Dysregulated Immune Response in Lymphopenic Community-Acquired Pneumonia Increases Mortality

Abstract

Introduction: Lymphopenic community-acquired pneumonia (L-CAP) is an immunophenotype with an increased risk of mortality but little is known about its immunological profile in CAP. We aimed to characterize the immunophenotypes of lymphopenic and non-lymphopenic CAP by analyzing lymphocyte subsets and the inflammatory response. Methods: This was a prospective study of 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. Findings: We recruited 217 patients of whom 59% showed lymphopenia (absolute lymphocyte count [ALC] <1000 cells/μL), with decrease in CD4 , CD8 , CD19 , and NK cells although there was a partial recovery on day 4. ALC was strongly correlated with CD4 counts (rho 0.91). The L-CAP group showed initial higher levels of interleukin (IL)-2, IL-8, IL-10, IL-17, granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein-1, and macrophage inflammatory protein-1 beta (MIP-1β) with persistence on day 4 of IL-8 and MIP-1β. Initial IgG2 levels were positively correlated with ALC, CD4 , and CD19 cell counts. Low CD4 counts (<129 cells/μL) also independently predicted 30-day mortality (Odds ratio 5.07 [1.12-23.01, 95% confidence interval]) after adjusting for age, gender, and the CURB-65 score. Conclusions: L-CAP presents features of dysregulated immune response, characterized principally by CD4 cell depletion, with a higher inflammatory response. Low lymphocyte count correlated with low IgG2 levels and is ultimately associated with a worse prognosis. Better immunoprofiling could contribute to personalize treatment in CAP. Funding Statement: This work was supported by Grant from Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR) [2012/145, 2014/72]; Sociedad Valenciana de Neumologia (SVN) [2013, 2015]. The funders of the study had no role in the design, data collection, data analysis, data interpretation, writing, review, or approval of the manuscript. The first author and the corresponding author have had full access to all the data in the study and had final responsibility for the decision to submit for publication. Declaration of Interest: All authors declare that they have no conflicts of interest regarding this submission, and each has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Ethics Approval Statement: The local ethics committee approved the study (code: 2011/0859) and patients or their next of kin provided written informed consent.