Effect of alfa-fetoprotein on monocytes expression of CD86 and secretion of tumour necrosis factor-alpha in patients with hepatocellular carcinoma

ABSTRACT

Hepatocellular carcinoma [HCC] constitutes a major health problem in Egypt due to the high prevalence of Hepatitis C virus [HCV]. Alfa-fetoprotein [AFP] is a tumour-associated antigen [Ag], and its serum level is elevated in patients with HCC. In vitro, AFP induces functional impairment of monocytes cells. This was demonstrated by the down-regulation of CD86 and tumour necrosis factor-a [TNF-alpha]. This study aimed to evaluate the effect of AFP level on monocytes function as a source of TNF-alpha and the expression of surface co-stimulatory molecule CD86 in patients with histopathologically proven HCC. This study comprised 23 patients. They were classified into group I [comprised 13 patients with AFP level >200 ng/ml] and group II [comprised 10 patients with API level<200ng/m1] in addition 10 cirrhotic patients with AFP level <200 ng/ml [group III] and 10 apparantely healthy individuals as a control group [group IV] were also included in this work. Serum AFP, CD86 and TNF-alpha were measured in all subjects using Enzyme Immunoassay [EIA], flow cytometery and Enzyme Linked Immunosorbent Assay [ELISA] respectively. CD86 and TNF-alpha were significantly reduced in patients of group I than those of groups II, III and IV [P<0.001]. Serum AFP level had a significant negative correlation with TNF-alpha level and CD86 expression in patients with HCC. On the other hand liver transaminases and total bilirubin level were significantly increased in groups I, II and III when compared to control group IV. The percent of patients infected with HCV was significantly higher in patients groups [I, II, III] when compared to control group while there was no significant difference between them as regard the percent of HBV infection. Serum albumin level in patients groups was significantly decreased when compared with control group. It can be concluded that AFP markedly impairs the function of monocytes, in addition, the ability of antigen presenting cells [APCS] of patients with HCC and high level of serum AFP to produce proinflammatory cytokines is reduced. Although the number of patients in this study was small, it provides a new insight into understanding the mechanisms underlying the suppression of immune recognition of tumour in patients with HCC. Further studies are needed to correlate these finding, with the clinical outcome of patients with HCC