Serum IL-17 and IL-23 levels and autoantigen-specific Th17 cells are elevated in patients with ANCA-associated vasculitis

Nogueira, Estela; Hamour, Sally; Sawant, Devika; Henderson, Scott; Mansfield, Nicholas; Chavele, Konstantia-Maria; Pusey, Charles D.; Salama, Alan D.

doi:10.1093/ndt/gfp783

Cited by 199 publications

(165 citation statements)

References 39 publications

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“…In a mouse study, Th17 cells were observed to play a role in the pathogenesis of experimental anti-MPO glomerulonephritis by neutrophil accumulation in the kidney that is dependent on IL-8 and IL-17 [17]. In a human study, there was an increased percentage of Th17 cells in the periphery, and serum IL-17 levels were elevated in acute ANCA-associated vasculitis patients [18]. In brief, IL-6 may play an important role in leading to neutrophil activation, together with IL-8 and IL-17, in the pathogenesis of ANCA-associated vasculitis.…”

Section: Discussionmentioning

confidence: 95%

AP-VAS 2012 case report: a case of ANCA-negative pauci-immune crescentic glomerulonephritis associated with IL-6-producing adenosquamous cell carcinoma of the lung

et al. 2013

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A 76-year-old man with lung cancer and multiple metastases was admitted for purpura and rapidly progressive glomerulonephritis. Adenosquamous cell carcinoma of the lung had been diagnosed 6 months earlier.Two anti-cancer drug regimens had no effect. At admission, his survival with his malignancy was estimated to be several months. Renal biopsy revealed pauci-immune necrotizing crescentic glomerulonephritis (CrGN). Negative results were obtained for myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA) and proteinase-3-ANCA by enzyme-linked immunosorbent assay, and for peripheral-ANCA and cytoplasmic-ANCA by indirect immunofluorescence. He was diagnosed with ANCA-negative pauciimmune CrGN. Although steroids were initiated, the patient died of renal failure and intestinal bleeding 2 weeks later. It was later found that cancer cells were positive for interleukin (IL)-6 and that serum IL-6 levels were significantly elevated, concomitantly with increased IL-8, granulocyte-colony stimulating factor and transforming growth factor-b levels. Some kinds of lung cancer are known to produce IL-6 that activate neutrophils and are related to ANCA-associated CrGN. It appears that IL-6 can activate neutrophils in the pathogenesis of ANCA-negative pauciimmune CrGN with lung cancer. Therapy that blocks IL-6 may prove to be effective in vasculitis and cancer-related symptoms in such cases.

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Section: Discussionmentioning

confidence: 95%

AP-VAS 2012 case report: a case of ANCA-negative pauci-immune crescentic glomerulonephritis associated with IL-6-producing adenosquamous cell carcinoma of the lung

et al. 2013

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“…The cytokine profile of these recall responses suggests that Th1 responses drive MPO ANCA autoimmunity. However, patients with AAV have increased numbers of Th17-producing lymphocytes (12), and Th17-associated serum cytokine levels correlate with disease activity (13). Taken together, these observations suggest that CD4 cells (Th1 or Th17) are likely to be involved in both the generation of the causative humoral autoimmunity and the vascular effector response.…”

mentioning

confidence: 96%

Toll‐like receptor 2 induces Th17 myeloperoxidase autoimmunity while Toll‐like receptor 9 drives Th1 autoimmunity in murine vasculitis

Summers¹,

Steinmetz²,

Gan³

et al. 2011

Arthritis & Rheumatism

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Objective. Autoantibodies constitute the hallmark of antineutrophil cytoplasmic antibody-associated vasculitis (AAV); however, CD4؉ T cells play an essential role in the development of autoimmunity. Infection is associated with vasculitis, with Toll-like receptors (TLRs) a potential link between infection and autoimmunity. This study was undertaken to investigate the role of TLR ligation on cellular and humoral autoimmunity and glomerular injury in experimental myeloperoxidase (MPO)-induced AAV.Methods. We analyzed autoimmune responses in wild-type mice immunized with MPO alone or coimmunized with MPO and a TLR-2 or TLR-9 ligand. The major vascular injury found in human disease, glomerulonephritis with focal necrosis, was triggered by administering a subnephritogenic dose of nephrotoxic serum.Results. MPO alone induced low-titer antineutrophil cytoplasmic antibodies (ANCAs) without delayedtype hypersensitivity or CD4 cytokine responses. However, when MPO was given with either TLR ligand, cellular and humoral autoimmunity was enhanced, but with distinctly different CD4 subsets and IgG ANCA isotypes. TLR-2 ligand induced Th17 autoimmunity, with retinoic acid receptor-related orphan nuclear receptor ␥t-dependent interleukin-17A (IL-17A) production. TLR-9 ligand promoted Th1 autoimmunity, with enhanced production of interferon-␥ (IFN␥) and Th1-associated IgG subclasses. Glomerular vasculitis developed only after the administration of nephrotoxic serum in mice immunized with either TLR ligand and MPO. Glomerulonephritis directed by MPO and TLR-2 ligation was attenuated when IL-17A was neutralized, while glomerulonephritis induced by MPO and TLR-9 ligation was attenuated when IFN␥ was neutralized.Conclusion. Our findings indicate a pathogenic role of TLRs in initiating autoimmune AAV. TLR-2 induces Th17 CD4 cells while TLR-9 can also direct vasculitis, by directing Th1 autoimmunity.

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“…IL-17 cytokines mediate the chemotaxis of neutrophils to sites of infection and upregulate the intercellular adhesion molecule-1 [30]. IL-17A has been extensively studied in pulmonary infections, asthma, cancer, ANCA associated vasculitis, glomerulonephritis, and renal transplantation [30][31][32][33][34].…”

Section: Chemokines In Renal Diseasesmentioning

confidence: 99%

Chemokines as Potential Markers in Pediatric Renal Diseases

Silva¹,

Pereira²,

Teixeira³

et al. 2016

Biomarkers in Kidney Disease

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Glomerular diseases and obstructive uropathies are the two most frequent causes of chronic kidney disease (CKD) in children. Recently, biomarkers have become a focus of clinical research as potentially useful diagnostic tools in pediatric renal diseases. Among several putative biomarkers, chemokines emerge as promising molecules since they play relevant roles in the pathophysiology of pediatric renal diseases. The evaluation of these inflammatory mediators might help in the management of diverse renal diseases in children and the detection of patients at high risk to develop CKD. The aim of this paper is to revise general aspects of chemokines and the potential link between chemokines and the most common pediatric renal diseases by including experimental and clinical evidence.

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Serum IL-17 and IL-23 levels and autoantigen-specific Th17 cells are elevated in patients with ANCA-associated vasculitis

Abstract: These data implicate the Th17 axis and specifically IL-23 as mediators of more severe disease in AAV. Their persistence despite conventional treatment may contribute to high relapse rates.

Cited by 199 publications

References 39 publications

AP-VAS 2012 case report: a case of ANCA-negative pauci-immune crescentic glomerulonephritis associated with IL-6-producing adenosquamous cell carcinoma of the lung

AP-VAS 2012 case report: a case of ANCA-negative pauci-immune crescentic glomerulonephritis associated with IL-6-producing adenosquamous cell carcinoma of the lung

Toll‐like receptor 2 induces Th17 myeloperoxidase autoimmunity while Toll‐like receptor 9 drives Th1 autoimmunity in murine vasculitis

Chemokines as Potential Markers in Pediatric Renal Diseases

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