Apoptosis of Peripheral Blood Lymphocytes in Primary Nephrotic Syndrome

ABSTRACT:
Background: Apoptosis is a highly programmed form of cell death that has significant role in such physiological processes as normal cell turnover, as well as many pathological conditions. Several studies implicates altered lumphocyte function in the mechanisms underlying idiopathic nephrotic syndrome. An increased apoptosis rate may also contribute to the functional abnormalities of T-cells already found in these patients.
Objectives: The objectives of the present work were to investigate the phenotypic characteristic of T-lymphocyte subsets in newly diagnosed nephrotic children and after induction of remission. This study also aimed at detecting the percentage of apoptotic lymphocytes in the peripheral blood of the same group of the patients.
Methods: The study was carried out on 30 selected children. Twenty children with first attack nephrotic Syndrome suggestive of minimal change type and ten healthy children of comparable age as a control group. All children were subjected to history taking, clinical examination and laboratory investigations including complete blood picture, blood urea, serum creatinine, total serum proteins, serum cholesterol, serum C3, complete urine analysis and 24 hours urine for proteins. All children were also further subjected to specific  laboratory tests to study peripheral blood lymphocytes including  detection of lymphocytes subsets by three color flow analysis using monoclonal antibodies CD3 and CD4 and also determination of apoptotic lymphocytes in the peripheral blood by flow cytometry using annexin-v-flourecein isothiocynate (FITC)  and propidium iodide (PI).
Results: There was no statically significant difference between nephrotic patients at presentation and control group as regards percentage of CD3 and CD4 lymphocytes in peripheral blood (p=0.89 and 0.30 respectively). Also, the percentage of apoptotic lymphocytes in peripheral blood was significantly higher in the patient group at presentation of nephrotic disease than after induction of remission and than the control group (p=0.000 and 0.000 respectively). Finally, the percentage of apoptotic lymphocytes was significantly higher at remission of the disease than the control group (p=0.001).
Conclusions: In the present study increase in the apopotosis rate of CD3+Lymphocytes was found. This could be a crucial point in the pathogenesis of the nephrotic  syndrome but clearly more prospective studies of large groups are needed with the analysis of the apoptosis rate within different subsets of lymphocytes. It is very difficult at the moment to explain why the lymphocyte apoptosis is increased in nephrotic syndrome. This might result from impaired production of and dysregulation in the synthesis of different cytokines, which are essential for the normal life span of lymphocytes such as interleukin (IL)-2 and TNF- α. Another explanation for the abnormalities found in our study may be reduced anti-oxidant defense in patients with nephrotic syndrome which contribute to an increase in the apoptosis rate of circulating lymphocytes.