Immune deficiencies, infection, and systemic immune disordersAntibody deficiency in patients with ataxia telangiectasia is caused by disturbed B- and T-cell homeostasis and reduced immune repertoire diversity
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Patients
Peripheral blood samples and clinical data were collected from 15 patients with AT and 45 healthy age-matched control subjects. These studies were approved by the Medical Ethics Committees of the Radboud University Nijmegen Medical Center and Erasmus MC Rotterdam.
Flow cytometric analysis and high-speed cell sorting of blood B-cell subsets
Six-color flow cytometric immunophenotyping of peripheral blood was performed on a FACS LSR II (BD Biosciences, San Jose, Calif), and data were analyzed with FACSDiva software (BD Biosciences), as described previously.16 Memory B-cell
Patients
Patients' characteristics are summarized in Table I. Genotype-phenotype correlations of the patients (among others) have been reported elsewhere.15 Patients with AT were divided into 3 groups: classical AT plus hypogammaglobulinemia (n = 3), classical AT (n = 8), and variant AT (n = 4; ie, patients with late onset). None of the patients with classical AT showed ATM kinase activity, whereas patients with variant AT showed residual activity.
Patients with classical AT plus hypogammaglobulinemia
Discussion
In this study we demonstrated that the antibody deficiency in patients with AT is caused by disturbed naive B- and T-cell homeostasis, leading to reduced immune repertoire formation and reduced memory B-cell formation. Although these defects are present in all patients, 3 clinical subgroups can be defined, of which the disease severity correlated with numbers of circulating memory B cells and naive T cells.
Reduction of transitional and naive mature B-cell counts is the hallmark of abnormal
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Causative mechanisms and clinical impact of immunoglobulin deficiencies in ataxia telangiectasia
2024, Journal of Allergy and Clinical ImmunologyGenome integrity and inflammation in the nervous system
2022, DNA RepairAltered NK-cell compartment and dysfunctional NKG2D/NKG2D-ligand axis in patients with ataxia-telangiectasia
2021, Clinical ImmunologyCitation Excerpt :By the time of the present analysis, patients were in stable clinical conditions and not suffering from acute episodes of infection or other pathologies. NK cells within PBMCs of A-T patients and age-matched healthy donors (HDs) were analyzed by flow cytometry (Supplementary Fig. S1) showing that median NK-cell percentages were similar in patients and controls (Fig. 1a) as reported in previous studies [10,12,15]. In addition, absolute NK cell counts in A-T patients (260/127–493 cells/μl, median/25th–75th percentile) were within the normal reported range [39].
Neurofilament light chain: A novel blood biomarker in patients with ataxia telangiectasia
2021, European Journal of Paediatric NeurologyCitation Excerpt :Blood AFP concentrations correlate moderately with the severity of the A-T phenotype, with slight increase during the patient's life [8,9]. In addition, most patients with classic-A-T show decreased numbers of certain T-cells subsets and B-cells, and decreased concentrations of immunoglobulins (IgA and IgG2 in particular) [10,11]. In recent years, we have witnessed an increasing interest in neurofilaments (NFs) as biomarkers in neurodegenerative disorders.
Supported by grants from the foundation “Sophia Kinderziekenhuis Fonds” (grant 589 H.I.) and ZonMW (Vidi grant 91712323 to M.v.d.B.).
Disclosure of potential conflict of interest: H. IJspeert has been supported by one or more grants from Sophia Kinderziekenhuis Fonds (grant 589). Á. Haraldsson has received one or more grants from or has one or more grants pending with GlaxoSmithKline, has received one or more payments for lecturing from or is on the speakers' bureau for GlaxoSmithKline and Pfizer, and has received one or more payments for travel/accommodations/meeting expenses from GlaxoSmithKline, AstraZeneca, and CSL Behring. A. Warris has consultancy arrangements with and has received one or more grants from or has one or more grants pending with Pfizer and Gilead and has received one or more payments for the development of educational presentations for Pfizer. M. A. Taylor has been supported by one or more grants from Cancer Research UK. M. van der Burg has been supported by a VIDI grant of the Dutch Scientific Organization. The rest of the authors declare that they have no relevant conflicts of interest.
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These authors contributed equally to this work.