Table 3. Interactions underlying HLA class I disease associations in HCV infection HLA-B*57 is associated with increased odds of spontaneous clearance of HCV.
In this cohort the protective effect is attributable to B*57:02 with B*57:03 and B*57:05 apparently following the same trend (though due to low numbers it is impossible to be certain). For each B*57 allele of interest we sought to determine the underlying mechanism by performing five multivariate linear regressions (model 2–6), one for each of the distance metrics. The coefficient (Coeff) and P value for the index allele and the similarity metric are recorded below. HBV seropositivity, mode of infection, SNP rs1297986 and subcohort were included as additional covariates in all models. A coefficient >0 indicates a protective allele (increased odds of spontaneous clearance, P). Unlike the B*57 protective effect in HIV-1 infection, in HCV infection there appeared to be no contribution from activating KIR i.e. HLA with similar aKIR binding to B*57 were never significant protective despite sufficient power (model 4). The protective effect here appears to be entirely attributable to CD8+ T cells (model 2, shaded). In all cases the protective effect of alleles with similar TCR binding is actually more significant than the protective effect of the B*57 alleles themselves (model 1, index only). Significance codes: p<0.001 ***; p<0.01 **; p<0.05 *; p<0.1. ; P values are two tailed.
|
|
Index allele | |||||
|---|---|---|---|---|---|---|
| Model | COV. | B*57:02 | B*57:03 | B*57:05 | ||
| 1. Index only |
index | Coeff | 2.02 P |
0.57 P |
15.5 P |
|
| P val | 0.08 · |
0.16 | 0.99 | |||
| 2. Index+TCR.FS |
Index | Coeff | 2.10 | 0.67 | 15.9 | |
| P val | 0.07 · |
0.10 · |
0.99 | |||
| TCR.FS | Coeff | 1.04 P |
0.89 P |
1.19 P |
||
| P val | 0.05 * |
0.09 · |
0.04 * |
|||
| 3. Index+iKIR.FS |
Index | Coeff | 2.00 | 0.64 | 15.62 | |
| P val | 0.08 · |
0.12 | 0.99 | |||
| iKIR.FS | Coeff | 0.35 P |
0.40 P |
0.50 P |
||
| P val | 0.29 | 0.24 | 0.17 | |||
| 4. Index+aKIR.FS |
Index | Coeff | 2.06 | 0.58 | 15.49 | |
| P val | 0.07 · |
0.15 | 0.99 | |||
| aKIR.FS | Coeff | 0.66 P |
0.29 P |
0.54 P |
||
| P val | 0.15 | 0.56 | 0.30 | |||
| 5. Index+LILRB1.S |
Index | Coeff | 2.00 | 0.58 | 15.48 | |
| P val | 0.09 · |
0.16 | 0.99 | |||
| LILRB1.S | Coeff | −0.15 D |
0.15 P |
−0.37 D |
||
| P val | 0.90 | 0.91 | 0.77 | |||
| 6. Index+LILRB2.S |
Index | Coeff | 2.02 | 0.52 | 15.53 | |
| P val | 0.08 · |
0.20 | 0.99 | |||
| LILRB2.S | Coeff | −0.02 D |
−0.81 D |
−0.02 D |
||
| P val | 0.98 | 0.40 | 0.98 | |||