Multiple Sclerosis in North-East Scotland an Association With Hla-Dow1

Abstract

This study reports the frequencies of HLA antigens and the polymorphic variants of C4, C2, and Bf for 200 patients with multiple sclerosis (MS) living in the Grampian region of Scotland, an area of high disease prevalence. A group of 128 normal subjects from the same region were typed for comparison. Although the frequencies of HLA-B7 and DR2 in the patient group (43.3% and 49.4%, respectively) were found to be similar to those reported for other Northern European HLA studies on patients with MS, high frequencies of these antigens were also observed in the group of normal Grampian subjects (38.3% and 40.6%) the differences were not statistically significant. However, a significant association was found between the recently defined Class II HLA antigen, DQw1, and MS (P less than 0.006) when compared with controls. There were no significant differences in frequency of the polymorphisms of C4, C2, and Bf when the group of patients with MS was compared with the control group of normal subjects. The patients were subdivided according to disease severity, remittent versus progressive clinical course, age of onset of the disease and initial symptoms. The frequencies of the HLA and complement polymorphisms (C4, C2, and Bf) were analysed in these subdivisions. DQw1 was found with similar frequency in severe and benign disease (78% and 80%, respectively) but DR2 was most frequent in the group of patients with remittent disease (54%). There were no significant differences in frequency of the polymorphisms of C4, C2, and Bf between the above subgroups of patients and overall no significant HLA associations were found with age of onset of disease or initial symptoms. The findings suggest that in an area of high prevalence of MS, the disease is more closely associated with DQw1 than DR2. Furthermore, there was no evidence to support the hypothesis that the HLA region complement gene polymorphisms show significant association with a putative HLA-linked MS susceptibility gene.

Genetics of primary progressive multiple sclerosis

“…This study also found that HLA-DR2 was associated with relapsing MS but not patients with progressive MS; however, PPMS and SPMS patients were grouped together (Francis et al, 1987).…”

Primarily chronic progressive and relapsing/remitting multiple sclerosis: two immunogenetically distinct disease entities.

“…In Arabian (38) as well as in Sardinian (39) MS patients an association with the DR4 antigen has been found. A weak association with the DQwl antigen (DR2 associated) was found in Scottish MS patients (11), but this finding has not been confirmed (12,40). An association with the DPw4 specificity has been reported in Swedish MS patients (41).…”

“…It has been proposed that PCP MS and R/R MS may be separate disease entities (6) since they differ with respect to epidemiology (6), age at onset (4, 5, 7), initial symptoms (4,6), prognosis with regard to degree of disability (4,7) and to mortality (8), and response to immunosuppression (9). Efforts to differentiate between PCP MS and R/R MS by serological HLA class II typing have yielded divergent and inconclusive results (10)(11)(12) (16)(17)(18).…”

Multifactorial Inheritance and Recurrence Risks of Multiple Sclerosis in Italian Patients

“…The presence of a genetic component in the etiopathogenesis of multiple sclerosis (MS) has been frequently hypothesized on the basis of (1) family studies showing an increased prevalence of the disease among relatives of patients compared to the general population [1,2], (2) a higher concordance among monozygotic than dizygotic twins [3][4][5][6], and (3) the associations between MS and HLA antigens [7][8][9][10][11],…”