Relationship between the TLR9.rs352140 (G2848A) genotype and the HCV-specific IFN-γ ELISpot response
There was no relationship between the outcome of the HCV-specific CMI response and the TLR9.rs352140 (G2848A) genotype among the 258 HCWs subjects with valid CMI responses and TLR9.rs352140 genotyping tests (p= 0.356). Also, there was no significant difference (p= 0.299) in the proportion of the GG genotype in responding (46.4 %) and in the non-responding seronegative aviraemic subjects (31.4 %; Table 3).
The average totals (±SEM) of IFN-γ responses measured in SFC per million PBMCs in the responding total subjects were 587±176, 390±85, and 327±45, among those with the TLR9.rs352140 GG (n=24), GA (n=23) and AA (n=10) genotypes, respectively. On the other hand, among the non-responding subjects, the average totals (±SEM) of IFN-γ SFC per million PBMCs in the total subjects were 30±6, 31±6, and 26±7, among those with the TLR9.rs352140 (G2848A) GG (n=66), GA (n=86) and AA (n=49) genotypes, respectively. There was no significant difference between the responders of the total subjects with the TLR9.rs352140 genotypes (p =0.652; Figure 3A).
For the seronegative, aviraemic subjects, the average totals of HCV-specific IFN-γ SFC/106 PBMCs (±SEM) of theresponding subjects was 672±278.8, 307±86, and 357±68, among those with the TLR9.rs352140 GG (n=13), GA (n=10) and AA (n=5) genotypes, respectively. Differences were not statistically significant (p =0.594). On the other hand, the average totals of IFN-γ SFC/106 PBMCs (±SEM) among the non-responding seronegative, aviraemic subjects were 23±7, 31±8, and 17±5, among those with the TLR9.rs352140 GG (n=33), GA (n=43) and AA (n=29) genotypes, respectively (Figure 3B).
For seronegative, viraemic subjects, the average totals of HCV-specific IFN-γ SFC/106 PBMCs (±SEM) of the responding subjects were 214±24.2, and 853±689, among those with the TLR9.rs352140 GG (n=2) and GA (n=2) genotypes, respectively. There were no responding subjects with the AA genotype. Differences were not statistically significant (p =1.000). On the other hand, the average totals of IFN-γ SFC/106 PBMCs (±SEM) were 12±2.22, 30±10.4, and 60±47.6, among the non-responding seronegative , viraemic subjects with the TLR9.rs352140 (G2848A) GG (n=3), GA (n=9) and AA (n=4) genotypes, respectively (Figure 3C).
For spontaneously resolved subjects , the average totals of HCV-specific IFN-γ SFC/106 PBMCs (±SEM) of theresponding subjects were 244±48.2, and 619±301, among those with the TLR9.rs352140 GG (n=3) and GA (n=4) genotypes, respectively. There were no responding subjects with the AA genotype. Differences were not statistically significant (p =1.000). On the other hand, the average totals of IFN-γ SFC/106 PBMCs (±SEM) were 26±14.1, 60±26.9, and 10±10, among the non-responding spontaneously resolved subjects with the TLR9.rs352140 GG (n=11), GA (n=10) and AA (n=7) genotypes, respectively (Figure 3D).
For chronic HCV patients , the average totals of HCV-specific IFN-γ SFC/106 PBMCs (±SEM) of the responding subjects were 698±357.2, 245±51.5, and 296±57.8, among those with the TLR9.rs352140 GG (n=6), GA (n=7) and AA (n=5) genotypes, respectively. Differences were not statistically significant (p =0.775). On the other hand, the average totals of IFN-γ SFC/106 PBMCs (±SEM) of non-responding chronic HCV subjects were 46±13.8, 18±7.9, and 50.9±23.1, among those with the TLR9.rs352140 GG (n=19), GA (n=24) and AA (n=9) genotypes, respectively (Figure 3E).