David Stephen Pisetsky

David Stephen Pisetsky

Professor of Medicine

Studies in my laboratory concern the immunological properties of DNA as related to two main topics: 1) the induction of anti-DNA responses in systemic lupus erythematosus; and 2) the stimulation of innate immunity by bacterial DNA. These topics are closely linked since we have established novel disease models in which lupus-like illness can be induced in normal mice by bacterial DNA under conditions in which mammalian DNA is inactive. This model has been useful in elucidating mechanisms of DNA antigen drive in autoimmunity.

To pursue these studies, our laboratory conducts investigations in the following areas: 1) specificity of anti-DNA for epitopes on mammalian and bacterial DNA; 2) molecular analysis of murine mononclonal anti-DNA antibodies; 3) histopathological analyses of DNA-immunized mice; 4) in vitro analysis of proliferation, antibody production and cytokine expression in human and murine immune cells; and 5) analysis of DNA binding to cell surface molecules on B cells, T cells and macrophages. Results of these studies have allowed identification of at least two structural motifs that are immunoactive. We are also exploring the impact of chemical modifications of the DNA backbone.

In addition to work on the immunology of DNA, I am also involved in clinical trials related to new immunomodulatory agents in the treatment of rheumatoid arthritis as well as serological markers of disease activity.

The areas of research for which I am known nationally are anti-DNA antibodies, systemic lupus erythematosus and immunological properties of DNA. I have written textbook chapters and reviews on all these subjects.

Appointments and Affiliations

  • Professor of Medicine
  • Professor of Immunology
  • Member of the Duke Cancer Institute
  • Member of the Duke Human Vaccine Institute

Contact Information

  • Office Location: VA Med Ctr, 508 Fulton St, Durham, NC 27705
  • Office Phone: (919) 286-6835
  • Email Address: david.pisetsky@duke.edu

Education

  • Yale University School of Medicine, 1974
  • Yale University School of Medicine, 1974
  • M.D. Yeshiva University, Albert Einstein College of Medicine, 1973
  • Ph.D. Yeshiva University, Albert Einstein College of Medicine, 1972

Courses Taught

  • IMMUNOL 493: Research Independent Study
  • IMMUNOL 494: Research Independent Study

In the News

Representative Publications

  • Pisetsky, DS; Spencer, DM; Lipsky, PE; Rovin, BH, Response to 'Antinuclear antibodies by indirect immunofluorescence and solid phase assays' by Bossuyt et al., Ann Rheum Dis, vol 79 no. 6 (2020) [10.1136/annrheumdis-2019-215479] [abs].
  • Pisetsky, DS, Evolving story of autoantibodies in systemic lupus erythematosus., J Autoimmun, vol 110 (2020) [10.1016/j.jaut.2019.102356] [abs].
  • Pisetsky, DS; Bossuyt, X; Meroni, PL, ANA as an entry criterion for the classification of SLE., Autoimmun Rev, vol 18 no. 12 (2019) [10.1016/j.autrev.2019.102400] [abs].
  • Pisetsky, DS; Spencer, DM; Lipsky, PE; Rovin, BH, Response to: 'Antinuclear antibody as entry criterion for classification of systemic lupus erythematosus: pitfalls and opportunities' by Bossuyt et al., Ann Rheum Dis, vol 78 no. 8 (2019) [10.1136/annrheumdis-2018-213841] [abs].
  • Mobarrez, F; Fuzzi, E; Gunnarsson, I; Larsson, A; Eketjäll, S; Pisetsky, DS; Svenungsson, E, Microparticles in the blood of patients with SLE: Size, content of mitochondria and role in circulating immune complexes., J Autoimmun, vol 102 (2019), pp. 142-149 [10.1016/j.jaut.2019.05.003] [abs].
  • Pisetsky, DS; Spencer, DM; Lipsky, PE; Rovin, BH, Response to: 'Pitfalls of antinuclear antibody detection in systemic lupus erythematosus: the positive experience of a national multi-center study' by Pregnalato et al., Ann Rheum Dis, vol 78 no. 6 (2019) [10.1136/annrheumdis-2018-213582] [abs].
  • Pisetsky, DS; Spencer, DM; Lipsky, PE; Rovin, BH, Response to: 'Variation in antinuclear antibody detection by automated indirect immunofluorescence analysis' by van Hoovels et al., Ann Rheum Dis, vol 78 no. 6 (2019) [10.1136/annrheumdis-2018-213558] [abs].
  • Pisetsky, DS; Spencer, DM; Lipsky, PE; Rovin, BH, Response to: 'Unending story of the indirect immunofluorescence assay on HEp-2 cells: old problems and new solutions?' by Meroni et al., Ann Rheum Dis, vol 78 no. 6 (2019) [10.1136/annrheumdis-2018-213537] [abs].
  • Pisetsky, DS, Unexpected link between mitochondrial DNA and T cell help in systemic lupus erythematosus., Ann Rheum Dis, vol 78 no. 6 (2019) [10.1136/annrheumdis-2019-215597] [abs].
  • Pisetsky, DS; Lipsky, PE, Role of Antinuclear Antibody Determinations in Classification Criteria for Systemic Lupus Erythematosus: Comment on the Article by Leuchten et al., Arthritis Care Res (Hoboken), vol 71 no. 5 (2019) [10.1002/acr.23559] [abs].
  • Pisetsky, DS; Spencer, DM; Lipsky, PE; Rovin, BH, Response to: 'Lack of standardization of ANA and implications for drug development and precision medicine' by Mahler., Ann Rheum Dis, vol 78 no. 5 (2019) [10.1136/annrheumdis-2018-213399] [abs].
  • Mobarrez, F; Svenungsson, E; Pisetsky, DS, Microparticles as autoantigens in systemic lupus erythematosus., Eur J Clin Invest, vol 48 no. 12 (2018) [10.1111/eci.13010] [abs].
  • Putterman, C; Pisetsky, DS; Petri, M; Caricchio, R; Wu, AHB; Sanz, I; Oates, JC; Wallace, S; Sorek, R; Gerwien, R; Safer, P; Jakobi-Brook, K; Cohen, IR, The SLE-key test serological signature: new insights into the course of lupus., Rheumatology (Oxford), vol 57 no. 9 (2018), pp. 1632-1640 [10.1093/rheumatology/key149] [abs].
  • Pisetsky, DS, Role of Epstein-Barr virus infection in SLE: gene-environment interactions at the molecular level., Ann Rheum Dis, vol 77 no. 9 (2018), pp. 1249-1250 [10.1136/annrheumdis-2018-213783] [abs].
  • Rutledge, HR; Jiang, W; Yang, J; Warg, LA; Schwartz, DA; Pisetsky, DS; Yang, IV, Gene expression profiles of RAW264.7 macrophages stimulated with preparations of LPS differing in isolation and purity., Innate Immun, vol 18 no. 1 (2012), pp. 80-88 [10.1177/1753425910393540] [abs].
  • Distler, JHW; Akhmetshina, A; Dees, C; Jüngel, A; Stürzl, M; Gay, S; Pisetsky, DS; Schett, G; Distler, O, Induction of apoptosis in circulating angiogenic cells by microparticles., Arthritis Rheum, vol 63 no. 7 (2011), pp. 2067-2077 [10.1002/art.30361] [abs].
  • Ullal, AJ; Reich, CF; Clowse, M; Criscione-Schreiber, LG; Tochacek, M; Monestier, M; Pisetsky, DS, Microparticles as antigenic targets of antibodies to DNA and nucleosomes in systemic lupus erythematosus., J Autoimmun, vol 36 no. 3-4 (2011), pp. 173-180 [10.1016/j.jaut.2011.02.001] [abs].
  • Pisetsky, DS; Gauley, J; Ullal, AJ, Microparticles as a source of extracellular DNA., Immunol Res, vol 49 no. 1-3 (2011), pp. 227-234 [10.1007/s12026-010-8184-8] [abs].
  • Pisetsky, DS, Platelet microparticles: making blood a bad humor., The Journal of Rheumatology, vol 38 no. 4 (2011), pp. 590-592 [10.3899/jrheum.101359] [abs].
  • Pisetsky, DS, The role of HMGB1 in efferocytosis: when the dead go unburied. Focus on "HMGB1 inhibits macrophage activity in efferocytosis through binding to the alphavbeta3-integrin"., Am J Physiol Cell Physiol, vol 299 no. 6 (2010), pp. C1253-C1255 [10.1152/ajpcell.00397.2010] [abs].
  • Pisetsky, DS; Ullal, AJ, The blood nucleome in the pathogenesis of SLE., Autoimmun Rev, vol 10 no. 1 (2010), pp. 35-37 [10.1016/j.autrev.2010.07.007] [abs].
  • Pisetsky, DS, Charlie's List., Ann Intern Med, vol 153 no. 5 (2010) [10.7326/0003-4819-153-5-201009070-00012] [abs].
  • Pisetsky, DS; Lipsky, PE, Microparticles as autoadjuvants in the pathogenesis of SLE., Nat Rev Rheumatol, vol 6 no. 6 (2010), pp. 368-372 [10.1038/nrrheum.2010.66] [abs].
  • Gauley, J; Pisetsky, DS, The release of microparticles by RAW 264.7 macrophage cells stimulated with TLR ligands., J Leukoc Biol, vol 87 no. 6 (2010), pp. 1115-1123 [10.1189/jlb.0709465] [abs].
  • Ullal, AJ; Pisetsky, DS, The release of microparticles by Jurkat leukemia T cells treated with staurosporine and related kinase inhibitors to induce apoptosis., Apoptosis, vol 15 no. 5 (2010), pp. 586-596 [10.1007/s10495-010-0470-3] [abs].
  • Pisetsky, DS, HMGB1: a dangerous player in lupus pathogenesis., The Journal of Rheumatology, vol 37 no. 4 (2010), pp. 689-691 [10.3899/jrheum.091459] [abs].
  • Ullal, AJ; Pisetsky, DS; Reich, CF, Use of SYTO 13, a fluorescent dye binding nucleic acids, for the detection of microparticles in in vitro systems., Cytometry A, vol 77 no. 3 (2010), pp. 294-301 [10.1002/cyto.a.20833] [abs].
  • Grundtman, C; Bruton, J; Yamada, T; Ostberg, T; Pisetsky, DS; Harris, HE; Andersson, U; Lundberg, IE; Westerblad, H, Effects of HMGB1 on in vitro responses of isolated muscle fibers and functional aspects in skeletal muscles of idiopathic inflammatory myopathies., Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology, vol 24 no. 2 (2010), pp. 570-578 [10.1096/fj.09-144782] [abs].
  • Beyer, C; Pisetsky, DS, The role of microparticles in the pathogenesis of rheumatic diseases., Nat Rev Rheumatol, vol 6 no. 1 (2010), pp. 21-29 [10.1038/nrrheum.2009.229] [abs].
  • Pisetsky, DS; Vrabie, IA, Antibodies to DNA: infection or genetics?, Lupus, vol 18 no. 13 (2009), pp. 1176-1180 [10.1177/0961203309106492] [abs].
  • Su, K-Y; Pisetsky, DS, The role of extracellular DNA in autoimmunity in SLE., Scand J Immunol, vol 70 no. 3 (2009), pp. 175-183 [10.1111/j.1365-3083.2009.02300.x] [abs].
  • Pisetsky, DS; Rönnblom, L, Systemic lupus erythematosus: a matter of life and death., Arthritis and Rheumatism, vol 60 no. 6 (2009), pp. 1567-1570 [10.1002/art.24531] [abs].
  • Gauley, J; Pisetsky, DS, The translocation of HMGB1 during cell activation and cell death., Autoimmunity, vol 42 no. 4 (2009), pp. 299-301 [10.1080/08916930902831522] [abs].
  • Crowley, SD; Vasievich, MP; Ruiz, P; Gould, SK; Parsons, KK; Pazmino, AK; Facemire, C; Chen, BJ; Kim, H-S; Tran, TT; Pisetsky, DS; Barisoni, L; Prieto-Carrasquero, MC; Jeansson, M; Foster, MH; Coffman, TM, Glomerular type 1 angiotensin receptors augment kidney injury and inflammation in murine autoimmune nephritis., J Clin Invest, vol 119 no. 4 (2009), pp. 943-953 [10.1172/JCI34862] [abs].
  • Reich, CF; Pisetsky, DS, The content of DNA and RNA in microparticles released by Jurkat and HL-60 cells undergoing in vitro apoptosis., Exp Cell Res, vol 315 no. 5 (2009), pp. 760-768 [10.1016/j.yexcr.2008.12.014] [abs].
  • Pisetsky, DS, Microparticles as biomarkers in autoimmunity: from dust bin to center stage., Arthritis Research & Therapy, vol 11 no. 6 (2009) [10.1186/ar2856] [abs].