Programa de Virología, ICBM, Facultad de Medicina, Universidad de Chile, Av. Independencia 1027, Independencia, Santiago, Chile.
Programa de Inmunología, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Sci Rep. 2022 Jul 30;12(1):13145. doi: 10.1038/s41598-022-13063-x.
Community-acquired pneumonia (CAP) is a worldwide leading cause of death. Recognized risk factors in some severe cases have not been identified. Lymphocytopenia has been frequently described in CAP. Since IL-7, membrane-bound receptor (IL7Rα;CD127) and soluble IL7Rα (sIL7R) are critical in lymphocytes homeostasis, in this work we aimed to evaluate the involvement of the IL-7/IL7Rα axis in the severity of adult CAP, since it has not been explored. The IL7Rα SNPs rs6897932, rs987106, and rs3194051 SNPs in IL7α were genotyped, the systemic expression of the IL7R gene, sIL7R, IL-7, and levels of peripheral IL7Rα T lymphocytes were quantified in 202 hospitalized CAP cases. rs3194051GG was more frequent in non-survivors than in survivors; rs987106TT was more frequent and rs3194051AA less frequent in patients at intensive care unit (ICU) than in those not admitted to ICU. IL7Rα gene expression was lower in non-survivors than in survivors, and in severe than in mild cases. CD3CD127 lymphocytes were lower in severe than in mild cases; in non-survivors than in survivors and in ICU than in non- ICU admitted cases. sIL7Rα plasmatic levels were higher in non-survivors than in survivors, and in severe than in mild cases. rs6897932CC, rs987106AA and rs3194051GG carriers showed the highest while rs6897932TT showed the lowest sIL7Rα levels. The AUC of sIL7Rα levels predicting 30-day mortality was 0.71. Plasma IL-7 levels were lower in ICU-admitted than in not ICU-admitted and in non-survivors than in survivors. No additional association was detected. In conclusion, rs3194051GG and rs987106TT IL7R genotypes were associated with a poorer prognosis. A significant association between sIL7R levels and SNPs of the IL7R gene is described for the first time in adult CAP. Increased plasmatic sIL7R could contribute to identifying adult CAP cases at risk of death.
社区获得性肺炎（CAP）是全球范围内导致死亡的主要原因。在一些严重病例中，已识别出的危险因素尚未确定。淋巴细胞减少症在 CAP 中经常被描述。由于白细胞介素 7（IL-7）、膜结合受体（IL7Rα；CD127）和可溶性 IL7Rα（sIL7R）在淋巴细胞稳态中至关重要，因此本工作旨在评估 IL-7/IL7Rα 轴在成人 CAP 严重程度中的作用，因为尚未对此进行探索。在 202 例住院 CAP 患者中，对 IL7α 中的 IL7Rα 基因 rs6897932、rs987106 和 rs3194051 进行了基因分型，定量检测了系统表达的 IL7R 基因、sIL7R、IL-7 和外周 IL7Rα T 淋巴细胞水平。与幸存者相比，非幸存者中 rs3194051GG 更为常见；与未入住 ICU 的患者相比，入住 ICU 的患者中 rs987106TT 更为常见，而 rs3194051AA 较少。与幸存者相比，非幸存者的 IL7Rα 基因表达水平更低，与轻症病例相比，重症病例的表达水平更低。与轻症病例相比，严重病例中 CD3CD127 淋巴细胞水平更低；与幸存者相比，非幸存者中 CD3CD127 淋巴细胞水平更低，与非 ICU 入院病例相比，入住 ICU 的患者中 CD3CD127 淋巴细胞水平更低。与幸存者相比，非幸存者的 sIL7Rα 血浆水平更高，与轻症病例相比，重症病例的 sIL7Rα 血浆水平更高。rs6897932CC、rs987106AA 和 rs3194051GG 携带者的 sIL7Rα 水平最高，而 rs6897932TT 携带者的 sIL7Rα 水平最低。sIL7Rα 水平预测 30 天死亡率的 AUC 为 0.71。与未入住 ICU 的患者相比，入住 ICU 的患者以及幸存者的血浆 IL-7 水平更低。未发现其他关联。总之，IL7R 基因型 rs3194051GG 和 rs987106TT 与预后不良相关。在成人 CAP 中，首次描述了 sIL7R 水平与 IL7R 基因的 SNP 之间存在显著相关性。增加的血浆 sIL7R 可能有助于识别有死亡风险的成人 CAP 病例。
