IL-7/IL7R axis dysfunction in adults with severe community-acquired pneumonia (CAP): a cross-sectional study

Abstract

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. CD3⁺CD127⁺ 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.

Figure 1

Systemic CD3⁺ lymphocytes in CAP and asymptomatic adults (ASN) (A), according to age, sex (B), and outcome (C). Data are shown as median and 95% CI. P values were obtained by Mann–Whitney test.

Figure 2

Systemic CD3⁺CD127⁺ lymphocytes in CAP and asymptomatic adults (ASN) (A), according to age, sex (B) and outcome (C). Data are shown as median and 95% CI. P values were calculated by Mann–Whitney test.

Figure 3

CD3⁺CD127⁺ lymphocytes in blood from adults with CAP according to SNP. Data are shown as median and 95% CI. p > 0.1, by t test.

Figure 4

Systemic CD4⁺CD127⁺ (A) and CD8⁺CD127⁺ (B) T lymphocytes in CAP adult according to severity by PSI. Data are shown as median and 95% CI. P values were obtained by t test.

Figure 5

Plasmatic soluble IL7R from asymptomatic and CAP adults (A), according to age, sex (B) and outcome (C). Data are shown as median and 95% CI. P values were calculated by Mann–Whitney test.

Figure 6

Soluble IL7R according to the genotypes of the three SNPs in adult CAP. Median, 25–75% percentile, minimum and maximum are indicated. P values were obtained by Mann–Whitney test, (*) p < 0.05, (**) p < 0.01, (***) p < 0.001, (****) p < 0.0001.