IMMUNE COMPLEX MEDIATED TISSUE DAMAGE IN THE LUNGS OF CYSTIC FIBROSIS PATIENTS WITH CHRONIC PSEUDOMONAS AERUGINOSA INFECTION

Abstract

Høiby, N. and Schiøtz, P.O. (Statens Seruminstitut Department of Clinical Microbiology, Rigshospitalet and the Paediatric Department TG, Rigshospitalet, Copenhagen, Denmark). Immune complex mediated tissue damage in the lungs of cystic fibrosis patients with chronic Pseudomonas aeruginosa infection. Acta Paediatr Scand; suppl 301: 63‐73. — Evidence has accumulated which supports the following mechanism of tissue damage in the lungs of cystic fibrosis (CF) patients during chronic P. aeruginosa lung infection:In CF chronic P. aeruginosa infection with mucoid strains is characterized by persistent presence of P. aeruginosa antigens in the lungs and simultaneous presence of many precipitating antibodies against these antigens in serum and sputum.Formation of immune complexes in the lungs between these antigens and antibodies are indicated by the detection of immune complex activity in serum and especially in sputum. Immune complex‐mediated activation of complement components in the lungs of such CF patients has been demonstrated. The activation of complement leads to formation of C3a and C5a split products, which lead to liberation of histamine from basophil leukocytes, i.e. inflammation which is also reflected in elevated acute phase proteins in serum. Evidence of this process has also been found as a type I skin test when P. aeruginosa antigens are injected intracutaneously in these patients. Liberation of serotonin from thrombocytes mediated by P. aeruginosa antigens in the presence of antibodies from these CF patients, causing inflammation, has been shown. Attraction of neutrophils to the lungs mediated by immune complex activated complement split products, ingestion of the immune complexes by the neutrophils, and liberation of proteolytic enzymes from the neutrophils, i.e. tissue damage, has been demonstrated, and goes on because immune elimination of the bacteria is not accomplished. The therapeutic consequences are discussed.