Detection of restricted junctional diversity of peripheral T cells in SLE patients by spectratyping.
Analysis of somatic mutations revealed that anti-double-stranded DNA (dsDNA) autoantibodies from patients with systemic lupus erythematosus (SLE) share features of a T cell dependent, antigen driven immune response. Therefore we analysed the length diversity of the complementarity determining region 3 (CDR3) of T cell receptor (TCR) by high resolution gel electrophoresis of 16 V beta family specific RT PCR products (spectratyping). To enable statistical analysis we developed a quantitative scoring method for the histograms. We investigated 16 V beta gene families in peripheral T cells of SLE patients (n = 9) with active (n = 5) and inactive (n = 4) disease as well as normal healthy blood donors (NHD; n = 9). Analysis of TCR V beta spectratypes (active SLE, n = 59; inactive SLE, n = 51 and NHD n = 97) revealed statistically significant differences of CDR3 length distribution between SLE patients and NHD (P < 0.0001 (active SLE/NHD) and P = 0.0034 (inactive SLE/NHD). These results suggest that spectratyping is able to detect clonal activation of peripheral T cells which correlates to disease activity in SLE patients. We conclude that peripheral T cells from SLE patients display features of a secondary antigen driven immune response.
Kolowos
W
W
Department of Internal Medicine III, Friedrich-Alexander University of Erlangen-Nuremberg, Germany.
Herrmann
M
M
Ponner
B B
BB
Voll
R
R
Kern
P
P
Frank
C
C
Kalden
J R
JR
D000293:Adolescent; D000328:Adult; D002648:Child; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta