In a combined analysis of anti-IFN-β levels for DR4-positive and DR4-negative carriers of validation and study groups, a highly significant elevation of anti-IFN-β levels was found in carriers of DR4 alleles (median reactivity = 55.1%, p value ≤ 0.01) ( Figure 1). Fifty-four of 74 HLA-DRB1∗0401 carriers showed antibodies during IFN-β treatment. In DRB1∗0401- and ∗0408-negative subjects, 153 of 429 showed seroconversion, resulting in an odds ratio of 4.9 for HLA-DRB1∗0401-positive carriers. The odds ratio for DRB1∗0408 was 14.4, with four of five allele carriers being antibody positive. A highly significant increase of ELISA reactivities was observed in a comparison of all HLA-DRB1∗0401- and 0408-positive carriers versus HLA-DRB1∗0401- and ∗0408-negative carriers ( Figure 2) (p value ≤ 0.01). Furthermore, the difference of anti-IFN-β levels among DRB1∗0401 (median reactivity = 70.6%) and DRB1∗0408 (median reactivity = 96.4%) is significant (p value = 0.006). Because of the small number of homozygous DRB1∗04 carriers, a comparison with DRB1∗04-negative or heterozygous carriers was not possible.
Figure 1 Comparison of Anti-IFN-β Reactivities for HLA-DR Serological Equivalents in the Study Group
Median ELISA optical density (OD) of heterozygous DR4 carriers was significantly elevated compared to DR4-negative individuals (p value ≤ 0.01).
Figure 2 Comparison of Anti-IFN-β Reactivities for HLA-DRB1 Alleles in the Study and Validation Groups
A significant increase of ELISA reactivities was measured for HLA-DRB1∗0401 and HLA-DRB1∗0408 alleles (p value ≤ 0.01). DRB1∗0402, DRB1∗0403, and DRB1∗0404 seem to have a protective effect.