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The following is a summary of “Regulation of immune cell metabolism by therapeutic normal IgG intravenous immunoglobulin,” published in the May 2025 issue of Journal of Allergy and Clinical Immunology by Rambabu et al. 

Immune cell metabolism and its by-products influenced immune responses, and dysregulation in this process was linked to autoimmune and inflammatory diseases.  

Researchers conducted a retrospective study to examine how intravenous immunoglobulin (IVIG) influenced metabolic processes in human immune cells.  

They performed metabolic flux analyses on human peripheral blood mononuclear cells (PBMCs) stimulated with inflammatory mediators. Intracellular metabolites were then extracted from activated PBMCs and analyzed using liquid chromatography (LC) coupled with high-resolution mass spectrometry. Untargeted global metabolic profiling was performed to map the metabolic landscape and identify IVIG-induced metabolic reprogramming in PBMCs. Targeted lipidomics were applied to investigate the mechanisms underlying IVIG-induced lipogenesis.  

The results showed that IVIG and its Fc and F(ab’)₂ fragments modulated the Warburg effect in activated PBMCs based on glucose availability. Untargeted global metabolic profiling indicated that IVIG reshaped the metabolic profile of PBMCs stimulated with inflammatory mediators and inhibited the prenylation of the amino acid cysteine and enhanced the synthesis of anti-inflammatory lipids such as diacylglycerol and triacylglycerol by diverting acetyl-CoA from the mevalonate pathway. The IVIG-induced lipogenesis was driven by F(ab’)₂ fragments and required the presence of sialylated glycans on immunoglobulin G (IgG).  

Investigators concluded that IVIG targeted immune cell metabolism, highlighting a novel mechanism of action in the immunotherapy of autoimmune and inflammatory diseases. 

Source:jacionline.org/article/S0091-6749(25)00552-4/fulltext