Serotype-Specific Serum IgG Antibodies to Lipopolysaccharides of Pseudomonas aeruginosa in Cystic Fibrosis: Correlation to Disease, Subclass Distribution, and Experimental Protective Capacity

Abstract

ABSTRACT. Various studies have demonstrated pronounced systemic IgG response to Pseudomonas aevuginosa (PA) infection in cystic fibrosis (CF). However, antibody response to serotype-specific lipopolysaccharides (LPS) has never been studied. ELISA for detection of IgG antibodies to L P S of nine PA-serotypes and to toxin A were performed with serum of 78 C F patients. Anti-LPS profiles of antibodies were confirmed by SDS-PAGE and immunoblotting techniques. The most frequent PA-serotypes found were immunotypes (IT) IT-1 and IT-2, and Habs-3 and Habs-4. Ten patients without PA colonization showed no detectable antibody titers. In patients with chronic PA colonization (n = 46), these antibody titers were significantly (p < 0.005) higher than in patients with intermittent PA colonization (n = 22). Mean serum antibody titers to L P S of PA IT-1, IT-2, Habs-3, and Habs-4 correlated with duration of PA colonization and with disease severity. Subclass analysis of anti-LPS antibodies revealed elevated levels for all four IgG subclasses and for IgA,. The IgG antibodies to L P S of PA proved to be protective in a murine burn wound sepsis model. We conclude that anti-LPS antibodies to specific P A serotypes in serum may be a sensitive measure of severity and prognosis of CF. Patients with C F show adequate functional immune response to L P S of PA, and it is possible that vaccination against PA before colonization could induce protective immunity. (Pediatv Res 27: 508-513, 1990) Abbreviations CF, cystic fibrosis IT, immunotype LPS, lipopolysaccharide PA, Pseudomonas aeruginosa Tox A. toxin A PA is a persistent sputum pathogen in most patients with advanced CF (1). Pseudomonas pulmonary infections are the major determinant of quality and duration of life in these patients. Mechanisms of virulence and pathogenesis of PA are

Affinity Constants of Naturally Acquired and Vaccine-Induced Anti-Pseudomonas aeruginosa Antibodies in Healthy Adults and Cystic Fibrosis Patients

“…Healthy adults were staff members at the Tiefenau Hospital, Berne. Radiologic and pulmonary scores (Crispin-Norman and Bernese) and colonization with P. aeruginosa were determined at the time of immunization and at yearly intervals thereafter as previously described [5]. A patient classified as colonized had P. aeruginosa isolated from sputum or saliva samples on multiple occasions for at least 5 years before entry into this study.…”

“…Serum antibodies specific for LPS were quantitated by ELISA as described elsewhere [5,17,18]. For coating, purified LPS (5 mg/rnl) dissolved in 36 mM triethylamine was used.…”

“…The most widely held belief is that most naturally acquired antibodies possess a greatly reduced opsonic capacity [8,9]. However, serum from colonized CF patients can protect mice against experimental P. aeruginosa when passively transferred [5]. Furthermore, recent studies have found that CF serum can support the uptake of P. aeru-ginosa by polymorphonuclear leukocytes from healthy adults [8].…”

“…Several laboratories have found a positive correlation between severe disease and elevated anti-P, aeruginosa antibody levels [5,6]. In addition, circulating immune complexes formed during pulmonary exacerbations may contribute substantially to organ damage [6,7].…”

Immunization of Noncolonized Cystic Fibrosis Patients against Pseudomonas aeruginosa

“…However, such antibodies do not prevent or even ameliorate subsequent infections. In fact, several laboratories [5,6] have noted a positive correlation between elevated anti-P aeruginosa antibody titers and a more severe disease course. This may be the result ofimmune complexes being deposited in the lungs and other organs.…”