Impaired immune function in children with Fanconi anaemia

Br J Haematol. 2011 Jul;154(2):234-40. doi: 10.1111/j.1365-2141.2011.08721.x. Epub 2011 May 4.

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.

MeSH terms

  • Adaptive Immunity
  • Adolescent
  • B-Lymphocyte Subsets / immunology
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Fanconi Anemia / complications*
  • Fanconi Anemia / immunology
  • Female
  • Humans
  • Immunologic Deficiency Syndromes / etiology*
  • Immunologic Deficiency Syndromes / immunology
  • Killer Cells, Natural / immunology
  • Lymphocyte Count
  • Male
  • T-Lymphocyte Subsets / immunology