Dominant T cells in idiopathic nephrotic syndrome of childhood.
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.
Frank
C
C
Children's Hospital and Institute for Clinical Immunology, Friedrich-Alexander University, Erlangen-Nuremberg,and Children's Rheumatology Hospital, Garmisch-Partenkirchen, Germany.
Herrmann
M
M
Fernandez
S
S
Dirnecker
D
D
Böswald
M
M
Kolowos
W
W
Ruder
H
H
Haas
J P
JP
D017668:Age of Onset; D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D002648:Child; D022801:Complementarity Determining Regions; D015870:Gene Expression / Q000276:immunology; D019674:Genes, T-Cell Receptor beta / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008969:Molecular Sequence Data; D009404:Nephrotic Syndrome / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology; D011110:Polymorphism, Genetic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D017422:Sequence Analysis, DNA; D016176:T-Lymphocyte Subsets / Q000276:immunology
D022801:Complementarity Determining Regions; D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta