{
  "abstract": "Serological evaluation of antibody response using conventional indirect immunoassays cannot capture the full depth, diversity, and functional complexity of human polyclonal antibodies. Here, we developed mass spectrometry-based Proteome-Wide Serology (ProWiSe) assays for the identification and absolute quantification of antigen-specific human antibodies across isotypes, subclasses, and variable-region repertoires. Using ProWiSe, we measured the depth and diversity of serum antibodies to multiple antigens of respiratory syncytial virus (RSV), a pathogen associated with repeated reinfections and skewed immune response. IgG1 antibodies targeting the fusion glycoprotein F (RSVF) dominated the antibody response, with a background-corrected median level of 1,700 ng/mL across 214 healthy maternal serum samples from the general population. ProWiSe identified reproducible co-enrichment of complement component 1q complexes, revealed the usage of several dozen IGHV variable-region germline genes in the anti-RSVF polyclonal response, and suggested limited IGHV repertoire diversity in some individuals. In addition to IgG1, we discovered a complex antibody response characterized by significantly elevated levels of nearly all human immunoglobulin isotypes and subclasses, including previously unexplored IgG4 and IgD. The identification of high-affinity IgD against prefusion and postfusion RSVF, but not against other antigens studied, was the most unexpected observation, occurring in 52% of the healthy maternal serum samples. ProWiSe unambiguously identified the secreted IgD isoform P01880-1 and supported the IgD paradox of preferential {lambda} light-chain usage in secreted IgD. Detectable anti-RSVF IgD levels ([≥]0.11 ng/mL) correlated with broadly elevated antibody responses across all other isotypes and subclasses, except IgE. ProWiSe assays offer a versatile platform for quantitative serological diagnostics, exploration of depth, diversity, and dynamics of polyclonal antibody response, and discovery of rare antibody isotypes.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Laboratory Medicine and Pathology, University of Alberta"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "Z. Turner"
    },
    {
      "name": "W. Tang"
    },
    {
      "name": "Y. Rais"
    },
    {
      "affs": [
        0
      ],
      "name": "A. P. Drabovich"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b5v74076src3s.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.03.764056",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.764056v1.full",
  "id": "b5v74076src3s",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.764056v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.764056v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-03",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/b5v74076src3s.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:21:08Z",
      "native_id": "10.64898/2026.11.03.764056",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.03.764056v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Proteome-Wide Serology Identifies Secreted IgD against RSV Fusion Glycoprotein as a Signature of Broadly Elevated Antibody Response",
  "title_text": "Proteome-Wide Serology Identifies Secreted IgD against RSV Fusion Glycoprotein as a Signature of Broadly Elevated Antibody Response",
  "type": "preprint",
  "updated_at": "2026-11-04T12:21:08Z",
  "url": "https://research.draconitic.com/paper/b5v74076src3s",
  "venue": "bioRxiv",
  "versions": []
}