David Pisetsky

Overview:

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.

Positions:

Professor of Medicine

Medicine, Rheumatology and Immunology
School of Medicine

Professor of Immunology

Immunology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Member of the Duke Human Vaccine Institute

Duke Human Vaccine Institute
School of Medicine

Education:

Ph.D. 1972

Yeshiva University, Albert Einstein College of Medicine

M.D. 1973

Yeshiva University, Albert Einstein College of Medicine

Intern, Medicine

Yale University School of Medicine

Resident, Medicine

Yale University School of Medicine

Grants:

Live-Animal Micro-CT System

Administered By
Orthopaedics
Awarded By
National Institutes of Health
Role
Major User
Start Date
End Date

VA IPA: Diane Spencer

Administered By
Medicine, Rheumatology and Immunology
Awarded By
Durham Veterans Affairs Medical Center
Role
Principal Investigator
Start Date
End Date

Metabolomic Analysis of Paired Serum and Skeletal Muscle in Juvenile Inflammatory Myositis Compared to Controls

Administered By
Pediatrics, Rheumatology
Awarded By
Cure JM Foundation
Role
Co Investigator
Start Date
End Date

Determinants of ANA Expression in Patients with SLE

Administered By
Medicine, Rheumatology and Immunology
Awarded By
Lupus Research Institute
Role
Principal Investigator
Start Date
End Date

IPA - Diane Spencer

Administered By
Medicine, Rheumatology and Immunology
Awarded By
Durham Veterans Affairs Medical Center
Role
Principal Investigator
Start Date
End Date

Publications:

Reply to: Diagnostic role of anti-dsDNA antibodies: do not forget autoimmune hepatitis.

Authors
Pisetsky, DS; Lipsky, PE
MLA Citation
Pisetsky, David S., and Peter E. Lipsky. “Reply to: Diagnostic role of anti-dsDNA antibodies: do not forget autoimmune hepatitis.Nat Rev Rheumatol, vol. 17, no. 4, Apr. 2021, p. 245. Pubmed, doi:10.1038/s41584-021-00574-6.
URI
https://scholars.duke.edu/individual/pub1472670
PMID
33462416
Source
pubmed
Published In
Nat Rev Rheumatol
Volume
17
Published Date
Start Page
245
DOI
10.1038/s41584-021-00574-6

Using Clinical Characteristics and Patient-Reported Outcome Measures to Categorize Systemic Lupus Erythematosus Subtypes.

OBJECTIVE: The type 1 and type 2 systemic lupus erythematosus (SLE) categorization system was recently proposed to validate the patients' perspective of disease and to capture a more comprehensive spectrum of symptoms. The objective of this study was to characterize the clinical manifestations of SLE subtypes and to determine the correlation between the patient- and physician-reported measures used in the model. METHODS: This was a cross-sectional study of patients with SLE in a university clinic. Patients completed the Systemic Lupus Activity Questionnaire (SLAQ) and 2011 American College of Rheumatology fibromyalgia (FM) criteria. Active SLE was defined as Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score ≥6, clinical SLEDAI score ≥4, or active lupus nephritis. We identified 4 groups: type 1 SLE (active SLE without FM), type 2 SLE (inactive SLE with FM), mixed SLE (active SLE with FM), and minimal SLE (inactive SLE without FM). RESULTS: In this cohort of 212 patients (92% female, mean age 45 years), 30% had type 1 SLE, 8% had type 2 SLE, 13% had mixed SLE, and 49% had minimal SLE. Regardless of SLE disease activity, patients with FM (21%), reported higher SLAQ scores, patient global assessment scores, and self-reported lupus flare that resulted in discordance between patient- and physician-reported measures. CONCLUSION: Fatigue, widespread pain, sleep dysfunction, and mood disorders are common symptoms in SLE. Identifying these symptoms as type 2 SLE may be a method to improve patient communication and understanding. The level of type 2 SLE impacts patients' perception of disease and self-reported symptoms. The SLAQ may need to be reinterpreted based on the FM severity scale.
Authors
Rogers, JL; Eudy, AM; Pisetsky, D; Criscione-Schreiber, LG; Sun, K; Doss, J; Clowse, MEB
MLA Citation
Rogers, Jennifer L., et al. “Using Clinical Characteristics and Patient-Reported Outcome Measures to Categorize Systemic Lupus Erythematosus Subtypes.Arthritis Care Res (Hoboken), vol. 73, no. 3, Mar. 2021, pp. 386–93. Pubmed, doi:10.1002/acr.24135.
URI
https://scholars.duke.edu/individual/pub1426977
PMID
31909888
Source
pubmed
Published In
Arthritis Care Res (Hoboken)
Volume
73
Published Date
Start Page
386
End Page
393
DOI
10.1002/acr.24135

The role of TASL in the pathogenesis of SLE: X marks the spot.

Authors
MLA Citation
Pisetsky, David S. “The role of TASL in the pathogenesis of SLE: X marks the spot.Ann Rheum Dis, vol. 80, no. 1, Jan. 2021, pp. 6–7. Pubmed, doi:10.1136/annrheumdis-2020-218643.
URI
https://scholars.duke.edu/individual/pub1461487
PMID
32978239
Source
pubmed
Published In
Ann Rheum Dis
Volume
80
Published Date
Start Page
6
End Page
7
DOI
10.1136/annrheumdis-2020-218643

Immune phenotypes in individuals positive for antinuclear antibodies: The impact of race and ethnicity.

Authors
MLA Citation
Pisetsky, David S. “Immune phenotypes in individuals positive for antinuclear antibodies: The impact of race and ethnicity.J Allergy Clin Immunol, vol. 146, no. 6, Dec. 2020, pp. 1346–48. Pubmed, doi:10.1016/j.jaci.2020.09.006.
URI
https://scholars.duke.edu/individual/pub1461488
PMID
32971108
Source
pubmed
Published In
The Journal of Allergy and Clinical Immunology
Volume
146
Published Date
Start Page
1346
End Page
1348
DOI
10.1016/j.jaci.2020.09.006

DNA-nanoparticle interactions: Formation of a DNA corona and its effects on a protein corona.

There has been much recent interest in the protein "corona," the nonspecific adsorption of proteins on the surface of nanoparticles used in biological applications. This research investigates an analogous DNA corona. We find that particles (200 nm and 1 μm) incubated with DNA form a DNA corona, with a higher concentration of DNA adsorbed on the surface of cationic nanoparticles. With protein present, a combined DNA and protein corona is formed although DNA in solution displaces protein from the nanoparticle surface. Displacement of protein from the nanoparticle surface is dependent on the concentration of DNA in solution and was also observed for planar surfaces. Overall, we expect this investigation of the DNA corona to be important for nanomedicine applications, as well as disease states, especially systemic lupus erythematosus, in which biological particles with bound DNA are important mediators of inflammation and thrombosis.
Authors
Griffith, DM; Jayaram, DT; Spencer, DM; Pisetsky, DS; Payne, CK
MLA Citation
Griffith, Darbi M., et al. “DNA-nanoparticle interactions: Formation of a DNA corona and its effects on a protein corona.Biointerphases, vol. 15, no. 5, Oct. 2020, p. 051006. Pubmed, doi:10.1116/6.0000439.
URI
https://scholars.duke.edu/individual/pub1462599
PMID
33003950
Source
pubmed
Published In
Biointerphases
Volume
15
Published Date
Start Page
051006
DOI
10.1116/6.0000439