Kalyuzhin O V, Ponezheva Zh B, Semenova I V, Khokhlova O N, Serebrovskaya L V, Guseva T S, Parshina O V, Maleev V V
I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow, Russia.
Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare, Moscow, Russia.
Ter Arkh. 2017;89(11):14-20. doi: 10.17116/terarkh2017891114-20.
To determine whether there is a correlation of the composition of circulating lymphocyte subpopulations, the serum concentrations of interferon (IFN)-α, IFN-γ, and IFN-λ3, and the lymphocyte expression of types I and II IFN receptors with the species of a disease pathogen and the degree of liver fibrosis (LF) in patients with chronic hepatitis B (CHB) and in those with chronic hepatitis C (CHC).
The investigation enrolled 44 patients with CHC, 9 patients with CHB, and 13 clinically healthy donors. The degree of LF in the patients was determined using transient elastography. The composition of peripheral blood lymphocyte subpopulations was examined; the concentrations of IFN-α, IFN-γ, and IL-28B were estimated.
Lymphocyte counts were higher in patients with CHC and in those with CHB than those in healthy donors; and the number of neutrophils was lower. There were no differences between the groups in the composition of lymphocyte subpopulations with the exception of the number of CD3CD4 cells, which in patients with CHC was larger than in those with CHB. In CHC and CHB patients, the counts of CD118 lymphocytes were higher than those in healthy donors. Patients with CHB and those with CHC did not differ between themselves and from healthy donors in the expression of CD119 on the lymphocytes. In CHC patients, the relative CD119 cell counts were higher between CD4 lymphocytes than those in healthy donors. The serum levels of IFN-α and IFN-γ in CHC and CHB patients were similar, but higher in healthy donors. The concentration of IL-28B genotype in patients with CHC was twice as high as in those with CHB, but the differences were statistically insignificant. The number of lymphocytes increased with the progression of fibrosis; that of neutrophils decreased. There was an inverse relationship between platelet counts and LF severity. Multiple comparisons of the clusters of patients with different degrees of LF revealed no differences in the number of major lymphocyte subpopulations. However, the number of CD3CD16CD56 natural killer-like T (NKT) cells correlated with fibrosis severity. Patients with different degrees of LF showed no differences in the proportion of CD118 and CD119 cells between lymphocytes and in the serum levels of IFN-α, IFN-γ, and IL-28B levels. Patients with grade IV LF displayed a higher proportion of CD4CD119 lymphocytes between CD45 cells than did those with grade III LF.
Several new clinical and laboratory trends were identified and the nature and extent of previously described hematological and immunological changes were clarified in CHC or CHB patients with various degrees of LF. Some indicators may be used as additional criteria for the prognosis of the above forms of hepatitis, and a number of newly described facts suggest that it is necessary to revise the protective/phlogogenic value of types I, II, and III IFNs in chronic viral hepatitis C and B.
确定慢性乙型肝炎(CHB)和慢性丙型肝炎(CHC)患者循环淋巴细胞亚群的组成、血清干扰素(IFN)-α、IFN-γ和IFN-λ3浓度以及I型和II型IFN受体的淋巴细胞表达与疾病病原体种类和肝纤维化(LF)程度之间是否存在相关性。
本研究纳入44例CHC患者、9例CHB患者和13名临床健康供者。采用瞬时弹性成像法测定患者的LF程度。检测外周血淋巴细胞亚群的组成;估算IFN-α、IFN-γ和IL-28B的浓度。
CHC患者和CHB患者的淋巴细胞计数高于健康供者,中性粒细胞数量低于健康供者。除CD3CD4细胞数量外,各组淋巴细胞亚群组成无差异,CHC患者的CD3CD4细胞数量多于CHB患者。在CHC和CHB患者中,CD118淋巴细胞计数高于健康供者。CHB患者和CHC患者淋巴细胞上CD119的表达与健康供者之间无差异。在CHC患者中,CD4淋巴细胞中相对CD119细胞计数高于健康供者。CHC和CHB患者的血清IFN-α和IFN-γ水平相似,但健康供者的水平更高。CHC患者中IL-28B基因型的浓度是CHB患者的两倍,但差异无统计学意义。淋巴细胞数量随纤维化进展而增加,中性粒细胞数量减少。血小板计数与LF严重程度呈负相关。对不同程度LF患者组的聚类进行多重比较,发现主要淋巴细胞亚群数量无差异。然而,CD3CD16CD56自然杀伤样T(NKT)细胞数量与纤维化严重程度相关。不同程度LF患者淋巴细胞中CD118和CD119细胞比例以及血清IFN-α、IFN-γ和IL-28B水平无差异。IV级LF患者CD45细胞中CD4CD119淋巴细胞的比例高于III级LF患者。
在不同程度LF的CHC或CHB患者中发现了几种新的临床和实验室趋势,并阐明了先前描述的血液学和免疫学变化的性质和程度。一些指标可作为上述肝炎形式预后的附加标准,许多新描述的事实表明有必要重新审视I型、II型和III型IFN在慢性丙型和乙型病毒性肝炎中的保护/致炎价值。