Development of an ultra-sensitive human IL-33 biomarker assay for age-related macular degeneration and asthma drug development

• DOI: 10.1186/s12967-021-03189-3
• Publication Date: 2021-12-20T10:03:12Z
• Authors: Elaine Mai; Joyce Chan; Levina Goon; Braeden K. Ego; Jack Bevers; Tiffany Wong; Manda Wong; Racquel Corpuz; Hongkang Xi; Jia Wu; Kellen Schneider; Dhaya Seshasayee; Michele Grimbalde...; Gerald Nakamura; Vahan B. Indjeian; Menno van Lookere...; Kelly M. Loyet; Laetitia Comps-Agrar
• Keywords: Drug Development

Abstract Background Over the past decade, human Interleukin 33 (hIL-33) has emerged as a key contributor to pathogenesis of numerous inflammatory diseases. Despite existence several commercial hIL-33 assays spanning multiple platform technologies, their ability provide accurate concentration measurements and differentiate between active (reduced) inactive (oxidized) in various matrices remains uncertain. This is especially true for lower sample volumes, with low concentrations, elevated levels soluble 1 Receptor-Like (sST2), an form ST2 that competes membrane bound binding. Results We tested performance commercially available detection found most these lacked sensitivity accurately detect reduced at biologically relevant (sub-to-low pg/mL), presence sST2 (hsST2), and/or sufficient target specificity. To address this, we developed validated sensitive specific enzyme-linked immunosorbent assay (ELISA) capable detecting total even high concentrations sST2. By incorporating immuno-polymerase chain reaction (iPCR) platform, further increased this by ~ 52-fold. Using iPCR assay, detected postmortem vitreous humor (VH) samples from donors age-related macular degeneration (AMD) significantly when compared control individuals. No statistically significant difference was observed aqueous (AH) AMD nor plasma nasosorption fluid (NF) asthma patients Conclusions Unlike existing assays, our bioassays are highly can quantify clinical matrices, including those hsST2. Our results proof concept utility trials targeting hIL-33/hST2 pathway.