Evidence map›Paper›PMID 42218535›Full record

ArticleJournal of translational medicine2026

System-wide immunoregulation by polyvalent IgG: integrating transcriptomic, miRNA, and proteomic landscapes.

João Vitor da Silva Borges, Lhays Ozório Passos, Nicolle Rakanidis Machado, Lais Alves do Nascimento, Beatriz Oliveira Fagundes, Isabela Siuffi Bergamasco, Anna Luisa Baratelli Moreira, Natali Espasiani Cilento, Sabri Saeed Sanabani, Jefferson Russo Victor

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

João Vitor da Silva Borges *Medical School, Santo Amaro University (UNISA), Sao Paulo, Brazil.
Lhays Ozório Passos *Post Graduation Program in Health Sciences, Santo Amaro University (UNISA), Sao Paulo, Brazil.
Nicolle Rakanidis Machado *Laboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of São Paulo, 500 Av. Dr. Enéas Carvalho de Aguiar, São Paulo, 05403-000, Brazil.
Lais Alves do Nascimento *Laboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of São Paulo, 500 Av. Dr. Enéas Carvalho de Aguiar, São Paulo, 05403-000, Brazil.
Beatriz Oliveira FagundesLaboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of São Paulo, 500 Av. Dr. Enéas Carvalho de Aguiar, São Paulo, 05403-000, Brazil.
Isabela Siuffi BergamascoPost Graduation Program in Health Sciences, Santo Amaro University (UNISA), Sao Paulo, Brazil.
Anna Luisa Baratelli MoreiraLaboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of São Paulo, 500 Av. Dr. Enéas Carvalho de Aguiar, São Paulo, 05403-000, Brazil.
Natali Espasiani CilentoPost Graduation Program in Health Sciences, Santo Amaro University (UNISA), Sao Paulo, Brazil.
Sabri Saeed SanabaniLaboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of São Paulo, 500 Av. Dr. Enéas Carvalho de Aguiar, São Paulo, 05403-000, Brazil.
Jefferson Russo VictorMedical School, Santo Amaro University (UNISA), Sao Paulo, Brazil. victorjr@usp.br.ORCID 0000-0001-6092-8394

Funding

Conselho Nacional de Desenvolvimento Científico e Tecnológico 304459/2024-0 and 402406/2024-9Fundação de Amparo à Pesquisa do Estado de São Paulo 2021/08225-8
6 · The paper itself

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.

Indexed as

Immunoglobulin GMicroRNAsProteomicsTranscriptomeCell SurvivalCytokinesGene Expression ProfilingGene Expression RegulationHumansLeukocytes, MononuclearProteomeCytokinesImmunoglobulin GMicroRNAsProteomeAntibody repertoiresEpitope profilingIdiotypic networkIL-10–producing B cellsImmune regulationIntravenous immunoglobulin (IVIg)Lymphocyte modulationmicroRNAPolyvalent IgG (pIgG)Proteome microarrayRegulatory T cellsTh17 cellsTranscriptomicsTRIM21γδ T cells

Identifiers

PMID42218535
PMCPMC13430737

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.