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Pathogenetic and serological aspects of pulmonary aspergillosis
1Institute of Medical Microbiology, University of Aarhus, Denmark.
Abstract:
Af is an important pathogen of the bronchopulmonary system, and the clinical spectrum encompasses aspergilloma, CNPA, IPA, ABPA, bronchial asthma, and allergic alveolitis. Bronchial carriage may, however, not always be associated with pathological effects. The polymorphism of the aspergillus-related disorders seems mostly to depend upon the different responses of the hosts. This review considers the antigenic composition of Af and specific antibody responses in man in relation to the pathogenesis and diagnosis of the various forms of pulmonary aspergillosis. More than 200 macromolecular components have been listed for Af and more than 30 antigens found to react with human sera. Serum antibodies to Af are common in healthy subjects. Schønheyder and his associates (A-L) have shown that IgG, IgA and IgM antibodies in healthy subjects are directed towards antigens to which also patients with aspergillosis strongly react. With immunofluorescent staining these antigens were found to be associated with hyphal walls, and a MW 470,000 fraction from ruptured mycelium was most reactive in ELISA. The respiratory tract appears to be the major route for exposure since the humoral responses include IgA class antibodies, and sIgA antibodies are found in bronchial secretions. Moreover, IgG antibody levels to the MW 470,000 fraction correlate with occupational exposure and smoking habits. In patients with cystic fibrosis high IgG antibody levels to MW 470,000 and MW 25,000-50,000 antigen fractions were associated with the carriage of Af in the sputum. An individual patient's level of IgA antibodies to the MW 470,000 fraction was inversely related to the Af carrier rate, and this was also true for IgE dependent reactivity to Af antigens. These observations indicate that IgG antibodies to some antigens mirror the extent of antigenic exposure, whereas some IgA and IgE antibodies may play a protective role against bronchial colonization with Af. IgG antibody determinations by ELISA were found to provide a higher diagnostic efficacy in pulmonary aspergillosis than IgA antibody assays. With IgG antibodies there were statistically significant differences between patients and the controls and there was little overlap of ELISA values between the groups. The fractions of MW 250,000 with catalase activity and MW 25,000-50,000 with protease activity, were most suitable for serological diagnosis. A gel immunoelectrophoretic assay proved Af catalase to be a major diagnostic antigen in patients with aspergilloma or with an apical aspergillus lung infiltrate.(ABSTRACT TRUNCATED AT 400 WORDS)
Insights
This study explores Aspergillus fumigatus (Af) antigens and antibody responses in pulmonary aspergillosis. It suggests certain IgA and IgE antibodies may protect against Af colonization, while IgG levels indicate exposure, aiding diagnosis.
Area of Science:
- Medical Mycology
- Immunology
- Pulmonary Medicine
Background:
- Aspergillus fumigatus (Af) causes diverse bronchopulmonary diseases, including aspergilloma and invasive pulmonary aspergillosis.
- Host immune responses significantly influence the clinical presentation of Af-related disorders.
- Understanding Af antigens and host antibody profiles is crucial for pathogenesis and diagnosis.
Purpose of the Study:
- To review the antigenic composition of Af and human antibody responses.
- To correlate antibody profiles with the pathogenesis and diagnosis of pulmonary aspergillosis.
- To identify specific Af antigens and antibody classes relevant for serological diagnosis.
Main Methods:
- Review of literature on Af antigenic components and human serum/secretory antibody responses.
- Analysis of antibody reactivity (IgG, IgA, IgM, IgE) to Af antigens using ELISA and immunofluorescence.
- Correlation of antibody levels with clinical conditions, host factors (smoking, cystic fibrosis), and Af carriage.
Main Results:
- Over 200 macromolecular components and 30 reactive antigens identified in Af; common antibodies in healthy subjects.
- IgG antibodies to a 470,000 MW fraction correlate with exposure; IgA and IgE may protect against bronchial colonization.
- IgG antibody assays show higher diagnostic efficacy for pulmonary aspergillosis than IgA; specific fractions (MW 250,000 catalase, MW 25,000-50,000 protease) are promising for diagnosis.
Conclusions:
- Host immune responses, particularly IgA and IgE, play a role in controlling Af bronchial colonization.
- IgG antibody levels reflect antigenic exposure and are valuable for diagnosing pulmonary aspergillosis.
- Specific Af antigens, like catalase and protease fractions, are effective serological markers for diagnosis.