Plasma metabolome and cytokine profile reveal glycylproline modulating antibody fading in convalescent COVID-19 patients
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 (six cytokines and 11 metabolites). Overall accuracies of more than 90% were attained in at least six 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.
| Errataetall: |
CommentIn: Proc Natl Acad Sci U S A. 2023 Jan 17;120(3):e2220329120. - PMID 36623179 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:119 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 119(2022), 34 vom: 23. Aug., Seite e2117089119 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yang, Zhu [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 11.08.2022 Date Revised 27.02.2023 published: Print-Electronic CommentIn: Proc Natl Acad Sci U S A. 2023 Jan 17;120(3):e2220329120. - PMID 36623179 Citation Status MEDLINE |
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| doi: |
10.1073/pnas.2117089119 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM344633772 |
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| 245 | 1 | 0 | |a Plasma metabolome and cytokine profile reveal glycylproline modulating antibody fading in convalescent COVID-19 patients |
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| 500 | |a Date Revised 27.02.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: Proc Natl Acad Sci U S A. 2023 Jan 17;120(3):e2220329120. - PMID 36623179 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 (six cytokines and 11 metabolites). Overall accuracies of more than 90% were attained in at least six 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a convalescent COVID-19 patients | |
| 650 | 4 | |a cytokine profiling | |
| 650 | 4 | |a glycylproline | |
| 650 | 4 | |a metabolomics | |
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| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a Dipeptides |2 NLM | |
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| 650 | 7 | |a glycylproline |2 NLM | |
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| 700 | 1 | |a Wu, Di |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Shanxin |e verfasserin |4 aut | |
| 700 | 1 | |a Qiu, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Hua, Zhengyi |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Fancheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Cixiong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Ding-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Xi |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Zongwei |e verfasserin |4 aut | |
| 700 | 1 | |a Shang, You |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Shu-Hai |e verfasserin |4 aut | |
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