title: 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.
authors.affiliation: *Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Gifu, Japan †Institute of Innovative Science and Technology, Tokai University School of Medicine, Shimokasuya, Isehara, Kanagawa, Japan ‡Department of Emergency and Critical Care Medicine, Tokai University School of Medicine, Shimokasuya, Isehara, Kanagawa, Japan §Department of Immunology, Tokai University School of Medicine, Shimokasuya, Isehara, Kanagawa, Japan.
authors.forename: Kodai
authors.initials: K
authors.lastname: Suzuki
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Inoue
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Kametani
authors.forename: Yukako
authors.initials: Y
authors.lastname: Komori
authors.forename: Sayuri
authors.initials: S
authors.lastname: Chiba
authors.forename: Takehito
authors.initials: T
authors.lastname: Sato
authors.forename: Sadaki
authors.initials: S
authors.lastname: Inokuchi
authors.forename: Shinji
authors.initials: S
authors.lastname: Ogura
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016638:Critical Illness; D005260:Female; D005658:Fungi / Q000276:immunology / Q000472:pathogenicity; D006090:Gram-Negative Bacteria / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D056724:Immunity, Humoral / Q000502:physiology; D007121:Immunocompetence / Q000502:physiology; D007075:Immunoglobulin M / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000276:immunology*; D055815:Young Adult
chemical_list: D007075:Immunoglobulin M