Fanconi anemia and immune deficits in Egyptian children: A single-center analysis

Abstract

Inherited bone marrow failure syndromes (IBMFS) comprise a heterogeneous group of rare cancer prone genetic disorders with hematologic and physical abnormalities. The immune status of patients with an IBMFS is not entirely clear; however, there are some suggestions that a few patients exhibit various degrees of qualitative immune dysfunction. Recently, there are novel and rare PID syndromes that have been associated with cytopenia secondary to bone marrow failure, but they are not always taken into consideration, phenotypic overlap may impair the correct diagnosis. This study included 17 patients diagnosed with Fanconi anemia, evaluation of immune status was done by assessing complete blood count with differential leucocytic count, immunophenotyping of lymphocytes by Flow cytometry (CD3, CD4, CD8, CD19, CD56, B cell maturation, and naïve/memory T cells), as well as immunoglobulins assay (IgG, IgM, IgA levels). Results Neutropenia was detected in of FA patients 88% (N= 15/17) with severity ranging from mild (24%) to severe neutropenia (36%). Lymphopenia was detected in 70% of the patients (N=12/17). Low immunoglobulin levels for age were detected in 35% of the patients (N=6/17). Most of FA patients had low counts of CD19 B cells, CD27+IgD+ non class switched B cells, CD27+IgD- switched memory B cells, CD27-IgD+ naïve B cells, as well as, low CD4 T Helper cells, CD45 RA naïve T cells, CD56 NK cells, CD45RO memory T cells. A positive correlation between the frequency of hospitalization due to infections and degree of bone marrow hypocellularity was found. The degree of lymphopenia, low CD3, CD4, CD8, CD19 and defective T cell maturation subsets were statistically significant variables associated with occurrence of significant infections. Conclusion IBMFS patients, most commonly Fanconi anemia patients have altered immune status, possibility of the presence of some degree of overlap between IBMFS and certain PIDs associated with cytopenias and special somatic features might be found. Immunological assessment for patients with IBMFS should be considered as a part of routine work up of such patients.