A majority of DRB1∗04-positive patients included in the initial study group carried the DRB1∗0401 allele (n = 42), whereas only 12 subjects were DRB1∗0404-positive. Only four patients carried DRB1∗0408 ( Table 3). Differences of location parameters for DRB1∗0401 (FDR = 0.012) and DRB1∗0408 (FDR = 0.048) were significant after correction for multiple testing. On the other hand, average cELISA levels for DRB1∗0404 were lower compared to DRB1∗04-negative patients. After FDR correction, null hypothesis was kept for DRB1∗0404 despite a significant single test (p value = 0.031, FDR = 0.16).
Table 3 Anti-IFN-β Levels for Alleles of the HLA-DRB1 Locus in the Study and Validation Groups
Allele Carriersa,b Anti-IFN Reactivity (%)c Statistics
DRB1 n Median Range pd FDRe
Inital Study Group
0101 27 10.8 −0.83–100.5 0.12 0.45
0301 48 17.8 −3.16–110.8 0.34 0.66
0401 42 66.6 −3.18–119.3 4e-04 0.012
0404 12 6.6 −1.75–96.54 0.031 0.16
0408 4 98.5 90.5–109.8 0.003 0.048
0701 50 18.2 −9.2–119.3 0.41 0.66
0801 15 39.4 0.2–109.5 0.74 0.8
1001 5 6.7 1.79–43.4 0.14 0.47
1101 32 27.0 −4.6–112.1 0.013 0.13
1104 8 3.1 −0.6–48.62 0.02 0.14
1201 7 46.6 −4.8–78.0 0.69 0.8
1301 25 38.1 −2.1–102.9 0.74 0.8
1302 18 15.8 −9.2–110.8 0.35 0.66
1303 12 11.9 −1.61–81.7 0.24 0.6
1501 153 30.5 −4.6–112.1 0.43 0.66
1502 3 87.3 3.4–103.2 0.31 0.66
1601 17 90.8 0.1–102.9 0.02 0.13
1602 3 77.6 3.9–95.29 0.44 0.66
Validation Group
DR4− 183 5.5 −17.3–140.3 0.12 0.21
DR4+ 59 10.1 −8.3–123.1 0.12 0.21
0401 31 71.8 −5.4–120.4 0.005 0.03
0402 6 0.3 −7.0–23.17 0.01 0.21
0403 6 3.4 −8.3–89.6 0.37 0.43
0404 9 1.9 −5.9–84.1 0.22 0.31
0407 2 47.8 2.8–92.8 0.51 0.51
0408 5 91.6 −3.7–123.1 0.04 0.15
A significant elevation of IFN-β reactivity is seen for DRB1∗0401 and DRB1∗0408 (in bold) after adjustment for multiple testing. Only alleles that occurred more than twice are shown. In contrast to the findings in the low-resolution analysis, a significant increase of anti-IFN-β levels in DRB1∗1601-positive subjects vanishes after the FDR procedure. Likewise, the potential protective effect of DRB1∗0404 does not pass the significance criterion after adjustment for multiple testing. In the validation group, a significant elevation of IFN-β reactivity is seen in single tests for DRB∗0401 (in bold) as well as for DRB1∗0408. Because of an insufficient number of cases, however, significance vanishes after correction for multiple tests for DRB1∗0408. Because of the small number of cases, a potential protective effect of DRB1∗0402 did not pass the FDR significance criterion. The results in the validation group support our previous findings.
a For all alleles listed, note that heterozygous allele carriers occur twice, and homozygotic allele carriers occur only once. Only alleles that occurred more than twice are shown.
b Heterozygous allele carriers (∗0401+ and ∗0408+) occur twice.
c Anti-IFN reactivity was determined as described in the Material and Methods. Values above 25% identified patients with anti-IFN antibodies.
d p value was determined by comparison of the anti-IFN level of allele carriers to that of all nonallele carriers.
e p values have been adjusted to multiple testing by using the false-discovery rate method (FDR). Adjusted p values below 0.05 were considered to be statistically significant (in bold).