Study of HLA as a predisposing factor and its possible influence on the outcome of multiple sclerosis in the sanitary district of Calatayud, northern Spain.

ABSTRACT

The relationship between multiple sclerosis (MS) and the HLA antigens DR2 and DQ1 is well recognised, but, in Spain, it has not been clearly defined. The aim of our study was to investigate the relationship between MS and HLA antigens in the sanitary district of Calatayud, northern Spain, and to correlate these antigens with the progression of the disease. Thirty-four patients were selected from a long-term (October 1990 to July 1996) prospective survey in the region where there was a prevalence rate of 58 per 100,000 population. The HLA antigens were determined in 31 patients. A control group of 895 people of Caucasian race was recruited from the same population. We performed serologic tests on all participants. Nucleotide typing was carried out in DR2-positive patients. The most frequent antigens in excess in MS were A19 (odds ratio, OR 2.29, p = 0.04), B5 (OR 2.85, p = 0.02), B41 (OR 7.65, p = 0.04), CW7 (OR 3.4, p = 0.004), DR6 (OR 6.18, p = 0.0001) and DR10 (OR 3.4, p = 0. 004). The DR2 antigen was also more frequent in MS patients (39%) than in controls (19%; OR 2.69, p = 0.01). All positive DR2 patients showed the DR15(2) split but not the DR16(2) split. The frequency of antigens CW4 and DR1 was lower in MS patients than in controls. The CW4 antigen was detected in 12% of the patients and in 33% of the controls (OR 0.28, p = 0.04). The DR1 antigen was found in 20% of the controls and in none of the MS patients (OR undefined, p = 0.01). The DQ1 antigen was observed in 68% of the patients and in 50% of the controls (OR 2.1, p = 0.07). We did not find any relationship between HLA antigens and progression of the disease. Although we found that DR2 antigen is linked to MS, we also found other antigens related to the disease. This suggests a genetic heterogeneity in our geographic area. We also concluded that the DR1 antigen may play a protective role, as it was detected in 20% of the controls and in none of the MS cases.