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THU0218 IDENTIFICATION, VERIFICATION AND VALIDATION OF NEW BIOMARKER CANDIDATES FOR MONITORING ACTIVITY IN PSORIATIC ARTHRITIS AND OTHER IMMUNE-MEDIATED INFLAMMATORY DISEASES (IMIDS)

Background Immune-Mediated Inflammatory Diseases (IMIDs) are a group of conditions/diseases characterized by common pathways leading to inflammation, which may result from a dysregulation of the normal immune response. The activity of these diseases is usually measured by the assessment of clinical symptoms. Objectives To apply a three-stage proteomic strategy to find plasma biomarkers useful to monitor disease activity in patients three different IMIDs: rheumatoid arthritis (RA), psoriatic arthritis (PsA) and systemic lupus erythematosus (SLE). Methods A three-stage proteomic strategy was conducted: 1) Discovery stage: a random selection of 80 plasma samples from patients with different RA activities according to the DAS28, which were classified as low activity (LA, n=40) and high activity (HA, n=40). The analysis was conducted by shotgun mass spectrometry (MS) applying an iTRAQ 8-plex strategy, by nanoLC-MS/MS using three different MS instruments. 2) Verification stage: a targeted proteomics strategy was used to verify the candidate biomarkers from the screening, using the same 80 samples of this first stage. This analysis was performed by Multiple Reaction Monitoring (MRM) with the aid of synthetic heavy-labelled peptides, by nanoLC-MS/MS in an ESI-QTRAP 5500. 3) Validation stage: ELISA experiments were performed to confirm the previous results on an independent set of plasma samples from patients with RA (n=170), PsA (n=80) and SLE (n=80). Results 1) Discovery stage: The MS analysis led to the identification of 186 proteins. A panel of 9 proteins was identified as candidate biomarkers for disease activity monitoring in RA. Most of these proteins are related with the pathogenic process and the effects caused by this type of disease (inflammation and immune disorder in joints). 2) Verification stage: four from the 9 proteins (SAA1, AACT, HPT, A1AG1) were found to be quantitatively altered between patients with extreme disease activities (p<0.05). All these proteins were up-regulated in patients with HA. 3) Validation stage: as shown in the top row of the Figure, serum amyloid 1 (SAA1), alpha-1-antichymotrypsin (AACT) and haptoglobin (HPT) are higher in the three IMIDs compared to healthy controls, being the highest in RA. Regarding their levels in patients with different disease activities, they are all increased in the plasma of HA individuals compared to LA (bottom row). Interestingly, the levels of these 3 proteins are associated with the activity of PsA: HPT (p<0.0001), SAA (p=0.0209) and AACT (p=0.0418), showing a potential utility for the molecular monitoring of this disease. Conclusion Using a three-stage proteomic strategy, we have identified HPT, SAA1 and AACT as protein biomarker candidates for monitoring PsA activity. Disclosure of Interests Lucia Gonzalez Rodriguez: None declared, Valentina Calamia: None declared, Rocío Paz González: None declared, Patricia Fernández Puente: None declared, Cristina Ruiz-Romero: None declared, Juan D. Cañete: None declared, Antonio Julià: None declared, Antonio Fernández Nebro: None declared, Jesús Tornero: None declared, Sara Marsal: None declared, Francisco J. Blanco Consultant for: AbbVie, Bioiberica, BMS, GSK, Grünenthal, Janssen, Lilly, Pfizer, Regeneron, Roche, Sanofi, TRB Chemedica, and UCB