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

Area of Science:

• Immunology
• Molecular Biology
• Genomics

Background:

• Polyvalent IgG (pIgG/IVIg) is derived from thousands of donors and has broad immunomodulatory effects.
• Its precise cellular targets and genome-wide regulatory impacts are not fully understood.

Purpose of the Study:

• To define the direct cellular targets of pIgG.
• To elucidate the genome-wide regulatory impacts of pIgG on immune cells.

Main Methods:

• Peripheral blood mononuclear cells (PBMCs) from healthy donors were cultured with pIgG or mock conditions.
• Flow cytometry, RNA-seq, small-RNA sequencing, and proteome microarrays were used to assess cellular function, gene expression, and protein binding.
• Pathogen-derived epitope recognition was evaluated using infectious-disease microarrays.

Main Results:

• pIgG modulated immune cell populations, including T cells and B cells, altering cytokine production and chemokine receptor expression.
• Transcriptomic analysis revealed significant differential gene expression and pathway enrichment, including MHC class II and TCR signaling.
• Proteome-wide profiling identified numerous IgG-recognized proteins and pathogen-derived epitopes, indicating broad molecular interactions.

Conclusions:

• pIgG acts as a multilayered immunoregulator, attenuating inflammation and promoting regulatory immune circuits.
• It modulates receptor signaling and antigen-processing pathways, highlighting its therapeutic potential.