Dammacco F, Sansonno D, Han J H, Shyamala V, Cornacchiulo V, Iacobelli A R, Lauletta G, Rizzi R
Department of Biomedical Sciences, University of Bari Medical School, Italy.
Blood. 1994 Nov 15;84(10):3336-43.
Type II mixed cryoglobulinemia (MC) is an often progressive vasculitis characterized by circulating cold-precipitable proteins that usually consists of polyclonal IgG and monoclonal IgM kappa with rheumatoid factor (RF) activity. Its etiology is unknown, although recent evidence strongly suggests that hepatitis C virus (HCV) plays a major role. Plasmapheresis, corticosteroids, and cytotoxic drugs have been used in the therapy of MC patients. Recently, favorable results with recombinant interferon-alpha (rIFN alpha) have been reported. To further assess its effectiveness, we studied the effects of natural human interferon-alpha (nIFN alpha), alone and in combination with 6-methyl-prednisolone (PDN), in a prospective, randomized, controlled trial in patients with symptomatic MC. Sixty-five patients were enrolled onto the trial, 52 (80%) of whom presented serum anti-HCV antibodies and specific genomic RNA sequences. Fifteen patients received nIFN alpha (3 MU) intramuscularly (IM) three times weekly, whereas 17 patients also received 16 mg/d of PDN orally on non-IFN days. Moreover, 18 patients received 16 mg/d of PDN only, and 15 were untreated. Treatment was discontinued after 1 year and patients were monitored for 8 to 17 months (mean, 13). A complete response was achieved in eight of 15 patients (53.3%) treated with nIFN alpha and nine of 17 (52.9%) treated with nIFN alpha plus PDN, as compared with three of 18 patients (16.7%) who received PDN only (P < .05) and one of 15 (6.7%) untreated controls (P < .01). Partial response occurred in two of 15 (13.3%) patients treated with nIFN alpha, three of 17 (17.6%) who received nIFN alpha plus PDN, one of 18 (5.5%) who received PDN only, and one of 15 (6.7%) controls. A complete response in six patients (66.7%) was achieved within 3 months in the group that received nIFN alpha plus PDN, as compared with two patients (25%) of those who received nIFN alpha alone (P < .02). In anti-HCV-positive patients, the clinical response occurred in step with reduced or undetectable levels of HCV RNA and transaminase normalization. Quantification of circulating HCV RNA represented a good predictive response marker. The probability of relapse within 3 months after treatment was 100% (three of three patients) and 75% (six of eight patients), respectively, in patients who received PDN alone or nIFN alpha alone as compared with none of those who received nIFN alpha plus PDN (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)
II型混合性冷球蛋白血症（MC）是一种常呈进行性发展的血管炎，其特征为循环中可冷沉淀的蛋白，通常由具有类风湿因子（RF）活性的多克隆IgG和单克隆IgM κ组成。其病因不明，不过最近有证据强烈表明丙型肝炎病毒（HCV）起主要作用。血浆置换、皮质类固醇及细胞毒性药物已用于MC患者的治疗。最近，有报告称重组α干扰素（rIFNα）取得了良好疗效。为进一步评估其有效性，我们在一项针对有症状MC患者的前瞻性、随机、对照试验中，研究了天然人α干扰素（nIFNα）单独使用及与6-甲基泼尼松龙（PDN）联合使用的效果。65例患者纳入该试验，其中52例（80%）血清抗HCV抗体及特异性基因组RNA序列呈阳性。15例患者每周3次肌肉注射（IM）nIFNα（3 MU），而17例患者在非干扰素治疗日还口服16 mg/d的PDN。此外，18例患者仅接受16 mg/d的PDN，15例未接受治疗。治疗1年后停药，对患者进行8至17个月（平均13个月）的监测。接受nIFNα治疗的15例患者中有8例（53.3%）、接受nIFNα加PDN治疗的17例患者中有9例（52.9%）获得完全缓解，相比之下，仅接受PDN治疗的18例患者中有3例（16.7%）（P<0.05），未接受治疗的15例对照中有1例（6.7%）（P<0.01）。接受nIFNα治疗的15例患者中有2例（13.3%）、接受nIFNα加PDN治疗的17例患者中有3例（17.6%）、仅接受PDN治疗的18例患者中有1例（5.5%）以及15例对照中有1例（6.7%）出现部分缓解。接受nIFNα加PDN治疗的组中，6例患者（66.7%）在3个月内获得完全缓解，相比之下，仅接受nIFNα治疗的患者中有2例（25%）（P<0.02）。在抗HCV阳性患者中，临床反应与HCV RNA水平降低或检测不到及转氨酶正常化同步出现。循环HCV RNA定量是一个良好的预测反应标志物。单独接受PDN或nIFNα治疗的患者在治疗后3个月内复发概率分别为100%（3例患者中的3例）和75%（8例患者中的6例），而接受nIFNα加PDN治疗的患者无一例复发（P<0.001）。（摘要截取自250词）
