Abstract
Serum proteomics has matured and is now able to monitor hundreds of proteins quantitatively in large cohorts of patients. However, the fine characteristics of some of the most dominant proteins in serum, the immunoglobulins, are in these studies often ignored, due to their vast, and highly personalized, diversity in sequences. Here, we focus exclusively on these personalized features in the serum proteome and distinctively chose to study individual samples from a low diversity population: elderly donors infected by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). By using mass spectrometry-based methods, immunoglobulin IgG1 and IgA1 clonal repertoires were monitored quantitatively and longitudinally in more than 50 individual serum samples obtained from 17 Corona virus disease 2019 patients admitted to intensive care units. These clonal profiles were used to examine how each patient reacted to a severe SARS-CoV-2 infection. All 17 donors revealed unique polyclonal repertoires and substantial changes over time, with several new clones appearing following the infection, in a few cases leading to a few, very high, abundant clones dominating their repertoire. Several of these clones were de novo sequenced through combinations of top-down, middle-down, and bottom-up proteomics approaches. This revealed sequence features in line with sequences deposited in the SARS-CoV-specific antibody database. In other patients, the serological Ig profiles revealed the treatment with tocilizumab, that subsequently dominated their serological IgG1 repertoire. Tocilizumab clearance could be monitored, and a half-life of approximately 6 days was established. Overall, our longitudinal monitoring of IgG1 and IgA1 repertoires of individual donors reveals that antibody responses are highly personalized traits of each patient, affected by the disease and the chosen clinical treatment. The impact of these observations argues for a more personalized and longitudinal approach in patients' diagnostics, both in serum proteomics as well as in monitoring immune responses.
Original language | English |
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Article number | 100690 |
Pages (from-to) | 100690 |
Number of pages | 13 |
Journal | Molecular and Cellular Proteomics |
Volume | 23 |
Issue number | 1 |
Early online date | 6 Dec 2023 |
DOIs | |
Publication status | Published - Jan 2024 |
Bibliographical note
Publisher Copyright:© 2023 THE AUTHORS.
Funding
supported by Dutch Research Council (NWO) funding the Netherlands Proteomics Centre through the X-omics Road Map program (project 184.034.019) and the EU Horizon 2020 program INFRAIA project Epic-XS (Project 823839) and by the Dutch Research Council NWO Gravitation 2013 BOO, Institute for Chemical Immunology (ICI; 024.002.009) and the Utrecht Molecular Immunology Hub.
Funders | Funder number |
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Dutch Research Council NWO | 024.002.009 |
Netherlands Proteomics Centre | 184.034.019 |
Nederlandse Organisatie voor Wetenschappelijk Onderzoek | |
Horizon 2020 | 823839 |
Keywords
- COVID-19
- IgA1
- IgG1
- human antibodies
- immunoglobulin repertoire
- mass spectrometry
- personalized serology
- tocilizumab