Expression of Tumor Necrosis Factor Receptors on Granulocytes in Patients with Myeloperoxidase Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitis

Abstract

Background/Aims: To clarify the clinical significance of tumor necrosis factor (TNF) receptors in patients with myeloperoxidase (MPO)-anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, we evaluated the cell surface expression of TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2). Patients and Methods: 43 patients with MPO-ANCA-associated vasculitis, 16 patients with chronic renal failure, 10 patients with sepsis, 15 patients with systemic lupus erythematosus, and 18 healthy controls were enrolled in this study, and the surface expression levels of TNFR1, TNFR2, CD63, and CD64 on granulocytes were assessed. In 21 patients with MPO-ANCA-associated vasculitis, soluble TNFR1 (sTNFR1), soluble TNFR2(sTNFR2), and TNF-α in the serum were also measured. Results: The surface expression levels of TNFR1 and TNFR2 on granulocytes were significantly higher in patients with MPO-ANCA-associated vasculitis than in the healthy controls, and positively correlated with the Birmingham Vasculitis Activity Score (BVAS). The levels of sTNFR1, sTNFR2, and TNF-α in the serum were also significantly higher in patients with MPO-ANCA-associated vasculitis than in the healthy controls. Serum levels of sTNFR1 and sTNFR2 correlated with serum creatinine, while the surface expression of TNFR1 and TNFR2 on the granulocytes did not. There was no significant correlation between the BVAS and CD63 or BVAS and CD64. Conclusion: The surface expression levels of TNFR1 and TNFR2 on granulocytes were upregulated in patients with MPO-ANCA-associated vasculitis and reflected disease activity.

Circulating TNF Receptors Are Significant Prognostic Biomarkers for Idiopathic Membranous Nephropathy

“…Whereas, TNFR1, but not TNFR2, is expressed in the glomeruli in healthy subjects [25], TNFR1 and TNFR2 are expressed in glomerular and tubular cells after renal injury [20]. A large body of evidence explicates the association of TNFRs with inflammatory kidney disease [17], [18], [26], [27], [28], but there is a paucity of data on the correlation between clinical manifestations and cTNFRs levels in patients with iMN.…”

TNF receptors: signaling pathways and contribution to renal dysfunction

“…91 In patients with MPO-ANCA associated vasculitis, surface expression of TNFR1 and TNFR2 on neutrophils correlated with the Birmingham Vasculitis Activity Score (BVAS) while soluble TNFRs correlated with serum creatinine. 92 In addition, TNF was observed in infiltrating mononuclear cells and resident renal cells in biopsy specimens that correlated with histological signs of disease activity. 93 Urinary excretion and fractional excretion, but not plasma levels of TNF were increased in patients with ANCA-positive renal vasculitis that is active but not in cases where it was in remission.…”

“…The protective effect is associated with a marked reduction in tubulointerstitial macrophage infiltration. 27,29 TNFR1 and TNFR2 in endothelial cells promotes Type I IFNb production and subsequent autocrine signaling through the IFNa/b receptor to induce the transcription of mononuclear chemokines, such as Cxcl9, Cxcl10 and Urinary levels of soluble TNFR1 and TNFR2 were effective in predicting a favorable response to immunosuppressive treatments in patients with primary GN 87 Elevated urinary TNFR1 predicted progression of renal function impairment and advanced renal interstitial fibrosis in newly diagnosed primary GNs 88 ANCA In a murine model of ANCA mediated NCGN, anti-TNF antibody prior to induction of disease, reduced glomerular crescent formation and macrophage influx but did not improve renal function (Reference 87) 89 In a rat model of MPO-ANCA associated NCGN, anti-TNF antibody markedly reduced albuminuria and crescent formation even when administered after GN was established (Ref 88) 90 TNF and soluble TNFRs may serve as prognostic indicators of disease in patients (Refs 89-93) [91][92][93][94][95] LN No association between TNFR2-196M/R polymorphisms and SLE in Caucasians is detected using the transmission disequilibrium test. 102 Circulating levels of both TNFRs are significantly higher in SLE than in rheumatoid arthritis, and spondyloarthropathies.…”

Tumor Necrosis Factor Receptors: Biology and Therapeutic Potential in Kidney Diseases

“…As the kidney is frequently affected in inflammatory and autoimmune diseases, the contrasting proinflammatory and immunosuppressive roles of TNF-α have been studied in the inflammatory cascade leading to renal injury. Besides the experimental animal models of lupus nephritis, several studies have investigated the important role of TNF-α and its receptors in patients with glomerulonephritis [21,35,39,59,60,61,62,63,64]. An immunological injury is followed by an upregulation of TNF-α in the glomeruli, activating tubular epithelial cells and increasing the production of cytokines.…”