Exploratory Study of Autoantibody Profiling in Drug-Induced Liver Injury with an Autoimmune Phenotype.
Exploratory Study of Autoantibody Profiling in Drug-Induced Liver Injury with an Autoimmune Phenotype.
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DOI：
10.1002/hep4.1582
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发表时间：
2020-11
影响因子：
5.1
通讯作者：
Chalasani N
中科院分区：
文献类型：
--
作者：
Lammert C;Zhu C;Lian Y;Raman I;Eckert G;Li QZ;Chalasani N
药物性肝损伤(DILI)有时表现为自身免疫性肝炎样表型(AI-DILI)，与新发自身免疫性肝炎(AIH)相区别具有挑战性。我们进行了一项研究，通过分析血清自身抗体来识别AI-DILI特有的自身抗体。使用包含来自四个组的94个自身抗原的自身抗原阵列对自身抗体进行定量：AI-DILI组(n=65)、DILI对照组(n=67)、新发AIH组(n=17)和健康对照组(n=30hcs)。37例AI-DILI患者也在发病6个月后采集样本。AI-DILI和De-nevo AIH的抗中性粒细胞抗体和抗平滑肌抗体的患病率相似。与HCS相比，初治AIH患者的多种免疫球蛋白G(Ig G；35[46.1%])和Ig M(51[70%])自身抗体升高，而AI-DILI的Ig M(40[54.8%])升高，但未检测到Ig G自身抗体。与HCS相比，DILI对照组的免疫球蛋白和免疫球蛋白M谱相似。比较初治AIH和AI-DILI，发现18例(23.7%)Ig G升高，但仅1例(1.4%)Ig M自身抗体升高，提示初治AIH具有独特的Ig G自身抗体谱。与DILI和HCS相比，AI-DILI和新生AIH中IgM自身抗体升高是常见的，但不同药物诱导的AI-DILI表现出不同的IgM自身抗体频率，与呋喃妥因相关的AI-DILI表现出更高的IgM自身抗体水平。诊断时和6个月时AI-DILI自身抗体水平显示37例IgM自身抗体显著下降。对免疫球蛋白和免疫球蛋白M高度相关的模型进行多因素Logistic回归分析，曲线下面积为0.87(95%可信区间，0.79~0.95)，用于区分新发AIH和AI-DILI。结论：独有的Ig G和Ig M自身抗体特征有望成为鉴别AI-DILI和De-nevo AIH的有效生物标志物。
Drug‐induced liver injury (DILI) sometimes presents with an autoimmune hepatitis‐like phenotype (AI‐DILI), and it is challenging to distinguish it from de novo autoimmune hepatitis (AIH). We conducted a study to identify autoantibodies unique to AI‐DILI by profiling serum autoantibodies. Autoantibodies were quantified using an autoantigen array containing 94 autoantigens from four groups: AI‐DILI (n = 65), DILI controls (n = 67), de novo AIH (n = 17), and healthy controls (HCs; n = 30). In 37 patients with AI‐DILI, samples were also collected 6 months after presentation. AI‐DILI and de novo AIH had similar anti‐neutrophil antibody and anti‐smooth muscle antibody prevalence. Compared to HCs, de novo AIH had an increase in many immunoglobulin G (IgG; 35 [46.1%]) and IgM (51 [70%]) autoantibodies, whereas AI‐DILI had an increase of IgM (40 [54.8%]) but not IgG autoantibodies. DILI controls had a similar IgG and IgM profile compared to HCs. Comparing de novo AIH to AI‐DILI identified 18 (23.7%) elevated IgG but only one (1.4%) IgM autoantibodies, indicating the unique IgG autoantibody profile in de novo AIH. Compared to DILI and HCs, increased IgM autoantibodies in AI‐DILI and de novo AIH were common; however, AI‐DILI induced by different drugs showed different frequencies of IgM autoantibodies, with nitrofurantoin‐related AI‐DILI showing a higher number of increased IgM autoantibodies. AI‐DILI autoantibody levels at diagnosis and at 6 months showed a significant decline in 37 IgM autoantibodies. A model with highly correlated IgG and IgM was fitted into multivariate logistic regression and revealed an area under the curve of 0.87 (95% confidence interval, 0.79‐0.95) to distinguish de novo AIH from AI‐DILI. Conclusion: The unique IgG and IgM autoantibody signature appears to be a promising biomarker for distinguishing AI‐DILI from de novo AIH.
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DOI：
10.1073/pnas.1906593116
发表时间：
2020-01-07
影响因子：
11.1
作者：
Gourh, Pravitt;Safran, Sarah A.;Remmers, Elaine F.
通讯作者：
Remmers, Elaine F.
DOI：
10.1002/hep.29802
发表时间：
2019-03
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Church RJ;Kullak-Ublick GA;Aubrecht J;Bonkovsky HL;Chalasani N;Fontana RJ;Goepfert JC;Hackman F;King NMP;Kirby S;Kirby P;Marcinak J;Ormarsdottir S;Schomaker SJ;Schuppe-Koistinen I;Wolenski F;Arber N;Merz M;Sauer JM;Andrade RJ;van Bömmel F;Poynard T;Watkins PB
通讯作者：
Watkins PB
影响因子：
13.5
作者：
Russo, Mark W.;Hoofnagle, Jay H.;Gu, Jiezhun;Fontana, Robert J.;Barnhart, Huiman;Kleiner, David E.;Chalasani, Naga;Bonkovsky, Herbert L.
通讯作者：
Bonkovsky, Herbert L.
DOI：
10.15403/jgld.2014.1121.263.pak
发表时间：
2017-09-01
影响因子：
2.1
作者：
Parfieniuk-Kowerda, Anna;Swiderska, Magdalena;Flisiak, Robert
通讯作者：
Flisiak, Robert
DOI：
10.1016/j.cgh.2016.05.043
发表时间：
2017-01
期刊：
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
影响因子：
--
作者：
de Boer YS;Kosinski AS;Urban TJ;Zhao Z;Long N;Chalasani N;Kleiner DE;Hoofnagle JH;Drug-Induced Liver Injury Network
通讯作者：
Drug-Induced Liver Injury Network