Am. J. Respir. Crit. Care Med., Vol 153, No. 6, 06 1996, 1952-1957.
Specific IgG4 responses during chronic and transient antigen exposure in aspergillosis
JF Tomee, AE Dubois, GH Koeter, F Beaumont, TS van der Werf and HF Kauffman
Department of Allergology, University Hospital Groningen, The Netherlands.
The factors that lead to increased production of specific IgG subclasses
are still largely unknown. Recent studies suggest that increased IgG4
responses may be related to prolonged antigen exposure. We present data
showing that increased IgG4 responses are found under conditions of chronic
exposure to Aspergillus fumigatus (Af) antigen. IgG(total), IgG subclass,
and IgE responses were studied using ELISA, CAP-FEIA, and immunoblotting
techniques in patients with pulmonary aspergilloma (PA), which is a model
for chronic antigen exposure, and allergic bronchopulmonary aspergillosis
(ABPA), characterized by transient antigen exposure. Af-IgG1 was increased
in patients with PA compared with those with ABPA. Patients with PA and IgE
responses to Af and/or other inhalant allergens showed significantly higher
Af-IgG4 responses than did patients with PA and negative IgE responses or
patients with ABPA. Surveillance studies over time in individual patients
showed concordance in Af-IgG1 and Af-IgG4 responses. Both Af- IgG1 and
Af-IgG4 levels followed the course of disease progression and treatment.
Immunoblotting revealed correlations between Af-IgG1 and Af- IgG4 binding
to most, but not all, antigenic Af components. This study documents for the
first time increased IgG4 levels under conditions of chronic exposure to
fungal antigen in PA. Furthermore, a significantly higher IgG4 response was
found in those patients with PA who produced IgE. The transient exposure to
Af antigen during exacerbation of ABPA gives rise to transient elevations
in IgG4 levels.
