Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
University Hospital Brandenburg, Brandenburg Medical School, Center of Internal Medicine II, Hochstrasse 29, 14770, Brandenburg, Germany.
Med Microbiol Immunol. 2017 Oct;206(5):379-382. doi: 10.1007/s00430-017-0516-z. Epub 2017 Aug 16.
Autoantibodies against inosine-5'-monophosphate-dehydrogenase-2 (IMPDH2; "rods and rings" pattern) develop in chronic hepatitis C (CHC) patients under treatment with peg-interferon (IFN) and ribavirin (RBV), an inhibitor of IMPDH2. We investigated the influence of the alternative therapy with direct-acting antivirals (DAA)/ribavirin on anti-IMPDH2 autoantibody generation and the use of anti-IMPDH2 development as a marker for therapy outcome (sustained virologic response, SVR). We analyzed a "real life" cohort of 104 unselected CHC genotype 1 (GT1) patients treated with IFN/first-generation DAA/RBV prospectively compared to a historic cohort of 59 IFN/RBV-treated CHC GT1 patients. First-generation DAA were boceprevir (BOC) or telaprevir (TPR). Serum autoantibodies were tested by indirect immunofluorescence (IFA) using recombinant IMPDH2 expressing HEK293 cells and native HEp2-cells as substrates. 64/163 (39%) CHC patients turned anti-IMPDH2 positive during therapy, but only 43/163 (26%) showed also "rods and rings" structures. 99/163 (61%) were tested as anti-IMPDH2 negative. 53/104 (51%) CHC patients undergoing IFN/DAA/RBV therapy were anti-IMPDH2 positive and 38/104 (37%) were in parallel anti-"rods and rings" positive. HCV clearance/SVR rate after IFN/DAA/RBV therapy and anti-IMPDH2 status were not significantly dependent. CHC GT1 patients treated with IFN/first-generation DAA/RBV developed anti-IMPDH2 autoantibodies comparable to previous studies including patients under IFN/RBV therapy. Anti-IMPDH2 titers show no use as a marker for therapy outcome in CHC GT1 patients.
自身抗体针对肌苷-5'-单磷酸脱氢酶-2（IMPDH2；“杆和环”模式）在接受聚乙二醇干扰素（IFN）和利巴韦林（RBV）治疗的慢性丙型肝炎（CHC）患者中产生，后者是 IMPDH2 的抑制剂。我们研究了直接作用抗病毒药物（DAA）/利巴韦林的替代疗法对抗 IMPDH2 自身抗体产生的影响，并将抗 IMPDH2 发展用作治疗结果（持续病毒学应答，SVR）的标志物。我们前瞻性地分析了 104 例未经选择的 CHC 基因型 1（GT1）患者的“真实生活”队列，这些患者接受 IFN/第一代 DAA/RBV 治疗，并与 59 例接受 IFN/RBV 治疗的 CHC GT1 患者的历史队列进行比较。第一代 DAA 为博赛泼维（BOC）或特拉泼维（TPR）。通过间接免疫荧光（IFA）使用表达 HEK293 细胞和天然 Hep2 细胞的重组 IMPDH2 检测血清自身抗体。在治疗过程中，163 例 CHC 患者中有 64/163（39%）转为抗 IMPDH2 阳性，但只有 43/163（26%）显示也存在“杆和环”结构。163 例中有 99/163（61%）被检测为抗 IMPDH2 阴性。接受 IFN/DAA/RBV 治疗的 104 例 CHC 患者中有 53/104（51%）为抗 IMPDH2 阳性，38/104（37%）为抗“杆和环”阳性。IFN/DAA/RBV 治疗后的 HCV 清除率/SVR 率与抗 IMPDH2 状态无显著相关性。与包括接受 IFN/RBV 治疗的患者在内的以前的研究相比，接受 IFN/第一代 DAA/RBV 治疗的 CHC GT1 患者产生了抗 IMPDH2 自身抗体。抗 IMPDH2 滴度不能作为 CHC GT1 患者治疗结果的标志物。
