Introduction Several immunological parameters have been associated with clinical outcome of HCV infection. We have previously found that acute HCV-infected subjects progressing to chronicity had higher serum IP-10 levels than those who spontaneously resolved the infection, which is counterintuitive given the known pro-inflammatory role of this chemokine. IP-10 is subjected to physiological cleavage of two aminoacids by DPPIV (CD26), which produces an NH2-truncated form of the protein. The cleaved form (referred to as short IP-10) antagonises the biologically active longer form by competitively binding to the common receptor without inducing signalling. Most IP-10 assays quantify the total IP-10 protein; however, recently developed assays also allow the distinction of the two forms. The aim of this study was to investigate the role of antagonistic short IP-10 in influencing the clinical outcome of acute HCV infection.
Methods We analysed 16 patients with acute HCV infection who met the following criteria: ALT>10× upper limit normal (ULN), exposure to HCV within previous 4 months and HCV-RNA(+). Plasma was collected from these patients longitudinally at 12 timepoints. We quantified the long and short forms of IP-10 in these samples. Results were then analysed and correlated with the clinical outcome (chronic vs resolver). The longitudinal nature of the dataset was taken into account through the use of a “mixed model” analytical strategy for repeated measures.
Results Our investigation confirmed that subjects who progressed to chronicity (n=11) had higher serum concentrations of total IP-10 (p<0.001) compared to patients who resolved spontaneously (n=5). However, these higher amounts of detectable IP-10 were ascribable to increased levels of the antagonistic form (p=0.036), while serum concentrations of biologically active long IP-10 form were comparable with subjects who spontaneously resolved the infection (p=0.460).
Conclusion This study reports a novel mechanism of chemokine antagonism during acute HCV infection and may represent an additional factor in the failure of the host immune response in eradicating HCV infection. The results also reveal that the short IP-10 is a predictor of clinical outcome after acute HCV infection and may be used to aid treatment decisions during acute HCV infection.
Competing interests None declared.
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