1*15 and outcome in the total patient group or in patients with a disease duration of 10 years or longer. In patients with a disease duration of at least 15 years HLA-DRB1*15 negative status was associated with a worse prognosis, although this did not remain significant after correction for multiple testing. It is thus likely that the contribution of HLA in MS is primarily towards onset and initial triggering mechanisms rather than influencing disease progression, chronicity and severity.
Weatherby
S J
SJ
Keele Multiple Sclerosis Research Group, Postgraduate Medical School, Royal Infirmary, Stoke-on-Trent, UK. med13@keele.ac.uk
Thomson
W
W
Pepper
L
L
Donn
R
R
Worthington
J
J
Mann
C L
CL
Davies
M B
MB
Fryer
A A
AA
Boggild
M D
MD
Young
C A
CA
Jones
P W
PW
Strange
R C
RC
Ollier
W E
WE
Hawkins
C P
CP
D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D011379:Prognosis; D012720:Severity of Illness Index
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains