Aberrant cytokine pattern of the nasal mucosa in granulomatosis with polyangiitisReport as inadecuate




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Arthritis Research and Therapy

, 14:R203

First Online: 17 October 2012Received: 07 December 2011Revised: 11 June 2012Accepted: 16 August 2012

Abstract

IntroductionIn granulomatosis with polyangiitis GPA, a complex autoimmune small-vessel vasculitis frequently associated with chronic necrotizing inflammation of the nasal mucosa, elevated nasal Staphylococcus S. aureus carrier rates are a risk factor for relapse. As cytokines are primarily involved in the regulation of defense against potentially pathogenic microorganisms, the aim of this study was to compare healthy individuals and GPA patients with respect to their baseline cytokine expression of nasal epithelial cells NEC, which form the first barrier against such triggers. The ability of S. aureus to influence the nasal microenvironment-s cytokine secretion was assessed by exemplary stimulation experiments.

MethodsBaseline expression of 19 cytokines of primary NEC of GPA patients and normal controls NC was quantified by a multiplex cytokine assay. Stimulation experiments were performed with supernatants of S. aureus and expression of interleukin-8 was determined by ELISA.

ResultsIn GPA, an altered pattern of baseline cytokine expression with significantly up-regulated G-CSF and reduced interleukin IL-8 concentrations was observed. Both NEC of GPA patients and NC responded to stimulation with S. aureus, but GPA patients displayed a significantly lower IL-8 secretion and a diminished dynamic range of response towards the stimulus.

ConclusionsThe data presented underline the hypothesis of a disturbed epithelial nasal barrier function in GPA. The dysregulated baseline expression of G-CSF and IL-8 and the reduced response to microbial stimulation may facilitate changes in the composition of the nasal flora and favour an imbalanced inflammatory response, which might be relevant for the disease course.

AbbreviationsBVASBirmingham Vasculitis Activity Score

C-ANCAcytoplasmic anti-neutrophil cytoplasmatic antibodies

cPR3complementary PR3

CRPC-reactive protein

DEIDisease Extent Index

ELISAenzyme-linked immunosorbent assay

ESRerythrocyte sedimentation rate

EULAREuropean League Against Rheumatism

G-CSFgranulocyte colony-stimulating factor

GM-CSFgranulocyte macrophage colony-stimulating factor

GPAGranulomatosis with polyangiitis

IFN-γinterferon-γ

ILinterleukin

JNKJUN-N terminal protein kinase

MAPKmitogen-activated protein kinase

MCP-1monocyte chemotactic protein-1

MIP-1macrophage inflammatory protein-1

NCnormal controls

NECnasal epithelial cells

P-ANCAperinuclear anti-neutrophil cytoplasmatic antibodies

PMNpolymorphonuclear neutrophils

PR3proteinase 3; S. aureus Staphylococcus aureus

TNFtumor necrosis factor

VDIVasculitis Damage Index

WBCwhite blood cell count.

Electronic supplementary materialThe online version of this article doi:10.1186-ar4041 contains supplementary material, which is available to authorized users.

Janet Wohlers, Katrin Breucker contributed equally to this work.

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Author: Janet Wohlers - Katrin Breucker - Rainer Podschun - Jürgen Hedderich - Peter Lamprecht - Petra Ambrosch - Martin Laudien

Source: https://link.springer.com/







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