Profiling C‑Phycocyanin: From Extraction to Structure, IgE Recognition and Digestive Transformation of Spirulina’s Major Pigment‑Protein

Microalgae have emerged as promising sources of sustainable nutrients and bioactive compounds, attracting growing interest for their potential use in future food systems. Arthrospira platensis (commonly known as Spirulina) is particularly valued for its high protein content and functional pigments, among which C-phycocyanin (C-PC) is the most abundant. Although Spirulina is generally recognized as safe by regulatory agencies, recent reports have described allergic reactions in sensitized individuals, raising concerns about the allergenic potential of C-PC and related proteins. In this study, C-PC was extracted and purified from A. platensis, and its structural integrity and oligomeric state were characterized. Immunoreactivity was assessed using sera from Spirulina-sensitized patients and allergic to crustaceans, mites, and fish to explore potential cross-reactivity. Simulated gastrointestinal digestion was then performed to evaluate the stability and allergenic behavior of the protein. C-PC displayed clear IgE-binding activity in its intact form, confirming its relevance as a potential allergen. However, simulated gastrointestinal digestion reduced IgE-binding activity and caused extensive fragmentation and high-resolution LC–MS analysis. This work provides new insights into the digestive profile and immunoreactivity of Spirulina proteins, supporting a more accurate assessment of their safety and informing their responsible use in food and nutraceutical applications.