Presence of interferon-λ 4, male gender, absent/mild steatosis and low viral load augment antibody levels to hepatitis C virus

Abstract

Objectives

Despite recombinant interferon-λ 4 (IFN-λ4) demonstrating anti-viral activity in vitro and the ancestral functional gene (IFNL4) being conserved in all other primates, there has been speculation that IFN-λ4 may be detrimental in humans. In light of recent rekindled interest in humoral immunity, this study aimed at evaluating the impact of baseline characteristics, including IFNL4, on antibody levels to hepatitis C virus (HCV).

Materials and methods

Pretreatment sera from 279 well-characterized North European Caucasians with chronic HCV genotype 2 or 3 infection having undergone liver biopsy were analyzed regarding IFNL4 (rs12979860) and anti-HCV antibody levels using a commercially available assay.

Results

Patients producing IFN-λ4 had higher signal to cut-off (S/CO) anti-HCV antibody ratios as compared with those lacking IFN-λ4 (IFNL4_rs12979860 CT/TT versus CC, p<.0001, Mann–Whitney U-test). Additionally, in univariate analyses S/CO was significantly higher in men than women (p<.001), as well as in patients with absent/mild interface hepatitis (Ishak grade 0–2 versus 3–4, p = .009), and absent/mild steatosis (grade 0–1 versus 2–3, p = .0005). Also, an inverse correlation with HCV RNA level (r_s= −0.14, p = .02) was noted. In multivariate analysis IFN-λ4, gender, steatosis and viral load remained independently associated.

Conclusions

To our knowledge, this is the first report that demonstrates that the ability to produce IFN-λ4, in addition to male gender, absent/mild steatosis, and lower viral load, augments antibody levels against HCV. This indicates that IFN-λ4 may be associated with T helper cell 2 (Th2) immune skewing, which might have clinical implications beyond HCV infection. ClinicalTrials.gov Identifier: NCT00143000

Keywords:

• Interferon-λ 4
• IFN-λ4
• gender
• steatosis
• viral load
• antibody
• HCV RNA
• HCV

Acknowledgements

The authors thank Vilma Molnegren, Ludmila Adamek, Marliesa Griffin Wahlberg, and Anette Roth for technical assistance.

Disclosure statement

The authors report no conflict of interest.

Author contributions

Je.Wa.: concept and design, experiments and procedures, and writing of article; K.H.: experiments and procedures, and writing of article; Jo.We.: concept and design, and writing of article; S.N.: experiments and procedures, and writing of article; P.C.: concept and design, and writing of article; M.F.: concept and design, and writing of article; K.M.: concept and design, and writing of article; N.L.: concept and design, and writing of article; G.N.: concept and design, and writing of article; M.L.: concept and design, experiments and procedures, and writing of article.

Additional information

Funding

This work was supported by the Swedish Medical Research Council [Vetenskapsrådet; Diarienr 2017-00855] and ALF Funds at Sahlgrenska University Hospital [Diarienr ALFGBG-438371].