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Noninvasive Sampling of Mucosal Lining Fluid for the Quantification of In Vivo Upper Airway Immune-mediator Levels
Published on: August 7, 2017
Relationship of Pneumocystis antibody responses to paediatric asthma severity
Emily Rayens1, Brenda Noble1, Alfin Vicencio2
1Center for Vaccines and Immunology, University of Georgia College of Veterinary Medicine, Athens, Georgia, USA.
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.
Insights
Children with severe asthma have lower protective antibodies against Pneumocystis jirovecii, increasing infection risk. Measuring Kexin (KEX1) IgG antibody levels may help manage pediatric asthma treatment.
Area of Science:
- Immunology
- Microbiology
- Pediatric Respiratory Medicine
Background:
- Asthma pathogenesis involves complex genetic and environmental factors.
- The respiratory microbiome influences asthma severity.
- Pneumocystis jirovecii (PJP) airway colonization is linked to severe asthma (SA) and COPD.
- Antibody response to PJP antigen Kexin (KEX1) is associated with reduced PJP pneumonia and COPD severity.
Purpose of the Study:
- To investigate the association between Kexin (KEX1) IgG antibody titers and severe asthma in pediatric patients.
- To compare KEX1 IgG titers in children with severe asthma, mild/moderate asthma, cystic fibrosis, and non-asthma controls.
Main Methods:
- A cross-sectional study involving 104 pediatric patients.
- Screening for KEX1 IgG reciprocal end point titre (RET) in severe asthma, mild/moderate asthma, cystic fibrosis, and non-asthma groups.
- Statistical analysis to compare KEX1 RET between groups and assess odds of low titers.
Main Results:
- Severe asthma patients showed significantly reduced KEX1 IgG titers compared to mild/moderate asthma and cystic fibrosis patients.
- Severe asthma patients had significantly higher odds of having KEX1 RET below 1000.
- KEX1 IgG titers did not correlate with tetanus toxoid IgG or total IgE, indicating specificity.
Conclusions:
- Pediatric patients with severe asthma may have increased risk of chronic PJP infections and exacerbations due to lower protective KEX1 antibodies.
- Plasma KEX1 IgG titre could be a valuable marker for guiding treatment in pediatric asthma management.
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