“Identificación de biomarcadores diagnósticos y pronósticos en la artritis psoriásica mediante la aplicación del riesgo poligénico, transcriptómica y proteómica.”

Research Leader:: Roberto Díaz Peña
Institution:: Principal Researcher, Grupo de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago (FIDIS, SERGAS)

BACKGROUND

The so-called Spondylarthritides have been defined as a group of chronic inflammatory arthropathies that affect especially the spine and sacroiliac joint, although they could appear with peripheral symptoms and extra-articular manifestations. The prevalence of these diseases is estimated between the 1.2 and the 1.8% and there are classified according to clinical features in several types: Psoriatic Arthritis (PsA), Ankylosing Spondylitis (AS), SpA associated with inflammatory bowel disease (IBD), Reactive Arthritis, Undifferentiated SpA and Juvenile SpA (1-3). Similar clinical expression among SpA, common genetic basis, and similar therapeutic response to certain drugs, support the hypothesis of the existence of a common pathogenic mechanism.

PsA refers to an inflammatory disorder that affects numerous organs, including the skin and joints (4). The course of this disease is variable and unpredictable, ranging from mild and non-destructive joint involvement to a severe, debilitating, and erosive arthropathy (5). The etiopathogenic mechanisms for the development of PsA are not completely understood, but there is strong evidence that support a relevant genetic component (6, 7).

In the last 15 the continuous evolution of genome-wide association studies (GWAS) has allowed the increase of our knowledge in genetic susceptibility to complex pathologies and allowed the development of polygenic risk scores (PRS) (8). However, in the case of patients with PsA, we only partially know the genetic basis, so there is a need for GWAS studies in these patients.

HYPOTHESIS

Since the prognosis of patients with SpA is challenging in most of the cases, the general hypothesis of this work is that genomics can help us to improve prevention and intervention strategies in SpA. In addition, the development of this project will allow the generation and validation in independent cohorts of models for diagnosis and short- and long-term prognosis.

OBJECTIVES

The main objective of the project is the identification of diagnostic and prognostic biomarkers that allow the development and validation of precision medicine tools in PsA.

Specific objectives:

1.- To develop predictive models that allow the identification of patients with a predisposition to suffer from PsA through the integration of genetic and clinical data. We will identify genetic factors specifically associated with PsA, which allow us to advance in the knowledge of the genetic architecture of the disease, well below other rheumatic pathologies, and which make it impossible to apply genetic risk calculations and develop predictive models in PsA.

2.- To identify specific proteogenomic and clinical patterns in prospectively followed cohorts of patients with PsA. We will develop predictive models that allow the identification of subgroups of patients likely to evolve aggressively in the early stages of the disease

REFERENCES

1. López-Medina C et al. Best Pract Res Clin Rheumatol. 2018;32(2):241-53.

2. Amor B et al. Rev Rhum Mal Osteoartic. 1990;57(2):85-9.

3. Sepriano A et al. Ann Rheum Dis. 2016;75(6):1034-42.

4. Van den Bosch F et al. Lancet. 2018 Jun 2;391(10136):2285-94.

5. Taylor W et al. Arthritis Rheum. 2006 Aug;54(8):2665-73.

6. Chandran V et al. Ann Rheum Dis. 2009 May;68(5):664-7.

7. Karason A et al. Rheumatology (Oxford). 2009 Nov;48(11):1424-8.

8. Mills MC et al. Commun Biol. 2019;2:9.