血液透析患者中乙肝表面抗原抗体与干扰素-λ3的关系
Antibodies to HBV surface antigen in relation to interferon-λ3 in hemodialysis patients.
作者信息
Grzegorzewska Alicja E, Świderska Monika K, Mostowska Adrianna, Warchoł Wojciech, Jagodziński Paweł P
机构信息
Chair and Department of Nephrology, Transplantology and Internal Diseases, Poznan University of Medical Sciences, Poznań 60-355, Przybyszewskiego 49, Poland.
Student Nephrology Research Group, Chair and Department of Nephrology, Transplantology and Internal Diseases, Poznan University of Medical Sciences, Poznań 60-355, Przybyszewskiego 49, Poland.
出版信息
Vaccine. 2016 Sep 22;34(41):4866-4874. doi: 10.1016/j.vaccine.2016.08.073. Epub 2016 Aug 29.
AIM
To investigate circulating IFN-λ3 and IFNL3 polymorphisms in hemodialysis (HD) patients differing in HBV surface antigen antibody (anti-HBs) production.
METHODS
The 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.
RESULTS
HBV 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).
CONCLUSION
In 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.
目的
研究在乙肝表面抗原抗体（抗-HBs）产生情况不同的血液透析（HD）患者中循环干扰素-λ3（IFN-λ3）及IFNL3基因多态性。
方法
本研究纳入106例接种乙肝疫苗的HD患者（88例产生抗-HBs）和36例乙肝感染的HD受试者（27例产生抗-HBs）。分析血浆IFN-λ3（酶联免疫吸附测定）以及IFNL3中的rs12979860（C>T）和rs8099917（T>G）（高分辨率熔解曲线分析）与乙肝疫苗接种或感染后抗-HBs产生的相关性。结果根据性别、年龄、肾病病因、透析时间、透析方式、IFN-λ3和25(OH)D进行了适当调整。
结果
乙肝疫苗应答者的循环IFN-λ3（ng/L）高于无应答者（120，36 - 233对比53，33 - 109，P<0.000001）。乙肝感染后产生抗-HBs的患者其循环IFN-λ3水平也高于未产生者（133，35 - 215对比71，9 - 229，P = 0.043）。IFN-λ3浓度与接种疫苗（r = 0.614，P<0.000001）和感染患者（r = 0.589，P = 0.0002）的抗-HBs滴度相关。血浆IFN-λ3是乙肝疫苗接种反应性的唯一显著指标（校正P = 0.018），并且仍然是感染后抗-HBs产生的唯一显著相关因素（校正P = 0.049）。在整个HD患者组中，血浆IFN-λ3水平85.5ng/L是抗-HBs滴度低于与等于或高于10IU/L预后的临界值（ROC敏感性68.7%，特异性85.2%，AUC 0.827）。未发现IFN-λ3与IFNL3 rs12979860之间存在显著关联。rs8099917携带TT基因型的低通量HD治疗患者的IFN-λ3水平高于rs8099917携带G等位基因的患者（139，68 - 233对比103，9 - 208，P = 0.049）。
结论
在HD患者中，循环IFN-λ3与乙肝疫苗接种和感染后抗-HBs产生密切相关。IFNL3 rs8099917基因多态性似乎与HD受试者的血浆IFN-λ3水平相关。
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