{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T02:51:01Z","timestamp":1786243861838,"version":"build-2736575974"},"reference-count":123,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,11,4]],"date-time":"2023-11-04T00:00:00Z","timestamp":1699056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Otsuka Pharmaceutical Development &amp; Commercialization, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>A PRoliferation-Inducing Ligand (APRIL), the thirteenth member of the tumor necrosis factor superfamily, plays a key role in the regulation of activated B cells, the survival of long-lived plasma cells, and immunoglobulin (Ig) isotype class switching. Several lines of evidence have implicated APRIL in the pathogenesis of IgA nephropathy (IgAN). Globally, IgAN is the most common primary glomerulonephritis, and it can progress to end-stage kidney disease; yet, disease-modifying treatments for this condition have historically been lacking. The preliminary data in ongoing clinical trials indicate that APRIL inhibition can reduce proteinuria and slow the rate of kidney disease progression by acting at an upstream level in IgAN pathogenesis. In this review, we examine what is known about the physiologic roles of APRIL and evaluate the experimental and epidemiological evidence describing how these normal biologic processes are thought to be subverted in IgAN. The weight of the preclinical, clinical, and genetic data supporting a key role for APRIL in IgAN has galvanized pharmacologic research, and several anti-APRIL drug candidates have now entered clinical development for IgAN. Herein, we present an overview of the clinical results to date. Finally, we explore where more research and evidence are needed to transform potential therapies into clinical benefits for patients with IgAN.<\/jats:p>","DOI":"10.3390\/jcm12216927","type":"journal-article","created":{"date-parts":[[2023,11,4]],"date-time":"2023-11-04T15:41:41Z","timestamp":1699112501000},"page":"6927","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["A PRoliferation-Inducing Ligand (APRIL) in the Pathogenesis of Immunoglobulin A Nephropathy: A Review of the Evidence"],"prefix":"10.3390","volume":"12","author":[{"given":"Mohit","family":"Mathur","sequence":"first","affiliation":[{"name":"Visterra, Inc., Waltham, MA 02451, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tak Mao","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kook-Hwan","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Kooienga","sequence":"additional","affiliation":[{"name":"Colorado Kidney and Vascular Care, Denver, CO 80012, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0785-3183","authenticated-orcid":false,"given":"Min","family":"Zhuo","sequence":"additional","affiliation":[{"name":"Visterra, Inc., Waltham, MA 02451, USA"},{"name":"Division of Renal Medicine, Department of Medicine Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cibele S.","family":"Pinto","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development & Commercialization, Princeton, NJ 08540, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bobby","family":"Chacko","sequence":"additional","affiliation":[{"name":"Nephrology and Transplantation Unit, John Hunter Hospital, Newcastle, NSW 2305, Australia"},{"name":"School of Medicine and Public Health, University of Newcastle, Callaghan, NSW 2308, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1084\/jem.188.6.1185","article-title":"APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth","volume":"188","author":"Hahne","year":"1998","journal-title":"J. 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