AB1172 ARE CIRCULATING BLOOD BIOMARKERS FOR INFLAMMATORY RHEUMATIC DISEASES GENDER-DEPENDENT? – SYSTEMATIC REVIEW BASED ON OMICS DATA

Background Inflammatory rheumatic diseases (IRDs) are thought to be multifactorial diseases. Female-male ratio in IRDs differs according to the disease1. In Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) female prevalence is higher opposing to Ankylosing Spondylitis (AS)2,3.Until recently, differences on gender-bias observed in predisposition to IRDs, and to their pathophysiologies have been understudied and neglected. Recent research using omics approaches shows that gender-bias is outspread in a diversity of pathologies. The integration of omics results, spite the extremely complex crosstalk among the several biomolecules involved, places these methods at the lead of medical research, overcoming limitations and increasing the forecasts of targeted methodologies4–6. Objectives The purpose of this systematic review is to aggregate existing omics results on biomarkers for RA, SLE and AS to raise awareness about whether gender can actually play a role on their profiles. Methods Two searches were conducted on PUBMED database (22nd November 2018) with a final output of 81268 articles. Both searches were sorted by best matches and for the second thousandth articles ranked no relevance was found for the aim of this review. The first 1000 articles were further analyzed based on the title, abstract and content. Three articles having relevant results were selected from the first thousand publications. Ten more were identified from the cross-references of both searches. The PICO (P, population; I, intervention; C, comparison; O, outcome) concept was used to perform the analysis according to: Patients: adults (>18 years old) with RA, SLE or AS (SpA); Intervention: any –omic study; Comparison: gender information regarding results; Outcomes: identified genes, proteins or metabolites. Results Dectin-2, MCP-1 and DC-SIGN polymorphisms where proposed as possible accounts for gender-associated differences in susceptibility to RA7. Sex-differentiated and sex-interaction analyses of a GWA study revealed strong evidence of association in both sexes, highlighting links with RA only in one of the genders8. Several transcriptomic studies pointed to gender differences on biomarkers profiles for the three diseases. For instance, different expression levels of TNFα, IL-6, IL-17, IL-18, IFNα as well as X or Y chromosome-linked genes were found in SLE and/or AS9–11. In AS, male patients with syndesmophytes showed higher levels of TNFα and men without syndesmophytes presented higher levels of VEGF, IL-6, TNFα and IL-18 both compared to females-matched12. In RA patients, microRNAs 222, 532, 98, and 92a were found significantly down regulated in PBMC of female versus male13. Six genes displayed a gender-biased expression among male and female SLE patients14. Conclusion Blood biomarkers signatures for the IRDs analyzed in this study have been shown gender-biased. These will contribute for a better understanding of these diseases pathophysiology and probably to different gender approaches regarding diagnosis, monitoring and therapeutic approach. References [1] Amur S, et al. (2012),38,J254;Nussinovith U, Shoenfeld Y(2012),11,6; van Vollenhoven RF(2009),7,1; [2] Effler SW, et al. (2013),39,101; [3] Russell C et al(2013),4,395; [4] Song X, Lin Q(2017),37,1257; [5] Caliz R, et al. (2013),8,e72732; [6] Zhuang JJ,Morris AP(2009),3,Suppl 7:S90; [7] Gracey E et al(2016),68,679; [8] Hui-Yuen J et al(2016),45,394; [9] Wang XB et al(2017),18,184; [10] Huang WN et al(2012),15,163; [11] Khalifa Oet al(2016),17; [12] Martin AR et al(2018),1 Disclosure of Interests Ana Filipa Fernandes: None declared, Atlas Sardoo: None declared, Fernando Pimentel dos Santos Grant/research support from: From Abbvie and Novartis, Speakers bureau: Abbvie, Novartis, Pfizer, Biogen, Ana Varela Coelho: None declared