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Frontiers in immunology2024; 15; 1406794; doi: 10.3389/fimmu.2024.1406794

Aspergillus fumigatus binding IgA and IgG1 are increased in bronchoalveolar lavage fluid of horses with neutrophilic asthma.

Abstract: Equine asthma (EA) is a common lower airway disease in horses, but whether its pathogenesis is allergic is ambiguous. Extrinsic stimuli like hay dust induce acute exacerbation of clinical signs and sustained local neutrophilic inflammation in susceptible horses. is an EA stimulus, but it is unclear if it merely acts as an IgE-provoking allergen. We aimed to comprehensively analyze immunoglobulin (Ig) isotypes in EA, elucidating their binding to different antigens, and their quantities systemically in serum and locally in bronchoalveolar lavage fluid (BALF). Unassigned: Serum and BALF from healthy horses (HE, = 18) and horses with mild-moderate asthma (MEA, = 20) or severe asthma (SEA, = 24) were compared. Ig isotype (IgG1, IgG3/5, IgG4/7, IgG6, IgA, and IgE) binding to nine antigens ( lysate, and recombinant Asp f 1, Asp f 7, Asp f 8, dipeptidyl-peptidase 5, class II aldolase/adducin domain protein, glucoamylase, beta-hexosaminidase, and peptide hydrolase) was compared by enzyme-linked immunosorbent assays. Total Ig isotype contents were determined by bead-based assays. Unassigned: MEA and SEA differed from HE but hardly from each other. Compared to HE, asthmatic horses showed increased anti- binding of IgG (BALF and serum) and IgA (BALF). Serum and BALF IgE binding and total IgE contents were similar between HE and EA. Single antigens, as well as lysate, yielded similar Ig binding patterns. Serum and BALF IgG1 binding to all antigens was increased in SEA and to several antigens in MEA. Serum IgG4/7 binding to two antigens was increased in SEA. BALF IgA binding to all antigens was increased in SEA and MEA. Total BALF IgG1 and IgG4/7 contents were increased in SEA, and serum IgG4/7 content was increased in MEA compared to HE. Yet, total isotype contents differentiated EA and HE less clearly than antigen-binding Ig. Unassigned: immunogenicity was confirmed without identification of single dominant antigens here. provoked elevated BALF IgG1 and IgA binding, and these isotypes appear relevant for neutrophilic EA, which does not support allergy. BALF Ig isotype differentiation beyond IgE is crucial for a comprehensive analysis of immune responses to fungi in EA pathogenesis.
Copyright © 2024 Jentsch, Keilhaue, Wagner, Rhyner, Lübke, Karagulyan, Arnold, Lohmann and Schnabel.
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Publication Date: 2024-06-17 PubMed ID: 38953030PubMed Central: PMC11215007DOI: 10.3389/fimmu.2024.1406794Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research aims to analyze immunoglobulins in equine asthma and their binding to different antigens found in Aspergillus fumigatus, a fungal pathogen. Findings reveal that IgG1 and IgA are increased in bronchoalveolar lavage fluid in horses with neutrophilic asthma, suggesting an important role of these antibodies in equine asthma not related to allergy.

Research Objectives

  • The study was conducted with an objective to understand the role of immunoglobulins, specifically IgA and IgG1, in the pathogenesis of equine asthma.
  • The researchers wanted to clarify if these immunoglobulins were merely acting as allergens or playing a more critical role in the provocation of equine asthma.
  • The team also sought to decide whether the disease’s root cause was allergic in nature or not.

Methodology

  • To achieve this, serum and bronchoalveolar lavage fluid (BALF) samples were collected from healthy horses, and horses with mild to moderate (MEA) and severe asthma (SEA).
  • To better understand how immunoglobulins interact with different Aspergillus fumigatus antigens, the binding of different Ig isotypes (IgG1, IgG3/5, IgG4/7, IgG6, IgA, and IgE) to nine various antigens were compared using enzyme-linked immunosorbent assays.

Findings

  • The results demonstrated that both MEA and SEA horses, when compared to healthy horses, showed increased anti-Aspergillus fumigatus binding for IgG (both BALF and serum) and IgA (BALF).
  • Interestingly, the study found no fundamental difference in terms of Serum and BALF IgE binding and IgE contents between healthy horses and those suffering from equine asthma. This indicated that allergy may not be the primary cause of the disease.
  • The study also found increased IgG1 and IgA binding in SEA and MEA, suggesting their essential role in the pathogenesis of neutrophilic equine asthma. The IgG1 and IgA levels in a horse’s BALF were found to be an important factor differentiating asthma-affected horses from healthy ones.

Conclusion

  • The study confirms the immunogenicity of Aspergillus fumigatus and indicates that there is no single dominant antigen involved. These findings contradict the traditional understanding of the disease and may point to an immunological rather than an allergic root cause.
  • Paying attention to Ig isotypes other than IgE could open new pathways for understanding the immune responses to Aspergillus fumigatus in the pathogenesis of equine asthma.

Cite This Article

APA
Jentsch MC, Keilhaue A, Wagner B, Rhyner C, Lübke S, Karagulyan M, Arnold C, Lohmann KL, Schnabel CL. (2024). Aspergillus fumigatus binding IgA and IgG1 are increased in bronchoalveolar lavage fluid of horses with neutrophilic asthma. Front Immunol, 15, 1406794. https://doi.org/10.3389/fimmu.2024.1406794

Publication

Frontiers in immunology
ISSN: 1664-3224
NlmUniqueID: 101560960
Country: Switzerland
Language: English
Volume: 15
Pages: 1406794
PII: 1406794

Researcher Affiliations

Jentsch, Maria-Christin
  • Institute of Immunology, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.
Keilhaue, Aline
  • Institute of Immunology, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.
Wagner, Bettina
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
Rhyner, Claudio
  • Christine Kühne Center for Allergy, Research, and Education (CK-CARE), Davos, Switzerland.
  • Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland.
Lübke, Sabrina
  • Institute of Immunology, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.
Karagulyan, Mariam
  • Institute of Immunology, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.
Arnold, Corinna
  • Department for Horses, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.
Lohmann, Katharina L
  • Department for Horses, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.
Schnabel, Christiane L
  • Institute of Immunology, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.

MeSH Terms

  • Animals
  • Horses / immunology
  • Aspergillus fumigatus / immunology
  • Bronchoalveolar Lavage Fluid / immunology
  • Asthma / immunology
  • Asthma / microbiology
  • Immunoglobulin G / immunology
  • Immunoglobulin G / blood
  • Immunoglobulin A / immunology
  • Immunoglobulin A / blood
  • Immunoglobulin A / metabolism
  • Horse Diseases / immunology
  • Horse Diseases / microbiology
  • Antigens, Fungal / immunology
  • Male
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Female
  • Immunoglobulin E / immunology
  • Immunoglobulin E / blood
  • Antibodies, Fungal / immunology
  • Antibodies, Fungal / blood

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Citations

This article has been cited 2 times.
  1. Bartenschlager F, Kuropka B, Schmitz P, Dumke F, Landmann K, Gruber AD, Weise C, Schnabel CL, Gehlen H, Mundhenk L. Proteomic profiling of equine airway mucus reveals compositional changes in asthmatic phenotypes. Sci Rep 2026 Feb 10;16(1):5880.
    doi: 10.1038/s41598-026-38766-3pubmed: 41667845google scholar: lookup
  2. Wjst VF, Lübke S, Wagner B, Rhyner C, Jentsch MC, Arnold C, Lohmann KL, Schnabel CL. Aspergillus fumigatus antigen-reactive Th17 cells are enriched in bronchoalveolar lavage fluid in severe equine asthma. Front Immunol 2024;15:1367971.
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