Chemokine/Cytokine Levels Correlate with Organ Involvement in PR3-ANCA-Associated Vasculitis

Janina Müller-Deile,Marion Haubitz,Hermann Haller,Mario Schiffer,Christian Jaremenko,Silke Christiansen,Lena Schiffer,Christine Falk

doi:10.3390/jcm10122715

Abstract

Background: ANCA-associated vasculitis (AAV) is a rare small vessel disease characterized by multi-organ involvement. Biomarkers that can measure specific organ involvement are missing. Here, we ask whether certain circulating cytokines and chemokines correlate with renal involvement and if distinct cytokine/chemokine patterns can differentiate between renal, ear/nose/throat, joints, and lung involvement of AAV. Methods: Thirty-two sets of Birmingham vasculitis activity score (BVAS), PR3-ANCA titers, laboratory marker, and different cytokines were obtained from 17 different patients with AAV. BVAS, PR3-ANCA titers, laboratory marker, and cytokine concentrations were correlated to different organ involvements in active AAV. Results: Among patients with active PR3-AAV (BVAS > 0) and kidney involvement we found significant higher concentrations of chemokine ligand (CCL)-1, interleukin (IL)-6, IL21, IL23, IL-28A, IL33, monocyte chemoattractant protein 2 (MCP2), stem cell factor (SCF), thymic stromal lymphopoietin (TSLP), and thrombopoietin (TPO) compared to patients without PR3-ANCA-associated glomerulonephritis. Patients with ear, nose, and throat involvement expressed higher concentrations of MCP2 and of the (C-X-C motif) ligand-12 (CXCL-12) compared to patients with active AAV and no involvement of these organs. Conclusion: We identified distinct cytokine patterns for renal manifestation and for ear, nose and throat involvement of PR3-AAV. Distinct plasma cytokines might be used as non-invasive biomarkers of organ involvement in AAV.

Highlights

When we compared patients with joint involvement and kidney involvement versus joint involvement but no kidney involvement, we found significant elevation of Eotaxin3 and TRAIL next to IL-23, IL28A, monocyte chemoattractant protein 2 (MCP2), thymic stromal lymphopoietin (TSLP), and TPO seen in patients with kidney involvement before (Tables 4 and 5 and Figure 4a)
AAVpatient with glomerucause of end-stage renal disease (ESRD) that is associatedhigher with ainpoor outcome lonephritis compared to no renal involvement, it is important to diagnose and treat and prognosis
Well in line with previous studies, we found that the elevation of the inflammatory marker C-reactive protein (CRP) did not function as a predictor of relapse or organ manifestation [25]

Summary

Introduction

Antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis is a relatively rare and potential life threatening multi systemic autoimmune disease [1]. Nose, and throat (ENT); lung; heart; kidney; bowel; skin; nerves; and joints [2]. The serological presence of ANCA that recognize the neutrophil cytoplasmic antigens proteinase 3 (PR3) and myeloperoxidase (MPO) is the defining serological characteristic of all ANCA-associated vasculitides [3,4]. Entities of AAV include granulomatosis with polyangiitis (GPA; formerly known as Wegener’s Granulomatosis), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis

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