title: Impaired immune function in children with Fanconi anaemia.
abstract: Fanconi anaemia is an autosomal recessive or X-linked disease characterized by progressive bone marrow failure, variable congenital abnormalities and a predisposition to malignancy. Reports of immune function in this population are limited, and include only specific areas of immune performance, showing variable defects. We report a cross-sectional immunological assessment in 10 children with FA. Absolute numbers of B cells and natural killer (NK) cells were reduced compared to controls (P = 0·048 and P = 0·0002, respectively), while absolute number of T cells were within normal range. Perforin and granzyme content of NK cells was reduced (P < 0·00001 and P = 0·0057, respectively) along with the NK cell cytotoxicity (P < 0·001). Antigen proliferation in response to tetanus was decreased (P = 0·008) while responses to candida and phytohaemagglutinin were not. Cytotoxic T cell function was also reduced (P < 0·0001). Immunoglobulin G levels were normal in those evaluated. Our series represents the first attempt at a comprehensive quantitative and functional evaluation of immune function in this rare group of patients and demonstrates a significant deficit in the NK cell compartment, a novel quantitative B cell defect, along with abnormal cytotoxic function. These findings may be especially relevant in this patient population with known predisposition to DNA damage and malignancy.
authors.affiliation: Divisions of Bone Marrow Transplant and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital and Medical Center, Cincinnati, OH 45229, USA. kasiani.myers@cchmc.org
authors.forename: Kasiani C
authors.initials: KC
authors.lastname: Myers
authors.forename: Jack J
authors.initials: JJ
authors.lastname: Bleesing
authors.forename: Stella M
authors.initials: SM
authors.lastname: Davies
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Martin
authors.forename: Robin
authors.initials: R
authors.lastname: Mueller
authors.forename: Richard E
authors.initials: RE
authors.lastname: Harris
authors.forename: Alexandra H
authors.initials: AH
authors.lastname: Filipovich
authors.forename: Melinda B
authors.initials: MB
authors.lastname: Kovacic
authors.forename: Susanne I
authors.initials: SI
authors.lastname: Wells
authors.forename: Parinda A
authors.initials: PA
authors.lastname: Mehta
mesh_terms: D056704:Adaptive Immunity; D000293:Adolescent; D016175:B-Lymphocyte Subsets / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005199:Fanconi Anemia / Q000150:complications* / Q000276:immunology; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000209:etiology* / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D016176:T-Lymphocyte Subsets / Q000276:immunology