Longitudinal assessment of immunoglobulin response and disease progression in critically ill patients with community acquired pneumonia

Background: Low endogenous immunoglobulin(Ig)-levels are common in critically ill patients with sepsis, but it is unknown whether low Ig-levels are associated with poor outcome, and in which patients Ig-replacement therapy (IgRT) improves outcome. Given the crucial role of immunoglobulins in eliminating certain encapsulated pathogens, we examined the relationship between serial Ig-levels and disease course in critically ill patients with community acquired pneumonia (sCAP) caused by encapsulated or other pathogens.

Methods: We included a cohort of consecutive critically ill patients with CAP, and PaO₂/FiO₂-ratio < 200 with or without septic shock, from an existing biorepository where microbiological causes of infection had been adjudicated in a protocolized manner. We used generalized linear mixed models to assess the association between IgG and IgM (measured on admission days 1, 3 and 7) and disease course (Sequential Organ Failure Assessment (SOFA)-score on day 2, 4, and 8) for all-cause sCAP and for episodes caused by Streptococcus (S.) pneumoniae or Haemophilus (H.) influenzae.

Results: We included 255 eligible patients admitted with CAP, of which 82 (32%) episodes were caused by S. pneumoniae or H. influenzae. 151 (59%) patients had low IgG (< 7.0 g/L), 77 (30%) had low IgM (< 0.4 g/L), and 56 (22%) had both. A lower IgG-level was related to a slightly higher SOFA-score at admission (β = - 0.07 per 1 g/L IgG, p = 0.029), but an IgG-level decline over time was not associated with a SOFA-score increase (β = - 0.04, p = 0.564). IgM-levels were not associated with changes in SOFA-score over time. Neither association was affected by the presence or absence of S. pneumoniae and H. influenzae.

Conclusion: In critically ill patients with CAP, IgG and IgM dynamics in the first week of ICU stay are not associated with clinically relevant changes in disease course, regardless of the causative pathogen.