Keith B Elkon, MD | Division of Rheumatology

Professor

Division of Rheumatology

Adjunct Professor

Department of Immunology

Head, Division of Rheumatology

Mart Mannik, MD-Lucile T. Henderson Endowed Professor in Rheumatology

Sites of Practice:

South Lake Union

Faculty Information

Biography

Education & Training:

M.B., B.Ch. (M.D. equivalent)

University of the Witwatersrand

Johannesburg, South Africa

1974

Residency

Hammersmith Hospital and Guy's Hospital

London, UK

Fellowship

Weill Medical College, Cornell University

Ithaca, NY

Contact

Email:

elkon@uw.edu

Phone:

(206) 543-3414

Mailing Address:

750 Republican Street
Box 358060
Seattle, WA 98109

Elkon Lab

Research & Clinical Interests

Research Interests:

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

PubMed:

PubMed Bibliography

Publications:

Selected-

Lood C, Blanco LP, Purmalek MM, Carmona-Rivera C , De Ravin SS, Smith CK, Malech HL, Ledbetter JA, Elkon KB, Kaplan MJ (co-last authors). Mitochondrial ROS generate NETs enriched in oxidized interferogenic mitochondrial DNA and contribute to lupus-like disease. Nature Medicine, 22:146-53, 2016. PMID: 26779811.

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. Digestion of Chromatin in Apoptotic Cell Microparticles Prevents Autoimmunity. Cell. 2016 Jun 9. pii: S0092-8674(16)30585-2. doi: 10.1016/j.cell.2016.05.034. [Epub ahead of print]. PMID: 27293190

Barrat FJ, Elkon KB, Fitzgerald KA. Importance of nucleic acid recognition in inflammation and autoimmunity, Ann Rev Med, Ann Rev Med, 67:323-336, 2016 PMID: 26526766.

Han CY, Tang C, Guevara ME, Wei H, Wietecha T, Shao B, Subramanian S, Omer M, Wang S, O’Brien KD, Wight TN, Vaisar T, de Beer MC, de Beer FC, Osborne WR, Elkon KB, Chait A Serum Amyloid A contributes to inflammation-induced impairment in HDL function. J Clin Invest, 126:796, 2016.

An J, Woodward JJ, Sasaki T, Minie M, Elkon KB. Cutting Edge: Antimalarial Drugs Inhibit IFN-β Production through Blockade of Cyclic GMP-AMP Synthase-DNA Interaction. J Immunol. 194:4089-93, 2015.

Sisirak V, Ganguly D, Lewis KL, Couillault C, Tanaka L, Bolland S, D’Agati V, Elkon KB, Reizis B. Genetic evidence for the role of plasmacytoid dendritic cells in systemic lupus erythematosus. J Exp Med, 2011:1969-1976, 2014.

Colonna L, Lood C, Elkon KB. Beyond apoptosis in lupus. Curr Opin Rheumatol. 26:459-466, 2014.

Wiedeman A, Santer DM, Yan W, Miescher S, Kaisermann F, Elkon KB. Contrasting mechanisms of interferon-α inhibition by intravenous immunoglobulin after stimulation with immune complexes versus toll like receptor agonists. Arthritis Rheum, 65:2713-23, 2013.

Giltiay NV, Chappell CP, Sun X, Kolhatkar N, Teal T, Wiedeman A, Kim J, Tanaka L, Buechler MB, Hamerman JA, Imanishi-Kari T, Clark EA, Elkon KB. Overexpression of TLR7 promotes cell-intrinsic expansion and autoantibody production by transitional T1 B cells. J Exp Med, 210:2713-23, 2013.

Sun XZ, Wiedeman A, Agrawal N, Teal TH, Tanaka L, Hudkins KL, Alpers CE, Bolland S, Buechler M, Hamerman JA, Ledbetter JA, Liggitt D, Elkon KB. Increased RNase expression reduces inflammation and prolongs survival in TLR7 transgenic mice. J Immunol, 190:2536-2543, 2013.

Elkon KB, Wiedeman A. Type I IFN system in the development and manifestations of SLE. Current Opinion Rheumatol, 24:499-505, 2012.

Santer DM, Wiedeman AE, Teal T, Ghosh P, Elkon KB. Plasmacytoid dendritic cells and C1q differentially regulate inflammatory gene induction by lupus immune complexes. J Immunol, 188:902-15, 2012. PMCID: 22147767. PMC3238790

Peng Y-F, Elkon KB. Autoimmunity in MFG-E8-deficient mice is associated with altered trafficking and enhanced cross-presentation of apoptotic cell antigens. J Clin Invest, 121:2221-2241, 2011.
Elkon KB, Rönnblom L. Cytokines as therapeutic targets in SLE. Nat Reviews Rheumatol, 2010.

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