Journal Article

POS1155 STUDY OF LNCRNAS INVOLVED IN THE DIFFERENT RESPONSE TO BIOLOGICAL DRUGS IN PSORIATIC ARTHRITIS PATIENTS: EXPRESSION PROFILE AND GENOMIC VARIABILITY

D’antonio, A., Chimenti, M. S., Novelli, G., Latini, A., De Benedittis, G., Conigliaro, P., Borgiani, P., Triggianese, P., Ciccacci, C., Morgante, C., Bergamini, A.

2024

Overview

Background:Psoriatic arthritis (PsA) is a chronic inflammatory disease, characterized by heterogeneous articular and periarticular manifestations. The achievement of remission or low disease activity is the goal of therapy. However, some patients experience primary failure and lack or loss of response to cs-, b- and ts-DMARDs. The treatment response could be affected by multiple factors, including epigenetic factors. Recently, some studies have suggested the possible involvement of lncRNAs in modulating treatment response [1]. In this context, the identification of genetic and epigenetic factors associated to treatment response could help to define new biomarkers for a more effective and personalized therapy.Objectives:The main aim of this study was to prospectively investigate lncRNAs potentially related to treatment response in a cohort of PsA patients treated with TNFi and IL17i, to identify potential predictors of drug treatment effectiveness. In addition, we analysed retrospectively a cohort of PsA patients treated with TNFi to look for possible association between lncRNAs genetic variants and the response after 6 and 12 months of TNFi.Methods:For the expression study, a cohort of 48 PsA patients starting a TNFi (n=28) or IL17i (n=20) drugs was recruited, monitoring their treatment response for 12 months in order to identify subgroup of patients Reponder e Non-Responder. For the genotyping study, we retrospectively analysed 163 PsA patients treated with TNFi. For each patient was estimated the Disease Activity in Psoriatic Arthritis (DAPsA) score at 6 and 12 months after the beginning of therapy. The expression level of lncRNA was analysed in a panel of 84 lncRNAs, after the extraction of total RNA from PBMCs. Then we validated the differentially expressed lncRNAs, resulted from the array experiments, by qRT-PCR using specific primer assay. Web-based data analysis tool (NPInter v4.0 and DIANALncBase v3) were used to confirm miRNA target genes of the validated lncRNAs. For the genotyping study, we extracted genomic DNA from PBMCs and we performed allelic discrimination assay by TaqMan assays. We evaluated a possible association between the selected SNPs and the response to therapy at 6 and 12 months from the beginning of the TNFi treatment, using the clinical parameter of DAPsA value.Results:We observed a significant difference in the expression level between Responder and non-Responder patients, of 4 lncRNAs in the group of PsA patients treated with TNFi and of 3 lncRNAs in the group of patients treated with IL17i. Then, we confirmed a significant decrease of MEG3 expression in non-Responder patients compared to Responder patients, both considering the whole cohort (P= 0.01) and stratifying patients by drugs (P= 0.05 and P= 0.03, respectively for TNFi and IL17i) (Figure 1). In addition, we observed an association between the variant allele of rs7158663 and a lower expression of MEG3 compared to the wild-type allele, although without statistical significance. We also observed that the variant allele of rs941576 (MEG3) was associated with a better response at T6 and T12, with a linear decrease of mean DAPsA value among wildtype, heterozygous and homozygous variant patients. Interestingly, we noticed that the variant allele of rs941576 SNV resulted associated with a better response regarding joints involvement. Indeed, the number of TJ and SJ decreases more in patients carrying the variant allele, both at T6 and T12 (P= 0.0006 and P= 0.032, respectively) (Table 1).Conclusion:Our study suggests a possible role, both in terms of genetic variability and expression, of the lncRNA MEG3 in the treatment response to TNFi and IL17i in PsA patients.REFERENCES:[1] De Benedittis G, Latini A, Ciccacci C, et al. Impact of TRAF3IP2, IL10 and HCP5 Genetic Polymorphisms in the Response to TNF-i Treatment in Patients with Psoriatic Arthritis. J Pers Med. 2022;12(7):1094.Acknowledgements:NIL.Disclosure of Interests:None declared.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier Limited
• Subject: Alleles / biological DMARD / Epigenetics / Gene polymorphism / Genetic diversity / Genetic variability / Genetics / Genomics / Genotyping / Inflammatory diseases / Joint diseases / miRNA / Non-coding RNA / Patients / Psoriatic arthritis / Remission / Scientific Abstracts / Single-nucleotide polymorphism