Toda K, Kumagai N, Iwabuchi N, Suzuki T, Saito H, Morizane T, Hibi T, Ishii H, Tsuchimoto K
Biomedical Laboratory, Kitasato Institute Hospital.
Nihon Rinsho Meneki Gakkai Kaishi. 1997 Oct;20(5):428-36. doi: 10.2177/jsci.20.428.
Of 49 patients with chronic hepatitis C treated by interferon (IFN), we measured 2'-5'-oligoadenylate synthetase (2-5 AS) activity in peripheral blood mononuclear cells (PBMC) and serum before and after the IFN therapy and studied the correlation with the clinical outcome. Before IFN therapy, the levels of 2-5 AS in PBMC and serum were significantly higher in patients with chronic hepatitis C than in healthy controls, though there was no correlation between the 2-5 AS activity and the clinical outcome. When PBMC were stimulated with IFN in vitro, the induced 2-5 AS activities in patients with chronic hepatitis C were almost same as those in healthy controls. Among patients infected with hepatitis C virus (HCV) genotype II which was considered relatively resistant to IFN, patients whose HCV was disappeared from serum by IFN therapy showed good induction of 2-5 AS activity by IFN in vitro, whereas patients in which serum HCV remained positive after the therapy showed poor response to IFN in vitro. The levels of 2-5 AS in PBMC 2 months after IFN therapy were still higher in patients whose HCV was continuously disappeared from serum by the therapy (complete remission) than in healthy controls. The in vitro induction of 2-5 AS in patients whose HCV in serum remained positive after the therapy was significantly lower than in patients with complete remission. The induction of 2-5 AS activity in patients to whom IFN therapy was ineffective, significantly decreased after the IFN therapy as compared with the activity measured before the therapy. These findings suggest that measurement of 2-5 AS activity in PBMC in vitro through IFN therapy might be useful for predicting in vivo responsibility to IFN and also knowing the change of the responsibility.
在49例接受干扰素(IFN)治疗的慢性丙型肝炎患者中,我们检测了IFN治疗前后外周血单个核细胞(PBMC)和血清中的2'-5'-寡腺苷酸合成酶(2-5 AS)活性,并研究了其与临床疗效的相关性。IFN治疗前,慢性丙型肝炎患者PBMC和血清中的2-5 AS水平显著高于健康对照,尽管2-5 AS活性与临床疗效之间无相关性。当在体外用IFN刺激PBMC时,慢性丙型肝炎患者诱导的2-5 AS活性与健康对照几乎相同。在感染被认为对IFN相对耐药的丙型肝炎病毒(HCV)基因II型的患者中,通过IFN治疗血清中HCV消失的患者在体外对IFN诱导的2-5 AS活性良好,而治疗后血清HCV仍为阳性的患者在体外对IFN反应较差。IFN治疗2个月后,通过治疗血清中HCV持续消失(完全缓解)的患者PBMC中的2-5 AS水平仍高于健康对照。治疗后血清HCV仍为阳性的患者体外2-5 AS的诱导显著低于完全缓解的患者。与治疗前测得的活性相比,IFN治疗无效的患者中2-5 AS活性的诱导在IFN治疗后显著降低。这些发现表明,通过IFN治疗体外检测PBMC中的2-5 AS活性可能有助于预测体内对IFN的反应性,并了解反应性的变化。