Kallikrein genes are associated with lupus and glomerular basement membrane–specific antibody–induced nephritis in mice and humans

• DOI: 10.1172/jci36728
• Publication Date: 2009-04-07T20:32:19Z
• Authors: Kui Liu; Quan-Zhen Li; Angelica M. Delga...; Anna-Karin Abelson; Elena Sánchez; Jennifer A. Kelly; Li Li; Yang Liu; Jinchun Zhou; Mei Yan; Qiu Ye; Shenxi Liu; Chun Xie; Xin J. Zhou; Sharon A. Chung; Bernardo Pons-Estel; Torsten Witte; Enrique de Ramón; Sang-Cheol Bae; Nadia Barizzone; Gian Domenico Seb...; Joan T. Merrill; Peter K. Gregersen; Gary G. Gilkeson; Robert P. Kimberly; Timothy J. Vyse; Il Kim; Sandra D’Alfonso; Javier Martin; John B. Harley; Lindsey A. Criswell; Edward K. Wakeland; Marta E. Alarcón-...; Chandra Mohan
• Keywords: Nephritis

Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous nephritis. Inbred mouse strains differ susceptibility anti-GBM antibody-induced This study sought clarify the genetic molecular factors that maybe responsible enhanced immune-mediated renal these models. When kidneys of 3 sensitive were compared with those 2 control using microarray analysis, one-fifth underexpressed genes belonged kallikrein gene family,which encodes serine esterases. Mouse upregulated urinary kallikreins exhibited less evidence disease. Antagonizing pathway augmented disease, while agonists dampened severity In addition, nephritis-sensitive had haplotypes distinct from strains, including several regulatory polymorphisms,some which associated functional consequences. Indeed, increased was achieved breeding mice a interval harboring onto disease-resistant background. Finally, both human SLE found be genes, particularly KLK1 KLK3 promoter, when DNA SNPs independent cohorts patients controls compared. Collectively, studies suggest are protective disease-associated lupus.