Mormile Raffaella
Division of Pediatrics and Neonatology, Moscati Hospital, Aversa, Italy.
Med Hypotheses. 2017 Jul;104:45-47. doi: 10.1016/j.mehy.2017.05.020. Epub 2017 May 25.
Unresponsiveness to Hepatitis B virus (HBV) vaccine has been associated with interleukins involved with Th1 functioning including Interleukin-8 (IL-18) and Interferon-γ (IFN-γ). IL-18 and IFN-γ have also been implicated in the onset of different types of immune-mediate inflammatory conditions such as Type 1 Diabetes (T1D), Celiac disease (CD), rheumatoid arthritis (RA), obesity and systemic lupus erythematosus (SLE). Taking into account that HBV vaccination is provided in the 1st year of life worldwide, I propose that all babies should be tested for anti-HBs response after completion of the vaccine series. And I suggest that children with undetectable anti-HBs titers after recommended immunization schedule as well as the additional booster doses should be followed up over time because they may be at risk of developing a number of autoimmune disorders. In this light, the non-responsiveness to HBV vaccine might be a predictor of latent autoimmunity. For that reason, research studies are needed in order to verify the existence of potential IL-18 and IFN-γ gene polymorphisms to utilize as biomarkers of latent autoimmunity. As a final point, administration of neutralizing antibodies against IFN-γ and/or IL-18 might represent a future target for immune-modulatory therapeutic approach to halt or even reverse autoimmune phenomena.
对乙型肝炎病毒（HBV）疫苗无反应与参与Th1功能的白细胞介素有关，包括白细胞介素-18（IL-18）和干扰素-γ（IFN-γ）。IL-18和IFN-γ也与不同类型的免疫介导炎症性疾病的发病有关，如1型糖尿病（T1D）、乳糜泻（CD）、类风湿性关节炎（RA）、肥胖症和系统性红斑狼疮（SLE）。考虑到全球范围内在出生后第一年就进行HBV疫苗接种，我建议在完成疫苗接种系列后对所有婴儿进行抗-HBs反应检测。并且我建议，在按照推荐的免疫程序以及额外的加强剂量接种疫苗后，抗-HBs滴度检测不到的儿童应长期随访，因为他们可能有患多种自身免疫性疾病的风险。鉴于此，对HBV疫苗无反应可能是潜在自身免疫的一个预测指标。因此，需要进行研究以验证是否存在潜在的IL-18和IFN-γ基因多态性，将其用作潜在自身免疫的生物标志物。最后一点，给予抗IFN-γ和/或IL-18的中和抗体可能代表免疫调节治疗方法的未来目标，以阻止甚至逆转自身免疫现象。
