1. Immune status of patients with inherited bone marrow failure syndromes.
- Author
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Giri N, Alter BP, Penrose K, Falk RT, Pan Y, Savage SA, Williams M, Kemp TJ, and Pinto LA
- Subjects
- Adolescent, Adrenal Cortex Hormones therapeutic use, Adult, Aged, Anemia, Aplastic, Anemia, Diamond-Blackfan drug therapy, Anemia, Diamond-Blackfan immunology, Anemia, Diamond-Blackfan pathology, B-Lymphocytes drug effects, B-Lymphocytes immunology, B-Lymphocytes pathology, Bone Marrow Diseases congenital, Bone Marrow Diseases drug therapy, Bone Marrow Diseases immunology, Bone Marrow Failure Disorders, Case-Control Studies, Child, Child, Preschool, Cytokines biosynthesis, Cytokines immunology, Dyskeratosis Congenita drug therapy, Dyskeratosis Congenita immunology, Dyskeratosis Congenita pathology, Exocrine Pancreatic Insufficiency congenital, Exocrine Pancreatic Insufficiency drug therapy, Exocrine Pancreatic Insufficiency immunology, Family, Fanconi Anemia drug therapy, Fanconi Anemia immunology, Fanconi Anemia pathology, Female, Granulocyte Colony-Stimulating Factor biosynthesis, Granulocyte Colony-Stimulating Factor immunology, Hemoglobinuria, Paroxysmal congenital, Hemoglobinuria, Paroxysmal drug therapy, Hemoglobinuria, Paroxysmal immunology, Humans, Immunoglobulins biosynthesis, Infant, Interferon-gamma biosynthesis, Interferon-gamma immunology, Killer Cells, Natural drug effects, Killer Cells, Natural immunology, Killer Cells, Natural pathology, Lipomatosis congenital, Lipomatosis drug therapy, Lipomatosis immunology, Male, Membrane Proteins biosynthesis, Membrane Proteins immunology, Phytohemagglutinins pharmacology, Primary Cell Culture, Shwachman-Diamond Syndrome, T-Lymphocytes drug effects, T-Lymphocytes immunology, T-Lymphocytes pathology, Tumor Necrosis Factor-alpha biosynthesis, Tumor Necrosis Factor-alpha immunology, Anemia, Diamond-Blackfan diagnosis, Bone Marrow Diseases diagnosis, Dyskeratosis Congenita diagnosis, Exocrine Pancreatic Insufficiency diagnosis, Fanconi Anemia diagnosis, Hemoglobinuria, Paroxysmal diagnosis, Lipomatosis diagnosis
- Abstract
Immune function abnormalities have been reported in patients with Fanconi anemia (FA), dyskeratosis congenita (DC) and, rarely, in Shwachman-Diamond syndrome (SDS), and Diamond-Blackfan anemia (DBA), but large systematic studies are lacking. We assessed immunological parameters in 118 patients with these syndromes and 202 unaffected relatives. We compared the results in patients with reference values, and with values in relatives after adjusting for age, sex, corticosteroid treatment, and severe bone marrow failure (BMF). Adult patients (≥18 years) with FA had significantly lower immunoglobulins (IgG, IgA and IgM), total lymphocytes, and CD4 T cells than reference values or adult relatives (P < 0.001); children with FA had normal values. Both children and adults with FA had lower B- and NK cells (P < 0.01) than relatives or reference values. Patients with DC had essentially normal immunoglobulins but lower total lymphocytes than reference values or relatives, and lower T-, B-, and NK-cells; these changes were more marked in children than adults (P < 0.01). Most patients with DBA and SDS had normal immunoglobulins and lymphocytes. Lymphoproliferative responses, serum cytokine levels, including tumor necrosis factor-α and interferon-γ, and cytokine levels in supernatants from phytohemagglutinin-stimulated cultures were similar across patient groups and relatives. Only patients with severe BMF, particularly those with FA and DC, had higher serum G-CSF and Flt3-ligand and lower RANTES levels compared with all other groups or relatives (P < 0.05). Overall, immune function abnormalities were seen mainly in adult patients with FA, which likely reflects their disease-related progression, and in children with DC, which may be a feature of early-onset severe disease phenotype., (© 2015 Wiley Periodicals, Inc.)
- Published
- 2015
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