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Cell viability, phenotype, memory subsets, chemokine receptors, and intracellular cytokines were assessed by flow cytometry. Differential gene expression, miRNA\/sRNA profiles, and pathway enrichments were analyzed by RNA-seq and small-RNA sequencing. Proteome-wide IgG binding was mapped using human proteome microarrays across lymphoid subsets, and pathogen-derived linear epitope recognition was evaluated using a 4,345-epitope infectious-disease microarray.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>pIgG preserved PBMC viability but significantly modulated immune function: it reduced IL-17\u207a CD4\u207a T cells and tissue-resident memory T cells, decreased IL-4\u207a CD8\u207a T cells, enhanced IFN-\u03b3\u207a \u03b3\u03b4 T cells, downregulated CCR5 and CCR6, and expanded IL-10\u207a B cells while reducing IL-13\u207a and IL-17\u207a B cells. Transcriptomic analysis revealed 4,820 upregulated and 2,160 downregulated genes, with enrichment of MHC class II and TCR-signaling pathways and selective modulation of cytokine, chemokine, CD, and HLA genes. Innate sensors\u2014including TLR4, TLR8, and NLR4\u2014were downregulated. Small-RNA analysis identified 19 differentially expressed miRNAs and 79 novel sRNAs, indicating epigenetic remodeling. Proteome-wide profiling detected\u2009~\u2009130 IgG-recognized proteins per lymphocyte subset and 180 shared targets enriched in cytosolic, vesicular, and endocytic pathways. Pathogen-epitope profiling identified 948 recognized sequences from 56 viruses, 21 bacteria, and 12 parasites.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>pIgG functions as a multilayered immunoregulator that attenuates Th17-associated inflammation, promotes IL-10\u2013mediated regulatory circuits, and modulates receptor signaling and antigen-processing pathways. These findings underscore its potential for broad therapeutic immunomodulation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-026-08289-6","type":"journal-article","created":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T05:24:43Z","timestamp":1780118683000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["System-wide immunoregulation by polyvalent IgG: integrating transcriptomic, miRNA, and proteomic landscapes"],"prefix":"10.1186","volume":"24","author":[{"given":"Jo\u00e3o Vitor da Silva","family":"Borges","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lhays Oz\u00f3rio","family":"Passos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolle Rakanidis","family":"Machado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lais Alves","family":"do Nascimento","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz Oliveira","family":"Fagundes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabela Siuffi","family":"Bergamasco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Luisa Baratelli","family":"Moreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natali Espasiani","family":"Cilento","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabri Saeed","family":"Sanabani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6092-8394","authenticated-orcid":false,"given":"Jefferson Russo","family":"Victor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,30]]},"reference":[{"key":"8289_CR1","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/j.molimm.2004.07.046","volume":"42","author":"R Lemieux","year":"2005","unstructured":"Lemieux R, Bazin R, N\u00e9ron S. 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