Luminita Pricop, MD

Research Description

Receptors for immunoglobulins: deregulation in autoimmune diseases

Receptors for antibodies and immune complexes form a central element in the inflammatory response. In human phagocytes and antigen presenting cells, receptors for the Fc portion of IgG exist in activation/inhibition pairs. A critical role for Fc receptors in determining susceptibility and severity of autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis, is now established. Our laboratory is involved in the identification and characterization of acquired and genetic factors that determine altered expression and function of Fc receptors in autoimmune diseases. The main goal of our research efforts is to verify these factors as disease markers, and as targets for therapeutic intervention.

Mutations in the regulatory regions of Fc receptors resulting in alterations in expression play a pivotal role in the development of autoimmunity in animal models. We have identified single nucleotide polymorphisms in the promoter of the human FcgRIIA and FcgRIIB genes. FcgRIIB promoter polymorphisms resulted in altered transcription, abnormal receptor expression on peripheral B cells, and associated with autoimmunity in humans.

Inhibitory FcgRIIB receptors function as suppressors of innate and adaptive immune responses. FcgRIIB receptors are modulators of peripheral tolerance and their deficiency is associated with increased susceptibility and severity to organ-specific and systemic autoimmunity. We found that inflammatory cytokines downregulate the expression of inhibitory Fc receptors and reduce their inhibitory potential in mononuclear phagocytes, contributing to the pathophysiology of chronic inflammatory diseases.

The laboratory also studies the dynamics of expression of various Fc receptor isoforms in human dendritic cells. Our recent results suggest that the expression of activating and inhibitory Fc receptors isoforms varies with the stage of differentiation of dendritic cells. Changes in expression and function of Fc receptors in human antigen presenting cells can result in altered uptake and presentation of immune complexes and could contribute to the abnormal afferent response in autoimmune diseases. The scope of our research is to use genetic and immunologic approaches to verify and validate mechanisms underlying autoimmune pathogenesis in the transition from animal models to human disease.

Appointments

Associate Scientist, Hospital for Special Surgery

Associate Professor, Department of Medicine, Weill Medical College of Cornell University

Associate Member, Research Division, Hospital for Special Surgery

Assistant Professor, Immunology Program, Weill Graduate School of Medical Sciences

Selected Publications

Liu Y, Gao X, Masuda E, Redecha PB, Blank MC, Pricop L. Regulated Expression of Fc{gamma}R in Human Dendritic Cells Controls Cross-Presentation of Antigen-Antibody Complexes. J Immunol. 2006 Dec 15;177(12):8440-7. PMID: 17142741

Olferiev M, Masuda E, Tanaka S, Blank MC, Pricop L. The role of activating protein 1 in the transcriptional regulation of the human FCGR2B promoter mediated by the -343 G to C polymorphism associated with systemic lupus erythematosus. J Biol Chem. 2006 Nov 27; [Epub ahead of print]   PMID: 17130130

Jacob CO, Pricop L, Putterman C, Koss MN, Liu Y, Kollaros M, Bixler SA, Ambrose CM, Scott ML, Stohl W. Paucity of clinical disease despite serological autoimmunity and kidney pathology in lupus-prone New Zealand mixed 2328 mice deficient in BAFF. J Immunol. 2006 Aug 15; 177(4):2671-80 PMID: 16888029

Blank MC, Stefanescu RN, Masuda E, Marti F, King PD, Redecha PB, Wurzburger RJ, Peterson MG, Tanaka S, Pricop L. (2005) Decreased transcription of the human FCGR2B gene mediated by the -343 G/C promoter polymorphism and association with systemic lupus erythematosus. Hum Genet. Jul;117(2-3):220-7.

Liu Y, Masuda E, Blank MC, Kirou KA, Gao X, Park MS, Pricop L. (2005) Cytokine-mediated regulation of activating and inhibitory Fc gamma receptors in human monocytes. J Leukoc Biol. 77(5):767-76.

Stefanescu RN, Olferiev M, Liu Y, and Pricop L. Inhibitory Fc gamma Receptors: From Gene to Disease. (in press) J. Clin. Immunol. 2004.

For more publications, please see the PubMed listing.