PTX3 genetic variations affect the risk of Pseudomonas aeruginosa airway colonization in cystic fibrosis patients

Abstract

Cystic fibrosis (CF) is a common life-threatening autosomal recessive disorder in the Caucasian population, and the gene responsible is the CF transmembrane conductance regulator (CFTR). Patients with CF have repeated bacterial infection of the airways caused by Pseudomonas aeruginosa (PA), which is one of the predominant pathogen, and endobronchial chronic infection represents a major cause of morbidity and mortality. Pentraxin 3 (PTX3) is a gene that encodes the antimicrobial protein, PTX3, which is believed to have an important role in innate immunity of lung. To address the role of PTX3 in the risk of PA lung colonization, we investigated five single nucleotide polymorphisms of PTX3 gene in 172 Caucasian CF patients who were homozygous for the F508del mutation. We observed that PTX3 haplotype frequencies were significantly different between patients with PA colonization, as compared with noncolonized patients. Moreover, a protective effect was found in association with a specific haplotype (odds ratio 0.524). Our data suggest that variations within PTX3 affect lung colonization of Pseudomonas in patients with CF.

The Therapeutic Potential of the Humoral Pattern Recognition Molecule PTX3 in Chronic Lung Infection Caused by Pseudomonas aeruginosa

“…Therefore, it was important to assess the actual therapeutic potential of PTX3 in a system representative of unmet medical needs, such as chronic infection in patients with CF (10). Moreover, we recently observed that PTX3 gene polymorphisms affect CF-associated P. aeruginosa lung infections (37), in line with previous findings on the links between PTX3 polymorphisms and tuberculosis infection (38). In the current study, we addressed the potential therapeutic role of recombinant PTX3 in a murine model of chronic lung infection with a clinical P. aeruginosa strain, which mimics the persistent and progressive colonization occurring in CF patients.…”

Pentraxin-3 in COPD: innocent bystander or amplifier?

“…For instance, PTX3 has been reported to correlate with disease severity in pulmonary infections (e.g. P. aeruginosa) and acute respiratory distress syndrome [8][9][10]. The results reported here in COPD provide an unexpected turn in efforts aimed at exploring the value of PTX3 as a disease marker.…”

“…In particular, PTX3 polymorphisms have provided genetic evidence in males of the role of this molecule in innate immunity [8,16,17]. It will be important to conduct genetic studies to further explore the significance of PTX3 in COPD progression and associated pathology.…”

Pentraxins in Humoral Innate Immunity

“…In addition, recent observations by Chiarini and colleagues have shown that polymorphisms in the PTX3 gene correlate with the risk of Pseudomonas aeruginosa infections in CF patients (Chiarini et al 2010). …”