Background: Because of several studies, idiopathic nephrotic syndrome (INS) of childhood is suspected to have an immunologic pathogenesis with T cells playing a major role. To investigate this hypothesis further, 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 three-year period to obtain longitudinal data on the repertoire of peripheral T cells. mRNA from peripheral mononuclear cells (PBMCs) of seven INS patients and two 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 Vbeta-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: The data give strong evidence for an direct involvement of CD8+ T cells in the complicated course of INS.
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