Into the dark serum proteome: personalized features of IgG1 and IgA1 repertoires in severe COVID-19 patients

Mol Cell Proteomics. 2023 Dec 6:100690. doi: 10.1016/j.mcpro.2023.100690. Online ahead of print.ABSTRACTSerum 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 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 COVID-19 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...
Source: Molecular and Cellular Proteomics : MCP - Category: Molecular Biology Authors: Source Type: research