Cremer, O. L. | bioRxiv Science

bioRxiv2023

Glycan-specific IgM is critical for human immunity to Staphylococcus aureus

Staphylococcus aureus is a major human pathogen but the immune factors that protect against it remain elusive. In particular, high opsonic IgG titers achieved in preclinical S. aureus animal immunization studies have consistently failed to translate to protection in human clinical trials. Here, we investigated the antibody responses to a conserved surface glycan, Wall Teichoic Acid (WTA). IgM and IgG antibodies specific to WTA were universally present in plasma from healthy individuals. Functionally, WTA-specific IgM outperformed IgG in opsonophagocytic killing of S. aureus and conferred passive protection against S. aureus infection in vivo. In the clinical setting, WTA-specific IgM responses, but not IgG responses, were significantly lower in S. aureus bacteremia patients compared to healthy individuals, correlated with mortality risk and showed impaired bacterial opsonization. Our findings can guide risk stratification of hospitalized patients and inform future design of antibody-based therapies and vaccines against serious S. aureus infection.

microbiology↗

bioRxiv2017

Myocardial injury in critically ill patients with community-acquired pneumonia

BackgroundMyocardial injury, as reflected by elevated cardiac troponin levels in plasma, is common in patients with community-acquired pneumonia (CAP), but its temporal dynamics and etiology remain unknown. Our aim was to determine the incidence of troponin release in patients with CAP and identify risk factors which may point to underlying etiologic mechanisms.\n\nMethodsWe included consecutive patients admitted with severe CAP to two intensive care units in the Netherlands between 2011 and 2015. High-sensitivity cardiac troponin I was measured daily during the first week. We used multivariable linear regression to identify variables associated with troponin release on admission, and mixed-effects regression to model the daily rise and fall of troponin levels over time.\n\nResultsAmong 200 eligible patients, 179 were included, yielding 792 observation days. A total of 152 (85%) patients developed raised troponin levels >26 ng/L. Baseline factors independently associated with troponin release included coronary artery disease (160% increase, 95% CI 7-529), smoking (304% increase, 95% CI 59-924), and higher APACHE IV score (2% increase, 95% CI 0.7-3.3), whereas Staphylococcus aureus as a causative pathogen was protective (67% reduction, 95% CI 9-88). Time-dependent risk factors independently associated with daily increase in troponin concentrations included reduced platelet count (1.7% increase, 95% CI 0.1-3.4), tachycardia (1.6% increase, 95% CI 0.3-3), hypotension (5.1% increase, 95% CI 1-9.4) and dobutamine use (38.4% increase 95% CI 8.8-76).\n\nConclusionsCardiac injury develops in a majority of patients with severe CAP. Myocardial oxygen supply-demand mismatch and activated coagulation are potential causes of this injury.

epidemiology↗