Serum markers of T cell activation in relapses of Wegener's granulomatosis

Abstract

SUMMARYLevels 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 histologicaliy proven relapses of Wegener's granulomatosis (WG). Levels of sIL-2R increased from 1065 U/ml (median, range 373-2345 U/ml)6monthsbefore the relapse to 1684 U/ml (median, range 486-3404 U/ml) at the moment of relapse for the whole group (P^OIO). The eight major relapses showed a profound rise in s!L-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 (/»< 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 (/'<0 05). Minor relapses were not accompanied by a significant rise in slL-2R levels. Titresofantineutrophilcytoplasmic 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 titreand an at least 15"At Increase in sIL-2R levels, the rise in ANCA preceded the rise in sIL-2R by at least 1 month, The level of slL-2R at the moment of relapse correlated with the level of C-reactive protein (r = 0 488. /'<0 ()5) and with the disease activity score (r=^0 824, P<0002). There were no significant changes in levels of sCD4 or sCDB. 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.

Cellular immunity in Wegener's granulomatosis: Characterizing T lymphocytes

“…Soluble IL‐2R levels increased prior to and remained high during relapses. Major relapses were characterized by profound rises in sIL‐2R (32, 33); however, elevated sIL‐2R levels were also reported in patients with clinical remission of disease (34), supporting the notion of persistent T cell activation (14, 22). Notwithstanding contrasting results concerning the relationship of sIL‐2R levels to disease activity, sIL‐2R levels could be a parameter in monitoring disease activity.…”

Cell-mediated autoimmunity in patients with Wegener's granulomatosis (WG)

“…[ DISCUSSION T cell-mediated autoimmune reactions have been suggested as an important factor in the pathogenesis of WG and other vasculitides, not only because of the influx of T lymphocytes in inflamed tissues, but also because of the formation of granulomas in WG patients [14,22]. Secondary evidence for T cell-mediated inflammatory processes in WG is found in the enhanced levels of sCD25 in the circulation of patients with active disease [16]. Although contradictory descriptions of the proliferative responses of PBMC of WG patients to PR3 and other constituents of the azurophilic granules of neutrophils have been published [17,42], the positive results suggest that T cell reactivity against target antigens of ANCA could be important in WG.…”

“…Extensive granuloma formation [14,15] suggests an important role of cell-mediated immune reactions in the pathogenesis of this disease. Furthermore, levels of soluble CD25 are elevated in patients with active WG, suggesting activation of the cellular immune system [16]. Moreover, a correlation was found between the number of T lymphocytes in renal interstitium and renal function of patients with rapid progressive glomerulonephritis [12].…”

The immunopathology of ANCA-associated vasculitis

“…Furthermore, these small studies incorporated patients with variable levels of disease activity and therapy at the time of sampling. The association of increased CD25 expression is a more robust finding, with increased levels of the soluble form of CD25 also correlating with disease activity [142, 143]. An increased circulating Th17 subset (IL-4 − IL-17 + ) has also been reported in the remission phase [144].…”