Blood leukocyte characterisation in Eosinophilic Granulomatosis with Polyangiitis (EGPA)

<bold>Background:</bold> Immunological mechanisms are poorly understood in EGPA, a rare disease whereby Severe Eosinophilic Asthmatics (SEA) develop blood & tissue eosinophilia, with associated comorbidities. Our objective was to measure blood leukocyte counts and activity from EGPA patients, including type 2-polarised Innate Lymphoid cells (ILC2s) & Type 2-T helper (Th) /cytotoxic (Tc) cell subsets, using chemokine receptor expression. <bold>Methods:</bold> Cytometry was performed on whole blood from stable EGPA (n=9), SEA (n=8) & healthy volunteers (n=10) to measure leukocyte populations, reported as /100µL blood, median [IQR]. EGPA/SEA patients were on OCS only, or with anti-IL5/IL5R. From PBMCs, we measured ILC subset counts (ILC1/ILC2/ILC3; n=5/group), reported /2x10<sup>6</sup> PBMCs, and maturity status using CD45RO<sup>+</sup>/CD45RA<sup>+</sup>, expressed as % of each ILC subset, mean [SD]. <bold>Results:</bold> Type 2-polarised lymphocyte (Th/Tc2, CD161<sup>+</sup> Th/Tc2) counts were similar between EGPA and SEA. Eosinophils, basophils, neutrophils, B cells, Th/c 1, 17 and 22 cell counts were also similar between EGPA and SEA. ILC2 counts were lower in EGPA (13.8[8.8-39.4]) & SEA (16.9[10.6-34.4]) compared to health (45[21.3-120.9]) in whole blood (p=0.0792; p=0.1363 respectively). In PBMCs, a greater proportion of ILC2s expressed CD45RO in EGPA (45.8[16.9]) versus SEA (23.3[14.4]) and health (22.7[4.4]) (p=0.0307; p=0.0259, respectively). <bold>Discussion:</bold> T2-polarised lymphocytes circulate at similar levels between health, SEA and EGPA. ILC2s in EGPA are decreased in blood, but show evidence of increased maturation compared to SEA, suggesting disease specific differences that require confirmation at the functional level.

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Published
2024-09-14
DOI
https://doi.org/10.1183/13993003.congress-2024.pa429
Primary Topic
Vasculitis and related conditions
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article
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article

Blood leukocyte characterisation in Eosinophilic Granulomatosis with Polyangiitis (EGPA)

Matthew Richardson, Harrison Turner, David J. Cousins, Salman Siddiqui et al.
Vasculitis and related conditions
article

Blood leukocyte characterisation in Eosinophilic Granulomatosis with Polyangiitis (EGPA)

Matthew Richardson, Harrison Turner, David J. Cousins, Salman Siddiqui, A. Jordan Wright, Michelle Bourne, Yassine Amrani, Tracy Thornton, R. Barry Dale, Amanda Charalambou, Kate Porter, Shamsa Naveed
article en

Abstract

<bold>Background:</bold> Immunological mechanisms are poorly understood in EGPA, a rare disease whereby Severe Eosinophilic Asthmatics (SEA) develop blood & tissue eosinophilia, with associated comorbidities. Our objective was to measure blood leukocyte counts and activity from EGPA patients, including type 2-polarised Innate Lymphoid cells (ILC2s) & Type 2-T helper (Th) /cytotoxic (Tc) cell subsets, using chemokine receptor expression. <bold>Methods:</bold> Cytometry was performed on whole blood from stable EGPA (n=9), SEA (n=8) & healthy volunteers (n=10) to measure leukocyte populations, reported as /100µL blood, median [IQR]. EGPA/SEA patients were on OCS only, or with anti-IL5/IL5R. From PBMCs, we measured ILC subset counts (ILC1/ILC2/ILC3; n=5/group), reported /2x10<sup>6</sup> PBMCs, and maturity status using CD45RO<sup>+</sup>/CD45RA<sup>+</sup>, expressed as % of each ILC subset, mean [SD]. <bold>Results:</bold> Type 2-polarised lymphocyte (Th/Tc2, CD161<sup>+</sup> Th/Tc2) counts were similar between EGPA and SEA. Eosinophils, basophils, neutrophils, B cells, Th/c 1, 17 and 22 cell counts were also similar between EGPA and SEA. ILC2 counts were lower in EGPA (13.8[8.8-39.4]) & SEA (16.9[10.6-34.4]) compared to health (45[21.3-120.9]) in whole blood (p=0.0792; p=0.1363 respectively). In PBMCs, a greater proportion of ILC2s expressed CD45RO in EGPA (45.8[16.9]) versus SEA (23.3[14.4]) and health (22.7[4.4]) (p=0.0307; p=0.0259, respectively). <bold>Discussion:</bold> T2-polarised lymphocytes circulate at similar levels between health, SEA and EGPA. ILC2s in EGPA are decreased in blood, but show evidence of increased maturation compared to SEA, suggesting disease specific differences that require confirmation at the functional level.

University of Leicester (GB), Glenfield Hospital (GB), University Hospitals of Leicester NHS Trust (GB), NIHR Imperial Biomedical Research Centre (GB)
Zero hunger
Openalex Percentile: Top 63%
Vasculitis and related conditions
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