Page 34 - The autoimmune hypothesis of narcolepsy and its unexplored clinical features M.S. Schinkelshoek

Chapter 2
Results
Participant characteristics
We included 525 NT1 patients (128 post-H1N1) and 1272 HLA-DQB1*06:02- positive controls. Participant characteristics are shown in Table 2.1. Notably, all but two NT1 patients were DQB1*06:02 positive. 158 patients had undergone a lumbar puncture for Hcrt-1 measurement; over 95% had Hcrt-1 values in the cerebrospinal fluid that were below the cut-off value of 110 pg/mL; all had Hcrt-1 values below 200 pg/mL.
Table 2.2. Differences between HLA-DQB1 alleles in trans with HLA-DQB1*06:02 between NT1 patients compared with HLA-DQB1*06:02-positive healthy controls. P-values are derived from Pearson Chi-Square tests. Pc-values are calculated using the Šidák-Holm correction for multiple comparisons based on k = 13.
N
DQ2
DQ4
DQ7
DQ8
DQ9 DQB1*05:01 DQB1*05:02 DQB1*05:03 DQB1*06:01 DQB1*06:02 DQB1*06:03 DQB1*06:04 DQB1*06:09
Healthy NT1 OR controls
1272 525 NA
95% CI p-value
NA NA
pc-value
NA
<0.001 0.658 0.002
1
0.977 <0.001 0.011
1
1 <0.001 <0.001 0.267
1
32
315 (24.8%) 37 (2.9%) 216 (17.0%) 137 (10.7%) 67 (5.3%) 187 (14.7%) 20 (1.6%) 36 (2.8%)
5 (0.4%) 91 (7.2%) 86 (6.8%) 64 (5.0%) 11 (0.9%)
82 (15.6%) 0.56 24 (4.6%) 1.6 130 (24.8%) 1.6 56 (10.6%) 0.99 21 (4.0%) 0.75 35 (6.6%) 0.42 22 (4.2%) 2.7 18 (3.4%) 1.2 2 (0.4%) 0.97 85 (16.1%) 2.5 6 (1.1%) 0.16 41 (7.8%) 1.6 3 (0.6%) 0.66
0.43-0.73 0.94-2.7 1.3-2.1 0.72-1.4 0.45-1.2 0.28-0.60 1.5-5.0 0.69-2.2 0.19-5.0 1.8-3.4 0.07-0.37 1.0-2.4 0.18-2.4
<0.001 0.079 <0.001 0.97 0.251 <0.001 0.001 0.499 0.966 <0.001 <0.001 0.024 0.516
HLA-DQ2/4/7/8/9 = human
DQB1*04:01/-DQB1*03:01 or -03:04/-DQB1*03:02 or -03:05/-DQB1*03:03 allele; NT1 = narcolepsy type 1; NA = not applicable; OR = Mantel-Haenszel common odds ratio; pc-value = corrected p-value.
The frequency of HLA-DQB1*06:02 homozygosity is unchanged between pre- and post-H1N1 NT1 patients
The important role of HLA-DQB1*06:02 in NT1 is demonstrated by its presence in almost all pre- and post-H1N1 NT1 patients (396/397 patients vs. 127/128 patients). Homozygosity for HLA-DQB1*06:02 is associated with NT1 with an odds ratio of 2.5 (7.2% in the healthy control population vs 16.2% in NT1 patients; Table 2.2). Furthermore, the percentage of NT1 patients homozygous
leucocyte antigen molecule encoded by the HLA-DQB1*02:01/-