scholarly journals Serum Cytokine Profiling Identifies Axl as a New Biomarker Candidate for Active Eosinophilic Granulomatosis With Polyangiitis

2021 ◽  
Vol 8 ◽  
Author(s):  
Jianjuan Ma ◽  
Cong Dong ◽  
Shushan Wei ◽  
Minzhi Qiu ◽  
Penghui Wu ◽  
...  
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
Expression Patterns ◽  
Serum Levels ◽  
Serum Biomarkers ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Blood Eosinophil ◽  
Peripheral Blood Eosinophil ◽  
Kegg Pathways ◽  
Eosinophilic Granulomatosis ◽  
Eosinophil Counts

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) prognosis is generally favorable and is treated with combined corticosteroids/immunosuppressor(s) therapy. However, disease flares increase the number of clinical visits. Therefore, discovering new serum biomarkers for early identification of active EGPA is crucial.Objective: To identify reliable serum biomarkers to measure EGPA activity.Methods: The expression of 160 proteins was compared in sera from 15 inactive and 13 active EGPA patients by antibody-based microarray. Network-based analysis identified patterns in the different groups. Differentially expressed proteins (DEPs) in active disease were identified, and the correlation between their serum levels and clinical parameters was assessed. DEPs were further analyzed for GO enrichment and KEGG pathways. Finally, DEP marker candidates were validated by ELISA and Bio-plex as well as against a second cohort of 22 inactive and 18 active EGPA patients.Results: The active group presented higher peripheral and sputum eosinophil counts, FeNO, and FEV1 (% predicted) (P < 0.05). Network-based analysis showed scattered expression patterns in active subjects, but no significant bias in inactive subjects. Significant differences were observed in serum levels of 19 candidate markers, all of which were higher in active EGPA (P < 0.05). KEGG analysis indicated that DEPs were mainly involved in the MAPK, PI3K-Akt, RAS and Rap1 related pathways. Nine out of 19 candidate markers were positively correlated with peripheral eosinophil counts including FGF-7, SCF, GDNF, β-NGF, IGFBP-4, Axl, PIGF, Insulin, NT-4, ErbB3, OPN and BMP-4 (r = 0.693, r = 0.692, r = 0.687, r = 0.683, r = 0.671, r = 0.606, r = 0.571, r = 0.570, r = 0.516, respectively; P < 0.05), while two, CD14 and MCP-3, were negatively correlated (r = −0.644 and r = −0.515; P < 0.05). The higher expression of Axl, OPN, HCC-4, GDNF, and MCP-3 in active EGPA subjects was confirmed by ELISA and Custom Multiplex Bio-plex analyses.Conclusion: The serum protein profiles were significantly different between active and inactive EGPA. The expression of the candidate proteins correlated with peripheral blood eosinophil count. Serum Axl, OPN, HCC-4, GDNF, and MCP-3 levels were consistently higher in active EGPA, independent of the assessment methods. Finally, Axl had the largest AUC, indicating that this cytokine may serve as novel biomarker for the diagnosis of active EGPA.

Clinical Features of Patients with Active Eosinophilic Granulomatosis with Polyangiitis Successfully Treated with Mepolizumab

2021 ◽  
pp. 1-13
Author(s):  
Naomi Tsurikisawa ◽  
Chiyako Oshikata ◽  
Maiko Watanabe ◽  
Nobuhiko Fukuda ◽  
Takanori Yamaguchi ◽  
...  
Keyword(s):  
Clinical Features ◽  
Granulomatosis With Polyangiitis ◽  
Marked Effect ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Blood Eosinophil ◽  
City Hospital ◽  
Weak Effect ◽  
Peripheral Blood Eosinophil ◽  
Serum Igg ◽  
Eosinophilic Granulomatosis

<b><i>Background:</i></b> In some patients with eosinophilic granulomatosis with polyangiitis (EGPA), remission cannot be induced, despite treatment with corticosteroids and immunosuppressants. We evaluated the clinical features of patients with EGPA in whom mepolizumab was effective. <b><i>Methods:</i></b> There were 59 EGPA patients treated at Hiratsuka City Hospital, Japan, between April 2018 and September 2020, and 30 of them received mepolizumab. Twenty (66.7%) experienced a “marked effect” (the daily dose of corticosteroid or immunosuppressant could be decreased, or the interval between intravenous immunoglobulin (IVIG) treatments could be prolonged) and 10 (33.3%) experienced a “weak effect” (these measures were not achieved). Eosinophil numbers, serum IgG levels, daily doses of corticosteroids and immunosuppressants, and the interval between IVIG treatments at diagnosis and before and after mepolizumab initiation were determined. <b><i>Results:</i></b> Eosinophil numbers at diagnosis were significantly higher in the marked-effect group than in the weak-effect group (<i>p</i> &#x3c; 0.05) but not before mepolizumab initiation or at the last visit. Birmingham Vasculitis Activity Scores (BVASs) before mepolizumab initiation (<i>p</i> &#x3c; 0.05) and at last visit (<i>p</i> &#x3c; 0.01), and frequency of relapse before treatment initiation (<i>p</i> &#x3c; 0.05) were significantly higher, and the serum IgG level before mepolizumab treatment was significantly lower in the weak-effect group than in the marked-effect group. The weak-effect group received higher doses of corticosteroids, even if the corticosteroid dose could be reduced for a while after mepolizumab initiation. <b><i>Conclusion:</i></b> High peripheral blood eosinophil numbers at EGPA diagnosis were suggestive of a positive clinical response to mepolizumab.

scholarly journals B-Cell-Depleting Therapy Improves Myocarditis in Seronegative Eosinophilic Granulomatosis with Polyangiitis

2021 ◽  
Vol 10 (19) ◽  
pp. 4577
Author(s):  
Chrong-Reen Wang ◽  
Yi-Shan Tsai ◽  
Hung-Wen Tsai ◽  
Cheng-Han Lee
Keyword(s):  
B Cell ◽  
Clinical Remission ◽  
Granulomatosis With Polyangiitis ◽  
Disease Onset ◽  
Cardiac Insufficiency ◽  
Induction Treatment ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Asthma Attack ◽  
Eosinophilic Granulomatosis ◽  
Eosinophil Counts

Cardiac involvement is a major mortality cause in eosinophilic granulomatosis with polyangiitis (EGPA), requiring novel therapeutics to spare the use of cyclophosphamide with known cardiotoxicity. Despite the observed efficacy of B-cell-depleting therapy in myocarditis of seropositive microscopic polyangiitis, it remains to be elucidated in seronegative EGPA. A retrospective study was performed in 21 hospitalized active patients aged 20 to 70 years with five-factor score 1 or 2, eosinophil counts 10,034 ± 6641/μL and vasculitis scores 27 ± 6. Overt myocarditis was identified in 10 cases, at disease onset in 6 and relapse in 4, with endomyocarditis in 4 and myopericarditis in 4. Five seronegative and one seropositive patient received rituximab with an induction regimen 375 mg/m2 weekly × 4 for refractory or relapse disease, and the same regimen for annual maintenance therapy. All cases had lower eosinophil counts, improved cardiac dysfunction and clinical remission with a relapse-free follow-up, 48 ± 15 months after the induction treatment. One seronegative endomyocarditis patient had eosinophilia and disease relapse with asthma attack and worsening cardiac insufficiency 24 months after induction, achieving clinical remission under anti-IL-5 therapy. Our findings suggest the suppression of IL-5-mediated eosinophilia as an action mechanism of B-cell-depleting therapy in seronegative EGPA myocarditis.

scholarly journals Longterm Outcomes of 188 Japanese Patients with Eosinophilic Granulomatosis with Polyangiitis

2018 ◽  
Vol 45 (8) ◽  
pp. 1159-1166 ◽  
Author(s):  
Aiko Saku ◽  
Shunsuke Furuta ◽  
Masaki Hiraguri ◽  
Kei Ikeda ◽  
Yoshihisa Kobayashi ◽  
...  
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Disease Onset ◽  
Japanese Patients ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Factors Associated ◽  
Hazards Model ◽  
Eosinophilic Granulomatosis ◽  
Eosinophil Counts

Objective.Patients with eosinophilic granulomatosis with polyangiitis (EGPA) frequently experience relapses, which lead to cumulative organ damage. In this retrospective observational study, we aimed to reveal the risk factors for relapse in EGPA.Methods.A total of 188 Japanese patients with EGPA diagnosed between 1996 and 2015 were identified from medical records in 10 hospitals. The diagnosis was based on the American College of Rheumatology 1990 criteria or Lanham’s criteria. Baseline characteristics, treatments, asthma exacerbation, and relapses were evaluated by retrospective chart review.Results.The median followup period was 56 months. The median age at disease onset was 59.7 years. At the disease onset, 95.2% of the patients had a history of bronchial asthma and 44.7% were positive for antineutrophil cytoplasmic antibodies. The cumulative survival and relapse-free survival rates at 5 years were 89.6% and 64.0%, respectively. Multivariate analysis with 2 models, proportional hazards, and competing risk models, was performed to identify the factors associated with relapse. The proportional hazards model identified azathioprine (AZA) maintenance therapy and high eosinophil counts at onset as independent factors with lower relapse risks, and high immunoglobulin E (IgE) levels at onset as a risk factor for relapse. The competing risk model identified no statistically significant factors.Conclusion.Although potential benefit of AZA maintenance therapy in preventing relapse of EGPA was suggested by the proportional hazards model, there was a discrepancy in the results between the models. Eosinophil counts and IgE levels at onset were also identified as candidates of factors associated with relapse in EGPA.

scholarly journals Serum Biomarkers in Patients with Relapsing Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss)

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0121737 ◽  
Author(s):  
Christian Dejaco ◽  
Bastian Oppl ◽  
Paul Monach ◽  
David Cuthbertson ◽  
Simon Carette ◽  
...  
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
Serum Biomarkers ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Eosinophilic Granulomatosis ◽  
Churg Strauss

Serum biomarkers during relapsing disease in eosinophilic granulomatosis with polyangiitis

2013 ◽  
Vol 42 (4) ◽  
pp. 700-701
Author(s):  
C. Dejaco ◽  
P. Monach ◽  
D. Cuthbertson ◽  
S. Carette ◽  
G. Hoffman ◽  
...  
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
Serum Biomarkers ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Eosinophilic Granulomatosis

scholarly journals Biological therapy improves myocarditis and disease activity in eosinophilic granulomatosis with polyangiitis patients

2020 ◽  
Author(s):  
Chrong-Reen Wang ◽  
Yi-Shan Tsai ◽  
Jiu-Yao Wang ◽  
Hung-Wen Tsai ◽  
Cheng-Han Lee
Keyword(s):  
Retrospective Study ◽  
Disease Activity ◽  
Cardiac Dysfunction ◽  
Granulomatosis With Polyangiitis ◽  
Biological Therapy ◽  
Cardiac Insufficiency ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Heart Involvement ◽  
Eosinophilic Granulomatosis ◽  
Eosinophil Counts

Abstract Background Cardiac insufficiency is a major cause of mortality in eosinophilic granulomatosis with polyangiitis (EGPA). Despite the dosages-related cardiotoxicity, cyclophosphamide is usually prescribed to induce disease remission in the presence of myocarditis with heart involvement. There is an imperative need of novel medications to efficiently control disease activity and spare the use of cyclophosphamide. Methods A retrospective study was carried out in hospitalized EGPA patients from January 1, 2008 to December 31, 2019, focusing on the use of biologics including benralizumab (BEN, anti-IL-5 receptor), mepolizumab (MEP, anti-IL-5), omalizumab (OMA, anti-IgE) and rituximab (RTX, anti-CD20). Results Sixteen admitted patients, 8 females aged 10 to 70 years (40.4 ± 15.5), had higher disease activities (Birmingham Vasculitis Activity Score 16 to 39, 26.8 ± 6.9), poorer prognostic factors (five-factor score 1 or 2, 1.4 ± 0.5) and elevated eosinophil counts (2,314 to 26,781/µL, 11,108 ± 7,060). BEN, MEP, OMA and RTX were prescribed in one, 2, one and 6 patients, respectively. Ten patients (63%) had myocarditis with impaired left ventricle ejection fraction and cardiac arrhythmia, and 7 received biological therapy without a combined use of cyclophosphamide. One patient obtained MEP with a 100 mg quadri-weekly × 13 regimen at induction for disease relapse. Six patients acquired RTX with a 375 mg/m2 weekly × 4 regimen at induction for refractory activity or relapsing disease, or plus a yearly maintenance schedule in 5. All patients received serial cardiac magnetic resonance imaging, transthoracic echocardiography and 24-hour Holter monitor to evaluate the therapeutic responses in heart involvement. After biological therapy, there were improved cardiac dysfunction, lower eosinophil counts and clinical remission (4 complete, 3 partial) with a relapse-free follow-up (13 to 61 months, 39.1 ± 16.0) after induction. Conclusions In this single-center retrospective study, we observed improved cardiac dysfunction and disease activity after biological therapy in EGPA patients with myocarditis.

scholarly journals Respiratory manifestations of eosinophilic granulomatosis with polyangiitis (Churg–Strauss)

2016 ◽  
Vol 48 (5) ◽  
pp. 1429-1441 ◽  
Author(s):  
Vincent Cottin ◽  
Elisabeth Bel ◽  
Paolo Bottero ◽  
Klaus Dalhoff ◽  
Marc Humbert ◽  
...  
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
Airflow Obstruction ◽  
Corticosteroid Treatment ◽  
Final Visit ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Blood Eosinophil ◽  
First Onset ◽  
Systemic Manifestations ◽  
Eosinophilic Granulomatosis

The respiratory manifestations of eosinophilic granulomatosis with polyangiitis (EGPA) have not been studied in detail.In this retrospective multicentre study, EGPA was defined by asthma, eosinophilia and at least one new onset extra-bronchopulmonary organ manifestation of disease.The study population included 157 patients (mean±sd age 49.4±14.1 years), with a mean±sd blood eosinophil count of 7.4±6.4×109 L−1 at diagnosis. There was a mean±sd of 11.8±18.2 years from the onset of asthma to the diagnosis of EGPA, of 1.4±8.4 years from the first onset of peripheral eosinophilia to the diagnosis of EGPA, and of 7.4±6.4 years from EGPA diagnosis to the final visit. Despite inhaled and oral corticosteroid treatment, the severity of asthma increased 3–6 months before the onset of the systemic manifestations. Asthma was severe in 57%, 48%, and 56% of patients at diagnosis, at 3 years, and at the final visit, respectively. Persistent airflow obstruction was present in 38%, 30%, and 46% at diagnosis, at 3 years, and at the final visit, respectively.In EGPA, asthma is severe, antedates systemic manifestations by a mean of 12 years, and progresses to long-term persistent airflow obstruction despite corticosteroids in a large proportion of patients, which affects long-term management and morbidity.

Atopische Dermatitis: Die Frage nach dem Einfluss von Vitaminen bleibt weiter offen

2020 ◽  
Vol 8 (1) ◽  
pp. 19-20
Author(s):  
Regina Fölster-Holst
Keyword(s):  
Atopic Dermatitis ◽  
Peripheral Blood ◽  
High Performance ◽  
Atopische Dermatitis ◽  
Serum Levels ◽  
Blood Eosinophil ◽  
Normal Children ◽  
Study Objective ◽  
Peripheral Blood Eosinophil ◽  
Eosinophil Counts

Background: Several studies have suggested that vitamin D (VD) deficiency (VDD) is associated with atopic dermatitis (AD). However, little is known about the relationship between AD and vitamin A (VA). The interaction between VA and VD on AD requires further study. Objective: We detected serum levels of VA and VD in children with AD to explore how VA deficiency (VAD) and VDD affect AD severity. Methods: We assessed the SCORing Atopic Dermatitis (SCORAD) index, total immunoglobin E levels and peripheral blood eosinophil counts. VA and VD levels were determined with high-performance liquid chromatography. Correlations among variables were investigated with Pearson's correlation analysis. Results: The VD and VA levels were significantly lower in children with AD than in normal children (p < 0.001, p = 0.0423). Both VD and VA levels were negatively correlated with SCORAD scores. The SCORAD scores were significantly higher in AD patients with both VDD and VAD (co-deficiency) than in other AD patients. Significant inverse correlations were observed between peripheral blood eosinophil counts and serum VA and VD levels. Conclusions: VA and VD co-deficiency may exacerbate AD symptoms in children, but the specific mechanism underlying this relationship requires further study. These findings may indicate the need for studies evaluating the use of VD and VA as potential treatments for AD patients.

scholarly journals Rapid effect of benralizumab in exacerbation of severe eosinophilic asthma associated with eosinophilic granulomatosis with polyangiitis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Carlos Martínez-Rivera ◽  
Ignasi Garcia-Olivé ◽  
Blanca Urrutia-Royo ◽  
Maria Basagaña-Torrento ◽  
Antoni Rosell ◽  
...  
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
Forced Expiratory Volume ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Blood Eosinophil ◽  
Rapid Improvement ◽  
Eosinophilic Asthma ◽  
Α Subunit ◽  
Severe Eosinophilic Asthma ◽  
First Case ◽  
Eosinophilic Granulomatosis

Abstract Background Eosinophilic granulomatosis with polyangiitis (EGPA) is a disease that is associated with severe uncontrolled eosinophilic asthma. Eosinophils play an important pathogenic role in the development of both diseases. Benralizumab is an antieosinophilic monoclonal antibody that binds to the α subunit of the human interleukin 5 receptor that is expressed on the surface of the eosinophil and basophil. We present the first case of rapid improvement in symptoms and lung function during admission for exacerbation of a severe eosinophilic asthma associated with EGPA. Case presentation A 57-year-old man diagnosed with severe eosinophilic asthma associated to EGPA was admitted to the Pulmonology Department due to severe bronchospasm. At admission he presented 2300 eosinophils/µl. Despite intensive bronchodilator treatment, intravenous methylprednisolone at a dose of 80 mg/d, oxygen therapy, and budesonide nebulization, the patient continued to present daily episodes of bronchospasm. Ten days after admission, with blood eosinophil levels of 1700 cells/µl, benralizumab 30 mg sc was administered. That day, the Forced Expiratory Volume in the first second (FEV1) was 28% of the theoretical value (1150 ml). AT three days, FEV1 increased to 110 ml (31%). On the 9th day FEV1 was 51% (2100 ml). The blood eosinophil level on the 9th day was 0 cells/µl. Conclusions The rapid improvement of FEV1 is in line with studies based on clinical trials that found improvement after two days in peak flow and one phase II study that showed rapid response in exacerbation of asthma in the emergency room. The antieosinophilic effect at 24 h and the effect in different tissues determine the rapid improvement and the potential advantage of benralizumab in the treatment of EGPA. This case suggests the usefulness of benralizumab in patients with EGPA and eosinophilic severe asthma who show bronchospasm refractory to conventional treatment during a hospitalization due to asthma exacerbation.

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