Changes of cytokine levels and T cell surface molecules in patients with chronic hepatitis B and the association with functional cure
Zhen Xu 1 2 3 , Ji-Zong Lin 4 , Ying-Fu Zeng 1 2 3 , Xiao-Hua Yang 1 2 3 , Zhe-Bin Wu 1 2 3 , Zhao-Xia Hu 1 2 3 , Qi-Yi Zhao 1 2 3 , Jing Liu 1 2 3 , Zhi-Liang Gao 1 2 3
Affiliations
Affiliations
1
Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen, University, Guangzhou, Guangdong, 510630, China.
2
Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated, Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
3
Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou, Guangdong, 510080, China.
4
General Surgery Department, Lingnan Hospital the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, China.
PMID: 33913556 DOI: 10.1002/jmv.27041
Abstract
Background: This study aimed to examine changes in levels of cytokine and T cell surface molecules in chronic hepatitis B (CHB) patients receiving sequential interferon therapy following 1-year nucleos(t)ide analogues (NAs) treatment.
Methods: Cytokine levels were measured in 30 patients, and T cell surface molecule expression was measured in 48 patients receiving sequential interferon therapy and 24 patients only receiving NA mono-therapy. A HBsAg titer of < 0.05 IU/ml was defined as a "functional cure".
Results: In the cured group (HBsAg < 0.05 IU/ml), a decreasing probability was observed in IFN-γ (after week 0), and IL-22 and IP-10 (after week 12). In the non-cured group (HBsAg ≥ 0.05 IU/ml), a probability of slightly decreasing was observed for IFN-γ (after week 12), and a probability of increasing IP-10 concentration (after week 0) was observed. GEE analyses showed significant differences in the levels of IL-10, IL-23, CCL-3, IL-1β, IL-2, and IL-12P70 between the two groups. In GEE analysis, there were significant differences in expressions of CD45RO+ between the cured group and the non-cured group. The frequencies of T cells expressing Tim-3, CD62L, and CD152 were significantly lower in the sequential interferon therapy group than in the NA mono-therapy group.
Conclusions: Changes in cytokine levels (IFN-γ, IP-10, IL-10, IL-23, CCL-3, IL-1β, IL-2, and IL-12P70) and T cell surface molecules (CD45RO+) may predict HBsAg seroconversion in CHB patients receiving sequential interferon therapy. The period from week 12 to week 24 during sequential interferon therapy may be a critical time of immune status change. This article is protected by copyright. All rights reserved.
方法：在30例患者中测量细胞因子水平，在48例接受序贯干扰素治疗的患者和24例仅接受NA单一疗法的患者中测量T细胞表面分子表达。 ＜0.05 IU / ml的HBsAg滴度定义为“功能性治愈”。
结果：在治愈组（HBsAg <0.05 IU / ml）中，观察到IFN-γ（第0周后），IL-22和IP-10（第12周后）降低的可能性。在非治愈组（HBsAg≥0.05 IU / ml）中，观察到IFN-γ略有降低的可能性（在第12周后），而IP-10浓度升高的可能性（在第0周后）。 GEE分析显示两组之间IL-10，IL-23，CCL-3，IL-1β，IL-2和IL-12P70的水平存在显着差异。在GEE分析中，治愈组和未治愈组之间CD45RO +的表达存在显着差异。序贯干扰素治疗组中表达Tim-3，CD62L和CD152的T细胞的频率显着低于NA单药治疗组。