Impaired immune function in children and adults with Fanconi anemia - PubMed (original) (raw)

. 2017 Nov;64(11):10.1002/pbc.26599.

doi: 10.1002/pbc.26599. Epub 2017 May 30.

Sharon Sauter 2, Xue Zhang 3, Jacob J Bleesing 1, Stella M Davies 1, Susanne I Wells 4, Parinda A Mehta 1, Ashish Kumar 1, Daniel Marmer 1, Rebecca Marsh 1, Darron Brown 5, Melinda Butsch Kovacic 2

Affiliations

Impaired immune function in children and adults with Fanconi anemia

Kasiani C Myers et al. Pediatr Blood Cancer. 2017 Nov.

Abstract

Background: Fanconi anemia (FA) is a rare genetic disorder characterized by genome instability, bone marrow failure, and cancer predisposition. Previously, small studies have reported heterogeneous immune dysfunction in FA.

Procedure: We performed a detailed immunologic assessment in a large FA cohort who have not undergone bone marrow transplantation or developed malignancies. Comprehensive quantitative and functional immunologic assessment of 29 FA individuals was compared to healthy age-matched controls.

Results: Compared to non-FA persons of similar ages, FA individuals showed lower absolute total B cells (P < 0.001), lower memory B cells (P < 0.001), and decreased IgM (P < 0.001) but normal IgG. NK cells (P < 0.001) and NK cytotoxicity (P < 0.001) were decreased. CD4+ T cells were decreased (P = 0.022), while CD8+ T cell and absolute T-cell numbers were comparable. Cytotoxic T cells (P < 0.003), and antigen proliferation response to tetanus (P = 0.019) and candida (P = 0.019), were diminished in FA. Phytohemagglutinin responses and plasma cytokines were normal. Within FA subjects, adults and older children (≥10 years) exhibited higher CD8+ T cells than younger children (P = 0.004). Documented atypical infections were infrequent, although oral human papilloma virus (HPV) prevalence was higher (31% positive) in FA.

Conclusions: Overall, these results demonstrate a high rate of significant humoral and cellular immune dysfunction. Continued longitudinal study of immune function is critical to understand evolution with age, bone marrow failure, and cancer development.

Keywords: Fanconi anemia; bone marrow failure; immune response.

© 2017 Wiley Periodicals, Inc.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors declare that there is no conflict of interest.

Figures

FIGURE 1

FIGURE 1. Quantitative immune assays

Age-specific z scores of each of the quantitative immune assays were shown as dots for the FA individuals. The lines showed the regression of the immune assay with age in the young and old age groups. The mean z scores of all the FA individuals were presented, and P values indicated the differences between FA to the non-FA population

FIGURE 2

FIGURE 2. Functional immune assays

Six immune assays for each of the FA individuals were categorized into high, normal, and low and shown as dots. The proportions of low in the FA patients were presented, and P values indicated the differences in the low% between FA and the non-FA population

References

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