J. Michelle Kahlenberg, M.D., Ph.D.
Systemic lupus erythematosus (SLE) is a devastating autoimmune disease with pleotropic manifestations, including scarring rashes, organ damage and elevated risk of cardiovascular death. Many patients experience periodic flares; however, our ability to predict which patients will flare and/or develop severe organ damage remains limited at best. Thus, treatment is often held until deterioration of organ function has occurred, leaving patients with irreversible damage that accrues over time. The incidence of cutaneous lupus ranges from 0.04-0.07%[2, 3], and up to 70% of patients with SLE have cutaneous manifestations. However, the signaling pathways which regulate inflammatory responses in the skin leading to rash induction in cutaneous lupus remain poorly understood. Further, how these pathogenic changes may potentially cross-talk with the systemic immune system and influence systemic disease development is virtually unknown.
Our lab is currently exploring the connections between cutaneous rashes and the development of systemic disease in SLE. Using both human tissues and murine models, we are using a combination of bioinformatic, immunologic and molecular approaches to dissect mechanisms by which cutaneous exposure and inflammation may influence systemic disease.
1. Manzi, S., et al., Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. American Journal of Epidemiology, 1997. 145(5): p. 408-415.
2. Mikita, N., et al., Recent advances in cytokines in cutaneous and systemic lupus erythematosus. J Dermatol, 2011. 38(9): p. 839-49.
3. Grönhagen, C.M., et al., Cutaneous lupus erythematosus and the association with systemic lupus erythematosus: a population-based cohort of 1088 patients in Sweden. British Journal of Dermatology, 2011. 164(6): p. 1335-1341.
4. Wieczorek, I.T., et al., SYstemic symptoms in the progression of cutaneous to systemic lupus erythematosus. JAMA Dermatology, 2014.
Research Opportunities for Rotating Students
Kahlenberg JM, Kaplan MJ. The Inflammasome and lupus- another innate immune mechanism contributing to disease pathogenesis? Current Opinion in Rheumatology 2014 epub ahead of print.
Kahlenberg JM, Yalavarthi S, Zhao W, Hodgin JB, Reed TJ, Tsuji NM, and Kaplan MJ. An essential role for caspase-1 in the induction of murine lupus and its associated vascular damage. Arthritis and Rheumatology 2014; 66(1):152-62.
Kahlenberg JM, Kaplan MJ. Little Peptide, Big Effects: the role of LL-37 in inflammation and autoimmune disease Journal of Immunology 2013; 191: 4895-4901
Kahlenberg JM, Carmona-Rivera C, Smith CK, and Kaplan MJ. Neutrophil Extracellular Trap-Associated Protein Activation of the NLRP3 Inflammasome Is Enhanced in Lupus Macrophages. Journal of Immunology 2013; 190:1217-1226.
Kahlenberg JM, Kaplan MJ. Mechanisms of premature atherosclerosis in rheumatoid arthritis and lupus. Annu Rev Med. 2013;64:249-63.
Kahlenberg JM, Thacker SG, Berthier CC, Cohen CD, Kretzler M, Kaplan MJ. Inflammasome activation of IL-18 results in endothelial progenitor cell dysfunction in systemic lupus erythematosus. J Immunol. 2011 Dec 1;187(11):6143-56.
Kahlenberg JM, Kaplan MJ. The interplay of inflammation and cardiovascular disease in systemic lupus erythematosus. Arthritis Res Ther. 2011 Feb 28;13(1):203.
Kahlenberg JM, Fox DA. Advances in the medical treatment of rheumatoid arthritis. Hand Clin. 2011 Feb;27(1):11-20.
Kahlenberg JM. Neuromyelitis optica spectrum disorder as an initial presentation of primary Sjögren's syndrome. Semin Arthritis Rheum. 2011 Feb;40(4):343-8.
Verhoef PA, Kertesy SB, Lundberg K, Kahlenberg JM, Dubyak GR. Inhibitory effects of chloride on the activation of caspase-1, IL-1beta secretion, and cytolysis by the P2X7 receptor. J Immunol. 2005 Dec 1;175(11):7623-34.
Kahlenberg JM, Lundberg KC, Kertesy SB, Qu Y, Dubyak GR. Differing caspase-1 activation states in monocyte versus macrophage models of IL-1beta processing and release. J Leukoc Biol. 2004 Sep;76(3):676-84. Epub 2004 Jul 7.
Kahlenberg JM, Dubyak GR. Mechanisms of caspase-1 activation by P2X7 receptor-mediated K+ release. Am J Physiol Cell Physiol. 2004 May;286(5):C1100-8.
Peña CE, Kahlenberg JM, Hatfull GF. Protein-DNA complexes in mycobacteriophage L5 integrative recombination. J Bacteriol. 1999 Jan;181(2):454-61.
Peña CE, Kahlenberg JM, Hatfull GF. The role of supercoiling in mycobacteriophage L5 integrative recombination. Nucleic Acids Res. 1998 Sep 1;26(17):4012-8.