Lymphopenic community-acquired pneumonia is associated with a dysregulated immune response and increased severity and mortality

Abstract

Objectives: Lymphopenic (<724 lymphocytes/µL) community-acquired pneumonia (L-CAP) is an immunophenotype with an increased risk of mortality. We aimed to characterize the l-CAP immunophenotype though lymphocyte subsets and the inflammatory response and its relationship with severity at presentation and outcome.

Methods: Prospective study of 217 immunocompetent patients hospitalized for CAP. Lymphocyte subsets (CD4⁺, CD8⁺, CD19⁺, and natural killer [NK] cells) and inflammatory cytokines were analyzed on days 1 and 4, and immunoglobulin subclasses were analyzed on day 1 in a nested group.

Results: 39% of patients showed l-CAP, with decreased levels of all lymphocyte subsets with a partial recovery of CD4⁺ and CD8⁺ cells by day 4. l-CAP patients exhibited higher initial severity and systemic levels of interleukin (IL)-8, IL-10, granulocyte colony-stimulating factor, and monocyte chemoattractant protein-1. Initial IgG2 levels were lower in patients with <724 lymphocytes/µL and positively correlated with ALC, CD4⁺, and CD19⁺ cell counts. Low CD4⁺ counts (<129 cells/µL) also independently predicted 30-day mortality after adjusting for age, gender, and the CURB-65 score.

Conclusions: l-CAP is characterized by CD4⁺ depletion, a higher inflammatory response, and low IgG2 levels that correlated with greater severity at presentation and worse prognosis. l-CAP is an immunophenotype useful for rapidly recognizing severity.

Keywords: Adaptive immunity; Host response; Pneumonia.