ArticleJournal of translational medicine2026
System-wide immunoregulation by polyvalent IgG: integrating transcriptomic, miRNA, and proteomic landscapes.
Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundPolyvalent IgG (pIgG/IVIg), derived from thousands of donors, exerts broad immunomodulatory effects; however, its direct cellular targets and genome-wide regulatory impacts remain incompletely defined.
methodsPeripheral blood mononuclear cells (PBMCs) from 20 healthy donors were cultured for 72 h with pIgG (100 µg/mL) or mock conditions. 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.
resultspIgG preserved PBMC viability but significantly modulated immune function: it reduced IL-17⁺ CD4⁺ T cells and tissue-resident memory T cells, decreased IL-4⁺ CD8⁺ T cells, enhanced IFN-γ⁺ γδ T cells, downregulated CCR5 and CCR6, and expanded IL-10⁺ B cells while reducing IL-13⁺ and IL-17⁺ 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-including TLR4, TLR8, and NLR4-were downregulated. Small-RNA analysis identified 19 differentially expressed miRNAs and 79 novel sRNAs, indicating epigenetic remodeling. Proteome-wide profiling detected ~ 130 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.
conclusionspIgG functions as a multilayered immunoregulator that attenuates Th17-associated inflammation, promotes IL-10-mediated regulatory circuits, and modulates receptor signaling and antigen-processing pathways. These findings underscore its potential for broad therapeutic immunomodulation.
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