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

• Published in: Shock (Augusta, Ga.) Vol. 46; no. 3; p. 270
• Main Authors: Suzuki, Kodai, Inoue, Shigeaki, Kametani, Yoshie, Komori, Yukako, Chiba, Sayuri, Sato, Takehito, Inokuchi, Sadaki, Ogura, Shinji
• Format: Journal Article
• Language: English
• Published: United States 01.09.2016
• Subjects: Adult; Aged; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Critical Illness; Female; Fungi - immunology; Fungi - pathogenicity; Gram-Negative Bacteria - immunology; Gram-Negative Bacteria - pathogenicity; Humans; Immunity, Humoral - physiology; Immunocompetence - physiology; Immunoglobulin M - metabolism; Male; Middle Aged; Prospective Studies; Sepsis - immunology; Young Adult
• DOI: 10.1097/SHK.0000000000000619

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.