O7‐5: The role of increasing TIM3 on T cells in patients with nontuberculous mycobacterial lung disease: From immune cell dysfunction to clinical severity

Background and Aims: Currently, there are no validated prognostic biomarkers for chronic pulmonary Pseudomonas aeruginosa infections.Here, we screened 11 P. aeruginosa regulatory genes known to promote chronic lung infection, toidentify an association with clinical status and chronic biofilm infection.Methods: RNA was extracted from 240 sputum samples derived from patients (n= 81) with chronic P. aeruginosa lung infection (Mean age; 29.3-56.2years of age; n=33 Females).Expression of tesG, algD, lasR, lasA, lasB, pelB, phzF, rhlA, rsmY, rsmZ, and sagS was determined by qRTpcr and compared to clinical, radiologic, and laboratory data to generate predictive models by mixed effects logistic regression to identify any potentialprognostic biomarker.Results: Higher levels of tesG, and sagS were associated with lower mortality (p<0.01),but significantly longer hospitalization/ICU stay (p<0.01).algD expression was associated higher mortality (p<0.01).Higher algD, lasR, pelB, phzF, rhlA, rsmY, or rsmZ, expression was associated with stronger biofilm biomass (p <0.01), while lasA, and lasB with a moderate biomass (p<0.01).Higher tesG expression was correlated with lower systemic/sputum inflammatory response, and poor lung function (p<0.01,r< À0.8).Higher LasR, Rhl, pelb, phz and algd expression was correlated (p<0.05,r> 0.9) with bacteria virulence.LasR, and pelb were accurate, sensitive, and specific (AUC = 0.94) biomarkers for biofilm biomass and tesG for chronic biofilm infection with inflammation and lung function (AUC = 0.95).Conclusions: Study provides the first clinical dataset related to tesG, LasR, and pelb, expression level as predictive biomarker, for chronic P. aeruginosa biofilm pulmonary infection.