title: Disrupted lymphocyte homeostasis in hepatitis-associated acquired aplastic anemia is associated with short telomeres.
abstract: Hepatitis-associated aplastic anemia (HAA) is a variant of acquired aplastic anemia (AA) in which immune-mediated bone marrow failure (BMF) develops following an acute episode of seronegative hepatitis. Dyskeratosis congenita (DC) is an inherited BMF syndrome characterized by the presence of short telomeres, mucocutaneous abnormalities, and cancer predisposition. While both conditions may cause BMF and hepatic impairment, therapeutic approaches are distinct, making it imperative to establish the correct diagnosis. In clinical practice, lymphocyte telomere lengths (TL) are used as a first-line screen to rule out inherited telomeropathies before initiating treatment for AA. To evaluate the reliability of TL in the HAA population, we performed a retrospective analysis of TL in 10 consecutively enrolled HAA patients compared to 19 patients with idiopathic AA (IAA). HAA patients had significantly shorter telomeres than IAA patients (P = 0.009), including four patients with TL at or below the 1st percentile for age-matched controls. HAA patients had no clinical features of DC and did not carry disease-causing mutations in known genes associated with inherited telomere disorders. Instead, short TLs were significantly correlated with severe lymphopenia and skewed lymphocyte subsets, features characteristic of HAA. Our results indicate the importance of caution in the interpretation of TL measurements in HAA, because, in this patient population, short telomeres have limited specificity.
authors.affiliation: Comprehensive Bone Marrow Failure Center, Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.|Division of Hematology-Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Daria V
authors.initials: DV
authors.lastname: Babushok
authors.affiliation: Comprehensive Bone Marrow Failure Center, Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Grignon
authors.affiliation: Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Yimei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Comprehensive Bone Marrow Failure Center, Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Jamie
authors.initials: J
authors.lastname: Atienza
authors.affiliation: Division of Health and Biomedical Informatics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Hongbo M
authors.initials: HM
authors.lastname: Xie
authors.affiliation: Comprehensive Bone Marrow Failure Center, Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Ho-Sun
authors.initials: HS
authors.lastname: Lam
authors.affiliation: Comprehensive Bone Marrow Failure Center, Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Helge
authors.initials: H
authors.lastname: Hartung
authors.affiliation: Comprehensive Bone Marrow Failure Center, Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Monica
authors.initials: M
authors.lastname: Bessler
authors.affiliation: Comprehensive Bone Marrow Failure Center, Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.|Division of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Olson
mesh_terms: D000293:Adolescent; D000741:Anemia, Aplastic / Q000097:blood* / Q000150:complications / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D020732:Cytogenetic Analysis; D005260:Female; D005434:Flow Cytometry; D006505:Hepatitis / Q000097:blood* / Q000150:complications / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D016131:Lymphocyte Subsets / Q000648:ultrastructure*; D008297:Male; D059505:Telomere Homeostasis / Q000235:genetics*; D059506:Telomere Shortening / Q000235:genetics*