Impaired immune function in children and adults with Fanconi anemia

Kasiani C. Myers, Sharon Sauter, Xue Zhang, Jacob J. Bleesing, Stella M. Davies, Susanne I. Wells, Parinda A. Mehta, Ashish Kumar, Daniel Marmer, Rebecca Marsh, Darron Brown, Melinda Butsch Kovacic

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
JournalPediatric Blood and Cancer
DOIs
StateAccepted/In press - 2017

Fingerprint

Fanconi Anemia
T-Lymphocytes
Bone Neoplasms
Papillomaviridae
B-Lymphocytes
Bone Marrow
Inborn Genetic Diseases
Genomic Instability
Tetanus
Phytohemagglutinins
Bone Marrow Transplantation
Candida
Natural Killer Cells
Immunoglobulin M
Longitudinal Studies
Anemia
Cell Count
Immunoglobulin G
Cytokines
Antigens

Keywords

  • Bone marrow failure
  • Fanconi anemia
  • Immune response

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

Myers, K. C., Sauter, S., Zhang, X., Bleesing, J. J., Davies, S. M., Wells, S. I., ... Butsch Kovacic, M. (Accepted/In press). Impaired immune function in children and adults with Fanconi anemia. Pediatric Blood and Cancer. https://doi.org/10.1002/pbc.26599

Impaired immune function in children and adults with Fanconi anemia. / Myers, Kasiani C.; Sauter, Sharon; Zhang, Xue; Bleesing, Jacob J.; Davies, Stella M.; Wells, Susanne I.; Mehta, Parinda A.; Kumar, Ashish; Marmer, Daniel; Marsh, Rebecca; Brown, Darron; Butsch Kovacic, Melinda.

In: Pediatric Blood and Cancer, 2017.

Research output: Contribution to journalArticle

Myers, KC, Sauter, S, Zhang, X, Bleesing, JJ, Davies, SM, Wells, SI, Mehta, PA, Kumar, A, Marmer, D, Marsh, R, Brown, D & Butsch Kovacic, M 2017, 'Impaired immune function in children and adults with Fanconi anemia', Pediatric Blood and Cancer. https://doi.org/10.1002/pbc.26599
Myers, Kasiani C. ; Sauter, Sharon ; Zhang, Xue ; Bleesing, Jacob J. ; Davies, Stella M. ; Wells, Susanne I. ; Mehta, Parinda A. ; Kumar, Ashish ; Marmer, Daniel ; Marsh, Rebecca ; Brown, Darron ; Butsch Kovacic, Melinda. / Impaired immune function in children and adults with Fanconi anemia. In: Pediatric Blood and Cancer. 2017.
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AU - Myers, Kasiani C.

AU - Sauter, Sharon

AU - Zhang, Xue

AU - Bleesing, Jacob J.

AU - Davies, Stella M.

AU - Wells, Susanne I.

AU - Mehta, Parinda A.

AU - Kumar, Ashish

AU - Marmer, Daniel

AU - Marsh, Rebecca

AU - Brown, Darron

AU - Butsch Kovacic, Melinda

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Bone marrow failure

KW - Fanconi anemia

KW - Immune response

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