HIV Pathogenesis Section
Irini Sereti, M.D., Ph.D.
Chief, Laboratory of Immunoregulation
Senior Investigator, Chief HIV Pathogenesis Section
Specialty(s): Infectious Disease, Internal Medicine Provides direct clinical care to patients at NIH Clinical Center
Major Areas of Research
• HIV pathogenesis and related CD4 lymphopenia and inflammation
• Immune reconstitution inflammatory syndrome
• Idiopathic CD4 lymphopenia (ICL)
• Immune-based therapies in HIV and ICL
• COVID-19 pathogenesis
Program Description
The primary research focus of our group is the study of inflammatory complication in HIV including immune reconstitution inflammatory syndrome (IRIS). IRIS is an aberrant immune response, frequently with an intense inflammatory component, that can occur in the context of immune restoration in patients with HIV infection and severe CD4 lymphopenia after initiation of antiretroviral therapy (ART). Chronically treated patients on the other hand may experience non-infectious complications of HIV, including cardiovascular disease, that seem to be driven by chronic residual immune activation and inflammation. The second interest is development of adjuvant immune-based therapies (IBT) to improve immune restoration in CD4 lymphopenic conditions such as HIV and idiopathic CD4 lymphopenia (ICL). ICL is a rare, likely heterogeneous condition characterized by low CD4 T-cell counts in the absence of HIV or other known infection or disease that can cause lymphopenia. Finally, new projects on COVID-19 pathogenesis pivoted on our previous work on lymphopenia and inflammation.
Biography
Education
Ph.D., University of Amsterdam - Netherlands
M.D., National Kapodistrian University of Athens in Greece
M.H.S., Duke University
Dr. Sereti is the Chief of the HIV Pathogenesis Section in the Laboratory of Immunoregulation at the National Institute of Allergy and Infectious Diseases (NIAID). She received her medical degree at the National Kapodistrian University of Athens in Greece and did her internal medicine residency and chief residency at Northwestern University in Chicago. She completed an M.H.S. from Duke University and her infectious diseases fellowship at NIAID and stayed as a clinical investigator receiving tenure in 2015.
Clinical Studies
International Study of COVID 19 vaccine to assess immunogenicity and efficacy (InVITE): NCT05096091
Phase I study of efineptakin alpha (IL-7) in COVID-19 (SPESELPIS): NCT04501796
COVID associated lymphopenia pathogenesis study in blood (CALYPSO): NCT04401436
Phase I study of belimumab in ICL patients with autoantibodies (PHOEBE): NCT04097561
FDG-PET scans and lymph node biopsies in HIV-IRIS (PANDORA): NCT02147405
Cohort study on immunopathogenesis and etiology of patients with idiopathic CD4 lymphopenia (ICL) (EPIC): NCT00867269
Study of stem cell mobilization in ICL (P-Mobile): NCT02015013
Herpesviruses Reactivation in HIV-Infected Women Initiating ART (HERA): NCT03092505
Selected Publications
Lisco A, Hsu AP, Dimitrova D, Proctor DM, Mace EM, Ye P, Anderson MV, Hicks SN, Grivas C, Hammoud DA, Manion M, Starrett GJ, Farrel A, Dobbs K, Brownell I, Buck C, Notarangelo LD, Orange JS, Leonard WJ, Orestes MI, Peters AT, Kanakry JA, Segre JA, Kong HH, Sereti I. Treatment of Relapsing HPV Diseases by Restored Function of Natural Killer Cells. N Engl J Med. 2021 Sep 2;385(10):921-929.
Lage SL, Wong CS, Amaral EP, Sturdevant D, Hsu DC, Rupert A, Wilson EMP, Qasba SS, Naqvi NS, Laidlaw E, Lisco A, Manion M, Sereti I. Classical complement and inflammasome activation converge in CD14highCD16- monocytes in HIV associated TB-immune reconstitution inflammatory syndrome. PLoS Pathog. 2021 Mar 31;17(3):e1009435.
Perez-Diez A, Wong CS, Liu X, Mystakelis H, Song J, Lu Y, Sheikh V, Bourgeois JS, Lisco A, Laidlaw E, Cudrici C, Zhu C, Li QZ, Freeman AF, Williamson PR, Anderson M, Roby G, Tsang JS, Siegel R, Sereti I. Prevalence and pathogenicity of autoantibodies in patients with idiopathic CD4 lymphopenia. J Clin Invest. 2020 Oct 1;130(10):5326-5337.
Sereti I, Sheikh V, Shaffer D, Phanuphak N, Gabriel E, Wang J, Nason MC, Roby G, Ngeno H, Kirui F, Pau A, Mican JM, Rupert A, Bishop R, Agan B, Chomchey N, Teeratakulpisarn N, Tansuphaswadikul S, Langat D, Kosgei J, French M, Ananworanich J, Sawe F. Prospective International Study of Incidence and Predictors of Immune Reconstitution Inflammatory Syndrome and Death in People Living With Human Immunodeficiency Virus and Severe Lymphopenia. Clin Infect Dis. 2020 Jul 27;71(3):652-660.
Vujkovic-Cvijin I, Sortino O, Verheij E, Sklar J, Wit FW, Kootstra NA, Sellers B, Brenchley JM, Ananworanich J, Loeff MSV, Belkaid Y, Reiss P, Sereti I. HIV-associated gut dysbiosis is independent of sexual practice and correlates with noncommunicable diseases. Nat Commun. 2020 May 15;11(1):2448.
Video
Using PET scans to study IRIS in people with HIV
Extreme immune decline in ART-treated HIV-infected individuals
Research Networks
Research Group
My group studies the inflammatory complications in people with HIV either in the form of acute Inflammatory immune reconstitution syndrome (IRIS) or in chronic treated HIV, focusing among other topics on the role of inflammasome, microbiome, genetics and immune senescence. We are also working on pathogenesis, genetics and potential treatments of Idiopathic CD4 lymphopenia including mouse models…