{
  "abstract": "IgA nephropathy (IgAN) is a common primary glomerulonephritis characterized by glomerular immune-complex deposits with (co)dominant IgA. These deposits are enriched for IgA1 glycoforms with some O- glycans deficient in galactose (Gd-IgA1). Circulating Gd-IgA1 is bound by IgG autoantibodies forming immune complexes, some of which deposit in glomeruli and induce kidney injury. Genomic and immunologic studies indicate involvement of pro-inflammatory signaling pathways in the production of Gd-IgA1 in IgAN. Genomic studies identified multiple genetic loci associated with IgAN and suggested a convergence on the NF-κB pathway, including RELA , the gene encoding the NF-κB subunit p65. However, the mechanisms by which NF-κB pathways may affect O -glycosylation in IgA1-producing cells are unknown. Using EBV-immortalized B cells derived from peripheral-blood mononuclear cells of IgAN patients and healthy controls, we report that inhibition of p65 NF-κB by an IKK-β inhibitor, TPCA-1, reduced phosphorylation of p65 NF-κB and decreased production of IgA1 and, conversely, increased Gd-IgA1 production. This effect on Gd-IgA1 was likely related to reduced expression of C1GALT1 gene that encodes the enzyme responsible for galactosylation of IgA1 O -glycans. Flow-cytometry imaging revealed changes in nuclear translocation and co-localization of p65 NF-κB with co-transcriptional factor SP1, a transcriptional activator of C1GALT1 , suggesting that NF-κB pathway and SP1 association affect IgA1 O -glycosylation through transcriptional control of C1GALT1 expression. Furthermore, prolonged IKK-β inhibition altered B-cell subpopulations, enhancing generation of cells with a plasmablast-like phenotype, characterized by high SSC MFI and CD138 expression. Together, these findings implicate p65 NF-κB and its transcriptional partners in IgA1 O -glycosylation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medicine, University of Alabama at Birmingham",
    "Department of Microbiology, University of Alabama at Birmingham"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Taylor Person"
    },
    {
      "affs": [
        0
      ],
      "name": "Maggie Phillips"
    },
    {
      "affs": [
        0
      ],
      "name": "Terri Rice"
    },
    {
      "affs": [
        1
      ],
      "name": "Stacy Hall"
    },
    {
      "affs": [
        0
      ],
      "name": "Bruce A. Julian"
    },
    {
      "affs": [
        0
      ],
      "name": "Dana V. Rizk"
    },
    {
      "affs": [
        1
      ],
      "name": "Jan Novak"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Colin Reily"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6sh3pxjwm310p.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1913226",
  "fulltext_url": null,
  "id": "6sh3pxjwm310p",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1913226/full",
  "language": null,
  "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": [
    [
      "openalex",
      "2727|Renal Diseases and Glomerulopathies"
    ]
  ],
  "openalex": "W7224095845",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1913226/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/6sh3pxjwm310p.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1913226",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1913226/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:1664-3224",
      "subfield": "immunology"
    }
  ],
  "title": "IKK-β inhibitor TPCA-1 increases Gd-IgA1 production and decreases C1GALT1 expression in EBV-immortalized B cells from human donors",
  "title_text": "IKK-β inhibitor TPCA-1 increases Gd-IgA1 production and decreases C1GALT1 expression in EBV-immortalized B cells from human donors",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:17Z",
  "url": "https://research.draconitic.com/paper/6sh3pxjwm310p",
  "venue": "Frontiers in Immunology",
  "versions": []
}