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Objectives Osteoarthritis has been the subject of abundant research in the last years with limited translation to the clinical practice, probably due to the disease’s high heterogeneity. In this study, we aimed to identify different phenotypes in knee osteoarthritis (KOA) patients with joint effusion based on their metabolic and inflammatory profiles. Methods A non-supervised strategy based on statistical and machine learning methods was applied to 45 parameters measured on 168 female KOA patients with persistent joint effusion, consecutively recruited at our hospital after a monographic OA outpatient visit. Data comprised anthropometric and metabolic factors and a panel of systemic and local inflammatory markers. The resulting clusters were compared regarding their clinical, radiographic and ultrasound severity at baseline and their radiographic progression at two years. Results Our analyses identified four KOA inflammatory phenotypes (KOIP): a group characterized by metabolic syndrome, probably driven by body fat and obesity, and by high local and systemic inflammation (KOIP-1); a metabolically healthy phenotype with mild overall inflammation (KOIP-2); a non-metabolic phenotype with high inflammation levels (KOIP-3); and a metabolic phenotype with low inflammation and cardiovascular risk factors not associated with obesity (KOIP-4). Of interest, these groups exhibited differences regarding pain, functional disability and radiographic progression, pointing to a clinical relevance of the uncovered phenotypes. Conclusion Our results support the existence of different KOA phenotypes with clinical relevance and differing pathways regarding their pathophysiology and disease evolution, which entails implications in patients’ stratification, treatment tailoring and the search of novel and personalized therapies.

Background Radiographic severity is used in routine clinical practice to evaluate knee osteoarthritis (KOA) structural damage. There are no conclusive studies on the associations between synovial inflammatory markers and the different features of radiographic damage in KOA. Objectives To evaluate the association between inflammatory markers in synovial fluid with the different features of radiographic severity in patients with KOA. Methods Cross-sectional study of 114 female patients aged 50-85 with symptomatic primary KOA with significant joint effusion (>4 mm at midline patellar line) confirmed by ultrasound. The following information was collected: age, KOA symptoms duration, body mass index; plain standing knee Rx in semi-flexion were evaluated for radiographic severity by modified OARSI atlas evaluating separately osteophytes (OPH) and joint space narrowing (JSN). The OPH score was obtained searching for marginal osteophytes in both medial and external femoral condyles and tibial plateaus, scoring 0 to 3 in each quadrant, for a total score ranging from 0-12. Due to the high number of different scores obtained, and sometimes with a low number of patients, we grouped osteophytes scores 1-2 as mild, 3-6 as moderate and seven or more as severe osteophyte count. The JSN score was calculated in both medial and lateral knee compartments, grading the joint space 0 to 3 in each one, for a total score ranging from 0 to 6. A JSN score of 0 was considered as normal, 1-2 as moderate and 3 or more as high JSN severity. Five inflammatory markers: TNF alpha, high sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), interleukin 8 (IL-8) and calprotectin were measured by ELISA following manufacturer recommendations for synovial fluid dilutions. A comparison between medians of the three groups was carried out and a multivariate analysis controlled by age, symptom duration, BMI and all five inflammatory markers were performed. Results A significant association for symptom duration and synovial IL8 was observed for osteophytes (p For JSN, in the adjusted analysis, patients with a high JSN score had synovial IL-8 levels of 40% more than those with JSN 0 (p=0.035), while no differences were found between the moderate JSN score and the other two degrees. Regarding hsCRP, 30% higher levels were found in patients with a JSN moderate degree compared with JSN 0 (p=0.033), while no significant differences were observed between severe and the other two degrees. Conclusion Interleukin-8 IL 8 was the inflammatory marker associated to radiographic severity as evaluated by osteophyte count and joint space narrowing score on plain radiography in patients with knee osteoarthritis. Disclosure of Interests Silvia Garcia-Cirera: None declared, Joan Calvet: None declared, CRISTOBAL ORELLANA: None declared, Noemi Navarro: None declared, Maria Garcia Manrique de Lara: None declared, Jordi Gratacos-Masmitja Grant/research support from: Pfizer Inc, Consultant for: Pfizer Inc, Speakers bureau: Pfizer Inc

Background:Rheumatoid Arthritis (RA) is a systemic autoimmune disease, associated with hiperproduction of autoantibodies (AAb), in which the most specific are the AAb against citrullinated peptides (ACPA). RA is influenced by genetic factors, specifically, there is a strong genetic association with the shared epitope (SE), a five amino acid sequence motif in positions 70–74 of HLA-DRβ1 chains encoded by HLA-DRB1 alleles: QKRAA, QRRAA and RRRAA.The present study aims to analyze whether SE-peptides (SE-p) can be a target of the autoimmune response in RA.Objectives:To analyze the presence of AAb against the unmodified (Un) SE-p, citrullinated (Cit) SE-p and carbamylated (Car) SE-p.Methods:Sera from consecutive 117 RA patients and 21 psoriasic arthritis (PsA) from our outpatient clinic were collected by venopunture. Also 138 sera from blood donors were obtained as healthy controls (HC). All participants signed the informed consent.We perfomed a homemade ELISA test using a sequence of 15 aminoacid peptides from positions 65-79 of HLA-DRB1 containing the 3 different SE sequences, in the Un, Cit and Car SE-p, synthesized in a linear and cycled form. We established a 90% of specificity using a ROC curve obtained from HC and PsA for each ELISA test.HLA-DRB1 polymorphism was performed using a HLA-DRB1 sequence specific oligonucleotide typing kit (Lifecodes) in 95 RA and in 15 PsA.ACPA and RF were determined with commercial assays (Inova Diagnostics and Binding Site, respectively).Results:The overall sensitivity of the different SE-p AAb tests ranged from 5.1-21.4%.RRRAA SE polymorphism was associated with AAb against cycled CitCitCitAA SE-p (p=0.025), QKRAA polymorphism was almost significantly associated with AAb against cycled QKCitAA SE-p (p=0.067), whereas there was no association between QRRAA polymorphism and AAb against cycled QCitCitAA SE-p (p=0.690). On the other hand, there was no association between SE polymorphisms and AAb to any other peptide used in the ELISA test.Significant differences were observed in the presence of AAb against lineal RRRAA, lineal CitCitCitAA and cycled CitCitCitAA SE-p when comparing RA vs. HC patients (p=0.022, 0.044, 0.022, respectively). Moreover, there also were significant differences in the presence of AAb against cycled CitCitCitAA SE-p between RA and PsA patients (sensitivity 21.4%, specificity 100%; p=0.014).It must be highlighted that cycled CitCitCitAA SE-p AAb were detected in 20.0% of RA patient sera that were negative for RF and ACPA.There was no association between RF or ACPA with the presence of any SE-p AAb.Conclusion:RA patients have autoantibodies against the Shared Epitope (SE). The cycled CitCitCitAA SE peptide (SE-p) shows the best performance among all the peptides tested and could identify patients seronegative for ACPA and RF, both analyzed by commercial assays.Additional studies must be performed to verify the diagnostic and utility of these new autoantibodies against SE-p in RA.Acknowledgements:This work was granted by the 2018 call of the “Fundación Española de Reumatologia” and the 2017 call grant “Fundació Parc Taulí”.Disclosure of Interests:None declared

Background:Androgen deprivation therapy (ADT), by inducing severe hypogonadism, leads to a loss of bone mineral density (BMD) and an increased risk of fragility fractures after 6 months of treatment in men with prostate cancer1. However, its effect on bone quality has not been described.Objectives:To evaluate the changes on bone microarchitecture (bone quality) assessed by TBS (trabecular Bone Score) in male patients with prostate cancer after one year of treatment with ADT.Methods:All patients diagnosed with prostate cancer candidates for long-term ADT admitted to Urology department of Hospital Universitari Parc Tauli (reference population of 450,000 inhabitants) between April 2017 and December 2019 were included. Patients who received chemotherapy, previous hormonal therapy or specific treatment for osteoporosis in the last year or those who had a very impaired functional capacity (Barthel index Demographic, clinical and analytical data (testosterone, calcium, phosphorous, alkaline phosphatase, 25-hidroxyvitamin D, PTH) were collected in all patients. A bone densitometry (GE-Lunar Prodigy) including the measurement of lumbar spine TBS (L1-L4) using Medimaps Software was performed at baseline and at 12 months of treatment with ADT.Results:78 patients were included. Mean age 77,9±8,3 years. The median Gleason score was 7,88±1,05. 3 patients had previous fragility fracture (one sacral fracture, one fibula and one multiple vertebral fracture). Baseline analytical values in patients were the following: testosterone11,6±74,9 nmol/L.; 25-hidroxyvitamin D 20,8±10,4 ng/ml; PTH 51,8±23,0 pg/ml; CTX 0,58±0,66. The daily calcium intake was 573±207 mg/day.According to BMD, 17 patients (21,8%) had osteoporosis before starting ADT, with the following average T-score values: lumbar spine +0,15±1,85, femoral neck -1,75±1,00, and total hip -1,19±1,16. Mean baseline TBS value of the entire cohort was 1,279±0,122. 30,5% of the patients showed very degraded microarchitecture (TBS1,310).After one year of ADT treatment, TBS mildly worsened in this cohort, with a median value of 1,256±0,131 (p = NS). However up to 43% of patients reached highly degraded microarchitecture, 27% partially degraded and only 29,5% had a normal TBS (p = NS).Conclusion:Most patients with prostate cancer have an altered bone quality before starting ADT. After 12 months of treatment, the percentage of patients with highly degraded bone microarchitecture increases, although not significantly. More studies are needed to confirm this trend and to evaluate if these patients present more long-term fractures.References:[1]Lee R, et al. Bone 2011; 48 (1): 88-95Disclosure of Interests:Silvia Garcia-Cirera: None declared, Enrique Casado Speakers bureau: UCB, Lilly, Amgen, Theramex, Gebro, Gedeon-Richter, Stada, Jesús Muñoz: None declared, Luis Del Río: None declared, Marta Arévalo: None declared, Menna Rusiñol: None declared, Noemí Navarro: None declared, Víctor Parejo: None declared, Jordi Gratacos-Masmitja Grant/research support from: a grant from Pfizzer to study implementation of multidisciplinary units to manage PSA in SPAIN, Consultant of: Pfizzer, MSD, ABBVIE, Janssen, Amgen, BMS, Novartis, Lilly, Speakers bureau: Pfizzer, MSD, ABBVIE, Janssen, Amgen, BMS, Novartis, Lilly