Identification of Autoantigens in EGPA and Severe Eosinophilic Asthma

NCT04671446 | Completed Results

• 2 other identifiers: IRAS 27409720/PR/0004
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 2

Brief Summary

In this project the investigators will look for auto-antibodies to relevant proteins both in native form and importantly in post-translationally modified forms. Potential modified auto-antigens are eosinophil proteins (analogous to the cytoplasmic neutrophil proteins identified in vasculitides such as Granulomatosis with Polyangiitis (formerly known as Wegener's granulomatosis) and alternatively structural proteins such as collagen V. As well as advancing the understanding of asthma pathology, identifying a serum auto-antibody that could then be used as a clinical blood test, analogous to anti-cyclic citrullinated peptide (CCP) antibodies in rheumatoid arthritis, may revolutionise diagnosis of severe eosinophilic asthma and Eosinophilic Granulomatosis with Polyangiitis (EGPA). There is a considerable burden of undiagnosed severe eosinophilic asthma in part due to difficulties in definitive diagnosis and a diagnostic blood test would help diagnose these patients, allowing them to receive necessary treatment.

Conditions

Churg-Strauss Syndrome; Eosinophilic Asthma; Eosinophilic Esophagitis; Eosinophilic Pneumonia

Outcome Measures

Primary Outcomes (1)

• Number and Percentage of Patients With a Positive Autoantibody ELISA

  Serum tested for novel autoantibodies against candidate auto-antigens by ELISA. Outcome: Positive OD by ELISA (serum samples) to autoantigen panel (MPO, Collagen V, TREM1, IL1R2).

  Baseline, at study entry

Secondary Outcomes (1)

• Number and Percentage of Patients With Positive Granulocyte Immunofluorescence

  Baseline, at study entry

Study Arms (4)

Severe eosinophilic asthma

Patients with eosinophilic asthma meeting ERS/ATS criteria for severe asthma.

Diagnostic Test: Autoantibody ELISA; Diagnostic Test: Granulocyte Immunofluorescence

Other respiratory conditions

Milder asthma, other vasculitides, eosinophilic COPD, and/or eosinophilic oesophagitis

Diagnostic Test: Autoantibody ELISA; Diagnostic Test: Granulocyte Immunofluorescence

Healthy controls

Healthy patients with no chronic lung condition.

Diagnostic Test: Autoantibody ELISA; Diagnostic Test: Granulocyte Immunofluorescence

EGPA

Patients with asthma meeting criteria for a diagnosis of EGPA (eosinophilic granulomatosis with polyangiitis) as per Wechsler et al. \[N Engl J Med. 2017 May 18;376(20):1921-1932\]

Diagnostic Test: Autoantibody ELISA; Diagnostic Test: Granulocyte Immunofluorescence

Interventions

Autoantibody ELISA DIAGNOSTIC_TEST

Serum will be tested for novel autoantibodies against candidate auto-antigens by ELISA, such as those previously identified as of importance (e.g. eosinophil peroxidase, EPX) and also novel candidate proteins specific to eosinophils as identified by FANTOM5 geneset analysis.

EGPA; Healthy controls; Other respiratory conditions; Severe eosinophilic asthma

Granulocyte Immunofluorescence DIAGNOSTIC_TEST

The presence of auto-antibodies in patient serum to inactive and activated neutrophils / eosinophils, with and without post-translational modification, will be examined by indirect immunofluorescence.

EGPA; Healthy controls; Other respiratory conditions; Severe eosinophilic asthma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients will be recruited via Outpatient Clinics conducted at St Bartholomew's (Bart's) Hospital, The Royal London Hospital, and Mile End Hospital (all Bart's Health NHS Trust), as well as from inpatients at these hospitals under the care of the Respiratory Medicine and Rheumatology teams (including those under other services needing inpatient respiratory medicine or rheumatology review).

You may qualify if:

• Severe Eosinophilic Asthma (with multi-disciplinary diagnosis as per ERS/ATS Criteria, blood eosinophils ≥ 0.3 x109/L on inhaled corticosteroids); or
• EGPA (as per American College of Rheumatology (ACR) Criteria); or
• Eosinophilic COPD (post-bronchodilator FEV1/FVC \< 70% predicted, absence of bronchodilator reversibility, \> 20 pack year smoking history, no history of asthma, blood eosinophils ≥ 0.3 x109/L); or
• Eosinophilic oesophagitis (with diagnostic histology); or
• Granulomatosis with Polyangiitis (GPA, formerly called Wegener's) (as per American College of Rheumatology (ACR) Criteria)

You may not qualify if:

• Known Pregnancy
• Anaemia
• Hepatitis B Virus, Hepatitis C Virus or HIV infection
• Donation of more than 240mls blood in the last sixteen weeks (four months) to any other research study or as a donation to the National Blood Transfusion Service
• Rituximab, plasmapharesis or polyclonal immunoglobulin infusion (ever)

Sponsors & Collaborators

• Queen Mary University of London: lead

Study Sites (2)

Barts Health NHS Trust, Dept of Rheumatology, Mile End Hospital

London, E1 4DG, United Kingdom

Location

Barts Health NHS Trust, Dept of Respiratory Medicine, St Bartholomew's Hospital

London, EC1A 7BE, United Kingdom

Location

Related Publications (1)

• Esposito I, Kontra I, Giacomassi C, Manou-Stathopoulou S, Brown J, Stratton R, Verykokou G, Buccafusca R, Stevens M, Nissim A, Lewis MJ, Pfeffer PE. Identification of autoantigens and their potential post-translational modification in EGPA and severe eosinophilic asthma. Front Immunol. 2023 Jun 2;14:1164941. doi: 10.3389/fimmu.2023.1164941. eCollection 2023.

  PMID: 37334358 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples

MeSH Terms

Conditions

Churg-Strauss Syndrome; Pulmonary Eosinophilia; Eosinophilic Esophagitis

Condition Hierarchy (Ancestors)

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Granuloma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Lung Diseases; Respiratory Tract Diseases; Hypereosinophilic Syndrome; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Esophagitis; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Hypersensitivity, Immediate; Hypersensitivity

Results Point of Contact

• Title: Dr Myles Lewis, Dr Paul Pfeffer
• Organization: Queen Mary University of London

myles.lewis@qmul.ac.uk; p.pfeffer@qmul.ac.uk

+4420 7882 5555

Study Officials

• Myles J Lewis, MD PhD FRCP

  Queen Mary University of London

  STUDY CHAIR

• Paul Pfeffer, MD

  Barts & The London NHS Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2020
• First Posted: December 17, 2020
• Study Start: December 10, 2020
• Primary Completion: October 12, 2022
• Study Completion: May 5, 2024
• Last Updated: January 30, 2025
• Results First Posted: January 30, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)