دورية أكاديمية
Identification of pediatric activated T-cell hepatitis using clinical immune studies.
| العنوان: | Identification of pediatric activated T-cell hepatitis using clinical immune studies. |
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| المؤلفون: | Chapin CA; Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA; Division of Gastroenterology, Hepatology and Nutrition, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA. Electronic address: cchapin@luriechildrens.org., Diamond T; Department of Pediatrics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA; Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. Electronic address: diamondt@chop.edu., Perez A; Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, USA., Kreiger PA; Department of Clinical Pathology and Laboratory Medicine, Perelman School of Medicine, Philadelphia, PA, USA; Division of Anatomy Pathology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA., Loomes KM; Department of Pediatrics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA; Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, USA., Behrens EM; Department of Pediatrics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA; Division of Rheumatology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA., Alonso EM; Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA; Division of Gastroenterology, Hepatology and Nutrition, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA. |
| المصدر: | Clinics and research in hepatology and gastroenterology [Clin Res Hepatol Gastroenterol] 2024 Aug; Vol. 48 (7), pp. 102407. Date of Electronic Publication: 2024 Jun 25. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Masson Country of Publication: France NLM ID: 101553659 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2210-741X (Electronic) Linking ISSN: 22107401 NLM ISO Abbreviation: Clin Res Hepatol Gastroenterol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Paris : Elsevier Masson |
| مواضيع طبية MeSH: | CD8-Positive T-Lymphocytes*/immunology, Humans ; Retrospective Studies ; Child ; Male ; Female ; Child, Preschool ; Liver Failure, Acute/immunology ; Liver Failure, Acute/blood ; Adolescent ; Hepatitis/immunology ; Hepatitis/blood ; Lymphocyte Activation ; Infant ; Receptors, Interleukin-2/blood ; Granzymes/blood |
| مستخلص: | Background and Aims: The majority of indeterminate pediatric acute liver failure (PALF) cases are secondary to immune dysregulation, labeled activated T-cell hepatitis (TCHep). We aimed to describe a cohort of children with acute severe hepatitis and PALF and define how clinical immune labs may help identify the TCHep group. Methods: Retrospective review of children with acute hepatitis and PALF between March 2020 and August 2022. Patients were classified as known diagnosis, indeterminate hepatitis (IND-Hep), or TCHep (defined by liver biopsy with predominant CD8 T-cell inflammation or development of aplastic anemia). Results: 124 patients were identified: 83 with known diagnoses, 16 with TCHep, and 25 with IND-Hep. Patients with TCHep had significantly increased median total bilirubin levels (7.5 mg/dL (IQR 6.8-8.9) vs 1.5 mg/dL (IQR 1.0-3.6), p < 0.0001), soluble interleukin-2 receptor levels (4512 IU/mL (IQR 4073-5771) vs 2997 IU/mL (IQR 1957-3237), p = 0.02), and percent of CD8+ T-cells expressing perforin (14.5 % (IQR 8.0-20.0) vs 1.0 % (IQR 0.8-1.0), p = 0.004) and granzyme (37.5 % (IQR 15.8-54.8) vs 4.0 % (IQR 2.5-5.5), p = 0.004) compared to IND-Hep patients. Clinical flow cytometry showed that TCHep patients had significantly increased percent CD8+ T cells (29.0 % (IQR 24.5-33.5) vs 23.6 % (IQR 19.8-25.8), p = 0.04) and HLA-DR+ (16.0 % (IQR 14.5-24.5) vs 2.7 (1.8-5.3), p < 0.001) compared to IND-Hep patients indicative of increase in CD8+ T cells that are activated. Conclusions: Peripheral blood clinical immune studies demonstrate increased markers of CD8 T-cell activation, proliferation, and cytotoxic function for TCHep patients. These readily available immune function labs can be used to help distinguish patients with TCHep from those with other causes. This provides a non-invasive tool for early detection of potential TCHep before progression to liver failure. Competing Interests: Declaration of competing interest The authors state they have nothing to declare. (Copyright © 2024 Elsevier Masson SAS. All rights reserved.) |
| معلومات مُعتمدة: | KL2 TR001879 United States TR NCATS NIH HHS |
| فهرسة مساهمة: | Keywords: Acute hepatitis; Aplastic anemia; Immune dysregulation; Pediatric acute liver failure |
| المشرفين على المادة: | 0 (Receptors, Interleukin-2) EC 3.4.21.- (Granzymes) |
| تواريخ الأحداث: | Date Created: 20240627 Date Completed: 20240808 Latest Revision: 20240808 |
| رمز التحديث: | 20240809 |
| DOI: | 10.1016/j.clinre.2024.102407 |
| PMID: | 38936769 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 2210-741X |
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| DOI: | 10.1016/j.clinre.2024.102407 |