Antibodies to HBV surface antigen in relation to interferon-λ3 in hemodialysis patients

Abstract

AimTo investigate circulating IFN-λ3 and IFNL3 polymorphisms in hemodialysis (HD) patients differing in HBV surface antigen antibody (anti-HBs) production. MethodsThe study included 106 HBV-vaccinated HD patients (88 developed anti-HBs) and 36 HBV-infected HD subjects (27 developed anti-HBs). Plasma IFN-λ3 (enzyme-linked immunosorbent assay) and rs12979860 (C>T) and rs8099917 (T>G) in IFNL3 (high-resolution melting curve analysis) were analyzed with regard to the association with anti-HBs production in response to HBV vaccination or infection. The results were adjusted for gender, age, cause of renal disease, dialysis vintage, dialysis modality, IFN-λ3, and 25(OH)D as appropriate. ResultsHBV vaccine responders had higher circulating IFN-λ3 (ng/L) than non-responders (120, 36–233 vs. 53, 33–109, P<0.000001). Patients who generated anti-HBs after HBV infection also had higher circulating IFN-λ3 levels than those who did not (133, 35–215 vs. 71, 9–229, P=0.043). The IFN-λ3 concentration correlated with the anti-HBs titer in vaccinated (r=0.614, P<0.000001) and infected patients (r=0.589, P=0.0002). Plasma IFN-λ3 was the only significant indicator of responsiveness to HBV vaccination (adjusted P=0.018) and remained the only significant associate for the development of post-infection anti-HBs (adjusted P=0.049). A plasmaIFN-λ3 level of 85.5ng/L was thecut-off value for theprognosis of an anti-HBs titer below vs. equal to or over 10IU/L in the entire group of HD patients (ROC sensitivity 68.7%, specificity 85.2%, and AUC 0.827). Significant associations were not found between IFN-λ3 and IFNL3 rs12979860. Subjects treated with low flux HD that harbored the TT genotype in rs8099917 showed higher IFN-λ3 levels than patients bearing the G allele in rs8099917 (139, 68–233 vs. 103, 9–208, P=0.049). ConclusionIn HD patients, circulating IFN-λ3 strongly correlates with anti-HBs production after HBV vaccination and infection. IFNL3 rs8099917 polymorphisms seem to be associated with IFN-λ3 plasma levels in HD subjects.