A proliferation-inducing ligand (APRIL) is a key member of the tumor necrosis factor superfamily of cytokines and plays a central role in B-cell survival, proliferation, and Ig class switching. Recently, there has been increasing interest in the role of APRIL and the related cytokine B-cell activating factor in several glomerular diseases, because of their importance in the above processes. The therapeutic inhibition of APRIL represents a potentially attractive immunomodulatory approach that may abrogate deleterious host immune responses in autoimmune diseases while leaving other important functions of humoral immunity intact, such as memory B-cell function and responses to vaccination, in contrast to B-cell-depleting strategies. In this review, we describe the physiological roles of APRIL in B-cell development and their relevance to glomerular diseases, and outline emerging clinical trial data studying APRIL inhibition, with a focus on IgA nephropathy where the clinical development of APRIL inhibitors is in its most advanced stage.

Department of Cardiovascular Sciences University of Leicester Leicester UK; John Walls Renal Unit University Hospitals of Leicester National Health Service Trust Leicester UK

Department of Nephrology General University Hospital Charles University Prague Czech Republic

Department of Nephrology Juntendo University Faculty of Medicine Tokyo Japan

Department of Renal Medicine Concord Repatriation General Hospital Concord Australia; Department of Medicine University of Sydney Camperdown Australia

Division of Nephrology Department of Medicine Stanford University School of Medicine Stanford University Stanford California USA

Division of Nephrology University of Alabama at Birmingham Birmingham Alabama USA

Nephrology Service and Kidney Transplant Unit Hospital Británico de Buenos Aires Buenos Aires Argentina

Renal Division Peking University 1st Hospital Peking University Institute of Nephrology Beijing People's Republic of China

The Kidney and Transplant Practice Mount Elizabeth Novena Hospital Singapore

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