Kyriakos A. Kirou, MD, FACR

Appointments

Assistant Attending Physician, Hospital for Special Surgery

Assistant Professor of Medicine, Weill Medical College of Cornell University

Assistant Scientist, Hospital for Special Surgery

 

Kyriakos A. Kirou, MD, FACR is the author of the following articles on HSS.edu:

Selected Publications

Kirou KA, Lee C, George S, Louca K, Peterson MG, Crow MK. Interferon-alpha pathway activation identifies a subgroup of systemic lupus erythematosus patients with distinct serologic features and active disease. Arthritis Rheum 52:1491-1503;2005.

Liu Y, Masuda E, Blank MC, Kirou K, Gao X, Park MS, and Pricop L. Cytokine-mediated regulation of activating and inhibitory Fc receptors in human monocytes. J Leukoc Biol 77:767-776;2005.

Crow MK, Kirou KA. Interferon-alpha in systemic lupus erythematosus. Curr Opin Rheumatol 16:541-547;2004.

Kirou KA, Lee C, George S, Louca K, Papagiannis IG, Peterson MG, Ly N, Woodward RN, Fry KE, Lau AY, Prentice JG, Wohlgemuth JG, Crow MK. Coordinate overexpression of interferon-alpha-induced genes in systemic lupus erythematosus. Arthritis Rheum 50:3958-3967;2004.

Kirou KA, Lee C, Crow MK. Measurement of Cytokines in Autoimmune Disease. Methods Mol Med. 102:129-154;2004.

For more publications, please see the PubMed listing.  

Research Description

Pathogenesis of Systemic Rheumatic Autoimmune Diseases

The aim of our research is to characterize the activation of molecular pathways that contribute to immune system dysfunction and disease in systemic autoimmune diseases and especially systemic lupus erythematosus (SLE). SLE is the prototypic systemic autoimmune disease and affects primarily young women. Patients may have various clinical manifestations, some of which may be serious or life-threatening. Our studies so far have focused on the measurement of the expression of IFN-alpha-inducible genes (IFIG) in freshly isolated blood cells from patients with lupus, using the real-time polymerase chain reaction (PCR) technology. We have shown that IFIG expression in SLE predominantly reflects IFN-alpha rather than IFN-gamma activity and that the activation of the IFN-alpha pathway in SLE is independently associated with the presence in the blood of autoantibodies against RNA-binding proteins (RBP), renal disease, increased serologic activity of the disease, disease-related damage and failure to treat with antimalarial medications. These studies have important implications for our understanding of the pathogenesis of SLE. More specifically, the independent association of anti-RBP autoantibodies with activation of the IFN-alpha pathway supports the notion that immune complexes containing these RNA-bound proteins may be responsible for induction of IFN-alpha in SLE. In addition, our classification of lupus patients into subgroups according to the presence or absence of activation of the IFN-alpha pathway is expected to facilitate conduct of clinical studies in this notoriously heterogeneous disease. Moreover, IFIG expression, given its association with disease activity, offers promise for use as a biomarker for lupus activity in patients. We are planning further studies to test the validity of such an application. In parallel we are also studying the expression of other important genes in this disease, including those that are associated with inflammation and key cellular signaling pathways. In summary, these studies are expected to offer new insights into the underlying molecular pathways that are responsible for lymphocyte activation in SLE, facilitate improved definition of disease subsets, and hopefully lead to new therapies for this disease.

Clinical Trials

• A Phase 1b Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation study with an open-label extension to evaluate the safety and tolerability of multiple IV doses of Medi-545, a fully Human Anti-interferon-alpha Monoclonal Antibody,
• A Phase I, Randomized, Double-blind, Placebo-controlled, Escalating Single- and Multiple-dose Study of the Safety, Tolerability, and Pharmakokinetics of RhuMab IFN alpha in Adults with Systemic Lupus Erythematosus
• The Systemic Lupus Erythematosus (SLE) Activity Gene Expression (SAGE) Study
• Gleevec in the Treatment of Systemic Sclerosis
• A Sequential Adaptive Phase II/III Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Abatacept Versus Placebo on a Background of Mycophenolate Mofetil and Glucocorticosteroids
• Scleroderma Cyclophosphamide or Transplantation (SCOT) Study
• Scleroderma Registry
• A Phase I, Randomized, Double-Blind, Placebo Controlled, Dose-Escalation Study To Evaluate Safety And Tolerability Of A Single IV Dose Of MEDI-545, A Fully Human Monoclonal Antibody Directed Against Interferon Alpha Subtypes
• Rituximab Therapy For The Induction Of Remission And Tolerance In ANCA-Associated Vasculitis