Department of Immunology

Keith B. Elkon, M.D.

PROFESSOR, MEDICINE AND HEAD, DIVISION OF RHEUMATOLOGY

Dr. Elkon received his medical degree from the University of Witwatersrand, Johannesburg South Africa in 1974 and membership to the Royal College of Physicians (MRCP) in 1978. He received postdoctoral training at the Hammersmith Hospital, London and at the Weill Medical College of Cornell University, New York. Dr. Elkon was formerly Director of the Graduate Program in Immunology and Professor of Medicine at Cornell. He was appointed as Head, Division of Rheumatology, at UW in August, 2001.

CONTACT

Department of Medicine,
Division of Rheumatology
University of Washington
750 Republican Street
Box 358060
Seattle, WA 98109
Phone: 206-543-3415
Fax: 206-685-8150

RESEARCH AREAS

Tolerance & Autoimmunity

LAB MEMBERS

Postdoctoral Fellows & Instructors
Jie An, jiean@uw.edu
Sladjana Skopelja Gardner 
ssg12@uw.edu

Rheumatology Administration
Jessica Bertram, Administrator,
soderljm@uw.edu
Kat McGhee, Program Coordinator, kmcghee@uw.edu

Laboratory Staff
Xizhang Sun, sunx@uw.edu
Lena Tanaka, lenat@uw.edu
Joyce Tai joycetai@uw.edu

LAB

PUBMED

Keith Elkon on PubMed

 

RESEARCH

Dr. Elkon’s research objective is to better define the molecular and genetic basis for autoimmune diseases such as lupus and arthritis. Current areas of investigation include the following:
Apoptosis and the Immune Response – especially as it relates to lupus (SLE). Loss of tolerance leads to autoantibody production in systemic autoimmune disorders such as systemic lupus erythematosus (SLE). There is considerable evidence to support the concept that autoantibodies are generated in response to impaired clearance of dead and dying cells. Dr. Elkon’s laboratory has identified novel pathways that involve opsonization of dying cells by serum factors (complement, CRP and natural antibodies) thereby promoting the phagocytosis of apoptotic cells. Deficiencies of these serum opsonins leads to delayed clearance of dying cells sequentially facilitating necrosis, an inflammatory response to self antigens and loss of tolerance. Current studies explore the how self antigens (e.g. nucleoprotein particles such as nucleosomes, spliceosomes and ribosomes) are processed and activate the innate immune system, especially plasmacytoid dendritic cells (pDCs) to induce IFN-a. In addition, apoptotic cell processing and the downstream molecular signals in DCs that lead to anergy or T cell activation are being investigated.
Removal of inflammatory nucleoprotein complexes. A related line of investigation explores how the debris derived from apoptotic cells, nucleoprotein particles, can be rendered less immunogenic. The research involves the creation of transgenic mice expressing “cleanup” molecules as well as biologics that can be administered exogenously.

PUBLICATIONS

  1. Inhibition of Cyclic GMP-AMP Synthase Using a Novel Antimalarial Drug Derivative in Trex1-Deficient Mice. An J, Woodward JJ, Lai W, Minie M, Sun X, Tanaka L, Snyder JM, Sasaki T, Elkon KB. Arthritis Rheumatol. 2018 May 21. doi: 10.1002/art.40559. [Epub ahead of print] PMID: 29781188
  2. Review: Cell Death, Nucleic Acids, and Immunity: Inflammation Beyond the Grave. Elkon KB. Arthritis Rheumatol. 2018 Jun;70(6):805-816. doi: 10.1002/art.40452. Epub 2018 Apr 18. Review. PMID: 29439290
  3. TLR7/8 activation in neutrophils impairs immune complex phagocytosis through shedding of FcgRIIA. Lood C, Arve S, Ledbetter J, Elkon KB. J Exp Med. 2017 Jul 3;214(7):2103-2119. doi: 10.1084/jem.20161512. Epub 2017 Jun 12. PMID: 28606989
  4. Expression of Cyclic GMP-AMP Synthase in Patients With Systemic Lupus Erythematosus. An J, Durcan L, Karr RM, Briggs TA, Rice GI, Teal TH, Woodward JJ, Elkon KB. Arthritis Rheumatol. 2017 Apr;69(4):800-807. doi: 10.1002/art.40002. Epub 2017 Mar 7. PMID: 27863149
  5. Ultraviolet B Irradiation Causes Stimulator of Interferon Genes-Dependent Production of Protective Type I Interferon in Mouse Skin by Recruited Inflammatory Monocytes. Sontheimer C, Liggitt D, Elkon KB. Arthritis Rheumatol. 2017 Apr;69(4):826-836. doi: 10.1002/art.39987. PMID: 27863141
  6. Antimalarial Drugs as Immune Modulators: New Mechanisms for Old Drugs. An J, Minie M, Sasaki T, Woodward JJ, Elkon KB. Annu Rev Med. 2017 Jan 14;68:317-330. doi: 10.1146/annurev-med-043015-123453. Epub 2016 Oct 21. Review. PMID: 27813878
  7. Blood-Borne RNA Correlates with Disease Activity and IFN-Stimulated Gene Expression in Systemic Lupus Erythematosus. Doedens JR, Jones WD, Hill K, Mason MJ, Gersuk VH, Mease PJ, Dall’Era M, Aranow C, Martin RW, Cohen SB, Fleischmann RM, Kivitz AJ, Burge DJ, Chaussabel D, Elkon KB, Posada JA. J Immunol. 2016 Oct 1;197(7):2854-63. doi: 10.4049/jimmunol.1601142. Epub 2016 Aug 17. PMID: 27534558
  8. Digestion of Chromatin in Apoptotic Cell Microparticles Prevents Autoimmunity. Sisirak V, Sally B, D’Agati V, Martinez-Ortiz W, Özçakar ZB, David J, Rashidfarrokhi A, Yeste A, Panea C, Chida AS, Bogunovic M, Ivanov II, Quintana FJ, Sanz I, Elkon KB, Tekin M, Yalçınkaya F, Cardozo TJ, Clancy RM, Buyon JP, Reizis B. Cell. 2016 Jun 30;166(1):88-101. doi: 10.1016/j.cell.2016.05.034. Epub 2016 Jun 9. PMID: 27293190
  9. Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease. Lood C, Blanco LP, Purmalek MM, Carmona-Rivera C, De Ravin SS, Smith CK, Malech HL, Ledbetter JA, Elkon KB, Kaplan MJ. Nat Med. 2016 Feb;22(2):146-53. doi: 10.1038/nm.4027. Epub 2016 Jan 18. PMID: 26779811