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慢性丙型肝炎患儿的非器官特异性自身抗体

Non-organ specific autoantibodies in children with chronic hepatitis C.

作者信息

Bortolotti F, Vajro P, Balli F, Giacchino R, Crivellaro C, Barbera C, Cataleta M, Muratori L, Pontisso P, Nebbia G, Zancan L, Bertolini A, Alberti A, Bianchi F

机构信息

Clinica Medica 2, Padua, Italy.

出版信息

J Hepatol. 1996 Nov;25(5):614-20. doi: 10.1016/s0168-8278(96)80228-5.

Abstract

BACKGROUND/AIMS: Recent studies in adult patients have established a relationship between hepatitis C virus infection and the presence of liver-kidney microsomal autoantibody type 1 (LKM1). Conversely, little is known regarding the relationship between hepatitis C and autoimmunity in children. In this study, we investigated non-organ specific autoantibodies in 40 otherwise healthy Italian children with chronic hepatitis C.

METHODS

All but four patients included in the study were asymptomatic. Liver histology, obtained in 35, showed features ranging from minimal to mild chronic hepatitis. Autoantibodies were investigated by indirect immunofluorescence. HCV RNA was assayed by the polymerase chain reaction in 34 cases and viral genotypes were determined.

RESULTS

Antinuclear antibodies were detected in three (7.5%) cases, one with a homogeneous pattern; smooth muscle autoantibodies in seven (17.5%) cases, always with V (vessels only) specificity and LKM1 in four (10%), at titers ranging from 1:20 and 1:2560. Clinical and virologic features did not significantly differ between autoantibody positive and negative cases, although infections with HCV genotypes 1a and 2 were more frequent in LKM1-positive patients. During observation, the child with the highest LKM1 titre was unsuccessfully treated with alpha interferon but responded to steroids. Twelve LKM1 negative children were also treated with interferon and one developed low LKM1 titers concomitant with an alanine aminotransferase flare. The sera of the five LKM1-positive children with investigated by immunoblotting with a human microsomal fraction and peptide 257-269 of cytochrome P450IID6. Only the serum of the child with the highest LKM1 titers was reactive.

CONCLUSIONS

These results show that a consistent proportion of children with chronic hepatitis C circulate non-organ specific autoantibodies. The prevalence of LKM1 is greater than in adults and this could raise problems for the treatment of the disease with interferon. The analysis of LKM1 target antigens might help to identify putative cases of "true" autoimmune hepatitis with concomitant HCV infection that could benefit from steroid treatment.

摘要

背景/目的:近期针对成年患者的研究已证实丙型肝炎病毒感染与1型肝肾微粒体自身抗体(LKM1)的存在之间存在关联。相反,关于丙型肝炎与儿童自身免疫之间的关系却知之甚少。在本研究中,我们调查了40名其他方面均健康的患有慢性丙型肝炎的意大利儿童的非器官特异性自身抗体。

方法

纳入研究的患者除4名外均无症状。35名患者进行了肝脏组织学检查,结果显示病变特征从轻度至中度慢性肝炎不等。通过间接免疫荧光法检测自身抗体。34例患者采用聚合酶链反应检测HCV RNA并确定病毒基因型。

结果

3例(7.5%)检测到抗核抗体,其中1例呈均质型;7例(17.5%)检测到平滑肌自身抗体,均仅对血管具有特异性,4例(10%)检测到LKM1,滴度范围为1:20至1:2560。自身抗体阳性和阴性病例的临床和病毒学特征无显著差异,不过LKM1阳性患者中HCV 1a型和2型感染更为常见。在观察期间,LKM1滴度最高的儿童接受α干扰素治疗未成功,但对类固醇有反应。12名LKM1阴性儿童也接受了干扰素治疗,其中1名出现低LKM1滴度并伴有丙氨酸转氨酶升高。对5名LKM1阳性儿童的血清用人微粒体组分和细胞色素P450IID6的257 - 269肽段进行免疫印迹分析。仅LKM1滴度最高的儿童血清呈反应性。

结论

这些结果表明,相当比例的慢性丙型肝炎儿童体内存在非器官特异性自身抗体。LKM1的患病率高于成人,这可能给干扰素治疗该疾病带来问题。对LKM1靶抗原的分析可能有助于识别合并HCV感染的“真正”自身免疫性肝炎的推定病例,这些病例可能从类固醇治疗中获益。

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