Research team members
Tore G. Abrahamsen (group leader), Dina Aresvik, Kiran Aftab Gul, Torstein Øverland, Lars O. Baumbusch, Kari Lima, and Rolf D. Pettersen.
Research goals and strategy
The research team of infections and immunology is currently working on general immune response, the use of antibiotics, bacterial resistance development, and primary immune deficiency, including the DiGeorge syndrome. The aim is to encourage the basic understanding of disease mechanisms and thus providing improved diagnosis and treatment of severe infections in children and patients with congenital immune diseases. The establishment of biobanks and quality management are also central for this work of this team. The research group also runs a Resource Centre for the DiGeorge syndrome.
The 22q11.2 deletion syndrome (DS) is the second most common childhood genetic disorder, behind Down's syndrome, with an estimated incidence of 1 in 4000 births. Patients with the 22q11.2 DS have a hemizygous deletion which usually (in about 90%) has a size of 3 Mb containing approximately 30 genes, whereas 8% have a smaller deletion of 1,5 Mb with 24 genes. The phenotype is highly variable and the size of the deletion does not predict end organ effects or disease severity. These patients may suffer from disorders of many organ systems, but cardiac malformations, thymic hypoplasia/aplasia, hypoparathyroidism, cleft palate and psychiatric disorders are most frequent. In addition, the incidence of autoimmune diseases is high.
Less than 1% of patients with 22q11.2 DS have true thymic aplasia requiring an urgent transplant. The majority of the patients has an immunodeficiency with mild to moderate deficit in T cell number and possibly also function. The clinical problems including the immunodeficiency in 22q11.2 DS are age dependent. This may be due to the fact that the greatest T-cell deficit occurs in the neonatal period. Interestingly, the physiologic, age-related decrease in T-cell numbers is slower in the patients than in healthy controls. It has been shown that compared to controls conversion of naïve to memory T-cells is accelerated in patients with 22q11.2 DS. Spontaneous apoptosis of both CD4+ and CD8+ T-cells from one patient with DiGeorge syndrome has been described.
The incidence of autoimmunity is increased in 22q11.2 DS and occurs in up to 10% of the patients. These diseases occur particularly in the older patient population. For example, autoimmune cytopenias, juvenile rheumatoid arthritis, autoimmune endocrinopathy, autoimmune hemolytic anemia, celiac disease and inflammatory bowl disease have been reported.
The aim of our study is to explain the clinical course of patients with 22q11.2 DS, particularly the development of autoimmune diseases.
Current research projects
- T-cells, autoimmunity and inflammation in 22q11.2 deletion syndrome (DiGeorge syndrome)
- Newborn screening for severe combined immunodeficiency (SCID)
- Immunological studies of patients with DiGeorge syndrome and its variants
Main national and international collaborators
- Liv Osnes, Børre Fevang, and Tom Eirik Mollnes.
- Avdeling for genetikk, OUS
- Immunologisk institutt, UiO
- Avdeling for medisinsk biokjemi, UiO
South-Eastern Norway Regional Health Authority, Renée og Bredo Grimsgaard's Stiftelse, and Legatet til Henrik Homans Minde.
Selected publications for 2012
- Nordgarden H, Lima K, Skogedal N, Følling I, Storhaug K, Abrahamsen TG Dental developmental disturbances in 50 individuals with the 22q11.2 deletion syndrome; relation to medical conditions? Acta Odontol Scand 2012, 70 (3), 194-201.
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