Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Front Immunol. 2023 Jan 5;13:1104329. doi: 10.3389/fimmu.2022.1104329. eCollection 2022.
Knowing about cytokine profile contributes to clarify the underling immune mechanism of HBsAg seroclearance rate increase. This study aims to investigate cytokine changes during nucleos(t)ide analogues (NAs) and peginterferon-α (Peg-IFNα) therapy and their impact on the HBsAg serologic response.
A total of 78 HBV DNA-negative chronic Hepatitis B (CHB) patients were studied after a lead-in phase of NAs with complete serum cytokines. Serum cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-17 and TNF-α) were quantified by flow cytometry (FCM) every 24 weeks, before, during and at the end of NAs and Peg-IFNα treatment. Clinical and laboratory data were also taken at the same time. Analysis was performed between cured and uncured groups characterized by HBsAg seroclearance. PBMCs samples from five patients (two in cured group and three in uncured group) were analyzed by FCM.
HBsAg seroclearance was achieved in 30 (38,5%) patients defined as the cured group. In comparison to uncured individuals, cured patients showed similar expressions of serum IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17 and TNF-α during the treatment of NAs and Peg-IFNα. Compared with the uncured groups, IL-5 was remarkably increased in cured patients. IL-5 at weeks 24 and 48 were associated with HBsAg seroconversion (p=0.033 and 0.027, respectively). PBMCs sample analysis confirmed the predicted value of IL-5 in response to NAs and Peg-IFNα treatment.
IL-5 at weeks 24 and 48 might be used as a biomarker for HBsAg seroclearance in NAs-experienced CHB patients treated with NAs combined with Peg-IFNα. More importantly, exploiting the expression of this cytokine may help to develop a better understanding of the immune pathogenesis of chronic HBV infection.
了解细胞因子谱有助于阐明 HBsAg 清除率增加的潜在免疫机制。本研究旨在探讨核苷(酸)类似物(NAs)和聚乙二醇干扰素-α(Peg-IFNα)治疗期间细胞因子的变化及其对 HBsAg 血清学反应的影响。
在 NAs 导入期后,对 78 例 HBV DNA 阴性的慢性乙型肝炎(CHB)患者进行了研究,他们的血清细胞因子(IL-1β、IL-2、IL-4、IL-5、IL-6、IL-8、IL-10、IL-12、IL-17 和 TNF-α)通过流式细胞术(FCM)每 24 周进行一次定量检测,在 NAs 和 Peg-IFNα 治疗前、治疗中和治疗结束时。同时还采集了临床和实验室数据。分析了以 HBsAg 清除为特征的治愈组和未治愈组之间的差异。对 5 名患者(治愈组 2 名,未治愈组 3 名)的 PBMC 样本进行了 FCM 分析。
30 例(38.5%)患者实现了 HBsAg 清除,定义为治愈组。与未治愈患者相比,治愈患者在接受 NAs 和 Peg-IFNα 治疗期间,血清 IL-1β、IL-2、IL-4、IL-6、IL-8、IL-10、IL-12、IL-17 和 TNF-α 的表达相似。与未治愈组相比,治愈组患者的 IL-5 在治疗过程中明显增加。第 24 周和第 48 周的 IL-5 与 HBsAg 血清转换相关(p=0.033 和 0.027)。PBMC 样本分析证实了 IL-5 在 NAs 和 Peg-IFNα 治疗反应中的预测价值。
第 24 周和第 48 周的 IL-5 可能作为 NAs 治疗的 CHB 患者联合 NAs 和 Peg-IFNα 治疗后 HBsAg 清除的生物标志物。更重要的是,利用这种细胞因子的表达可能有助于更好地了解慢性 HBV 感染的免疫发病机制。