POS0349 SEQUENCE COMPLEMENTARITY BETWEEN SARS-CoV-2 GENOME AND HUMAN NONCODING RNAS ASSOCIATED WITH IMMUNOLOGICAL DISORDERS: AN IN SILICO PIVOTAL STUDY

Background:Recent evidence shows that human cells may produce several noncoding (nc)RNAs in response to viral infections. Among them, a central role has been attributed to long noncoding (lnc)RNAs, more than 200 nucleotides in length, which are also crucially involved in cancer and autoimmunity. LncRNAs epigenetically control the transcription of genes presiding over cell proliferation, differentiation, migration and apoptosis, by directly or indirectly binding cellular or foreign nucleic acids, including viral genomes.Objectives:The objectives of this study were to evaluate in silico the presence of a nucleotide sequence complementarity between the RNA genome of Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) and human ncRNA genes and to analyze any associations between SARS-CoV-2 gene-matching ncRNAs and human diseases.Methods:The FASTA sequence of each of the 11 SARS-CoV-2 isolate Wuhan-Hu-1 genes (ORF1ab, ORF3a, ORF6, ORF7a, ORF7b, ORF8, ORF10, S, E, M, N) was retrieved from NCBI.nlm.nih.gov/gene (reference sequence NC_045512.2). The ensembl.org library for human ncRNA genes was interrogated for any base-pair match and detected human ncRNAs analyzed for their functional activity. Finally, the associations between ncRNAs and human diseases were searched on GWAS databases (https://www.ebi.ac.uk/gwas and https://www.genecards.org).Results:A total of 252 matches between SARS-CoV-2 genes and human ncRNAs were recorded (ORF1ab: 28; ORF3a: 9; ORF6: 50; ORF7a: 31; ORF7b: 16; ORF8: 23; ORF10: 5; S: 24; E: 17; M: 32; N: 17). With the exception of two small nuclear RNAs (RNVU1-4 and RNU4-74P corresponding to ORF6 and ORF10, respectively), all of them were lncRNAs, mostly expressed in testis and central nervous system under physiological conditions. Percentage of alignment ranged from 91.30% to 100%, with a mean nucleotide alignment length of 17.5±2.4. Polymorphic variants of these transcripts have mostly been reported in patients with neuropsychiatric disorders, cancer and dysmetabolism. Of note, we found 13 and 15 complementarities with lncRNAs associated with immune-mediated diseases Table 1. and immunological pathways (IL-2, IL-6, IL-12, IL-12R, IL-13, IL-17, M-CSF, CXCL-10, TRAIL-R2 and IgG glycosylation), respectively.Conclusion:This pivotal study shows that SARS-CoV-2 genes contain complementary sequences to human ncRNAs in turn associated with several diseases, including autoimmunity. The biological effects of this interaction remain to be elucidated.Table 1.SARS-CoV-2 complementary ncRNAs and associated immunological disordersSARS-CoV-2 geneLncRNAGenomic locationNucleotide alignment lengthAlignment percentageAssociated immunological disorderSXACTX:113705866-11370588318100%Crohn's diseaseNLINC013581:59082428-5908257417100%Acute Graft-versus-Host DiseaseECOX10-AS117:14029229-1402924517100%Systemic lupus erythematosusORF8AC093765.34:116752764-1167527842195.24%Ulcerative colitisORF6CDKN2B-AS19:22033529-2203354618100%Multiple sclerosisCHROMR2:178433948-1784339682195.24%Multiple sclerosisPsoriasisAtopic eczemaWAKMAR26:137857643-13785765715100%Atopic eczemaHay feverAllergic rhinitisMultiple sclerosisPsoriasisSystemic sclerosisSystemic lupus erythematosusRheumatoid arthritisAC008691.15:159362809-159362828(promoter flank)2095%SarcoidosisPsoriasisPsoriatic arthritisSclerosing cholangitisCeliac diseaseType I diabetes mellitusSystemic lupus erythematosusJuvenile idiopathic arthritisUlcerative colitisCrohn's diseaseTakayasu arteritisMultiple sclerosisLMCD1-AS13:7953602-7953616(enhancer)15100%Systemic sclerosisMLINC019342:181403969-18140398416100%Multiple sclerosisAnkylosing spondylitisCeliac diseaseRheumatoid arthritisORF7bXACTX:113959816-11395983116100%Crohn's diseaseLINC0262110:62289643-6230233515100%Rheumatoid arthritisLINC019913:187966255-18796626915100%IgA deficitAtopic asthmaAllergic rhinitisDisclosure of Interests:None declare

JAK-Inhibitors for the Treatment of Rheumatoid Arthritis : A Focus on the Present and an Outlook on the Future

Janus kinase inhibitors (JAKi) belong to a new class of oral targeted disease-modifying drugs which have recently revolutionized the therapeutic panorama of rheumatoid arthritis (RA) and other immune-mediated diseases, placing alongside or even replacing conventional and biological drugs. JAKi are characterized by a novel mechanism of action, consisting of the intracellular interruption of the JAK-STAT pathway crucially involved in the immune response. The aim of this narrative review is to globally report the most relevant pharmacological features and clinical outcomes of the developed and incoming JAKi for RA, based on the available preclinical and clinical evidence. A total of 219 papers, including narrative and systematic reviews, randomized controlled trials (RCTs), observational studies, case reports, guidelines, and drug factsheets, were selected. The efficacy and safety profile of both the first generation JAKi (baricitinib and tofacitinib) and the second generation JAKi (upadacitinib, filgotinib, peficitinib, decernotinib and itacitinib) were compared and discussed. Results from RCTs and real-life data are encouraging and outline a rapid onset of the pharmacologic effects, which are maintained during the time. Their efficacy and safety profile are comparable or superior to those of biologic agents and JAKi proved to be efficacious when given as monotherapy. Finally, the manufacturing of JAKi is relatively easier and cheaper than that of biologics, thus increasing the number of compounds being formulated and tested for clinical use

Microbial Agents as Putative Inducers of B Cell Lymphoma in Sjögren's Syndrome through an Impaired Epigenetic Control : The State-of-The-Art

Introduction: Understanding the mechanisms underlying the pathogenesis of Sj\uf6gren's syndrome (SS) is crucially important in order to be able to discriminate the steps that lead to B cell transformation and promptly identify the patients at risk of lymphomagenesis. The aim of this narrative review is to describe the evidence concerning the role that infections or dysbiosis plays in the epigenetic control of gene expression in SS patients and their possible involvement in B cell lymphomagenesis. Materials and Methods: We searched the PubMed and Google Scholar databases and selected a total of 92 articles published during the last 25 years that describe experimental and clinical studies of the potential associations of microbiota and epigenetic aberrations with the risk of B cell lymphoma in SS patients. Results and Discussion: The genetic background of SS patients is characterized by the hyperexpression of genes that are mainly involved in regulating the innate and adaptive immune responses and oncogenesis. In addition, salivary gland epithelial cells and lymphocytes both have an altered epigenetic background that enhances the activation of proinflammatory and survival pathways. Dysbiosis or chronic latent infections may tune the immune response and modify the cell epigenetic machinery in such a way as to give B lymphocytes an activated or transformed phenotype. It is also worth noting that transposable integrated retroelements may participate in the pathogenesis of SS and B cell lymphomagenesis by inducing DNA breaks, modulating cell gene expression, or generating aberrant transcripts that chronically stimulate the immune system. Conclusions: Microorganisms may epigenetically modify target cells and induce their transcriptome to generate an activated or transformed phenotype. The occurrence of lymphoma in more than 15% of SS patients may be the end result of a combination of genetics, epigenetics, and dysbiosis or latent infections

Pain in systemic sclerosis

Chronic pain is a healthcare problem that significantly affects the mental health, and the professional and private life of patients. It can complicate many disorders and represents a common symptom of rheumatologic diseases, but the data on its prevalence is still limited. Pain is a ubiquitous problem in systemic sclerosis (SSc). SSc-related pain has been studied on the basis of biomedical models and is considered a symptom caused by the disease activity or previous tissue damage. Effective pain management is a primary goal of the treatment strategy, although this symptom in SSc has not yet been investigated in detail. However, these patients do not all respond adequately to pharmacological pain therapies, therefore in these cases a multimodal approach needs to be adopted