Higher expression of inhibitory CD158b and CD158e NK cell receptor and age predicts treatment response in children with chronic hepatitis C

• Published in: Medical microbiology and immunology 2018-02, Vol.207 (1), p.55-63
• Main Authors: Mania, Anna, Kaczmarek, Mariusz, Kemnitz, Paweł, Mazur-Melewska, Katarzyna, Figlerowicz, Magdalena, Sikora, Jan, Służewski, Wojciech, Żeromski, Jan
• Format: Article
• Language: English
• Subjects: Age; Biomedical and Life Sciences; Biomedicine; Children; Flow cytometry; Fluorescence; Hepatitis; Hepatitis C; Immunology; Interferon; Medical Microbiology; Multivariate analysis; Natural killer cells; NKG2 antigen; Original Investigation; Peripheral blood; Phenotypes; Polyethylene glycol; Ribavirin; T cell receptors; Virology
• ISSN: 0300-8584; 1432-1831
• DOI: 10.1007/s00430-017-0526-x

Treatment with pegylated interferon-α and ribavirin (PEG–IFN/RBV) is the only choice for chronic hepatitis C (CHC) in children. Natural killer (NK) cells were described to play a vital role in CHC. The aim of this study was to analyze the expression of peripheral blood NK cell receptors in their relation to PEG–IFN/RBV treatment response. Study included 26 children with CHC—13 boys, age range 13.42 ± 3.28 years. Blood for biochemical, virological and cytometric testing was taken for evaluation prior to the antiviral treatment. NK cell receptors were detected by flow cytometry and the results were presented as proportion of cells and mean fluorescence intensity (MFI). Therapy consisted of PEG–IFNα-2b (60 μg/m 2 s.c 1×/week) and RBV (15 mg/kg p.o. daily). Treatment duration was response-related and varied from 12 to 72 weeks. Rapid virological response (RVR) was evaluated in the 4th week and sustained virological response (SVR) 6 months after completion of the therapy. RVR children were younger (11.67 ± 3.74 vs 15.35 ± 2.42; p  = 0.001) and displayed higher CD158b (3.58 ± 0.16 vs 3.45 ± 0.13; p  = 0.038) and CD158e expression (4.33 ± 0.21 vs 4.03 ± 0.16; p  = 0.039). Density of CD158b (logMFI = 3.68 ± 0.22 vs 3.36 ± 0.16; p  = 0.036) and CD158e expression was significantly higher (4.37 ± 0.14 vs 4.12 ± 0.21; p  = 0.046) and NKG2D expression significantly lower (97.50 ± 3.46 vs 94.92 ± 5.93; p  = 0.049) in SVR children. SVR children were also significantly younger (12.40 ± 3.66 vs 15.13 ± 2.83; p  = 0.003). Significance of the age of patients, and expression of CD158b and CD158e were confirmed in univariate and multivariate analysis. Age of patients is negatively related to RVR and SVR. NK cell phenotype with higher expression density of CD158b and CD158e receptor was a positive predictor of SVR.