PERSISTING T-CELL POPULATION IN IDIOPATHIC NEPHROTIC SYNDROME OF CHILDHOOD
J.P.Haas(1), C.Frank(1), D.Dirnecker(1), W.Kolowos(2), M.Herrmann(2) and H.Ruder(3); (1)Children´s hospital, (2)Institute for clinical Immunology, Friedrich-Alexander University Erlangen-Nuremberg, Germany (3)Children´s Rheumatology hospital Garmisch-Partenkirchen, Germany
Aims: Susceptibility for idiopathic nephrotic syndrome of childhood (INS) was shown to be associated with certain HLA-Alleles (HLA-DR7, HLA-DQ2). Moreover several studies have pointed out that T-cells are involved in the pathogenesis of INS. Supernatants of peripheral lymphocytes and hybridomas deriving from patients´ T-cells have been demonstrated to induce nephrotic syndrome in the rat model. We have established an experimental setting to identify and characterize T-cells from patients suffering from INS. We studied the diversity of the CDR3 region of the T cell receptor (TCR) beta-chain from peripheral T cells isolated from patients with INS.
Methods: The study was performed over a 3 years period to obtain longitudinal data on the repertoire of peripheral T cells. mRNA from peripheral mononuclear cells (PBMC) of 10 INS patients and four healthy controls (NHD) was prepared and analyzed for CDR3 length polymorphism of TCR beta-chain by spectratyping.
Results: All INS patients presented individually skewed spectratype histograms in at least one V beta-family. Patients suffering from a frequent relapsing course of INS or a focal global sclerosis showed some alterations to persist in all samples isolated in the observation period (up to 3 years). In addition, sequence analyses of the beta-chain of the TCR CDR3 region confirmed clonal expansion of peripheral T cells in those patients who had displayed spectratype alterations.
Conclusions: Each person analysed so far established an individual repertoire of persisting oligoclonal T-cells. This was the case even in HLA-identical twins. Although we were not able to detect a disease specific TCR epitope the data give strong evidence for an direct involvement of CD8+ T cells in complicated courses of INS.