Major Areas of Research
- Autoimmune Lymphoproliferative Syndrome (ALPS), one of the first inherited autoimmune diseases whose genetic basis was defined
- Readily available biomarkers of ALPS-like vitamin B12, IL-10, and double-negative T cells (DNT cells) providing diagnostic clues
- Importance of apoptosis in remodeling the lymphocyte repertoire and deleting cells with autoimmune and oncogenic potential
- Studying and understanding B-cell consequences of T-cell dysfunction leading to lymphoma, infections, and cytopenias in ALPS patients
- Pathobiology of sporadic conditions due to immune dysfunction
- Role of new mutations and modifier genes in health and disease
Autoimmune Lymphoproliferative Syndrome (ALPS) is an inherited disorder of the immune system that affects both children and adults. In ALPS and related disorders with defective cell kill and proliferation pathways, unusually high numbers of white blood cells, called lymphocytes, accumulate in the lymph nodes, liver, and spleen, which can lead to enlargement of these organs. ALPS can also cause a variety of autoimmune problems such as anemia (low red blood cell count), thrombocytopenia (low platelets), and neutropenia (low neutrophil count). Lymphocytes infiltrating the bone marrow, lungs, liver, and brain can also lead to clinical symptoms. The ALPS Unit aims to better understand these rare diseases of lymphocyte apoptosis and immune homoeostasis, to find their genetic causes, and to uncover new ways to treat them. Its ultimate goal is to find a cure for these disorders of the immune system.
Michael J. Lenardo, M.D.
Susan Price, R.N.
Elaine Smoot, R.N.
Morgan Butrick, ScM, Certified Genetic Counselor
Aaron Morawski, M.S., Biologist
Calvo KR, Price S, Braylan RC, Oliveira JB, Lenardo M, Fleisher TA, Rao VK. JMML and RALD (RAS-associated autoimmune leukoproliferative disorder): common genetic etiology yet clinically distinct entities. Blood. 2015 Apr 30; 125(18): 2753-8.
Price S, Shaw PA, Seitz A, Joshi G, Davis J, Niemela JE, Perkins K, Hornung RL, Folio L, Rosenberg PS, Puck JM, Hsu AP, Lo B, Pittaluga S, Jaffe ES, Fleisher TA, Rao VK, Lenardo MJ. Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations. Blood. 2014 Mar 27;123(13):1989-99.
Rudman Spergel A, Walkovich K, Price S, Niemela JE, Wright D, Fleisher TA, Rao, VK. Autoimmune lymphoproliferative syndrome misdiagnosed as hemophagocytic lymphohistiocytosis. Pediatrics. 2013 Nov;132(5):e1440-4.
Rao VK, Oliveira JB. How I treat autoimmune lymphoproliferative syndrome. Blood. 2011 Nov 24;118(22):5741-51.
Oliveira JB, Bleesing JJ, Dianzani U, Fleisher TA, Jaffe ES, Lenardo MJ, Rieux-Laucat F, Siegel RM, Su HC, Teachey DT, Rao VK. Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome: report from the 2009 NIH International Workshop. Blood. 2010 Jun 10.
Dowdell KC, Niemela JE, Price S, Davis J, Hornung RL, Oliveira JB, Puck JM, Jaffe ES, Pittaluga S, Cohen JI, Fleisher TA, Rao VK. Somatic FAS mutations are common in patients with genetically undefined autoimmune lymphoproliferative syndrome.Blood. 2010 Jun 24;115(25):5164-9.
Turbyville JC, Rao VK. The autoimmune lymphoproliferative syndrome: A rare disorder providing clues about normal tolerance.Autoimmun Rev. 2010 May;9(7):488-93.
Current Clinical Protocols
- 12-I-0184: Use of fluorodeoxyglucose (FDG) positron emission tomography (PET) with computed tomography (CT) for the Evaluation of Autoimmune Lymphoproliferative Syndrome (ALPS) Lymphadenopathy Suggestive of Lymphoma
- 06-I-005: Screening Protocol for Genetic Diseases of Lymphocyte Homeostasis and Programmed Cell Death
- 93-I-0086: Evaluation and long term follow up of patients with acute and chronic inflammatory disorders
- 95-I-0066: Genetic Analysis of Immune Disorders
- 93-I-0063: Study of the Immunopathogenesis, Natural History, and Genetics of Autoimmune Lymphoproliferative Syndrome (ALPS) Associated with an Expansion of CD4-8-/TCR alpha/beta+ T Cells and Defective Lymphocyte Apoptosis