Control of T and B cell development by TREC/ KREC analysis in primer immunodeficiency patients

Primer immunodeficiency (PID); is a rare genetic disorder that disrupts the function of the immune system. It is important to examine T and B cell development in terms of PID diagnosis. The TREC ( T cell reseptor excision circle) and KREC (kappa-deleting excision circle) are formed during somatic recombination of T and B cell development that are the circular DNA fragments of T and B cells. Therefore, they can use T and B cell development for PID as a biomarker. In this thesis TREC/KREC analysis were performed with real time quantitative polymerase chain reaction (RT-PCR) from patients and age related controls in order to examine T and B cell development in PID patients. TREC/KREC levels were also determined in patients with pre-mutations and/or different genetic syndromes. As a control group, patients who applied to biochemical unit, exculuding immunodeficiency and hematologic diseases, were used to determine healty reference value. According to the study, adult PID patients were found to have significantly lower levels of TREC copy number than control group (t test p<0.0001). In contrast, KREC was not significant in the number of copies, but was founda to be less than control group ( t test p= 0.1461) In pediatric PID patients, TREC/KREC copy numbers were found to have a significantly lower number of copies (t test p<0.0001). It was determined that the number of TREC copies of adult patients decreased significanty over time when separated into age groups, while the number of KREC copies did not change as age related. Age- related changes in the number of TREC/KREC levels were determined in patients with mutations related to immunodeficiency reveal the functional effects of the mutations. It has been found that TREC / KREC copy numbers in immunodeficient and mutated individuals are lower than controls because of T and B cells can not be functional or mature. Decreased thymic activity with time in age-related changes led to a reduction in the number of copies of TREC. Since KREC copy numbers are bone marrow origin, it has been shown that they do not change with age.