Metabolomics

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Absolute quantification of serum cytokines and metabolome reveals the glycylproline regulating antibody-fading in convalescent COVID-19 patients


ABSTRACT:

The COVID-19 pandemic has incurred tremendous costs worldwide and is still threatening public health in the 'new normal'. The association between neutralizing antibody levels and metabolic alterations in convalescent patients with COVID-19 is still poorly understood. In the present work, we conducted absolutely quantitative profiling to compare the plasma cytokines and metabolome of ordinary convalescent patients with antibodies (CA), convalescents with rapidly faded antibodies (CO) and healthy subjects. As a result, we identified that cytokines such as M-CSF and IL-12p40 and plasma metabolites such as glycylproline (gly-pro) and long-chain acylcarnitines could be associated with antibody fading in COVID-19 convalescent patients. Following feature selection, we built machine-learning-based classification models using 17 features (6 cytokines and 11 metabolites). Overall accuracies of more than 90% were attained in at least 6 machine-learning models. Of note, the dipeptide gly-pro, a product of enzymatic peptide cleavage catalyzed by dipeptidyl peptidase 4 (DPP4), strongly accumulated in CO individuals compared with the CA group. Furthermore, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination experiments in healthy mice demonstrated that supplementation of gly-pro down-regulates SARS-CoV-2-specific receptor-binding domain antibody levels and suppresses immune responses, whereas the DPP4 inhibitor sitagliptin can counteract the inhibitory effects of gly-pro upon SARS-CoV-2 vaccination. Our findings not only reveal the important role of gly-pro in the immune responses to SARS-CoV-2 infection but also indicate a possible mechanism underlying the beneficial outcomes of treatment with DPP4 inhibitors in convalescent COVID-19 patients, shedding light on therapeutic and vaccination strategies against COVID-19.

INSTRUMENT(S): Liquid Chromatography MS - alternating - reverse phase

PROVIDER: MTBLS3305 | MetaboLights | 2024-08-26

REPOSITORIES: MetaboLights

Dataset's files

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Action DRS
Q300_20210202-G14.mzML Mzml
Q300_20210202-G16.mzML Mzml
Q300_20210202-G2.mzML Mzml
Q300_20210202-G21.mzML Mzml
Q300_20210202-G3.mzML Mzml
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Publications

Plasma metabolome and cytokine profile reveal glycylproline modulating antibody fading in convalescent COVID-19 patients.

Yang Zhu Z   Wu Di D   Lu Shanxin S   Qiu Yang Y   Hua Zhengyi Z   Tan Fancheng F   Zhang Cixiong C   Zhang Lei L   Zhang Ding-Yu DY   Zhou Xi X   Cai Zongwei Z   Shang You Y   Lin Shu-Hai SH  

Proceedings of the National Academy of Sciences of the United States of America 20220809 34


The COVID-19 pandemic has incurred tremendous costs worldwide and is still threatening public health in the "new normal." The association between neutralizing antibody levels and metabolic alterations in convalescent patients with COVID-19 is still poorly understood. In the present work, we conducted absolutely quantitative profiling to compare the plasma cytokines and metabolome of ordinary convalescent patients with antibodies (CA), convalescents with rapidly faded antibodies (CO), and healthy  ...[more]

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