Reduced Immunocompetent B Cells and Increased Secondary Infection in Elderly Patients With Severe Sepsis
Reduced Immunocompetent B Cells and Increased Secondary Infection in Elderly Patients With Severe Sepsis
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DOI：
10.1097/shk.0000000000000619
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发表时间：
2016-09
期刊：
影响因子：
3.1
通讯作者：
Kodai Suzuki;S. Inoue;Y. Kametani;Yukako Komori;S. Chiba;Takehito Sato;S. Inokuchi;S. Ogura
中科院分区：
文献类型：
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作者：
Kodai Suzuki;S. Inoue;Y. Kametani;Yukako Komori;S. Chiba;Takehito Sato;S. Inokuchi;S. Ogura
淋巴细胞耗竭是脓毒症免疫抑制的一种机制。虽然已知B细胞在细菌感染和脓毒症中起关键作用，但尚未在重症脓毒症患者中评价B细胞介导的体液免疫的变化。我们的目的是研究严重脓毒症期间B细胞功能缺陷引起的体液免疫变化。前瞻性入组了33例严重脓毒症患者和44例健康受试者。在脓毒症发作后72小时内和8至11小时内从患者采集血液，以测量B细胞亚型、血清免疫球蛋白M浓度和CpG-B寡脱氧核苷酸诱导的免疫球蛋白M（IgM）离体产生。参与者分为两个年龄组：成人（18-64岁）和老年人（≥65岁）。急性脓毒症患者外周血CD 21-/低耗竭B细胞比例（3.18%）明显高于健康献血员（0.77%，P <0.01）。老年脓毒症患者（≥65岁）血清IgM水平与急性生理学和慢性健康评价Ⅱ评分呈显著负相关（r =-0.57，P <0.05）。在体外刺激的B细胞中，衰老和脓毒症均诱导上清液IgM显著降低（P <0.01）。这一发现具有临床意义，因为IgM产生减少的老年患者可能更容易受到革兰氏阴性细菌和真菌的感染。免疫活性B细胞减少可能与脓毒症后继发感染增加有关，尤其是在老年人中。最后，体液免疫受损，CD 21-/低耗竭B细胞增加和免疫球蛋白M产生不足可能是脓毒症的关键免疫学变化。
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–/low 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−/low exhausted B cells and insufficient immunoglobulin M production may be a critical immunological change in sepsis.