2001 B Cells
2005 Biomarkers, General Immune System Function
In 2001, the LRI awarded Dr. Weigert funding to determine the genetic mechanisms controlling the appearance of DNA-specific autoantibodies in healthy people—and the reasons these mechanisms fail in people with lupus.
Dr. Weigert subsequently discovered that a large proportion of DNA-specific auto-antibodies in lupus are generated by a process known as “receptor editing.”
In addition to having papers on the subject published, Dr. Weigert has presented this LRI-funded work extensively at national and international meetings, and in 2005 was awarded the Carol Nachman prize for work in autoimmunity.
In 2005, the LRI awarded Dr. Weigert another grant. He set out to examine the role of Light Chain (L-Chain) editors in producing the self-targeted antibodies that can cause damage to organs and tissues in lupus.
The study examined whether the expression of L chain editors correlates with disease activity. If successful, Dr. Weigert's research could lead to the development of a revealing novel lupus assay (test) and new treatment.
In journal articles generated by his LRI work, Dr. Weigert describes how the presence of particular autoantibodies in the serum of people with lupus can be used to track disease. Since these antibodies arise early in disease, they can be used to diagnose new lupus patients, and also can be used to monitor disease progression during flares and remission periods. The work forms the basis of a recently approved patent.
“One of the things I have been able to do under the auspices of the LRI is to develop what we hope will become a new diagnostic tool for detecting lupus susceptibility as well for monitoring disease development before, during, and after therapy with drugs such as Rituximab.” – Dr. Weigert
Anti-DNA B cells in MRL/lpr mice show altered differentiation and editing pattern. Li Y, Li H, Ni D, Weigert M. J Exp Med. 2002 Dec 16;196(12):1543-52.
Secondary heavy chain rearrangement: a mechanism for generating anti-double-stranded DNA B cells. Sekiguchi DR, Eisenberg RA, Weigert M. J Exp Med. 2003 197(1):27-39.
Development and Selection of Edited B Cells in B6.56R Mice. Sekiguchi DR, Yunk L, Gary D, Charan D, Srivastava B, Allman D, Weigert MG, Prak ET. J Immunol. 2006 176(11):6879-87.
Light chain editing generates polyreactive antibodies in chronic graft-versus-host reaction. Witsch EJ, Cao H, Fukuyama H, Weigert M. J Exp Med 2006 Jul 10;203(7):1761-72. Epub 2006 Jun 26
Intra-Golgi Formation of IgM-Glycosaminoglycan Complexes Promotes Ig Deposition. Khan SN, Cox JV, Nishimoto SK, Chen C, Fritzler MJ, Hendershot LM, Weigert M, Radic M. J Immunol. 2011 Sep 15;187(6):3198-207. Epub 2011 Aug 12.
As a result of this LRI work, Dr. Weigert won a $250,000 NIH R21 grant in 2004, and an NIH R01 in 2005 for $1.75 million.
Along with LRI researchers Zhixin Zhang, PhD, and Marko Radic, PhD, in 2008 Dr. Weigert also secured a $600,000 grant (to be divided among the three) to pursue a collaborative work: “Systemic Analysis of Autoantibody Repertoire in SLE Patients Consortium.”
Rev. September 2011