Relationship of Pneumocystis antibody responses to paediatric asthma severity

Background Although asthma is the most commonly diagnosed respiratory disease, its pathogenesis is complex, involving both genetic and environmental factors. A role for the respiratory microbiome in modifying asthma severity has been recently recognised. Airway colonisation by Pneumocystis jirovecii...

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Main Authors: Alfin Vicencio, Emily Rayens, Brenda Noble, David L Goldman, Supinda Bunyavanich, Karen A Norris
Format: Article
Language:English
Published: BMJ Publishing Group 2021-01-01
Series:BMJ Open Respiratory Research
Online Access:https://bmjopenrespres.bmj.com/content/8/1/e000842.full
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author Alfin Vicencio
Emily Rayens
Brenda Noble
David L Goldman
Supinda Bunyavanich
Karen A Norris
author_facet Alfin Vicencio
Emily Rayens
Brenda Noble
David L Goldman
Supinda Bunyavanich
Karen A Norris
author_sort Alfin Vicencio
collection DOAJ
description Background Although asthma is the most commonly diagnosed respiratory disease, its pathogenesis is complex, involving both genetic and environmental factors. A role for the respiratory microbiome in modifying asthma severity has been recently recognised. Airway colonisation by Pneumocystis jirovecii has previously been associated with multiple chronic lung diseases, including chronic obstructive pulmonary disease (COPD) and severe asthma (SA). Decreased incidence of Pneumocystis pneumonia in HIV-infected individuals and reduced severity of COPD is associated with naturally occurring antibody responses to the Pneumocystis antigen, Kexin (KEX1).Methods 104 paediatric patients were screened for KEX1 IgG reciprocal end point titre (RET), including 51 with SA, 20 with mild/moderate asthma, 20 non-asthma and 13 with cystic fibrosis (CF) in a cross-sectional study.Results Patients with SA had significantly reduced Pneumocystis KEX1 titres compared with patients with mild/moderate asthma (p=0.018) and CF (p=0.003). A binary KEX1 RET indicator was determined at a threshold of KEX1 RET=1000. Patients with SA had 4.40 (95% CI 1.28 to 13.25, p=0.014) and 17.92 (95% CI 4.15 to 66.62, p<0.001) times the odds of falling below that threshold compared with mild/moderate asthma and patients with CF, respectively. Moreover, KEX1 IgG RET did not correlate with tetanus toxoid IgG (r=0.21, p=0.82) or total IgE (r=0.03, p=0.76), indicating findings are specific to antibody responses to KEX1.Conclusions Paediatric patients with SA may be at higher risk for chronic Pneumocystis infections and asthma symptom exacerbation due to reduced levels of protective antibodies. Plasma KEX1 IgG titre may be a useful parameter in determining the clinical course of treatment for paediatric patients with asthma.
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spelling doaj-art-a38c81fb693e4455810532316cdf5fb02024-11-24T11:00:08ZengBMJ Publishing GroupBMJ Open Respiratory Research2052-44392021-01-018110.1136/bmjresp-2020-000842Relationship of Pneumocystis antibody responses to paediatric asthma severityAlfin Vicencio0Emily Rayens1Brenda Noble2David L Goldman3Supinda Bunyavanich4Karen A Norris5Pediatrics, Division of Pediatric Pulmonology, Icahn School of Medicine at Mount Sinai, New York, New York, USACenter for Vaccines and Immunology, University of Georgia College of Veterinary Medicine, Athens, Georgia, USACenter for Vaccines and Immunology, University of Georgia College of Veterinary Medicine, Athens, Georgia, USADepartments of Pediatrics, Microbiology & Immunology, Children`s Hospital at Montefiore, Bronx, New York, USAPediatrics, Division of Pediatric Pulmonology, Icahn School of Medicine at Mount Sinai, New York, New York, USACenter for Vaccines and Immunology, University of Georgia College of Veterinary Medicine, Athens, Georgia, USABackground Although asthma is the most commonly diagnosed respiratory disease, its pathogenesis is complex, involving both genetic and environmental factors. A role for the respiratory microbiome in modifying asthma severity has been recently recognised. Airway colonisation by Pneumocystis jirovecii has previously been associated with multiple chronic lung diseases, including chronic obstructive pulmonary disease (COPD) and severe asthma (SA). Decreased incidence of Pneumocystis pneumonia in HIV-infected individuals and reduced severity of COPD is associated with naturally occurring antibody responses to the Pneumocystis antigen, Kexin (KEX1).Methods 104 paediatric patients were screened for KEX1 IgG reciprocal end point titre (RET), including 51 with SA, 20 with mild/moderate asthma, 20 non-asthma and 13 with cystic fibrosis (CF) in a cross-sectional study.Results Patients with SA had significantly reduced Pneumocystis KEX1 titres compared with patients with mild/moderate asthma (p=0.018) and CF (p=0.003). A binary KEX1 RET indicator was determined at a threshold of KEX1 RET=1000. Patients with SA had 4.40 (95% CI 1.28 to 13.25, p=0.014) and 17.92 (95% CI 4.15 to 66.62, p<0.001) times the odds of falling below that threshold compared with mild/moderate asthma and patients with CF, respectively. Moreover, KEX1 IgG RET did not correlate with tetanus toxoid IgG (r=0.21, p=0.82) or total IgE (r=0.03, p=0.76), indicating findings are specific to antibody responses to KEX1.Conclusions Paediatric patients with SA may be at higher risk for chronic Pneumocystis infections and asthma symptom exacerbation due to reduced levels of protective antibodies. Plasma KEX1 IgG titre may be a useful parameter in determining the clinical course of treatment for paediatric patients with asthma.https://bmjopenrespres.bmj.com/content/8/1/e000842.full
spellingShingle Alfin Vicencio
Emily Rayens
Brenda Noble
David L Goldman
Supinda Bunyavanich
Karen A Norris
Relationship of Pneumocystis antibody responses to paediatric asthma severity
BMJ Open Respiratory Research
title Relationship of Pneumocystis antibody responses to paediatric asthma severity
title_full Relationship of Pneumocystis antibody responses to paediatric asthma severity
title_fullStr Relationship of Pneumocystis antibody responses to paediatric asthma severity
title_full_unstemmed Relationship of Pneumocystis antibody responses to paediatric asthma severity
title_short Relationship of Pneumocystis antibody responses to paediatric asthma severity
title_sort relationship of pneumocystis antibody responses to paediatric asthma severity
url https://bmjopenrespres.bmj.com/content/8/1/e000842.full
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