Journal of Clinical and Cellular Immunology
Open Access
ISSN: 2155-9899
ISSN: 2155-9899
Gerard Pasternak, Aleksandra Lewandowicz-Uszynska, Marta J. Podralska, Agnieszka Stembalska and Robert Smigiel
Wroclaw Medical University, Poland
Polish Academy of Sciences, Poland
Posters & Accepted Abstracts: J Clin Cell Immunol
Ataxia telangiectasia is a very rare primary immunodeficiency with a circle of chromosomal instability occurring around
the world with a known genetic defect in the gene ATM.
These patients have a number of progressive abnormalities, neurological (ataxia, intention tremor) and the variable
irregularities in the immune system (progressive decrease in the number of T cells, the deficit of the major classes of
immunoglobulins and IgG subclasses, inability to repair DNA strands), hypersensitivity to ionizing radiation and the huge
trend the occurrence of neoplastic diseases.
Analysis covered 11 patients (aged 2 to 22 years old, 7 women and 3 men) who are under the care of the Department of
Clinical Immunology and Pediatrics who have been identified for the treatment of intravenous immunoglobulins because of
recurrent infections and deficit of IgG or IgG subclasses.
Analyzed: Clinical course (the first neurological symptoms, the first clinical signs of immunodeficiency) selected
immunological tests (the concentration of the major classes of immunoglobulins, IgG subclasses, haemolytic activity of
complement, properties of neutrophils phagocytosis, a panel of T cells, B cells and NK cells, and the concentration of AFP)
depending on the performance of the individual mutations in the ATM gene.
Among the changes detected mutations: c.6754_6754delAfs5X c.434T> G c.6145T> G were not previously reported in
the literature. Mutations c.6095G> A c.7630-2A> C are the most commonly detected mutations among patients with ataxia
telangiectasia in Poland. Mutations detected in the study group were generally localized in the domain of N-Terminal domain
protein and FAT domain.
At the two boys in whom the disease manifested itself very early we observed specific mutation and rapid and extremely
aggressive course of the disease. These two brothers both carry a novel mutations: c.434T>G, p.L145R, c.6145T>G p.Y2049D. First
mutation replaces non-polar, hydrophobic leucine with basic amino arginine at position 145. Second mutation is a substitution
of aromatic tyrosine for acidic amino aspartic acid at position 2049 in the protein sequence. To predict the biological effect
of two missense changes, in silico analysis was performed using the Protein Variation Effect Analyzer (PROVEAN, J. Craig
Venter Institute). The algorithm of analysis predicted c.434T>G (score 3.403) and c.6145T>G (score 6.956) to be pathogenic.
Gerard Pasternak was graduated from the Medical University Wroclaw in 2008. Since 2015, he has been the Assistant at the Department and Clinic of Pediatrics, Immunology and Rheumatology of Developmental Age MU Wroclaw and the Department of Immunology and Pediatrics, Provincial Hospital J. Gromkowski, Wroc�?�?aw (since 2010). He serves as a didactic Assistant Professor in the Department. He participates in conducting activities in the field of primary immunodeficiency for students of III-VI of the year and takes part in the preparation and conducting of workshops for patients with PID and their families. His professional interests and research are concentrated on the diagnosis and treatment of primary and secondary immunodeficiencies with particular emphasis on deficit of the IgG subclasses.