title: Immune status of patients with inherited bone marrow failure syndromes.
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.
authors.affiliation: Division of Cancer Epidemiology and Genetics, Clinical Genetics Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
authors.forename: Neelam
authors.initials: N
authors.lastname: Giri
authors.affiliation: Division of Cancer Epidemiology and Genetics, Clinical Genetics Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
authors.forename: Blanche P
authors.initials: BP
authors.lastname: Alter
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Human Papillomavirus Immunology Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland.
authors.forename: Keri
authors.initials: K
authors.lastname: Penrose
authors.affiliation: Division of Cancer Epidemiology and Genetics, Hormonal Reproductive Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
authors.forename: Roni T
authors.initials: RT
authors.lastname: Falk
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Human Papillomavirus Immunology Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland.
authors.forename: Yuanji
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Division of Cancer Epidemiology and Genetics, Clinical Genetics Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Savage
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Human Papillomavirus Immunology Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland.
authors.forename: Marcus
authors.initials: M
authors.lastname: Williams
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Human Papillomavirus Immunology Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland.
authors.forename: Troy J
authors.initials: TJ
authors.lastname: Kemp
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Human Papillomavirus Immunology Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland.
authors.forename: Ligia A
authors.initials: LA
authors.lastname: Pinto
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic; D029503:Anemia, Diamond-Blackfan / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D001855:Bone Marrow Diseases / Q000151:congenital / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D000080983:Bone Marrow Failure Disorders; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D019871:Dyskeratosis Congenita / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D010188:Exocrine Pancreatic Insufficiency / Q000151:congenital / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D005190:Family; D005199:Fanconi Anemia / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis / Q000276:immunology; D006457:Hemoglobinuria, Paroxysmal / Q000151:congenital / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008068:Lipomatosis / Q000151:congenital / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000276:immunology; D010835:Phytohemagglutinins / Q000494:pharmacology; D061251:Primary Cell Culture; D000081003:Shwachman-Diamond Syndrome; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D000305:Adrenal Cortex Hormones; D016207:Cytokines; D007136:Immunoglobulins; D008565:Membrane Proteins; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; C084881:flt3 ligand protein; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma