Study of IFN-gamma/STAT and TGF-beta/SMAD pathways in lupus patients with skin involvement. Role in the evolution to fibrosis.

With this project we aim at studying the status of the IFN-gamma/STAT and the TGF-beta/Smad intracellular signal pathways in cutaneous biopsies of patients with lupus. We are now analyzing the expression of several molecules involved in these pathways to be able both to discern the main differences among the different types of cutaneous lupus and to interpret the residual fibrotic lesions observed in discoid lupus.

José Ordi Ros

Lupus and apoptosis: Mechanisms of action of thalidomide and its analogues in refractory cutaneous lupus. Clinic and therapeutic implications.

The main goal of this research line consists on studying the effect that thalidomide may have in the skin viability and cellular proliferation processes. These mechanisms contribute to wound reepithelization in patients with cutaneous lupus. We are currently analyzing the expression level of several molecules involved in the apoptotic phenomena (Fas/FasL, Bcl-2, Bax,…) and the cell matrix regeneration in keratinocyte and fibroblast primary cell cultures treated with different doses of thalidomide.

Jesus Castro Marrero

DNA methylation study in Systemic Lupus Erythematosus (SLE) patients.

DNA is hypomethylated in T cells from SLE patients. It may lead to an increase in the expression of some genes that are usually silenced and, consequently, autoimmune phenomena may develop. On the other hand, this «unprotected» DNA could be the responsible for triggering anti-DNA antibodies. To find out the reason why this DNA hypomethylation is taking place, we have evaluated the expression level of different DNA methylases and demethylases. We have observed that two demethylases (MBD2 and MBD4) are overexpressed in T CD4+ lymphocytes of patients with SLE. We are now studying the effect the overexpression of these proteins may have in the expression regulation of different molecules involved in the immunologic response.

Eva Balada Prades

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Infection and Autoimmunity: relevance of Human Endogenous Retrovirus (HERV) in Systemic Lupus Erythematosus (SLE).

Antibodies against HERVs have been detected in patients suffering from some autoimmune diseases such as SLE, rheumatoid arthritis, Sjögren’s syndrome, and multiple sclerosis. We mainly focus our research on trying to detect these antibodies in our patients affected with SLE. We have recently cloned some recombinant proteins specific for HERVs. We are simultaneously evaluating the transcription levels of several HERV proteins in T CD4+ lymphocytes from SLE patients.

Eva Balada Prades

Detection of retrovirus XMRV in peripheral blood mononuclear cells of patients with Systemic Lupus Erythematosus.

The presence of the recently discovered retrovirus XMRV («xenotropic murine leukaemia virus-related virus») is being currently studied in our lab in patients with SLE. This virus has been detected in blood samples of patients suffering from chronic fatigue syndrome (CFS). Interestingly, many patients with lupus also suffer from CFS. Based on these facts, with this project we establish as a hypothesis the possibility of finding XMRV DNA and RNA sequences in peripheral blood mononuclear cells from SLE patients, especially in those with CFS. We are nowadays setting up the already described XMRV-specific PCR and RT-PCR assays. We will also study the immunologic response of these patients against particular XMRV proteins.

Eva Balada Prades

Urinary biomarkers detection in lupus nephritis.

Our main goal in this project is to try to avoid the repeated renal biopsies needed for establishing both the diagnosis and the following up of patients who suffer with lupus nephritis. By using just urine from the patients, we want to find out whether there is one/some biomarker/s (MCP-1, TWEAK, NGAL, APRIL, RANTES,…) that allow us to establish particular diagnosis and prognosis criteria  equally effective or even more accurate than those obtained with the renal biopsy.

José Ordi Ros