Abstract
Patients with Nijmegen Breakage Syndrome (NBS) suffer from recurrent infections due to humoral and cellular immune deficiency. Despite low number of T lymphocytes and their maturation defect, the clinical manifestations of cell-mediated deficiency are not as severe as in case of patients with other types of combined immune deficiencies and similar T cell lymphopenia. In this study, multicolor flow cytometry was used for evaluation of peripheral T lymphocyte maturation according to the currently known differentiation pathway, in 46 patients with genetically confirmed NBS and 46 sex and age-matched controls. Evaluation of differential expression of CD27, CD31, CD45RA, CD95, and CD197 revealed existence of cell subsets so far not described in NBS patients. Although recent thymic emigrants and naïve T lymphocyte cell populations were significantly lower, the generation of antigen-primed T cells was similar or even greater in NBS patients than in healthy controls. Moreover, the senescent and exhausted T cell populations defined by expression of CD57, KLRG1, and PD1 were more numerous than in healthy people. Although this hypothesis needs further investigations, such properties might be related to an increased susceptibility to malignancy and milder clinical course than expected in view of T cell lymphopenia in patients with NBS.
Highlights
Nijmegen Breakage Syndrome (NBS) (MIM #251260) is a rare autosomal recessive disease belonging to a group of chromosomal instability disorders
The most differentiated stage of CD27−CD45RA−CD197− T lymphocytes composed patients significantly greater proportion of both CD4+ and CD8+ cell subsets in NBS patients in comparison to healthy controls, but statistical difference in absolute count was found only in case of CD4+ cell subset (44 vs. 30 cells/μl, p < 0.01), with similar counts of terminally differentiated subsets (TD) cells within CD8+ subset (22 vs. 15 cells/μl, p = NS; Figures 3, 4)
This study for the first time presents a detailed analysis of T lymphocytes and their subpopulations that reflect the development of T cells in periphery in a large cohort of patients with Nijmegen breakage syndrome
Summary
Nijmegen Breakage Syndrome (NBS) (MIM #251260) is a rare autosomal recessive disease belonging to a group of chromosomal instability disorders. Severe impairment in T-cell dependent antigen response and features of defective cellular immunity have been attributed to T cell lymphopenia and defective T lymphocyte maturation [13, 18, 19] This prospective study was initiated in attempt to describe peripheral T lymphocyte maturation profile in patients with NBS according to the currently known differentiation pathway [20]. Written consent for participation was obtained from all patients older than 16 years, and parents or legal guardians in case of patients younger than 16 years
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