Circulating Immune Complexes in Lung Disease

Abstract

Hypersensitivity lung diseases, of which allergic aspergillosis is a prototype, are an immunologic curiosity. Organisms usually of little virulence grow in plugs of airway mucus. These organisms are protected by the mucous matrix which seems to serve as an adjuvant. The ensuing brisk immunologic response is ineffective in clearing the bronchial tree. The presence in the airway of high titers of antibody and complement plus soluble antigen from the microbes causes intense complement-mediated damage of surrounding airway tissues. High dosage corticosteroid therapy inhibits inflammation and shuts down the disease process, possibly by diminishing neutrophil response to complement fragment chemo-attractants. The acute phase of the disease is marked by the presence in the sera of circulating immune complexes (CIC).1Geha RS Circulating immune complexes and activation of the complement sequence in acute allergic bronchopulmonary aspergillosis.J Allergy Clin Immunol. 1977; 60: 357-359Abstract Full Text PDF PubMed Scopus (26) Google Scholar These presumably represent a complex of microbial antigens, complement, and excess antibody which occupies all of the antigenic sites and forms a soluble unit rather than a precipitating lattice. These CIC do not appear to cause disease elsewhere in the body and are regarded as immunologic flotsam from a reaction originating in the airways. There is increasing evidence that the airway disease in cystic fibrosis (CF) may in part be due to a hypersensitivity pneumonitis. Sera of CF patients contain factors which influence ciliary and mucus activity of cells2Wilson GB Fudenberg HH Ciliary dyskinesia factors in cystic fibrosis and asthma.Nature. 1977; 266: 463-464Crossref PubMed Scopus (15) Google Scholar and inhibit the phagocytosis of Pseudomonas aeruginosa by alveolar macrophages.3Thomassen MJ Boxerbaum B Demko CA et al.Inhibitory effect of cystic fibrosis serum on Pseudomonas phagocytosis by rabbit and human alveolar macrophages.Pediatr Res. 1979; 13: 1085-1088Crossref PubMed Scopus (62) Google Scholar Certainly the colonization of CF mucus by a variety of organisms, and the magnitude of the IgE and IgG response to these organisms, set the stage for immune complex formation.4Moss RB Hsu Y-P Lewiston NJ 125I-Clq binding and specific antibodies as indicators of pulmonary disease activity in cystic fibrosis.J Pediatr. 1981; (in press)Google Scholar Nelson et al5Nelson LA Callermane ML Schwartz RH Aspergillosis and atopy in cystic fibrosis.Am Rev Respir Dis. 1979; 120: 863-873PubMed Google Scholar reported a high incidence of allergic aspergillosis in CF using rigorous adherence to diagnostic criteria. Poor prognosis in CF is associated with high antibody titers to specific pathogens,6Hoiby N Flensborg EW Beck B et al.Diagnostic and prognostic significance of Pseudomonas aeruginosa precipitins determined by means of crossed immunoelectrophoresis.Scand J Resp Dis. 1977; 58: 65-79PubMed Google Scholar and good prognosis in younger children is associated with hypogammaglobulinemia.7Matthews WJ Williams M Oliphint B et al.Hypogammaglobulinemia in patients with cystic fibrosis.N Engl J Med. 1980; 302: 245-249Crossref PubMed Scopus (92) Google Scholar The presence of CIC in high concentrations in the sera of CF patients may be a clue to the pathophysiology of the lung disease. In this issue of Chest (see page 405), Church and colleagues have confirmed the presence of CIC in CF sera, particularly during acute illness. They also have begun the important task of evaluating the various means of measuring CIC. What do the CIC mean? Do they represent merely the normal opsoninization of large numbers of airway pathogens? Are they a sensitive, quantitative indicator of airway pathogen burden? Do they represent a significant hypersensitivity airway reaction to Pseudomonas sp or other organisms? The therapeutic implications of such questions are important. The hypersensitivity pneumonias do not respond well to specific antimicrobial therapy alone; in fact, treatment of allergic aspergillosis with parenteral amphotericin B was a failure. The 20,000-40,000 CF patients in the United States seem doomed to progressive pulmonary disease despite antimicrobial therapy. Should they be treated with anti-inflammatory agents as soon as the sputum is colonized and before widespread lung damage takes place? Are there alternatives to high-dose corticosteroids in the treatment of hypersensitivity pneumonias? Further developments in this field may alter the therapeutic approach and prognosis in CF. Circulating Immune Complexes in Patients with Cystic FibrosisCHESTVol. 80Issue 4PreviewCirculating immune complexes (CICs) were measured in the sera of clinically stable and acutely infected patients with cystic fibrosis (CF). Twenty CF patients were studied when clinically stable; an additional 18 patients were studied during an acute exacerbation of pulmonary infection as evidenced by fever, tachypnea, increased white blood cell count, increased sputum production, and acute chest x-ray film changes. Three methods for determining CICs were employed: polyethylene glycol precipitation, a C1q solid phase assay, and the Raji cell radioimmune assay. Full-Text PDF