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Biomarkers and targeted new therapies for IgA nephropathy

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Abstract

IgA nephropathy (IgAN) has variable clinical presentation and outcome. There is a need to identify children who have the potential to progress to end stage renal disease (ESRD). Biomarkers related to the pathogenetic process of IgAN can detect risk factors and identify targets for new therapies. Galactose-deficient IgA1 (Gd-IgA1) is a specific biomarker of IgAN and could be the first treatment target. In experimental mice, reduction of IgA1 deposits and hematuria was observed after treatment with a bacterial protease that selectively cleaves human IgA1. Glycan-targeted drugs that may act to neutralize Gd-IgA1 inhibit abnormal enzymatic glycosylation of IgA1 or deplete cells producing Gd-IgA1. The autoimmune response to Gd-IgA1 produces autoantibodies that are sensitive and specific biomarkers of IgAN development and progression and suggests the possible benefits of anti-B cell therapies directed against CD20, B-cell activating factor (BAFF), or B cell receptor, and also proteasome inhibitors. The activation of complement in IgAN offers new biomarkers and the rationale for using complement inhibitors, including eculizumab. Renal pathological features represent sensitive biomarkers of added value over clinical data and may drive steroid therapy in selected cases. Finally, the hypothesis of the involvement of intestinal mucosal immunity in the pathogenesis of IgAN suggests the possibility of avoiding the systemic effect of steroid. Enteric budesonide targeting Peyer’s patches at the ileocecal junction is an interesting option that has provided some preliminary favorable results in IgAN. In conclusion, the identification of new biomarkers is a promising area for therapies targeting IgAN in patients at risk of progression.

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Article 11 February 2016

Kar Neng Lai, Sydney C. W. Tang, … Richard J. Glassock

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  1. Nephrology, Dialysis and Transplantation, Regina Margherita Hospital, Fondazione Ricerca Molinette, Turin, Italy

    Rosanna Coppo

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Coppo, R. Biomarkers and targeted new therapies for IgA nephropathy. Pediatr Nephrol 32, 725–731 (2017). https://doi.org/10.1007/s00467-016-3390-9

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