Paradigm shift in activity assessment of IgA nephropathy - optimizing the next generation of diagnostic and therapeutic maneuvers via glycan targeting.

INTRODUCTION: IgA nephropathy (IgAN) is the most common glomerular disease and has a poor prognosis. Appropriate therapeutic strategies are not currently available due to the lack of information regarding IgAN pathogenesis and the absence of appropriate tools to assess disease activity in IgAN, a long-term chronic disease. However, recent evidence revealed that aberrantly glycosylated serum IgA1, mostly galactose-deficient IgA1 (Gd-IgA1) and immune complexes (ICs) with autoantibodies against glycan-containing epitopes on Gd-IgA1 are essential effector molecules. AREAS COVERED: Assessing disease activity by urinalysis/renal biopsy has some limitations, resulting in conflicts regarding the efficacy of possible IgAN-specific therapies. We summarize the characteristics and molecular basis of Gd-IgA1 and related ICs, their clinical application for activity assessment and early diagnosis, and discuss glycan as a potent target of therapeutic agents based on glycan engineering in IgAN. EXPERT OPINION: Recently, Gd-IgA1 and related ICs have shown clinical value for disease activity assessment and IgAN diagnosis. This suggests a paradigm shift in IgAN treatment thus allowing development of appropriate clinical trials of patients with IgAN stages and objective evaluation of the efficacy of future treatments. Early screening and diagnosis may increase therapeutic options, including quantitative regulation of nephritogenic Gd-IgA1 using therapeutic antibodies and selective depletion of Gd-IgA1-producing cells via glycan engineering.