ADVANCED GLYCATION END PRODUCTS IN SYSTEMIC SCLEROSIS

L. Triginer, L. Tío, I. Carrion, A. Guillen-Del-Castillo, A. Ribes, L. Valencia Muntalà, J. Monfort, T. C. Salman, A. Pros, J. Narváez, C. P. Simeon AznarIDIBELLL, Unitat Funcional de Malalties Autoinmunes Sistèmiques (UFMAS), Barcelona, Spain IMIM (Hospital del Mar Medical Research Institute), Barcelona, Infammation and Cartilage Cellular Reseach Group, Barcelona, Spain Hospital del Mar, Servei de Reumatologia, Barcelona, Spain Hospital Universitario Vall d’Hebron, Department of Internal Medicine, Barcelona, Spain VHIR, Systemic Diseases, Barcelona, Spain Hospital Universitari de Bellvitge, Department of Rheumatology, Barcelona, Spain Barcelona, Servei de Reumatologia, Barcelona, Spain  Background Studies have postulated that advanced glycation end products (AGEs) could have a relevant role as inducers in the chronic inflammatory pathway present in various diseases -- including systemic sclerosis (SSc). Similarly, that the concentration of AGEs maybe related to nailfold capillaroscopy SSc changes, the diffuse skin subtype, or calcinosis. Validation studies have shown that skin autofluorescence is strongly related to AGEs levels in skin biopsies. Objectives To characterize and identify association between the concentrations of AGEs, measured by cutaneous autofluorescence, and disease parameters in SSc patients. Methods AGEs concentrations were measured by skin autofluorescence (Age Reader Mu Connect from Diagnostics Technologies BV®) in 179 SSc patients and correlated with demographic and clinical data. Cumulated AGEs were distributed in tertiles. Categorical data was described with frequencies, whereas continuous variables were displayed as mean (standard deviation). ANOVA tests were conducted to explore the linear association of demographics and clinical features with the cumulated AGEs value. Regression models were adjusted by age (M1), and also by smoking status (M2 = M1 + smoker). Results Table 1 shows the distribution and correlation of the most relevant patients characteristics studied according to AGEs levels classified in tertiles. Male gender (p-value M1=0.008, M2=0.003) and anticentromere antibodies (ACA) (p-value M1=0.010, M2=0.034) were statistically significant associated with higher AGEs levels. In addition, AGEs levels were inversely correlated with obesity as a categorical variable with statistical significance (p-value M1=0.036, M2=0.022). Although not statistically significant, there was a trend towards higher values of AGES (p-value 0.05 - 0.1) in patients with esophageal involvement and skin manifestations (either diffuse or limited cutaneous subtype) and lower prevalence of anti-topoisomerase antibodies (ATA). No associations with other characteristics were found. Conclusion Higher AGEs levels were independently associated to male gender, ACA positivity and inversely with obesity. AGEs might be involved in the aethiopathological pathways leading to skin and esophageal manifestations. Finally, the disease mechanism in obese SSc patients might indicate a milder disease, as they present lower AGEs values, opposing to what has been described in healthy subjects. This could indicate less severe gastrointestinal disease leading to malnourishment. References Murray, Andrea K., et al. The Journal of Rheumatology 39.8 (2012): 1654-1658. Kaloudi, O., et al. Rheumatology 46.3 (2007): 412-416. Davies, Christine A., et al. Rheumatology 48.8 (2009): 876-882. Meerwaldt R., et al. Ann N Y Acad Sci 2005;1043:290–298. Villanueva-Martin, G., et al. J. Clin. Med. 2022, 11, 6014. Table 1. Correlations of our cohort characteristics according to advanced glycation end products levels. c: categorized; M1: adjusted for age; M2 adjusted for age and tobacco. BMI: body mass index. * Not adjusted age. Bold indicates statistically significant differences (p<0.05). All First tertile [1.4,2.4) Second tertile [2.4,2.9] Third tertile [2.9,6.7] p-value M1 p-value M2 N=179 N=60 N=62 N=57 Gender (Male) 17 (9.5%) 4 (6.7%) 5 (8%) 8 (14%) 0.008 0.003 Age 61.0 (12.6) 55.7 (13.4) 61.7 (11.9) 65.8 (10.4) 0.000* Smoking status 16 (8.94%) 2 (3.33%) 6 (9.68%) 8 (14.0%) 0.031 Skin involvement 161 (89.9%) 50 (83.3%) 58 (93.5%) 53 (93.0%) 0.100 0.085 Esophageal involvement 155 (86,6) 49 (81,7%) 55 (88,7%) 51 (89,5%) 0.113 0.078 Anti-topoisomerase antibodies 21 (14.7%) 10 (20.4%) 6 (11.8%) 5 (11.6%) 0.076 0.071 Anti-centromere antibodies 70 (47.3%) 21 (41.2%) 26 (50.0%) 23 (51.1%) 0.010 0.034 Obesity 39 (21.8%) 15 (25.0%) 14 (22.6%) 10 (17.5%) 0.036 0.022 BMI 26.0 (5.42) 26.4 (6.20) 25.8 (4.91) 25.8 (5.13) 0.457 0.603 cBMI: 0.370 0.387 Healthy 84 (47.5%) 28 (46.7%) 29 (48.3%) 27 (47.4%) Overweight 66 (37.3%) 21 (35.0%) 22 (36.7%) 23 (40.4%) Obesity 27 (15.3%) 11 (18.3%) 9 (15.0%) 7 (12.3%) Acknowledgements Project “202022-33” is funded by FUNDACIÓ LA MARATÓ DE TV3 Disclosure of Interests None Declared. Keywords: Prognostic factors, Organ damage, Biomarkers DOI: 10.1136/annrheumdis-2023-eular.4730Citation: , volume 82, supplement 1, year 2023, page 1655Session: Scleroderma, myositis and related syndromes (Publication only)