TY - JOUR
T1 - Exploratory Study of Autoantibody Profiling in Drug-Induced Liver Injury with an Autoimmune Phenotype
AU - Lammert, Craig
AU - Zhu, Chengsong
AU - Lian, Yun
AU - Raman, Indu
AU - Eckert, George
AU - Li, Quan Zhen
AU - Chalasani, Naga
N1 - Publisher Copyright:
© 2020 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of the American Association for the Study of Liver Diseases.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - 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.
AB - 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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U2 - 10.1002/hep4.1582
DO - 10.1002/hep4.1582
M3 - Article
C2 - 33163835
AN - SCOPUS:85102355154
SN - 2471-254X
VL - 4
SP - 1651
EP - 1663
JO - Hepatology Communications
JF - Hepatology Communications
IS - 11
ER -