Complex Immunoglobulin Preparation Exposed to Acidic Conditions: Will It Retain Its Physiological Functions?

Oral immunoglobulin preparations are a promising therapeutic approach for inflammatory bowel diseases. During enteral administration, antibodies inevitably encounter low pH conditions in the stomach, which can alter their conformation and functions. Understanding how acidic exposure influences the activity of therapeutic immunoglobulins is essential for improving their stability and clinical efficacy. In this study, a human plasma-derived immunoglobulin preparation containing IgG, IgA, and IgM was exposed to mildly and strongly acidic buffers. The treated samples were analyzed using dynamic light scattering to assess structural stability, enzyme-linked immuno-sorbent assay and Western blotting to evaluate antigen-binding specificity, and flow cytometry and confocal microscopy to study neutrophil functions. Acidic treatment did not induce aggregation or major structural destabilization but caused marked functional changes. Exposure to low pH in-creased the polyreactivity of IgG and IgA toward bacterial and viral antigens, while IgM lost its binding specificity. Acid-modified immunoglobulins enhanced bacterial recognition by neutrophils without affecting phagocytosis or oxidative activity but promoted the release of extracellular DNA structures, a hallmark of neutrophil activation. These findings indicate that short-term acidic expo-sure modifies antibody specificity and immune function without compromising structural integrity. Such effects may be relevant for optimizing therapeutic formulations and understanding antibody behavior in acidic mucosal environments.