Table 3.
Correlations Between Cytomegalovirus (CMV)-Induced T-Cell Responses and Markers of Systemic Inflammation and Immune Activation that were Large (≥0.6 or ≤ −0.6) and Significant (P < .05), Before and After Adjustment for Multiple Comparisons
| T-cell responses (to all 19 CMV ORFs) | Inflammatory markers | IFN-γ | IL-2 | TNF-α | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HIV/Frailty | HIV/Frailty | HIV/Frailty | |||||||||||||||||
| −/− | −/+ | P for diff b | +/− | +/+ | P for diff | −/− | −/+ | P for diff | +/− | +/+ | P for diff | −/− | −/+ | P for diff | +/− | +/+ | P for diff | ||
| r | r a | r | r | r | r | r | r | r | r | r | r | ||||||||
| CD4-specific | IFN-γ | 0.09 | 0.67 | .18 | 0.5 | 0 | 0.18 | 0.6 | 0.51 | 0.12 | 0.1 | 0.58 | 0.67 | 0.17 | .2 | ||||
| IL-6 | −0.14 | 0.16 | 0.45 | 0.16 | 0.22 | −0.07 | 0.75 | −0.01 | .049 | −0.14 | −0.03 | 0.58 | 0.3 | ||||||
| IP-10 | −0.26 | 0.22 | 0.52 | 0.15 | −0.15 | 0.26 | 0.15 | −0.01 | −0.36 | −0.02 | 0.71 | 0.4 | .35 | ||||||
| MCP-4 | −0.33 | −0.6 | 0.06 | 0.22 | −0.12 | −0.65 | .22 | 0.05 | −0.11 | −0.28 | −0.21 | 0.25 | 0.45 | ||||||
| MDC | 0.1 | −0.66 | .09 | 0.35 | 0.09 | −0.33 | −0.47 | 0.15 | −0.15 | −0.04 | −0.48 | 0.44 | 0.32 | ||||||
| TARC | −0.24 | −0.72 | .22 | 0.09 | −0.05 | −0.52 | −0.55 | 0.14 | 0.23 | −0.14 | −0.47 | 0.34 | 0 | ||||||
| Activated CD4 | 0.08 | 0.07 | 0.43 | 0.36 | 0.56 | 0.02 | 0.65 | 0.18 | .24 | 0.07 | 0.18 | 0.33 | 0.66 | .37 | |||||
| Activated CD8 | 0.02 | 0.07 | 0.46 | −0.32 | 0.47 | −0.2 | 0.66 | 0.02 | .12 | 0.02 | 0.13 | 0.59 | 0.15 | ||||||
| CD8-specific | TNF-α | 0.18 | −0.28 | −0.61 | 0.08 | .11 | −0.04 | −0.44 | −0.49 | 0.12 | 0.01 | −0.43 | −0.49 | 0.1 | |||||
| IL-8 | −0.49 | −0.28 | −0.73 | 0.33 | .011 | −0.75 | −0.37 | .27 | 0.32 | 0.03 | −0.64 | −0.52 | .73 | −0.56 | 0.2 | ||||
| Eotaxin | −0.02 | 0.08 | 0.32 | 0.09 | −0.25 | 0.73 | .027 | 0.25 | −0.18 | −0.04 | 0.24 | 0.28 | −0.01 | ||||||
| IP-10 | −0.45 | −0.37 | −0.47 | −0.35 | −0.61 | 0.25 | 0.12 | −0.15 | −0.65 | −0.01 | .15 | −0.26 | −0.25 | ||||||
| MCP-1 | −0.38 | 0.16 | 0.01 | 0.3 | −0.66 | 0.41 | .022 | 0.51 | 0.22 | −0.53 | 0.36 | 0.02 | 0.28 | ||||||
| MCP-4 | −0.31 | 0.39 | −0.7 | 0.43 | .008 | −0.33 | −0.08 | 0.35 | 0.36 | −0.41 | 0.14 | −0.57 | 0.38 | ||||||
| MDC | −0.19 | −0.18 | −0.67 | −0.17 | .20 | −0.25 | −0.39 | 0.29 | 0.06 | −0.26 | −0.65 | .34 | −0.44 | −0.14 | |||||
| MIP-1β | −0.7 | −0.41 | .42 | −0.35 | 0.29 | −0.43 | −0.33 | −0.4 | 0.3 | −0.72 | −0.66 | .83 | −0.45 | 0.31 | |||||
| TARC | 0.43 | 0.33 | −0.47 | 0.21 | 0.25 | 0.13 | 0.62 | 0.54 | .81 | 0.38 | −0.02 | −0.25 | 0.25 | ||||||
| CRP | −0.4 | 0.12 | 0.16 | 0.57 | −0.35 | −0.37 | −0.51 | 0.47 | −0.57 | −0.04 | −0.16 | 0.62 | .08 | ||||||
| Activated CD4 | −0.3 | 0.18 | 0.41 | 0.3 | 0.12 | −0.18 | 0.34 | 0.27 | −0.35 | 0.4 | 0.63 | 0.31 | .40 | ||||||
| Total (CD4+CD8) | IFN-γ | −0.01 | 0.76 | .06 | 0.31 | −0.32 | −0.02 | 0.7 | .1 | 0.07 | −0.21 | 0.05 | 0.77 | .07 | 0.26 | −0.15 | |||
| IL-6 | −0.44 | 0.19 | 0.14 | 0.35 | −0.12 | −0.27 | 0.67 | 0.43 | .48 | −0.43 | −0.36 | 0.29 | 0.4 | ||||||
| IL-8 | −0.52 | −0.78 | .38 | −0.53 | 0.31 | −0.41 | −0.47 | −0.06 | 0.13 | −0.48 | −0.38 | −0.42 | 0.12 | ||||||
| MCP-4 | −0.45 | −0.32 | −0.42 | 0.39 | −0.25 | −0.68 | .28 | 0.25 | 0.25 | −0.49 | 0.04 | −0.33 | 0.34 | ||||||
| MDC | −0.18 | −0.94 | .004 | −0.3 | −0.24 | −0.36 | −0.56 | 0.29 | −0.42 | −0.16 | −0.66 | .24 | −0.05 | 0.03 | |||||
| MIP-1β | −0.71 | −0.72 | 0.97 | −0.14 | 0.16 | −0.14 | −0.31 | −0.06 | 0.2 | −0.5 | −0.47 | −0.23 | 0.08 | ||||||
| Activated CD4 | −0.44 | 0.17 | 0.85 | 0.37 | .08 | 0.47 | 0.18 | 0.62 | 0.16 | .26 | −0.18 | 0.53 | 0.8 | 0.47 | .24 | ||||
| Activated CD8 | −0.26 | 0.13 | 0.66 | 0.02 | .12 | 0.38 | −0.08 | 0.42 | 0.45 | −0.07 | 0.35 | 0.69 | 0.16 | .17 | |||||
Abbreviations: CRP, C-reactive protein; IFN-γ, interferon-γ; IL, interleukin; ORF, open reading frame; TNF-α, tumor necrosis factor-α.
a Associations between T-cell responses (T-cell subset in left-most column, cytokine response in top row, of table) and inflammatory biomarkers (second column of table), as assessed by Spearman’s rank correlation coefficients. Biomarkers for which no correlations were significant are not shown.
b Comparison of correlation coefficients between nonfrail and frail men was done after Fisher r-to-z transformation and was performed only when there was a statistically significant correlation in at least 1 of the 2 groups.
Bold text indicates statistically significant (P < .05) correlations or P values. Black boxes indicate values that were statistically significant after adjustment for multiple comparisons.
Adjustments for multiple comparisons: For correlation coefficients, adjustments were performed within each HIV status-frailty status subgroup, by maintaining a false discovery rate of 0.2. Because total T-cell responses are sums, and thus correlates, of CD4- and CD8-specific responses, total T-cell responses were adjusted separately from CD4- and CD8-specific responses.
For P values, adjustments were performed within each HIV status group stratified by frailty, by maintaining a false discovery rate of .05; again, adjustment was done separately for CD4- and CD8-specific responses, and for total T-cell responses.