Kasiani C Myers1, Sharon Sauter2, Xue Zhang3, Jacob J Bleesing1, Stella M Davies1, Susanne I Wells4, Parinda A Mehta1, Ashish Kumar1, Daniel Marmer1, Rebecca Marsh1, Darron Brown5, Melinda Butsch Kovacic2. 1. Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 2. Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 3. Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 4. Experimental Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 5. Division of Infectious Diseases, Indiana School of Medicine, Indianapolis, Indiana.
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.
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.
Authors: Paul A Harris; Robert Taylor; Robert Thielke; Jonathon Payne; Nathaniel Gonzalez; Jose G Conde Journal: J Biomed Inform Date: 2008-09-30 Impact factor: 6.317
Authors: Graça A Justo; Marco A Bitencourt; Ricardo Pasquini; Morgana T L Castelo-Branco; Aline Almeida-Oliveira; Hilda Rachel Diamond; Vivian M Rumjanek Journal: Ann Hematol Date: 2013-11-16 Impact factor: 3.673
Authors: Elisabeth T Korthof; Johanna Svahn; Regis Peffault de Latour; Paola Terranova; Helene Moins-Teisserenc; Gérard Socié; Jean Soulier; Marleen Kok; Robbert G M Bredius; Maarten van Tol; Els C M Jol-van der Zijde; Angela Pistorio; Fabio Corsolini; Alessia Parodi; Florinda Battaglia; Vito Pistoia; Carlo Dufour; Enrico Cappelli Journal: Am J Hematol Date: 2013-05-02 Impact factor: 10.047
Authors: Miguel L Stein; Joyce M Villanueva; Bridget K Buckmeier; Yoshiyuki Yamada; Alexandra H Filipovich; Amal H Assa'ad; Marc E Rothenberg Journal: J Allergy Clin Immunol Date: 2008-04-14 Impact factor: 10.793
Authors: Philip E Castle; Carolina Porras; Wim G Quint; Ana Cecilia Rodriguez; Mark Schiffman; Patti E Gravitt; Paula González; Hormuzd A Katki; Sandra Silva; Enrique Freer; Leen-Jan Van Doorn; Silvia Jiménez; Rolando Herrero; Allan Hildesheim Journal: J Clin Microbiol Date: 2008-08-20 Impact factor: 5.948
Authors: Hongbin Dong; Daniel W Nebert; Elspeth A Bruford; David C Thompson; Hans Joenje; Vasilis Vasiliou Journal: Hum Genomics Date: 2015-11-24 Impact factor: 4.639
Authors: Ruby Khoury; Sharon Sauter; Melinda Butsch Kovacic; Adam S Nelson; Kasiani C Myers; Parinda A Mehta; Stella M Davies; Susanne I Wells Journal: Viruses Date: 2018-01-20 Impact factor: 5.048
Authors: Tuna Toptan; Marion G Brusadelli; Brian Turpin; David P Witte; Jordi Surrallés; Eunike Velleuer; Martin Schramm; Ralf Dietrich; Ruud H Brakenhoff; Patrick S Moore; Yuan Chang; Susanne I Wells Journal: PLoS One Date: 2018-12-27 Impact factor: 3.240
Authors: Tafadzwa Chihanga; Sara Vicente-Muñoz; Sonya Ruiz-Torres; Bidisha Pal; Mathieu Sertorio; Paul R Andreassen; Ruby Khoury; Parinda Mehta; Stella M Davies; Andrew N Lane; Lindsey E Romick-Rosendale; Susanne I Wells Journal: Cancers (Basel) Date: 2022-04-18 Impact factor: 6.575
Authors: Sharon L Sauter; Xue Zhang; Lindsey Romick-Rosendale; Susanne I Wells; Kasiani C Myers; Marion G Brusadelli; Charles B Poff; Darron R Brown; Gitika Panicker; Elizabeth R Unger; Parinda A Mehta; Jack Bleesing; Stella M Davies; Melinda Butsch Kovacic Journal: Cancers (Basel) Date: 2021-03-18 Impact factor: 6.639