Secretory IgA response against Pseudomonas aeruginosa in the upper airways and the link with chronic lung infection in cystic fibrosis

Abstract

We assessed the diagnostic ability of an enzyme-linked immunosorbent assay test for measurement of specific secretory IgA (sIgA) in saliva to identify cystic fibrosis (CF) patients with Pseudomonas aeruginosa chronic lung infection and intermittent lung colonization. A total of 102 Brazilian CF patients and 53 healthy controls were included. Specific serum IgG response was used as a surrogate to distinguish CF patients according to their P. aeruginosa colonization/infection status. The rate of sIgA positivity was 87.1% in CF chronically infected patients (median value = 181.5 U/mL), 48.7% in intermittently colonized patients (median value = 45.8 U/mL) and 21.8% in free of infection patients (median value = 22.1 U/mL). sIgA levels in saliva were significantly associated with serum P. aeruginosa IgG and microbiological culture results. The sensitivity, specificity, PPV and NPV for differentiation between presence and absence of chronic lung infection were 87%, 63%, 51% and 92%, respectively. Measurement of sIgA in saliva may be used for screening patients in risk of developing P. aeruginosa chronic lung infection in CF and possibly also for paranasal sinusitis, and, most importantly, to efficiently rule out chronic P. aeruginosa lung infection.

Antibody response against Pseudomonas aeruginosa and its relationship with immune mediators in the upper and lower airways of cystic fibrosis patients

“…There were increased NLF IgA and IS IgA levels in patients without chronic UAW and LAW infection, respectively, which led to the absence of statistical difference in relation to their chronically infected counterparts, in this aspect. This is contrasting with previous studies of our group that showed agreement between IgA levels and P. aeruginosa UAW and LAW colonization/infection 13,14 . We can speculate that these results mean the presence of UAW infection not detected by microbiological NL culture but indicated by increased local IgA response, as most patients without chronic UAW infection had a history of LAW infection with P. aeruginosa , and the UAW can be the first niche of infection 5,19 .…”

“…This is contrasting with previous studies of our group that showed agreement between IgA levels and P. aeruginosa UAW and LAW colonization/infection. 13,14 We can speculate Table 3 that these results mean the presence of UAW infection not detected by microbiological NL culture but indicated by increased local IgA response, as most patients without chronic UAW infection had a history of LAW infection with P. aeruginosa, and the UAW can be the first niche of infection. 5,19 Moreover, not all sinuses are likely to be sampled by nasal lavage 28 ; thus, P. aeruginosa detection may be underestimated.…”

Can secretory immunoglobulin A in saliva predict a change in lung infection status in patients with cystic fibrosis? A prospective pilot study

“…However, the model did not reach statistical significance probably due to limited power, and it must, therefore, be confirmed in larger prospective studies. Nevertheless, the results from this study are supported by a recent study by Mauch et al who concluded that s‐IgA measurement can be used as a screening model for patients at risk of chronic infection.…”

Host responses to mucosal biofilms in the lung and gut

“…64,67,68 CF patients chronically infected with P. aeruginosa have higher levels of interleukin (IL)-3, IL-4, and secreted immunoglobulin A (sIgA; Th2 markers) and lower interferon gamma (IFNγ; Th1 marker), compared to non-chronically infected patients. 65,[69][70][71] Th2 responses have also been observed in vitro and in murine mouse models of CF in response to challenge with P. aeruginosa and/or its gene products. 72,73 These studies suggest that approaches to enhance a Th1 intrapulmonary immune response could be beneficial to CF patients and help overcome P. aeruginosa biofilm-associated infections.…”

“…29,63 P. aeruginosa biofilm-mediated infections in vivo are associated with leukocyte mobilization and bacterial-specific antibody production to clear the pathogen. 59,[64][65][66] Multiple studies have established that P. aeruginosa triggers a predominant Th2 immune response in the human CF lung and in murine CF models. 64,67,68 CF patients chronically infected with P. aeruginosa have higher levels of interleukin (IL)-3, IL-4, and secreted immunoglobulin A (sIgA; Th2 markers) and lower interferon gamma (IFNγ; Th1 marker), compared to non-chronically infected patients.…”