The candidate, Violeta Rus, is a rheumatology fellow and future Clinical Instructor at the University of Maryland Medical School, where she is developing a career in clinical research in lupus. The proposed work draws on her bench-research experience on the role of cytokines in a murine models of lupus, and requests support for a Mentored Patient-Oriented Career Development Award to acquire new expertise in the science of clinical investigation in order to be able to translate new biomedical advances to the bed-side. The candidate will work under the mentorship of Dr. Charles S. Via and Marc C. Hochberg in the superb research environment, resources and opportunities for career development at the University of Maryland Medical School. The candidate's immediate goals are to obtain the training necessary to become a successful, independent clinical investigator able to pursue high quality hypothesis-driven disease oriented research. The proposal is an outgrowth of the PIs previous work in a murine model of lupus where she identified the role of several cytokines important in driving autoantibody production. The present study will define the cytokine pattern in active and inactive lupus patients and determine whether changes in cytokine levels will predict future flares. Hypothesis: High levels of B cell stimulatory cytokines IL-10 and IL-6 and low or variable levels of IFN-g and TNF-a will correlate with disease activity in lupus patients and precede disease flare. Conversely, reciprocal changes of these cytokines will accompany or precede disease remission.
Specific Aim 1) Determine in a cross sectional study whether disease activity is correlated with altered serum or mRNA levels of IL-10, IL-6, IFN-g and TNF-a. Cytokines will be measured in serum specimens by ELISA and in peripheral blood mononuclear cells mRNA by semiquantitative RT-PCR.
Specific Aim 2) Determine in a longitudinal study whether alterations in these cytokines precede or accompany disease flare and post-flare improvement. Samples of serum and mRNA from 50 patients followed longitudinally will be tested every 3 month in stable patients, biweekly during flares and monthly until remission. For both aims, flares will be defined using SLEDAI and Physician Global Assessment scores. Statistical analysis using exploratory analyses and regression models will be used. The proposed research will have high relevance to our understanding of the role of cytokines in inducing flares and remissions in SLE, assess their predictive value for future flares, and develop a rationale for future cytokine-based therapies.
| Rus, Violeta; Nguyen, Vinh; Puliaev, Roman et al. (2007) T cell TRAIL promotes murine lupus by sustaining effector CD4 Th cell numbers and by inhibiting CD8 CTL activity. J Immunol 178:3962-72 |
| Rus, Violeta; Zernetkina, Valentina; Puliaev, Roman et al. (2005) Increased expression and release of functional tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) by T cells from lupus patients with active disease. Clin Immunol 117:48-56 |
| Rus, Violeta; Chen, Hegang; Zernetkina, Valentina et al. (2004) Gene expression profiling in peripheral blood mononuclear cells from lupus patients with active and inactive disease. Clin Immunol 112:231-4 |
| Rus, Violeta; Atamas, Sergei P; Shustova, Valentina et al. (2002) Expression of cytokine- and chemokine-related genes in peripheral blood mononuclear cells from lupus patients by cDNA array. Clin Immunol 102:283-90 |
