Molecular and Cellular Bases in Rheumatic Diseases

Description

Our group belongs to the consolidated groups of the Complutense University of Madrid ““Molecular and cellular bases of inflammatory / autoimmune diseases ” nº 910012.

Website: (http://www.ucm.es/vip)

The Research Group has a double aspect, teacher and researcher. As part of a University Department, a cardinal objective of the group is to train future teachers and researchers and contribute to the generation of new knowledge. In its research aspect, our team, along its long trajectory, has contributed to the knowledge of the basic mechanisms of different pathologies, as well as to the study of the VIP axis / receptors as a biomarker of rheumatic diseases. Thus, it has generated sufficient information, from a basic research in its origins, it has been approached, thanks to the collaboration with clinical researchers, to its translational application.

The most outstanding translational results that confirm the importance of the axis as a prognostic / activity marker are: 1) Low serum VIP levels correlate inversely with the activity of RA and Spondyloarthritis. 2) Those patients who, after two years of follow-up, continue to have moderate or high levels of disease activity, show the lowest baseline VIP levels. This finding is even more relevant, bearing in mind that this behavior is observed despite the tendency to prescribe higher doses of FAMEs (disease-modifying anti-rheumatic drugs) to patients with low VIP levels. 3) The VPAC1 receptor can be considered a marker of activity, since patients with more severe inflammation and higher disease activity have lower levels of VPAC1. 4) Our most recent and relevant result points to a clear correlation of genetic variants of the VIP gene with its serum levels and treatment requirements.

The group has recently registered two patents with the La Princesa Hospital Foundation, one of them European: “Prognosis method of autoimmune diseases by genotyping genetic variations of the vasoactive intestinal peptide” EP3121290 A4.

As members of the Inflammation Network in Inflammatory and Rheumatic Diseases, we actively collaborate with the groups of Isidoro González-Álvaro of the Hospital of La Princesa (Madrid), Mario Mellado of the CNB-CSIC (Madrid), José Luis Pablos of the Hospital October 12 (Madrid), Francisco Blanco from CHUAC (A Coruña) and Marina Garín from CIEMAT (Madrid).

Current priority lines:

1. To study the contribution of fibroblastic synoviocytes to the destruction of cartilage in osteoarthritis.
   For this, we are analyzing the role of ADAMTS-7 and -12, produced by the synoviocyte, in the destruction of the extracellular matrix and the potential effect of VIP on them. We are also studying the secretome of co-cultures of synoviocytes and chondrocytes, analyzing molecules involved in the destruction of cartilage and its modulation by VIP.
2. To study the neuro-immuno-osteogenic interactions in patients with rheumatoid arthritis.
   This line of research has three important subdivisions:
   • To study the correlation between serum VIP levels and the expression of VPAC1 and VPAC2 with radiological parameters in patients with recent AR.
   • The characterization of the expression pattern of VIP receptors in differentiated osteoclasts from monocytes of healthy donors and patients with RA. As well as studying the effect of VIP on the osteoclastogenic potential of these cells and on the contribution of the fibroblastic synoviocyte to osteoclastogenesis.
   • The characterization of the pattern of expression of VIP receptors during the differentiation / activation of Th lymphocytes in donors and patients with recent AR. To determine the effect of VIP on the phenotype of Th cells involved in the process of osteoclast differentiation and in bone resorption.

3. The recognition and validation of other biomarkers in inflammatory and autoimmune diseases (epigenetic studies and miRNAs involved in the gene regulation of the VIP axis / receptors)
   The main objectives that are being addressed following this line of research are:
   • To identify epigenetic variants of VIP receptors by analyzing methylation levels of different regions of them, in samples from different cohorts of patients with recent-onset arthritis.
   • To analyze whether the methylation pattern of these variants can be useful as a prognostic biomarker studying its association with clinical severity parameters.
   • To correlate in serum the presence of microRNAs with the levels of expression of the VIP axis / receptors in samples from patients with different inflammatory and autoimmune diseases.