ABIN1 Dysfunction as a Genetic Basis for Lupus Nephritis

• DOI: 10.1681/asn.2013020148
• Publication Date: 2013-08-23T04:49:04Z
• Authors: Dawn J. Caster; Erik A. Korte; Sambit K. Nanda; Kenneth R. McLeish; Rebecca K. Oliver; Rachel T. G'Sell; Ryan M. Sheehan; Darrell W. Freeman; Susan C. Coventry; Jennifer A. Kelly; Joel M. Guthridge; Judith A. James; Kathy L. Sivils; Marta E. Alarcon-...; R. Hal Scofield; Indra Adrianto; Patrick M. Gaffney; Anne M. Stevens; Barry I. Freedman; Carl D. Langefeld; Betty P. Tsao; Bernardo A. Pons-...; Chaim O. Jacob; Diane L. Kamen; Gary S. Gilkeson; Elizabeth E. Brown; Graciela S. Alarcon; Jeffrey C. Edberg; Robert P. Kimberly; Javier Martin; Joan T. Merrill; John B. Harley; Kenneth M. Kaufman; John D. Reveille; Juan-Manuel Anaya; Lindsey A. Criswell; Luis M. Vila; Michelle Petri; Rosalind Ramsey-G...; Sang-Cheol Bae; Susan A. Boackle; Timothy J. Vyse; Timothy B. Niewold; Philip Cohen; David W. Powell
• Keywords: Nephritis; Pathogenesis

The genetic factors underlying the pathogenesis of lupus nephritis associated with systemic erythematosus are largely unknown, although animal studies indicate that nuclear factor (NF)-κB is involved. We reported previously a knockin mouse expressing an inactive form ABIN1 (ABIN1[D485N]) develops lupus-like autoimmune disease and demonstrates enhanced activation NF-κB mitogen-activated protein kinases in immune cells after toll-like receptor stimulation. In current study, we show ABIN1[D485N] mice develop progressive GN similar to class III IV humans. To investigate clinical relevance dysfunction, genotyped five single-nucleotide polymorphisms gene encoding ABIN1, TNIP1, samples from European-American, African American, Asian, Gullah, Hispanic participants Large Lupus Association Study 2. Comparing cases without revealed strong associations at rs7708392 European Americans rs4958881 Americans. healthy controls stronger association but not Our data suggest variants TNIP1 risk for could be mechanistically involved development via aberrant regulation kinase activity.