{
  "abstract": "Introduction: Pregnancy-specific glycoprotein 9 (PSG9) is one of 10 members of a conserved glycoprotein family within the carcinoembryonic antigen superfamily expressed by placental trophoblasts and secreted into maternal circulation. PSG1 and PSG9 induce the conversion of naïve T cells into regulatory T cells by increasing active transforming growth factor-beta (TGF-β) availability and were predicted to share anti-inflammatory activity in innate immune cells. However, while maternal PSG1 concentrations are lower in preeclampsia, PSG9 levels are reported to be elevated, suggesting PSG1 and PSG9 may differ in some immune-regulatory functions. Here, we characterized the immunomodulatory effects of PSG9 on myeloid cells.\n\nMethods: Recombinant PSG9 was produced in Chinese hamster ovary (CHO) cells using standard expression protocols and evaluated for biological activity in human and murine myeloid cells.\n\nResults: Results: Recombinant PSG9 preparations initially displayed batch-dependent variability, with some preparations eliciting Toll-like receptor 2 (TLR2)-mediated immunostimulatory responses in monocytes and macrophages, while others exhibited anti-inflammatory effects. Label-free quantitative proteomics revealed that pro-inflammatory preparations contained CHO host cell proteins (HCPs). Further purification by cation exchange chromatography (CIEX) substantially removed these immunomodulatory impurities, resolving batch-to-batch variations.\n\nDiscussion: These findings demonstrate that, like PSG1, fully purified PSG9 exerts anti-inflammatory activity in myeloid cells. Furthermore, process-related impurities such as HCPs can significantly confound the observed bioactivity of recombinant proteins, highlighting the critical need for rigorous impurity control during functional characterization.",
  "abstract_shown": true,
  "affiliations": [
    "Office of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration",
    "National Institute on Deafness and Other Communication Disorders (NIH), Section on Sensory Physiology and Biophysics",
    "Uniformed Services University of the Health Sciences, Pathology",
    "Facility for Biotechnology Resources, Center for Biologics Evaluation and Research, Food and Drug Administration"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Mirian Mendoza"
    },
    {
      "affs": [
        0
      ],
      "name": "Uriel Ortega-Rodriguez"
    },
    {
      "affs": [
        0
      ],
      "name": "Ha-Na Lee"
    },
    {
      "affs": [
        1
      ],
      "name": "Angela Ballesteros"
    },
    {
      "affs": [
        2
      ],
      "name": "James Warren"
    },
    {
      "affs": [
        2
      ],
      "name": "Maria Rendon-Correa"
    },
    {
      "affs": [
        3
      ],
      "name": "Wells W. Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Daniela Verthelyi"
    },
    {
      "affs": [
        2
      ],
      "name": "Gabriela Dveksler"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4m6dvn3b60w4m.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1882381",
  "fulltext_url": "https://europepmc.org/articles/PMC13713651",
  "id": "4m6dvn3b60w4m",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1882381/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "1312|Protein purification and stability"
    ]
  ],
  "openalex": "W7221831527",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1882381/pdf",
  "pmcid": "PMC13713651",
  "pmid": "42952918",
  "published": "2026-10-14",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/4m6dvn3b60w4m.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1882381",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1882381/full"
    },
    {
      "first_seen": "2026-10-31T00:20:41Z",
      "native_id": "MED:42952918",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42952918"
    },
    {
      "first_seen": "2026-10-31T12:24:10Z",
      "native_id": "PMC13713651",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fimmu.2026.1882381"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein purification and stability",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Host cell protein impurities modify the immunomodulatory profile of pregnancy-specific glycoprotein 9, a cautionary tale",
  "title_text": "Host cell protein impurities modify the immunomodulatory profile of pregnancy-specific glycoprotein 9, a cautionary tale",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:21:17Z",
  "url": "https://research.draconitic.com/paper/4m6dvn3b60w4m",
  "venue": "Frontiers in Immunology",
  "versions": []
}