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IL-6 Receptor Expression on the Surface of T Cells and Serum Soluble IL-6 Receptor Levels in Patients with Microscopic Polyangiitis and Granulomatosis with Polyangiitis

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We investigated the IL-6 receptor (IL-6R) expression on the surface of T cells isolated from peripheral blood mononuclear cells (PBMCs) of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) patients and measured the serum soluble IL-6R (sIL-6R) levels in these patients. Sera and PBMCs were obtained from 51 patients with MPA (n = 32) and GPA (n = 19), with 25 patients having active disease (defined as a Birmingham Vasculitis Activity Score [BVAS] ≥ 5). The median age of patients was 67.0 years, and 52.9% were women. Serum IL-6 levels were significantly correlated with the BVAS (r = 0.384); however, IL-6R expression on the surface of T cells did not significantly differ based on disease activity. Meanwhile, IL-6R expression on the surface of stimulated CD4+ (median mean fluorescence intensity [MFI] 588.0 vs. 1314.8; p < 0.001), CD4+CD25+ (MFI 853.3 vs. 1527.3; p < 0.001), and CD4+CD45RO+ (MFI 679.5 vs. 1241.5; p < 0.001) T cells was significantly reduced compared with unstimulated conditions. Conversely, patients with active disease exhibited a significantly higher median serum sIL-6R level than those with inactive disease (38.1 ng/mL vs. 34.7 ng/mL; p = 0.029). These results imply that the trans-signalling IL-6 pathway may be more activated than the classical signalling pathway in patients with MPA and GPA, suggesting the therapeutic potential of targeting sIL-6R.
Title: IL-6 Receptor Expression on the Surface of T Cells and Serum Soluble IL-6 Receptor Levels in Patients with Microscopic Polyangiitis and Granulomatosis with Polyangiitis
Description:
We investigated the IL-6 receptor (IL-6R) expression on the surface of T cells isolated from peripheral blood mononuclear cells (PBMCs) of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) patients and measured the serum soluble IL-6R (sIL-6R) levels in these patients.
Sera and PBMCs were obtained from 51 patients with MPA (n = 32) and GPA (n = 19), with 25 patients having active disease (defined as a Birmingham Vasculitis Activity Score [BVAS] ≥ 5).
The median age of patients was 67.
0 years, and 52.
9% were women.
Serum IL-6 levels were significantly correlated with the BVAS (r = 0.
384); however, IL-6R expression on the surface of T cells did not significantly differ based on disease activity.
Meanwhile, IL-6R expression on the surface of stimulated CD4+ (median mean fluorescence intensity [MFI] 588.
0 vs.
1314.
8; p < 0.
001), CD4+CD25+ (MFI 853.
3 vs.
1527.
3; p < 0.
001), and CD4+CD45RO+ (MFI 679.
5 vs.
1241.
5; p < 0.
001) T cells was significantly reduced compared with unstimulated conditions.
Conversely, patients with active disease exhibited a significantly higher median serum sIL-6R level than those with inactive disease (38.
1 ng/mL vs.
34.
7 ng/mL; p = 0.
029).
These results imply that the trans-signalling IL-6 pathway may be more activated than the classical signalling pathway in patients with MPA and GPA, suggesting the therapeutic potential of targeting sIL-6R.

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