Keith Elkon, M.D.
Professor, Medicine and Head, Division of Rheumatology
Adjunct Professor, Immunology

Department of Medicine
University of Washington
Box 356428
1959 NE Pacific, BB-561 Health Sciences
Seattle, WA 98195-6428
Phone: 206.543-3414
Fax: 206.685-9397
email: elkon@u.washington.edu

Elkon Lab Members
Elkon Lab Website

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.

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 recently identified novel pathways that involve opsonization of dying cells by serum factors (complement, CRP and natural antibodies) thereby promoting the phagocytosis of apoptotic cells. One hypothesis currently being explored is that 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, the molecular signals whereby apoptotic cells turn off inflammatory cytokines such as IL-12 in DCs and anergize T cells under homeostatic conditions, are also being investigated.

Removal of inflammatory nucleoprotein complexes. A related line of investiagation 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 administrered exogenously.

Neuropsychiatric Lupus (NPSLE). The pathogenesis of NPSLE is poorly understood. This laboratory has had a longstanding interest in NPSLE. We are currently examining the role of type 1 interferons in the induction of certain clinical manifestations of NPSLE. Regulation of inflammation by serologic factors is also under investigation.

Students currently training in the Elkon lab: Alice Wiedeman

Recent publications:

Elkon, KB, Ronnblom L. Cytokines as therapeutic targets in SLE. Nat Reviews Rheumatol, 2010.

Elkon, KB, News and Views. Autoimmunity: apoptotic fats grease transcription. Nature Medicine, 15:1246-8, 2009.

Peng YF, Latchman Y, Elkon KB. Monocytes differentiate into dendritic cells and cross-tolerize T cells through PDL-1, J Immunol, 182: 2777-2785, 2009.

Elkon, KB. Cell Survival and Death in Rheumatic Diseases. In: Kelley's Textbook of Rheumatology. Ruddy S., Harris ED, Sledge CB, Budd RC, Sergent JS (eds). W.B. Saunders Company, Philadelphia, 8th edition, pp. 379-396, 2009.

Santer DM, Yoshio T, Minota S, Moeller T, Elkon KB. Potent induction of interferon-a and chemokines by autoantibodies in the cerebrospinal fluid of patients with neuropsychiatric lupus. J Immunol, 182:1192-1201, 2009.

Okamoto A, Fujio K, van Rooijen N, Tsuno NH, Takahashi K, Tsurui H, Hirose S, Elkon KB, Yamamoto K. Splenic phagocytes promote responses to nucleosomes in (NZB x NZW) F1 mice. J Immunol, 181: 5264-5271, 2008.

Duan H, Fleming J, Pritchard DK, Amon LM, Xue J, Arnett HA, Chen G, Breen P, Buckner JH, Molitor JA, Elkon KB, Schwartz S. Combined analysis of monocyte and lymphocyte mRNA expression with serum protein profiles in patients with scleroderma. Arthritis Rheum, 58:1465-1474, 2008.

Martin DM, Zhang K, Kenkel J, Hughes G, Clark E, Davidson A, Elkon KB. Autoimmunity stimulated by adoptively transferred dendritic cells is initiated by both a/b and g/d T-cells but does not require MyD88 signaling. J Immunol, 179: 5819-5828, 2007.

Martin, D.A., Elkon, KB. Intracellular mammalian DNA stimulates myeloid dendritic cells to produce Type I interferons independently of MyD88 or TLR9. Arthritis Rheum, 54:951-962, 2006.

Martin, D.A., and Elkon, KB. 2005. Autoantibodies make a U-turn: the toll hypothesis for autoantibody specificity. J Exp Med 202:1465-1469, 2005.

Kim SJ, Elkon KB, Ma X. Transcriptional suppression of interleukin-12 gene expression following phagocytosis of apoptotic cells. Immunity 2004;21:643-53.

Kim S-J, Gershov D, Brot N, Elkon KB. 1-PLA2 activation during apoptosis promotes the exposure of membrane lysophosphatidylcholine leading to binding by natural IgM antibodies and complement activation. J Exp Med. 196: 655-665, 2002.

COS Expertise Profile

Medline database search for this researcher

Updated 8/27/10