Identification and characterization of natural antibodies against tau protein in an intravenous immunoglobulin product

• Natural anti-tau antibodies from Flebogamma® IVIG product were isolated.
• The reactivity of isolated antibodies was not exclusively phospho-specific.
• The isolated antibodies showed the highest reactivity with truncated tau form.
• The isolated antibodies were determined as low-avidity.

The latest therapeutic approaches to Alzheimer disease are using intravenous immunoglobulin (IVIG) products. Therefore, the detailed characterization of target-specific antibodies naturally occurring in IVIG products is beneficial. We have focused on characterization of antibodies isolated against tau protein, a biomarker of Alzheimer's disease, from Flebogamma IVIG product. The analysis of IgG subclass distribution indicated skewing toward IgG3 in anti-tau-enriched IgG fraction. The evaluation of their reactivity and avidity with several recombinant tau forms was performed by ELISA and blotting techniques. Truncated non-phosphorylated tau protein (amino acids 155–421) demonstrated the highest reactivity and avidity index. We provide the first detailed insight into the reactivity of isolated natural antibodies against tau protein.