Development of monoclonal antibodies and antigens as liquid biopsy reagents for IgA nephropathy

Abstract

Abstract IgA nephropathy (IgAN) is the most common primary autoimmune glomerular disorder across the world. A renal biopsy examination is absolutely required for final diagnosis. In particular, IgAN has been categorized as an autoimmune disease that features IgA-ICs formed by galactose-deficient (Gd)-IgA1 (autoantigen) and corresponding IgG anti-Gd-IgA1 (autoantibody). Therefore, it is clinically warranted to develop a liquid kidney biopsy for non-invasive or only minimally invasive approaches for early diagnosis of IgAN and to ease monitoring the evolution of the disease. We have recently developed three monoclonal antibodies namely EASON1, EASON2, and EASON3, and each of them shows high discriminative rate in differentiating IgAN patients and healthy control subjects by doing ELISA-based analyses to determine serum Gd-IgA1 levels (Provisional patent - T2392-US, USAentitled “Production of IgG monoclonal antibody series anti-galactose deficient IgA1 and IgA1 bearing O-linked glycans; Provisional patent - 63/119,215, USAentitled “Development of a series of IgM monoclonal antibodies as non-invasive diagnostic reagents for IgA nephropathy; a regular patent application under review). Moreover, we have successfully developed 62 human hybridoma cell lines that produce Gd-IgA1, each of which will be useful in designing tests for the detection of serum IgG autoantibodies against Gd-IgA1 levels (Provisional patent - T2392-US, USA). In conclusion, both the 3 mouse monoclonal antibodies and 62 human Gd-IgA1-producing hybridoma cell lines may be further developed as promising diagnostic reagents for a liquid kidney biopsy for IgAN, allowing for early, rapid, and non-invasive tests for the renal disease. Supported by grants from Ministry of Science and Technology, Taiwan (MOST 108-2321-B-016-002, 109-2314-B-016 -034 -MY3)