Immune status of patients with inherited bone marrow failure syndromes: 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 twenty-one patients diagnosed with IBMFS; 17 Fanconi anemia patients and 4 Diamond-Blackfan anemia patients. 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 74% of (N= 15/21) with severity ranging from mild (24%) to severe neutropenia (36%), and all were FA patients. Lymphopenia was detected in 57% of the patients (N=12/21). Low immunoglobulin levels for age were detected in 28.6% of the patients (N=6/21). 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. In DBA, limited by small sample size, no abnormalities were detected in T cell population, low NK cell counts were reported in two patients. Low CD27-IgD+, CD27+Ig D+ and CD27+IgD were detected in 2/4 of the patients while CD45RA naïve T cells were reduced in only one patient. 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 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.