Sputum Antineutrophil Cytoplasmic Antibodies in Serum Antineutrophil Cytoplasmic Antibody–Negative Eosinophilic Granulomatosis with Polyangiitis

Mukherjee, Manali; Thomas, Sruthi; Radford, Katherine; Dvorkin‐Gheva, Anna; Davydchenko, Svetlana; Kjarsgaard, Melanie; Svenningsen, Sarah; Almas, Sarah; Felix, Lindsey C.; Stearns, Jennifer; Li, Quan Zhen; Khalidi, Nader; Lacy, Paige; Nair, Parameswaran

doi:10.1164/rccm.201804-0809oc

Cited by 45 publications

(20 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The CXCL12 chemokine axis can chemotactically accumulate inflammatory cells to local tissues and regulate the release of inflammatory factors. In AAV, increased CXCL12 levels have been previously described in the sputum of ANCA+ patients [ 43 ]. Well in line with our finding, Radjewski et al described CXCL12 as a biomarker whose levels can be increased in chronic inflammation of the paranasal tissue in general [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

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

Müller-Deile

Jaremenko

Haller

et al. 2021

JCM

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Müller-Deile

Jaremenko

Haller

et al. 2021

JCM

View full text Add to dashboard Cite

show abstract

“…Intriguingly, ANCA have been detected in sputum samples of EGPA patients, irrespective to their serum ANCA-status. Despite unknown specific targets, sputum autoantibodies induced both neutrophil and eosinophil extracellular traps in vitro, suggesting their possible pathogenicity (114). It is tempting to speculate that sputum-ANCA may preceded the development of serum-ANCA positivity in a subset of EGPA patients.…”

Section: Origin Of Pathogenic-ancamentioning

confidence: 99%

Eosinophilic Granulomatosis With Polyangiitis: Dissecting the Pathophysiology

2021

View full text Add to dashboard Cite

Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare multisystemic disease classified both amongst hypereosinophilic disorders and ANCA-associated vasculitis. Vessel inflammation and eosinophilic proliferation are the hallmarks of the disease and main effectors of organ damage. Two distinct disease phenotypes have classically been described according to ANCA-status: the ANCA-negative subset with eosinophil-driven manifestation and the ANCA-positive one with vasculitic manifestations. An analogous dichotomization has also been backed by histological findings and a distinct genetic background. EGPA is typically consider a Th2-mediated disease and blood and tissue eosinophilia represent the cornerstone of diagnosis. Besides, ANCA are known for inducing endothelial injury and vascular inflammation by activating the circulating neutrophils. Thus, the pathogenesis of EGPA seems to be mediated by two coexisting mechanisms. However, the verbatim application of this strict dualism cannot always be translated into routine clinical practice. In the present review we describe the current knowledge on the eosinophilic and ANCA-mediated aspects of EGPA pathogenesis. Finally, we review the rationale of the currently proposed EGPA dichotomy and future research perspectives.

show abstract

“…Particularly, the origin of the DNA involved in EET formation is still a matter of debate [51,52]. EET formation has been reported to rely on a mtDNA scaffold from live cells [4,[44][45][46]48,53,54] or respectively on a nuclear DNA scaffold from lytic cells undergoing eosinophil extracellular trap death (EETosis) [55][56][57][58][59][60]. ATG5-knockout eosinophils have been demonstrated with an increased ability to form EETs and consequently increased bacterial killing of Escherichia coli (E. coli) in vitro, as well as clearance of Citrobacter rodentium (C. rodentium) in vivo [44].…”

Section: The Close Relationship Between Degranulation and Dsdna Release In Eet Formationmentioning

confidence: 99%

The Enigma of Eosinophil Degranulation

Fettrelet

Gigon

Karaulov

et al. 2021

IJMS

View full text Add to dashboard Cite

Eosinophils are specialized white blood cells, which are involved in the pathology of diverse allergic and nonallergic inflammatory diseases. Eosinophils are traditionally known as cytotoxic effector cells but have been suggested to additionally play a role in immunomodulation and maintenance of homeostasis. The exact role of these granule-containing leukocytes in health and diseases is still a matter of debate. Degranulation is one of the key effector functions of eosinophils in response to diverse stimuli. The different degranulation patterns occurring in eosinophils (piecemeal degranulation, exocytosis and cytolysis) have been extensively studied in the last few years. However, the exact mechanism of the diverse degranulation types remains unknown and is still under investigation. In this review, we focus on recent findings and highlight the diversity of stimulation and methods used to evaluate eosinophil degranulation.

show abstract

Sputum Antineutrophil Cytoplasmic Antibodies in Serum Antineutrophil Cytoplasmic Antibody–Negative Eosinophilic Granulomatosis with Polyangiitis

Cited by 45 publications

References 35 publications

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

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

Eosinophilic Granulomatosis With Polyangiitis: Dissecting the Pathophysiology

The Enigma of Eosinophil Degranulation

Contact Info

Product

Resources

About