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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