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.