Impaired immune function in children and adults with Fanconi anemia

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.