Luminita Pricop, MD

Previously at Hospital for Special Surgery, New York, NY; Currently at Roche (pharmaceutical industry)

2003/2004 General Immune System Function, Human Lupus Biology

In lupus, helper T cells overreact and mistake a body's own cells as an antigen. This triggers a series of immune responses aimed against the false enemy.

These helper cells stimulate B-cells and other white cells to attack the antigen. They also produce cytokines, powerful immune factors that have an important role in the inflammatory process. T cells have special receptors attached to their surface that recognize specific antigens presented by Fc receptor-positive antigen presenting cells.

With LRI funding, Dr. Pricop examined how a genetic mutation on the Fc receptor may stimulate the inflammatory cascade that is a hallmark of lupus.

What role do inhibitory Fc receptors play in stimulating B and T cells?

“Once this genetic mutation is confirmed to have a functional effect in humans, it could be a genetic marker that could tell people if they have a predisposition to develop lupus,” Dr. Pricop said.

Dr. Pricop and colleagues studied the mutation in a group of people with lupus and compared them with a group of lupus-free controls.

“We know that patients with lupus have more of this mutation than healthy people, although it does not occur in everyone with lupus,” she explained.

So far, estimates suggest that about 7 percent to 8 percent of people with S.L.E. bear this mutation. “No one gene can give you lupus, so there could be many genes that have a similar function to Fc receptor that can also have mutations,” she said.

Dr. Pricop’s results were widely published.

Although she left academic medicine in 2008, Dr. Pricop notes that the mutation she and colleagues identified in people with lupus has been recently identified in another inflammatory disease: chronic inflammatory demmyelinating polyneuropathy (CIDP).

“The -386C/-120A FcgammaRIIB promoter polymorphism resulting in reduced promoter activity associated with SLE identified by Dr. Pricop’s lab was recently reported to also be overrepresented in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) , a common acquired chronic polyneuropathy. (Tackenberg B PNAS 2009 Mar 24;106(12):4788-92. Impaired inhibitory Fcgamma receptor IIB expression on B cells in chronic inflammatory demyelinating polyneuropathy). Taken together the results of these studies not only suggest that the mutations in this gene may be present in patients with other inflammatory conditions, but also that strategies aimed at upregulating FcgammaRIIB expression in patients bearing these mutations might be a promising approach to efficiently limit antibody-mediated immunopathology in SLE and CIDP.” – Dr. Pricop, July 2010

Select publications:

Cytokine-mediated regulation of activating and inhibitory Fc{gamma} receptors in human monocytes. Liu, Y., E. Masuda, M. C. Blank, K. A. Kirou, X. Gao, M. S. Park, and L. Pricop. 2005. J Leukoc Biol 77:767.

Regulated expression of Fc gamma receptors in human dendritic cells controls cross-presentation of antigen-antibody complexes. Y. Liu, X. Gao, E. Masuda, P.B. Redecha, M. C. Blank and L. Pricop. 2006. J Immunol. 15;177(12):8440-7, 2006.

Systemic lupus erythematosus. J.E. Salmon, L. Pricop, V. D'Agati. Immunopathology. Chapter 117, Rheumatology 4e - Edited by Hochberg, Silman, Smolen, Weinblatt & Weisman, Elsevier Ltd, 2007.

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. Olferiev M, Masuda E, Tanaka S, Blank MC, Pricop L. J Biol Chem. 282:1738-46, 2007.

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

Rev. July 2010