A study of aging characteristics of evaluation indicators system for tumor-related human immune function / 中华老年医学杂志

ABSTRACT

Objective:To find the age-related indicators of human immune function in the blood, to explore the possibility to standardize the evaluation criterion of immune function in Chinese population.Methods:The peripheral blood samples from 478 healthy individuals with complete medical data collected at the Beijing Hospital from January 2019 to December 2019, were chosen and analyzed.The volunteers were divided into young(<40 years old)and elderly(≥70 years old)groups.The differences in RNA, cytokines and immune cell function(the proliferation of T cell as well as the ability of T cells and natural killer cells to lyse target cells)were compared between the young group versus the elderly group.Results:Real-time quantitative fluorescence RT-PCR detection method was used for detecting the following tumor immune-related genes in the peripheral blood of healthy people in young versus old groups programmed death 1( PD1)gene, complement C3 gene( C3), complement C4 gene( C4), high sensitivity C-reactive protein gene( HsCRP), tumor necrosis factor alpha gene( TNFA), interferon gamma gene( INF- γ), interleukin-6 gene( IL-6), interleukin-8 gene( IL-8), cytotoxic T lymphocyte-associated antigen-4 gene( CTLA-4), nuclear transcription factor-κB gene( NF- κB), long intergenic noncoding RNA-erythroid pro-survival gene( lincRNA- EPS), long non-coding RNA-myeloid RNA regulator of Bim-induced death gene( lncRNA- Morrbid), lincRNA-cyclooxygenase 2 gene( lincRNA- Cox2), Lnc-Dendritic cells( Lnc- DC), and circRNA-7 gene( ciRS-7). The mRNA level of C4 was significantly lower in elderly people than in young controls[young group(1.01±0.18) vs.old group(0.64±0.13), P=0.047], while others showing a non-statistically significant difference( P>0.05). The protein levels of programmed death 1(PD1), complement C3(C3), complement C4(C4), high sensitivity C-reactive protein(HsCRP), tumor necrosis factor alpha(TNF-α), interferon gamma(INF-γ), interleukin-6(IL-6), interleukin-8(IL-8), cytotoxic T lymphocyte-associated antigen-4(CTLA-4)and nuclear transcription factor-κB(NF-κB)in plasma were detected by enzyme-linked immunosorbent assay(ELISA). The following protein levels were significantly higher in the elderly group than in the young group IL-6 protein[young group(249.30±100.02)ng/L vs.old group(283.00±94.98)ng/L, P=0.021], HsCRP protein[young group(2543.00±1111.89)ng/L vs.old group(3056.00±1056.61)ng/L, P=0.002], INF-γ protein[young group(362.40±383.67)ng/L vs.old group(500.40±502.27)ng/L, P=0.047]and TNF-α protein[young group(20.74±29.47)ng/L vs.old group(33.09±48.91)ng/L, P=0.042]. While the level of C4 was significantly lower in the elderly group than in the young group[young group(449.50±51.17)ng/L vs.old group(407.10±59.78)ng/L, P<0.0001]. T-cell proliferation, quantified by flow cytometry-based fluorescent dye dilution, showed that the CD3 + T cells of elder people had proliferated through 4 generations, while the CD3 + T cells of young people had proliferated through 5 generations.As shown in the NK killing assays, the secretion of LDH in the target A549 tumor cells decreased significantly after treated with NK cells belonging to elder individuals.The result demonstrated that individuals over 70 years old have significantly lower levels of the killing activity of NK cells( P<0.05). However, there was not statistically significant in T lymphocyte killing activity between different ages( P>0.05). Conclusions:IL-6, HsCRP, INF-γ and TNF-α levels are increased with aging, while the level of C4 significantly is decreased.The proliferation ability of T cells and the ability of NK cells to kill tumor cells are weakened.