Serum markers of T cell activation in relapses of Wegener's granulomatosis.
Levels of soluble IL-2 receptor (sIL-2R), soluble CD4 (sCD4) and CD8 (sCD8) were measured by sandwich ELISA as markers for T cell activation in serial serum samples from 16 patients showing 18 histologically proven relapses of Wegener's granulomatosis (WG). Levels of sIL-2R increased from 1065 U/ml (median, range 373-2345 U/ml) 6 months before the relapse to 1684 U/ml (median, range 486-3404 U/ml) at the moment of relapse for the whole group (P = 0.10). The eight major relapses showed a profound rise in sIL-2R levels, from 1008 U/ml (median, range 686-1553 U/ml) 6 months before the relapse, to 1994 U/ml (median, range 1469-3404 U/ml) at the moment of relapse (P < 0.01). The levels of sIL-2R at the moment of relapse were significantly higher at the eight major relapses than at the time of the 10 minor relapses (P < 0.05). Minor relapses were not accompanied by a significant rise in sIL-2R levels. Titres of antineutrophil cytoplasmic antibodies (ANCA) rose by two or more titresteps or from negative to positive in 15/18 patients during the 6 months period before the relapse. In all seven cases with both a rise of the ANCA titre and an at least 25% increase in sIL-2R levels, the rise in ANCA preceded the rise in sIL-2R by at least 1 month. The level of sIL-2R at the moment of relapse correlated with the level of C-reactive protein (r = 0.488, P < 0.05) and with the disease activity score (r = 0.824, P < 0.002). There were no significant changes in levels of sCD4 or sCD8, although the levels of sCD4 tended to be higher at the time of major relapses. We conclude that major relapses of Wegener's granulomatosis are accompanied by systemic T cell activation. T cell activation, however, does not appear to precede the rise in ANCA titre.
Stegeman
C A
CA
Department of Internal Medicine, University Hospital Groningen, The Netherlands.
Tervaert
J W
JW
Huitema
M G
MG
Kallenberg
C G
CG
D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies / Q000032:analysis; D015415:Biomarkers; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D014890:Granulomatosis with Polyangiitis / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D008213:Lymphocyte Activation / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D015415:Biomarkers; D015704:CD4 Antigens; D016827:CD8 Antigens; D007074:Immunoglobulin G; D015375:Receptors, Interleukin-2