D1.508 - Assessment of automated serum sIgG testing for key bacterial pathogens in Cystic Fibrosis

Cystic fibrosis (CF) is a genetic disease caused by mutations in the CFTR gene, resulting in dehydrated airway secretions and impaired mucociliary clearance. These abnormalities favor recurrent and chronic airway colonization by pathogenic microorganisms, driving persistent inflammation and progressive lung damage. The introduction of highly effective CFTR modulators has markedly reduced sputum production, complicating routine culture-based microbiological surveillance. Therefore, alternative biomarkers of airway infection are increasingly needed. Pathogen-specific serum IgG (sIgG) reflects cumulative microbial exposure and may enable monitoring of airway infection when respiratory samples are unavailable. However, automated assays for sIgG detection are currently lacking for most CF-relevant bacteria. This study aimed to evaluate ImmunoCAP sIgG prototype assays targeting five clinically relevant bacterial pathogens in CF patients.

Prospective, non-interventional study including serum samples from 128 CF patients from Basque Country (North-East Spain). sIgG levels were measured against antigens from Stenotrophomonas maltophilia (U1380), Pseudomonas aeruginosa (U1381), Burkholderia multivorans (U1382), Staphylococcus aureus (U1383), and Haemophilus influenzae (U1384). ImmunoCAP prototype assays were provided by the Special Allergen Service (Thermo Fisher Scientific, Uppsala) and performed according to manufacturer specifications for marketed sIgG tests. Demographic data, antibiotic consumption, lung function and prior culture positivity for the target organisms were collected when available. Associations between sIgG levels and culture history were assessed using Spearman’s correlation.

The cohort had a balanced sex distribution (54% male) and a median age of 23 years. Median sIgG levels varied across pathogens, with the highest values observed for S. aureus (30.5 mg_A/ml (Q1–Q3: 25.5–34.9)), max 57.1 and H. influenzae (15.8 mg_A/ml (Q1–Q3: 10.16–26.6), max 72.8). A significant positive correlation between sIgG levels and history of culture positivity was identified for P. aeruginosa (p < 0.05) and Burkholderia spp. (p < 0.05). No statistically significant associations were observed for the remaining organisms. In all cases, higher sIgG loads were associated with impaired lung function. 

ImmunoCAP sIgG prototypes successfully quantified pathogen-specific IgG responses against key CF-associated bacteria. Higher sIgG levels against S. aureus likely reflect its early acquisition and prolonged exposure in CF patients. The strong association between sIgG levels and prior culture positivity for P. aeruginosa and Burkholderia spp. supports the potential utility of these assays as adjunctive infection markers. Further studies including larger cohorts and comparisons with established precipitin assays are needed to better define the clinical role of ImmunoCAP sIgG testing in CF care.