Reduced Immunocompetent B Cells and Increased Secondary Infection in Elderly Patients With Severe Sepsis

Abstract

Lymphocyte exhaustion was recently recognized as a mechanism of immunosuppression in sepsis. While B cells are known to play pivotal roles in bacterial infection and sepsis, changes in B-cell-mediated humoral immunity have not been evaluated in critically ill septic patients. We aimed to investigate changes in humoral immunity caused by defective B-cell function during severe sepsis. Thirty-three severe sepsis patients and 44 healthy subjects were prospectively enrolled. Blood was collected from patients within 72 h of and 8 to 11 h after sepsis onset to measure B-cell subtypes, serum immunoglobulin M concentration, and CpG-B oligodeoxynucleotide-induced immunoglobulin M (IgM) production ex vivo. Participants were divided into two age groups: adults (18-64 years) and elderly (≥65 years). The fraction of CD21 exhausted B cells in acute sepsis patients (3.18%) was higher than that observed in healthy donors (0.77%, respectively, P <0.01). Significantly, serum IgM in elderly septic patients (≥65 years) was negatively correlated with acute physiology and chronic health evaluation II score (r = -0.57, P <0.05). Consistently, in B cells stimulated ex vivo, both aging and sepsis induced significant reductions in supernatant IgM (P <0.01). This finding was clinically relevant, as elderly patients with decreased IgM production might be more susceptible to infection by Gram-negative bacteria and fungi. Reduced immunocompetent B cells may be related to increased secondary infection after sepsis, especially in the elderly. Finally, impaired humoral immunity with increased CD21 exhausted B cells and insufficient immunoglobulin M production may be a critical immunological change in sepsis.

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

“…However, MZ B cells are worst affected as compared to follicular B cells [333]. The early alteration in B cells number and response is also observed in human patients of severe sepsis and septic shock that is responsible for increased chances of secondary infection in elderly patients with severe sepsis [337,338].…”

The immune system's role in sepsis progression, resolution, and long‐term outcome

“…Lastly, IRA B‐cell generation of IL‐3 has been revealed to greatly enhance sepsis‐associated inflammation, induce myeloid production of Ly‐6C hi mononuclear cells, and potentiate cytokine production, while elevated plasma IL‐3 levels correlate with increased human sepsis mortality . B cells stimulated ex vivo in both aging and sepsis patients demonstrate significant reductions in supernatant IgM production . This finding is clinically relevant and interesting and may explain why elderly patients with decreased IgM production are more susceptible to Gram‐negative bacteria and fungal infection.…”

“…It is evident that sepsis induces a pathologic state of immune suppression that prompts the development of secondary infections while still in the ICU setting . Several reports over the past 5 years demonstrate that sepsis survivors experience dramatically higher rates of subsequent infections long after the initial episode of sepsis has resolved . The increased hospital readmission rates due to infectious complications among sepsis survivors is a sign of ongoing immune suppression and dysregulation that if not corrected, diminishes life quality and durable survival.…”

Neutrophil Elastase Damages the Pulmonary Endothelial Glycocalyx in Lipopolysaccharide-Induced Experimental Endotoxemia

“…Samples were prepared as previously described. 17 Cells were stained with the following antibodies (Bio-Legend, San Diego, CA) for 5 minutes at room temperature: anti-mouse CD45eperidinin chlorophyll protein complex (clone: 30-F11), anti-mouse CD11b-phycoerythrin (clone: M1/70), anti-mouse Ly6G-fluorescein isothiocyanate (clone: 1A8), and anti-mouse F4/80-Alexa Fluor 647 (clone: BM8). Neutrophils were defined as the CD45 þ CD11b þ Ly6G þ F4/80 À white blood cell population.…”