Exploratory Study of Autoantibody Profiling in Drug‐Induced Liver Injury with an Autoimmune Phenotype

• Published in: Hepatology communications Vol. 4; no. 11; pp. 1651 - 1663
• Main Authors: Lammert, Craig, Zhu, Chengsong, Lian, Yun, Raman, Indu, Eckert, George, Li, Quan‐Zhen, Chalasani, Naga
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins 01.11.2020; John Wiley and Sons Inc; Wolters Kluwer Health/LWW
• Subjects: Antibiotics; Antibodies; Antigens; Biomarkers; Causality; Hepatitis; Immunoglobulins; Laboratories; Liver; Lupus; Neutrophils; Noise; Original; Phosphatase; Principal components analysis; Rheumatoid arthritis; Smooth muscle; Statistical analysis; Indiana; United States > US
• ISSN: 2471-254X; 2471-254X
• DOI: 10.1002/hep4.1582

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.