Autoimmunity against pancreatic islets and other tissues before and after interferon-α therapy in patients with hepatitis C virus chronic infection
Autoimmunity against pancreatic islets and other tissues before and after interferon-α therapy in patients with hepatitis C virus chronic infection
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DOI：
10.2337/diacare.23.8.1177
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发表时间：
2000-08-01
期刊：
影响因子：
16.2
通讯作者：
de Lalla, F
中科院分区：
文献类型：
--
作者：
Betterle, C;Fabris, P;de Lalla, F
目的-本研究的目的是调查意大利丙型肝炎病毒（HCV）慢性感染患者的临床和潜伏性自身免疫性疾病的患病率与干扰素-α（IFN-α）治疗前后-临床自身免疫性疾病的证据和自身抗体的存在进行了评估70例HCV慢性感染。采用经典的间接免疫荧光技术检测胰岛细胞（伊卡）、胰高血糖素产生细胞（GCA）、壁细胞（PCA）、肾上腺皮质（ACA）、肾上腺髓质（AdMA）、细胞核（ANA）、肝肾微粒体（LKM-Ab）、线粒体和平滑肌（SMA）的自身抗体。GAD自身抗体（GADAb），第二胰岛细胞自身抗原（IA 2-Ab），胰岛素（IAA）进行了放射免疫测定，甲状腺微粒体自身抗体（TMHA）和甲状腺球蛋白自身抗体（TGHA）进行了评估，通过血凝试验。伊卡阳性1例（1.4%），GCA阳性2例（2.8%），GADAb阳性2例（2.8%），PCA阳性5例（7.1%），ANA阳性2例（2.8%），SMA阳性3例（3.7%），TMHA阳性4例（5.7%），TGHA阳性2例（2.8%）。与健康对照组相比，这些频率没有显著差异。有29例（41%）患者IAA低滴度阳性，而对照组为2%（P < 0.0001）。1例伊卡/GADAb阳性患者的伊卡滴度在IFN-α治疗期间增加，该患者在治疗开始后5个月发展为1型糖尿病。在治疗过程中，IAA水平没有变化，没有一个IAA（+）患者发展为糖尿病。在IFN-α治疗期间，4例初始阳性患者中有3例甲状腺自身抗体滴度升高，其中1例患者变为阳性，2例甲状腺抗体阳性患者出现明显的甲状腺功能减退症。5例阳性患者中有1例PCA滴度升高。其他自身抗原的抗体在治疗过程中没有变化。结论-我们没有发现慢性HCV感染患者的临床或潜伏性自身免疫性疾病的频率增加。然而，这项研究表明，在IFN-α治疗前和治疗期间筛查患者的自身抗体（特别是甲状腺和胰腺）可能有助于评估患者发生自身免疫性疾病的风险。
OBJECTIVE - The aim of the study was to investigate the prevalence of clinical and latent autoimmune diseases in Italian patients with hepatitis C virus (HCV) chronic infection before and after treatment with interferon-oc (IFN-alpha).RESEARCH DESIGN AND METHODS - The evidence of clinical autoimmune disease and the presence of autoantibodies were assessed in 70 patients with HCV chronic infection. Autoantibodies to islet cell (ICA), glucagon-producing cells (GCA),parietal cell (PCA), adrenal cortex (ACA), adrenal medulla (AdMA), nuclei (ANA), liver-kidney microsomal (LKM-Ab), mitochondrial, and smooth muscle (SMA) were tested using the classic indirect immunofluorescence technique. Autoantibodies to GAD (GADAb), second islet cell autoantigen (IA2-Ab), and insulin (IAA) were tested by radioimmunoassay, and thyroid microsomal autoantibodies (TMHA) and thyroglobulin autoantibodies (TGHA) were assessed by hemoagglutination test.RESULTS - None of the 70 patients studied showed evidence of clinical disease before treatment with IFN-a. However, 1 (1.4%) patient was positive for ICA, 2 (2.8%) were positive for GCA, 2 (2.8%) for GADAb, 5 (7.1%) for PCA, 2 (2.8%) for ANA, 3 (3.7%) for SMA, 4 (5.7%) for TMHA, and 2 (2.8%) for TGHA. These frequencies were not significantly different when compared with healthy control subjects. There were 29 (41%) patients who were positive for IAA at low titers compared with 2% of the control subjects (significantly different P < 0.0001). ICA titers of one patient positive for ICA/GADAb increased during the IFN-alpha therapy, and the patient developed type 1 diabetes 5 months after the beginning of treatment. IAA levels did not change during the course of treatment, and none of the IAA(+) patients developed diabetes. Thyroid autoantibody titers increased in 3 of the 4 initially positive patients, with 1 patient becoming positive and 2 thyroid antibody-positive patients developing overt hypothyroidism during IFN-alpha treatment. PCA titers increased in 1 of 5 positive patients. Antibodies to other auto-antigens did not change during the course of treatment.CONCLUSIONS - We have not found an increased frequency of clinical or latent autoimmune diseases in patients with chronic HCV infection. However, this study suggests that screening patients for autoantibodies tin particular thyroid and pancreas) before and during IFN-alpha therapy may be useful in assessing the risk of patients developing autoimmune disease.