The Role of IgG Subclass Antibodies in Chronic Infection: The Case of Cystic Fibrosis

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Abstract:

Our studies have revealed that patients with Cystic Fibrosis CF who are infected with P. aeruginosa have grossly elevated serum levels of IgG antibodies to the opsonic immunodeterminant, type-specific LPS. Second, this elevation is distributed among all four IgG subclasses, with a significant shift towards IgG3. Third, sera from colonized CF patients shows diminished opsonic capacity, although complement dependent human neutrophil phagocytosis is not notably impaired. Fourth, functional polyclonal or monoclonal antibody opsonins exhibit prozone inhibition of phagocytosis at high concentrations. Fifth, sera from uninfected CF patients have lower levels and proportions of IgG2 antibodies to P. aeruginosa LPS, and higher levels and proportions of IgG4 antibodies, than normal controls. Finally, levels of IgG4 antibodies, but not IgG1, 2, or 3, correlate inversely with opsonic capacity.

We therefore make several speculations. High levels of IgG4 antibodies to opsonic immunodeterminants may inhibit normal pulmonary clearance of P. aeruginosa by alveolar macrophages in vivo. Second, high levels of opsonic antibodies may also contribute to the problem in vivo by the phenomenon of prozone inhibition. Third, reduced levels of IgG2 antibodies in uninfected CF patients raises the intriguing possibility of an wider polysaccharide antigen-related isotype-restricted immunodeficiency, with an attempted compensatory shift to IgG4 doomed to failure.

Document Type: Research Article

DOI: http://dx.doi.org/10.2500/108854188778984491

Publication date: January 1, 1988

More about this publication?
  • Allergy and Asthma Proceedings is a peer reviewed publication dedicated to distributing timely scientific research regarding advancements in the knowledge and practice of allergy, asthma and immunology. Its primary readership consists of allergists and pulmonologists.

    The goal of the Proceedings is to publish articles with a predominantly clinical focus which directly impact quality of care for patients with allergic disease and asthma.

    Featured topics include asthma, rhinitis, sinusitis, food allergies, allergic skin diseases, diagnostic techniques, allergens, and treatment modalities. Published material includes peer-reviewed original research, clinical trials and review articles.

    Articles marked "F" offer free full text for personal noncommercial use only.

    The journal is indexed in Thomson Reuters Web of Science and Science Citation Index Expanded, plus the National Library of Medicine's PubMed service.
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