1 2556 68 EPIGENETICS IN RHEUMATOID ARTHRITIS. EPIGENETICS IS A STEADILY GROWING RESEARCH AREA. IN MANY HUMAN DISEASES, ESPECIALLY IN CANCERS, BUT ALSO IN AUTOIMMUNE DISEASES, EPIGENETIC ABERRATIONS HAVE BEEN FOUND. RHEUMATOID ARTHRITIS IS AN AUTOIMMUNE DISEASE CHARACTERIZED BY CHRONIC INFLAMMATION AND DESTRUCTION OF SYNOVIAL JOINTS. EVEN THOUGH THE ETIOLOGY IS NOT YET FULLY UNDERSTOOD, RHEUMATOID ARTHRITIS IS GENERALLY CONSIDERED TO BE CAUSED BY A COMBINATION OF GENETIC PREDISPOSITION, DEREGULATED IMMUNOMODULATION, AND ENVIRONMENTAL INFLUENCES. TO GAIN A BETTER UNDERSTANDING OF THIS DISEASE, RESEARCHERS HAVE BECOME INTERESTED IN STUDYING EPIGENETIC CHANGES IN RHEUMATOID ARTHRITIS. HERE, WE WANT TO REVIEW THE CURRENT KNOWLEDGE ON EPIGENETICS IN RHEUMATOID ARTHRITIS. 2010 2 4845 28 ONE YEAR IN REVIEW 2020: PATHOGENESIS OF RHEUMATOID ARTHRITIS. RHEUMATOID ARTHRITIS (RA) IS A CHRONIC INFLAMMATORY AUTOIMMUNE DISEASE INFLUENCED BY BOTH GENETIC, EPIGENETIC AND ENVIRONMENTAL FACTORS. THE DISCOVERY OF NEW GENE POLYMORPHISMS AND THEIR ASSOCIATION WITH DISEASE SUSCEPTIBILITY HAVE ADDED NEW ELEMENTS TO BETTER CLARIFY RA PATHOGENESIS. IN THE LAST YEAR, IMPORTANT ELEMENTS HAVE BEEN ADDED TO THE CURRENT KNOWLEDGE OF MECHANISMS REGULATING INNATE AND ADAPTIVE IMMUNITY IN RA, LEADING TO DISCOVERING NEW TARGETS FOR THE DEVELOPMENT OF DISEASE-MODIFYING THERAPIES. THUS, IN THIS REVIEW WE SUMMARISE THE NEW INSIGHTS RESULTING FROM A LITERATURE RESEARCH DATA PUBLISHED IN THE LAST YEAR. 2020 3 4842 30 ONE YEAR IN REVIEW 2017: PATHOGENESIS OF RHEUMATOID ARTHRITIS. RHEUMATOID ARTHRITIS (RA) IS A CHRONIC INFLAMMATORY AUTOIMMUNE DISEASE INFLUENCED BY BOTH GENETIC AND ENVIRONMENTAL FACTORS. IT HAS BEEN POSTULATED THAT A HIGH-RISK GENETIC BACKGROUND, IN COMBINATION WITH EPIGENETIC MARKS AND ENVIRONMENTAL EXPOSURES, LEADS TO A CASCADE OF EVENTS INDUCING SYNOVITIS AND CONSEQUENT DESTRUCTIVE ARTHRITIS. THE CLINICAL PICTURE OF JOINT INVOLVEMENT IN RA IS THE RESULT OF CHRONIC INFLAMMATION OF THE SYNOVIUM, CHARACTERISED BY INTERACTIONS OF RESIDENT CELLS SUCH AS FIBROBLAST-LIKE SYNOVIOCYTES (FLS) WITH CELLS OF THE INNATE (E.G. MACROPHAGES, DENDRITIC CELLS, MAST CELLS AND NK CELLS, NEUTROPHILS) AND ADAPTIVE IMMUNE SYSTEM (E.G. B AND T LYMPHOCYTES). CURRENTLY, OUR UNDERSTANDING OF THE ROLE OF INNATE AND ADAPTIVE IMMUNITY IN THE PATHOGENESIS OF RA IS EXPANDING. THE CONCEPT OF HOW IMMUNE RESPONSES CONTRIBUTE TO THE DISEASE HAS DRAMATICALLY EVOLVED OVER THE LAST 50 YEARS. SHEDDING SOME LIGHT ON THE DIFFERENT ASPECTS OF RA PATHOGENESIS WILL HELP TO IDENTIFY NEW TARGETS FOR THE DEVELOPMENT OF DISEASE-MODIFYING THERAPIES. THUS, IN THIS REVIEW WE REPORT NEW INSIGHTS IN RA PATHOGENESIS, RESULTING FROM A LITERATURE RESEARCH DATE PUBLISHED IN THE LAST YEAR. 2017 4 5372 26 RECENT ADVANCES IN UNDERSTANDING THE PATHOGENESIS OF RHEUMATOID ARTHRITIS: NEW TREATMENT STRATEGIES. RHEUMATOID ARTHRITIS (RA) IS CONSIDERED A CHRONIC SYSTEMIC, MULTI-FACTORIAL, INFLAMMATORY, AND PROGRESSIVE AUTOIMMUNE DISEASE AFFECTING MANY PEOPLE WORLDWIDE. WHILE PATIENTS SHOW VERY INDIVIDUAL COURSES OF DISEASE, WITH RA FOCUSING ON THE MUSCULOSKELETAL SYSTEM, JOINTS ARE OFTEN SEVERELY AFFECTED, LEADING TO LOCAL INFLAMMATION, CARTILAGE DESTRUCTION, AND BONE EROSION. TO PREVENT JOINT DAMAGE AND PHYSICAL DISABILITY AS ONE OF MANY SYMPTOMS OF RA, EARLY DIAGNOSIS IS CRITICAL. AUTO-ANTIBODIES PLAY A PIVOTAL CLINICAL ROLE IN PATIENTS WITH SYSTEMIC RA. AS BIOMARKERS, THEY COULD HELP TO MAKE A MORE EFFICIENT DIAGNOSIS, PROGNOSIS, AND TREATMENT DECISION. BESIDES AUTO-ANTIBODIES, SEVERAL OTHER FACTORS ARE INVOLVED IN THE PROGRESSION OF RA, SUCH AS EPIGENETIC ALTERATIONS, POST-TRANSLATIONAL MODIFICATIONS, GLYCOSYLATION, AUTOPHAGY, AND T-CELLS. UNDERSTANDING THE INTERPLAY BETWEEN THESE FACTORS WOULD CONTRIBUTE TO A DEEPER INSIGHT INTO THE CAUSES, MECHANISMS, PROGRESSION, AND TREATMENT OF THE DISEASE. IN THIS REVIEW, THE LATEST RA RESEARCH FINDINGS ARE DISCUSSED TO BETTER UNDERSTAND THE PATHOGENESIS, AND FINALLY, TREATMENT STRATEGIES FOR RA THERAPY ARE PRESENTED, INCLUDING BOTH CONVENTIONAL APPROACHES AND NEW METHODS THAT HAVE BEEN DEVELOPED IN RECENT YEARS OR ARE CURRENTLY UNDER INVESTIGATION. 2021 5 4844 27 ONE YEAR IN REVIEW 2019: PATHOGENESIS OF RHEUMATOID ARTHRITIS. RHEUMATOID ARTHRITIS (RA) IS A CHRONIC INFLAMMATORY AUTOIMMUNE DISEASE INFLUENCED BY BOTH GENETIC AND ENVIRONMENTAL FACTORS. OVER THE LAST FEW YEARS, PARTICULAR ATTENTION HAS BEEN GIVEN TO NOVEL GENES AND TO THE CLOSE INTERACTION BETWEEN GENETIC FACTORS AND EPIGENETIC MECHANISMS. RESEARCH HAS ALSO FOCUSED ON THE INFLUENCE OF ENVIRONMENTAL FACTORS ON DISEASE DEVELOPMENT, AND ON NEW MECHANISMS OF THE INNATE AND ADAPTIVE IMMUNE SYSTEM THAT CAN INFLUENCE THE DIFFERENT STAGES OF RA. HOWEVER, THERE ARE STILL SEVERAL ASPECTS OF THE DISEASE THAT NEED FURTHER INVESTIGATION. SHEDDING SOME LIGHT ON THE DIFFERENT ASPECTS OF RA PATHOGENESIS WILL HELP TO IMPROVE THE CURRENT DIAGNOSTIC TOOLS AND TO IDENTIFY NEW TARGETS FOR THE DEVELOPMENT OF DISEASE-MODIFYING THERAPIES. THUS, IN THIS REVIEW WE SUMMARISE THE NEW INSIGHTS IN RA PATHOGENESIS, RESULTING FROM LITERATURE RESEARCH DATA PUBLISHED IN THE LAST YEAR. 2019 6 1608 25 DNA METHYLATION-GOVERNED GENE EXPRESSION IN AUTOIMMUNE ARTHRITIS. RHEUMATOID ARTHRITIS (RA) IS A CHRONIC INFLAMMATORY AUTOIMMUNE DISEASE HALLMARKED BY PROGRESSIVE AND IRREVERSIBLE JOINT DESTRUCTION. RA PATHOGENESIS IS A T CELL-REGULATED AND B CELL-MEDIATED PROCESS IN WHICH ACTIVATED LYMPHOCYTE-PRODUCED CHEMOKINES AND CYTOKINES PROMOTE LEUKOCYTE INFILTRATION THAT ULTIMATELY LEADS TO DESTRUCTION OF THE JOINTS. THERE IS AN OBVIOUS NEED TO DISCOVER NEW DRUGS FOR RA TREATMENT THAT HAVE DIFFERENT BIOLOGICAL TARGETS OR MODES OF ACTION THAN THE CURRENTLY EMPLOYED THERAPEUTICS. ENVIRONMENTAL FACTORS SUCH AS CIGARETTE SMOKE, CERTAIN DIET COMPONENTS, AND ORAL PATHOGENS CAN SIGNIFICANTLY AFFECT GENE REGULATION VIA EPIGENETIC FACTORS. EPIGENETICS OPENED A NEW FIELD FOR PHARMACOLOGY, AND DNA METHYLATION AND HISTONE MODIFICATION-IMPLICATED FACTORS ARE FEASIBLE TARGETS FOR RA THERAPY. EXPLORING RA PATHOGENESIS INVOLVED EPIGENETIC FACTORS AND MECHANISMS IS CRUCIAL FOR DEVELOPING MORE EFFICIENT RA THERAPIES. HERE WE REVIEW EPIGENETIC ALTERATIONS ASSOCIATED WITH RA PATHOGENESIS INCLUDING DNA METHYLATION AND INTERACTING FACTORS. ADDITIONALLY, WE WILL SUMMARIZE THE LITERATURE REVEALING THE INVOLVED MOLECULAR STRUCTURES AND INTERACTIONS. FINALLY, POTENTIAL EPIGENETIC FACTOR-BASED THERAPIES WILL BE DISCUSSED THAT MAY HELP IN BETTER MANAGEMENT OF RA IN THE FUTURE. 2019 7 1136 26 COMPREHENSIVE OVERVIEW OF MICRORNA FUNCTION IN RHEUMATOID ARTHRITIS. MICRORNAS (MIRNAS), A CLASS OF ENDOGENOUS SINGLE-STRANDED SHORT NONCODING RNAS, HAVE EMERGED AS VITAL EPIGENETIC REGULATORS OF BOTH PATHOLOGICAL AND PHYSIOLOGICAL PROCESSES IN ANIMALS. THEY DIRECT FUNDAMENTAL CELLULAR PATHWAYS AND PROCESSES BY FINE-TUNING THE EXPRESSION OF MULTIPLE GENES AT THE POSTTRANSCRIPTIONAL LEVEL. GROWING EVIDENCE SUGGESTS THAT MIRNAS ARE IMPLICATED IN THE ONSET AND DEVELOPMENT OF RHEUMATOID ARTHRITIS (RA). RA IS A CHRONIC INFLAMMATORY DISEASE THAT MAINLY AFFECTS SYNOVIAL JOINTS. THIS COMMON AUTOIMMUNE DISORDER IS CHARACTERIZED BY A COMPLEX AND MULTIFACETED PATHOGENESIS, AND ITS MORBIDITY, DISABILITY AND MORTALITY RATES REMAIN CONSISTENTLY HIGH. MORE IN-DEPTH INSIGHTS INTO THE UNDERLYING MECHANISMS OF RA ARE REQUIRED TO ADDRESS UNMET CLINICAL NEEDS AND OPTIMIZE TREATMENT. HEREIN, WE COMPREHENSIVELY REVIEW THE DEREGULATED MIRNAS AND IMPAIRED CELLULAR FUNCTIONS IN RA TO SHED LIGHT ON SEVERAL ASPECTS OF RA PATHOGENESIS, WITH A FOCUS ON EXCESSIVE INFLAMMATION, SYNOVIAL HYPERPLASIA AND PROGRESSIVE JOINT DAMAGE. THIS REVIEW ALSO PROVIDES PROMISING TARGETS FOR INNOVATIVE THERAPIES OF RA. IN ADDITION, WE DISCUSS THE REGULATORY ROLES AND CLINICAL POTENTIAL OF EXTRACELLULAR MIRNAS IN RA, HIGHLIGHTING THEIR PROSPECTIVE APPLICATIONS AS DIAGNOSTIC AND PREDICTIVE BIOMARKERS. 2023 8 2221 23 EPIGENETIC MODIFICATIONS IN RHEUMATOID ARTHRITIS, A REVIEW. RHEUMATOID ARTHRITIS IS AN AUTOIMMUNE DISEASE CHARACTERIZED BY CHRONIC JOINT INFLAMMATION AND PROGRESSIVE DESTRUCTION OF CARTILAGE AND BONE WHICH LEADS TO ULTIMATELY LOSS OF FUNCTION AND PAIN. ACTIVATED SYNOVIAL FIBROBLASTS ARE KEY EFFECTOR CELLS IN THE PATHOGENESIS OF RHEUMATOID ARTHRITIS. IN THE RECENT YEARS, EPIGENETIC CHANGES INCLUDING DNA METHYLATION, HISTONE ACETYLATION AND OTHER HISTONE MODIFICATIONS WERE IDENTIFIED THAT ARE ASSOCIATED WITH AN INTRINSIC ACTIVATION AND THE AGGRESSIVE PHENOTYPE OF THESE CELLS. SO FAR, NO THERAPIES TARGETING RHEUMATOID ARTHRITIS SYNOVIAL FIBROBLASTS EXIST. THIS REVIEW COMPRISES RECENT RESEARCH EFFORTS THAT PROPOSE EPIGENETIC MECHANISMS BEHIND THE ACTIVATION OF RHEUMATOID ARTHRITIS SYNOVIAL FIBROBLASTS AND OTHER CELL TYPES. 2013 9 783 25 CELL-SPECIFIC EPIGENETIC DRIVERS OF PATHOGENESIS IN RHEUMATOID ARTHRITIS. RHEUMATOID ARTHRITIS IS A COMPLEX, INFLAMMATORY AUTOIMMUNE DISEASE, WHICH IS CHARACTERIZED BY PAIN, SWELLING AND JOINT DAMAGE DRIVEN BY THE ALTERED BEHAVIOR OF A NUMBER OF DIFFERENT CELL TYPES SUCH AS SYNOVIAL FIBROBLASTS MACROPHAGES AND LYMPHOCYTES. THE MECHANISM UNDERLYING PATHOGENESIS IS UNCLEAR BUT INCREASING EVIDENCE POINTS TO ALTERED EPIGENETIC REGULATION WITHIN THESE CELL TYPES WHICH PROMOTES THE ACTIVATED DESTRUCTIVE BEHAVIOR THAT UNDERLIES DISEASE PATHOGENESIS. THIS REVIEW SUMMARIZES THE KEY EPIGENETIC MODIFICATIONS IN THE MOST IMPORTANT CELLS TYPES IN RHEUMATOID ARTHRITIS, WHICH ARE ASSOCIATED WITH DISEASE ACTIVITY. WE ALSO DISCUSS EMERGING AVENUES OF RESEARCH FOCUSING ON READERS OF EPIGENETIC MARKERS WHICH MAY SERVE TO BE POTENTIAL THERAPEUTIC TARGETS. 2021 10 6884 28 [RHEUMATOID ARTHRITIS]. RHEUMATOID ARTHRITIS ABSTRACT. RHEUMATOID ARTHRITIS (RA) IS THE MOST FREQUENT CHRONIC INFLAMMATORY JOINT DISEASE WITH A PREVALENCE OF APPROXIMATELY 1% WORLDWIDE. THE PATHOGENESIS IS A COMPLEX INTERPLAY OF GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS, WHICH ARE STILL INCOMPLETELY UNDERSTOOD. THE DISEASE IS CHARACTERIZED BY A POLYARTICULAR SYNOVITIS WITH SYMMETRICAL INVOLVEMENT OF SMALL AND LARGE JOINTS. THE MAJORITY OF PATIENTS HAS DETECTABLE AUTOANTIBODIES IN THE SERUM, RHEUMATOID FACTOR AND ANTI-CCP ANTIBODIES WHICH ARE SPECIFIC FOR RA. THE UNCONTROLLED CHRONIC JOINT INFLAMMATION RESULTS IN DESTRUCTIVE CHANGES OF JOINT CARTILAGE AND BONE. AN EARLY DIAGNOSIS AND INITIATION OF TREATMENT IS THEREFORE OF CENTRAL IMPORTANCE. DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS (DMARD) ARE ABLE TO INHIBIT JOINT DESTRUCTION AND SHOULD BE STARTED AS SOON AS POSSIBLE. THERAPY SHOULD BE TARGETED TO REACH A STATE OF REMISSION. THE INTRODUCTION OF HIGHLY EFFECTIVE BIOLOGIC AND TARGETED SYNTHETIC DMARD HAS ALLOWED TO REACH THIS GOAL OF THERAPY IN MANY PATIENTS AND TO PREVENT DISABILITY. HOWEVER, RISKS OF MEDICATION NEED TO BE CONSIDERED, AS WELL AS COMORBIDITIES. 2023 11 4685 22 NEW TARGETS AND STRATEGIES FOR RHEUMATOID ARTHRITIS: FROM SIGNAL TRANSDUCTION TO EPIGENETIC ASPECT. RHEUMATOID ARTHRITIS (RA) IS A CHRONIC AUTOIMMUNE DISEASE THAT CAN LEAD TO JOINT DAMAGE AND EVEN PERMANENT DISABILITY, SERIOUSLY AFFECTING PATIENTS' QUALITY OF LIFE. AT PRESENT, THE COMPLETE CURE FOR RA IS NOT ACHIEVABLE, ONLY TO RELIEVE THE SYMPTOMS TO REDUCE THE PAIN OF PATIENTS. FACTORS SUCH AS ENVIRONMENT, GENES, AND SEX CAN INDUCE RA. PRESENTLY, NON-STEROIDAL ANTI-INFLAMMATORY DRUGS, DRMADS, AND GLUCOCORTICOIDS ARE COMMONLY USED IN TREATING RA. IN RECENT YEARS, SOME BIOLOGICAL AGENTS HAVE ALSO BEEN APPLIED IN CLINICAL PRACTICE, BUT MOST HAVE SIDE EFFECTS. THEREFORE, FINDING NEW MECHANISMS AND TARGETS FOR TREATING RA IS NECESSARY. THIS REVIEW SUMMARIZES SOME POTENTIAL TARGETS DISCOVERED FROM THE PERSPECTIVE OF EPIGENETICS AND RA MECHANISMS. 2023 12 5739 24 SMOKING AND RHEUMATOID ARTHRITIS. RHEUMATOID ARTHRITIS (RA) IS A CHRONIC INFLAMMATORY DISEASE CAUSED BY BOTH GENETIC AND ENVIRONMENTAL FACTORS. SMOKING HAS BEEN IMPLICATED AS ONE OF THE MOST IMPORTANT EXTRINSIC RISK FACTORS FOR ITS DEVELOPMENT AND SEVERITY. RECENT DEVELOPMENTS HAVE SHED LIGHT ON THE PATHOPHYSIOLOGY OF RA IN SMOKERS, INCLUDING OXIDATIVE STRESS, INFLAMMATION, AUTOANTIBODY FORMATION AND EPIGENETIC CHANGES. THE ASSOCIATION OF SMOKING AND THE DEVELOPMENT OF RA HAVE BEEN DEMONSTRATED THROUGH EPIDEMIOLOGIC STUDIES, AS WELL AS THROUGH IN VIVO AND ANIMAL MODELS OF RA. WITH INCREASED USE OF BIOLOGICAL AGENTS IN ADDITION TO STANDARD DISEASE-MODIFYING ANTIRHEUMATIC DRUGS (DMARDS), THERE HAS BEEN INTEREST IN HOW SMOKING AFFECTS DRUG RESPONSE IN RA TREATMENT. RECENT EVIDENCE SUGGESTS THE RESPONSE AND DRUG SURVIVAL IN PEOPLE TREATED WITH ANTI-TUMOUR NECROSIS FACTOR (ANTI-TNF) THERAPY IS POORER IN HEAVY SMOKERS, AND POSSIBLE IMMUNOLOGICAL MECHANISMS FOR THIS EFFECT ARE PRESENTED IN THE CURRENT PAPER. 2014 13 6245 32 THE MECHANISMS UNDERLYING CHRONIC INFLAMMATION IN RHEUMATOID ARTHRITIS FROM THE PERSPECTIVE OF THE EPIGENETIC LANDSCAPE. RHEUMATOID ARTHRITIS (RA) IS A CHRONIC INFLAMMATORY AUTOIMMUNE DISEASE THAT IS CHARACTERIZED BY SYNOVIAL HYPERPLASIA AND PROGRESSIVE JOINT DESTRUCTION. THE ACTIVATION OF RA SYNOVIAL FIBROBLASTS (SFS), ALSO CALLED FIBROBLAST-LIKE SYNOVIOCYTES (FLS), CONTRIBUTES SIGNIFICANTLY TO PERPETUATION OF THE DISEASE. GENETIC AND ENVIRONMENTAL FACTORS HAVE BEEN REPORTED TO BE INVOLVED IN THE ETIOLOGY OF RA BUT ARE INSUFFICIENT TO EXPLAIN IT. IN RECENT YEARS, ACCUMULATING RESULTS HAVE SHOWN THE POTENTIAL ROLE OF EPIGENETIC MECHANISMS, INCLUDING HISTONE MODIFICATIONS, DNA METHYLATION, AND MICRORNAS, IN THE DEVELOPMENT OF RA. EPIGENETIC MECHANISMS REGULATE CHROMATIN STATE AND GENE TRANSCRIPTION WITHOUT ANY CHANGE IN DNA SEQUENCE, RESULTING IN THE ALTERATION OF PHENOTYPES IN SEVERAL CELL TYPES, ESPECIALLY RASFS. EPIGENETIC CHANGES POSSIBLY PROVIDE RASFS WITH AN ACTIVATED PHENOTYPE. IN THIS PAPER, WE REVIEW THE ROLES OF EPIGENETIC MECHANISMS RELEVANT FOR THE PROGRESSION OF RA. 2016 14 3699 22 INFLAMMATORY MEMORIES: IS EPIGENETICS THE MISSING LINK TO PERSISTENT STROMAL CELL ACTIVATION IN RHEUMATOID ARTHRITIS? RHEUMATOID ARTHRITIS (RA) IS A CHRONIC INFLAMMATORY DISEASE LEADING TO JOINT DESTRUCTION. SYNOVIAL FIBROBLASTS ARE RECOGNIZED AS KEY CELLS IN THE PATHOGENESIS OF RA SINCE THEY ATTRACT AND ACTIVATE IMMUNE CELLS AND PRODUCE MATRIX DEGRADING ENZYMES. MOST NOTABLY SYNOVIAL FIBROBLASTS FROM PATIENTS WITH RA ARE STABLY ACTIVATED AND PRODUCE HIGH LEVELS OF DISEASE-PROMOTING MOLECULES WITHOUT FURTHER STIMULATION BY IMMUNE CELLS. ACCUMULATING DATA SUGGEST THAT EPIGENETIC CHANGES IN STROMAL CELL POPULATIONS MIGHT BE CRUCIALLY INVOLVED IN THE PATHOLOGY OF RA AND OTHER CHRONIC INFLAMMATORY DISEASES. IN THE CURRENT REVIEW, WE DISCUSS THE MECHANISMS BY WHICH EPIGENETIC CHANGES MIGHT CAUSE THE STABLE ACTIVATION OF SYNOVIAL FIBROBLASTS IN RA AND HOW CHANGES IN THE EPIGENOME MIGHT ALTER IMMUNE FUNCTION AND INFLAMMATORY RESPONSE AND THEREBY PROMOTE THE DEVELOPMENT OF CHRONIC DISEASES. 2011 15 6328 18 THE ROLE OF CELL ORGANELLES IN RHEUMATOID ARTHRITIS WITH FOCUS ON EXOSOMES. AUTO-IMMUNE DISEASES INVOLVED AT LEAST 25% OF THE POPULATION IN WEALTHY COUNTRIES. SEVERAL FACTORS INCLUDING GENETIC, EPIGENETIC, AND ENVIRONMENTAL ELEMENTS ARE IMPLICATED IN DEVELOPMENT OF RHEUMATOID ARTHRITIS AS AN AUTOIMMUNE DISEASE. AUTOANTIBODIES CAUSE SYNOVIAL INFLAMMATION AND ARTHRITIS, IF LEFT UNTREATED OR BEING UNDER CONTINUAL EXTERNAL STIMULATION, COULD RESULT IN CHRONIC INFLAMMATION, JOINT INJURY, AND DISABILITY. T- AND B-CELLS, SIGNALING MOLECULES, PROINFLAMMATORY MEDIATORS, AND SYNOVIUM-SPECIFIC TARGETS ARE AMONG THE NEW THERAPEUTIC TARGETS. EXOSOMES COULD BE EMPLOYED AS THERAPEUTIC VECTORS IN THE TREATMENT OF AUTOIMMUNE DISEASES. HEREIN, THE ROLE OF CELL ORGANELLE PARTICULARLY EXOSOMES IN RHEUMATOID ARTHRITIS HAD DISCUSSED AND SOME THERAPEUTIC APPLICATIONS OF EXOSOME HIGHLIGHTED. 2021 16 1565 25 DNA METHYLATION OF T LYMPHOCYTES AS A THERAPEUTIC TARGET: IMPLICATIONS FOR RHEUMATOID ARTHRITIS ETIOLOGY. RHEUMATOID ARTHRITIS (RA) IS AN AUTOIMMUNE DISEASE THAT CAN CAUSE JOINT DAMAGE AND DISABILITY. EPIGENETIC VARIATION, ESPECIALLY DNA METHYLATION, HAS BEEN SHOWN TO BE INVOLVED IN ALMOST ALL THE STAGES OF THE PATHOLOGY OF RA, FROM AUTOANTIBODY PRODUCTION TO VARIOUS SELF-EFFECTOR T CELLS AND THE DEFECTS OF PROTECTIVE T CELLS THAT CAN LEAD TO CHRONIC INFLAMMATION AND EROSION OF BONES AND JOINTS. GIVEN THE CRITICAL ROLE OF T CELLS IN THE PATHOLOGY OF RA, THE REGULATORY FUNCTIONS OF DNA METHYLATION IN T CELL BIOLOGY REMAIN UNCLEAR. IN THIS REVIEW, WE ELABORATE ON THE RELATIONSHIP BETWEEN RA PATHOGENESIS AND DNA METHYLATION IN THE CONTEXT OF DIFFERENT T CELL POPULATIONS. WE SUMMARIZE THE RELEVANT METHYLATION EVENTS IN T CELL DEVELOPMENT, DIFFERENTIATION, AND T CELL-RELATED GENES IN DISEASE PREDICTION AND DRUG EFFICACY. UNDERSTANDING THE EPIGENETIC REGULATION OF T CELLS HAS THE POTENTIAL TO PROFOUNDLY TRANSLATE PRECLINICAL RESULTS INTO CLINICAL PRACTICE AND PROVIDE A FRAMEWORK FOR THE DEVELOPMENT OF NOVEL, INDIVIDUALIZED RA THERAPEUTICS. 2022 17 5002 29 PERIODONTITIS AND PERIODONTOPATHIC BACTERIA AS RISK FACTORS FOR RHEUMATOID ARTHRITIS: A REVIEW OF THE LAST 10 YEARS. RHEUMATOID ARTHRITIS (RA) IS CHARACTERIZED BY CHRONIC INFLAMMATORY DESTRUCTION OF JOINT TISSUE AND IS CAUSED BY AN ABNORMAL AUTOIMMUNE RESPONSE TRIGGERED BY INTERACTIONS BETWEEN GENETICS, ENVIRONMENTAL FACTORS, AND EPIGENETIC AND POSTTRANSLATIONAL MODIFICATIONS. RA HAS BEEN SUGGESTED TO BE INTERRELATED WITH PERIODONTITIS, A SERIOUS FORM OR STAGE OF CHRONIC INFLAMMATORY PERIODONTAL DISEASE ASSOCIATED WITH PERIODONTOPATHIC BACTERIAL INFECTIONS, GENETIC PREDISPOSITION, ENVIRONMENTAL FACTORS, AND EPIGENETIC INFLUENCES. OVER THE LAST DECADE, A NUMBER OF ANIMAL AND CLINICAL STUDIES HAVE BEEN CONDUCTED TO ASSESS WHETHER OR NOT PERIODONTITIS AND ASSOCIATED PERIODONTOPATHIC BACTERIA CONSTITUTE RISK FACTORS FOR RA. THE PRESENT REVIEW INTRODUCES RECENT ACCUMULATING EVIDENCE TO SUPPORT THE ASSOCIATIONS OF PERIODONTITIS AND PERIODONTOPATHIC BACTERIA WITH THE RISK OF RA OR THE OUTCOME OF RA PHARMACOLOGICAL TREATMENT WITH DISEASE-MODIFYING ANTIRHEUMATIC DRUGS. IN ADDITION, THE RESULTS FROM INTERVENTION STUDIES HAVE SUGGESTED AN IMPROVEMENT IN RA CLINICAL PARAMETERS AFTER NONSURGICAL PERIODONTAL TREATMENT. FURTHERMORE, THE POTENTIAL CAUSAL MECHANISMS UNDERLYING THE LINK BETWEEN PERIODONTITIS AND PERIODONTOPATHIC BACTERIA AND RA ARE SUMMARIZED. 2023 18 2294 26 EPIGENETIC REGULATION IN THE PATHOGENESIS OF SJOGREN SYNDROME AND RHEUMATOID ARTHRITIS. AUTOIMMUNE RHEUMATIC DISEASES, SUCH AS SJOGREN SYNDROME (SS) AND RHEUMATOID ARTHRITIS (RA), ARE CHARACTERIZED BY CHRONIC INFLAMMATION AND AUTOIMMUNITY, WHICH CAUSE JOINT TISSUE DAMAGE AND DESTRUCTION BY TRIGGERING REDUCED MOBILITY AND DEBILITATION IN PATIENTS WITH THESE DISEASES. INITIATION AND MAINTENANCE OF CHRONIC INFLAMMATORY STAGES ACCOUNT FOR SEVERAL MECHANISMS THAT INVOLVE IMMUNE CELLS AS KEY PLAYERS AND THE INTERACTION OF THE IMMUNE CELLS WITH OTHER TISSUES. INDEED, THE OVERLAPPING OF CERTAIN CLINICAL AND SEROLOGIC MANIFESTATIONS BETWEEN SS AND RA MAY INDICATE THAT NUMEROUS IMMUNOLOGIC-RELATED MECHANISMS ARE INVOLVED IN THE PHYSIOPATHOLOGY OF BOTH THESE DISEASES. IT IS WIDELY ACCEPTED THAT EPIGENETIC PATHWAYS PLAY AN ESSENTIAL ROLE IN THE DEVELOPMENT AND FUNCTION OF THE IMMUNE SYSTEM. ALTHOUGH MANY PUBLISHED STUDIES HAVE ATTEMPTED TO ELUCIDATE THE RELATION BETWEEN EPIGENETIC MODIFICATIONS (E.G. DNA METHYLATION, HISTONE POST-TRANSLATIONAL MODIFICATIONS, MIRNAS) AND AUTOIMMUNE DISORDERS, THE CONTRIBUTION OF EPIGENETIC REGULATION TO THE PATHOGENESIS OF SS AND RA IS AT PRESENT POORLY UNDERSTOOD. THIS REVIEW ATTEMPTS TO SHED LIGHT FROM A CRITICAL POINT OF VIEW ON THE IDENTIFICATION OF THE MOST RELEVANT EPIGENETIC MECHANISMS RELATED TO RA AND SS BY EXPLAINING INTRICATE REGULATORY PROCESSES AND PHENOTYPIC FEATURES OF BOTH AUTOIMMUNE DISEASES. MOREOVER, WE POINT OUT SOME EPIGENETIC MARKERS WHICH CAN BE USED TO MONITOR THE INFLAMMATION STATUS AND THE DYSREGULATED IMMUNITY IN SS AND RA. FINALLY, WE DISCUSS THE INCONVENIENCE OF USING EPIGENETIC DATA OBTAINED FROM BULK IMMUNE CELL POPULATIONS INSTEAD SPECIFIC IMMUNE CELL SUBPOPULATIONS. 2019 19 1812 26 EFFECTS OF BIOLOGICAL THERAPIES ON MOLECULAR FEATURES OF RHEUMATOID ARTHRITIS. RHEUMATOID ARTHRITIS (RA) IS AN AUTOIMMUNE AND CHRONIC INFLAMMATORY DISEASE PRIMARILY AFFECTING THE JOINTS, AND CLOSELY RELATED TO SPECIFIC AUTOANTIBODIES THAT MOSTLY TARGET MODIFIED SELF-EPITOPES. RELEVANT FINDINGS IN THE FIELD OF RA PATHOGENESIS HAVE BEEN DESCRIBED. IN PARTICULAR, NEW INSIGHTS COME FROM STUDIES ON SYNOVIAL FIBROBLASTS AND CELLS BELONGING TO THE INNATE AND ADAPTIVE IMMUNE SYSTEM, WHICH DOCUMENTED THE ABERRANT PRODUCTION OF INFLAMMATORY MEDIATORS, OXIDATIVE STRESS AND NETOSIS, ALONG WITH RELEVANT ALTERATIONS OF THE GENOME AND ON THE REGULATORY EPIGENETIC MECHANISMS. IN RECENT YEARS, THE ADVANCES IN THE UNDERSTANDING OF RA PATHOGENESIS BY IDENTIFYING KEY CELLS AND CYTOKINES ALLOWED THE DEVELOPMENT OF NEW TARGETED DISEASE-MODIFYING ANTIRHEUMATIC DRUGS (DMARDS). THESE DRUGS CONSIDERABLY IMPROVED TREATMENT OUTCOMES FOR THE MAJORITY OF PATIENTS. MOREOVER, NUMEROUS STUDIES DEMONSTRATED THAT THE PHARMACOLOGICAL THERAPY WITH BIOLOGIC DMARDS (BDMARDS) PROMOTES, IN PARALLEL TO THEIR CLINICAL EFFICACY, SIGNIFICANT IMPROVEMENT IN ALL THESE ALTERED MOLECULAR MECHANISMS. THUS, CONTINUOUS UPDATING OF THE KNOWLEDGE OF MOLECULAR PROCESSES ASSOCIATED WITH THE PATHOGENESIS OF RA, AND ON THE SPECIFIC EFFECTS OF BDMARDS IN THE CORRECTION OF THEIR DYSREGULATION, ARE ESSENTIAL IN THE EARLY AND CORRECT APPROACH TO THE TREATMENT OF THIS COMPLEX AUTOIMMUNE DISORDER. THE PRESENT REVIEW DETAILS BASIC MECHANISMS RELATED TO THE PHYSIOPATHOLOGY OF RA, ALONG WITH THE CORE MECHANISMS OF RESPONSE TO BDMARDS. 2020 20 3039 19 GENOME ENGINEERING FOR PERSONALIZED ARTHRITIS THERAPEUTICS. ARTHRITIS REPRESENTS A FAMILY OF COMPLEX JOINT PATHOLOGIES RESPONSIBLE FOR THE MAJORITY OF MUSCULOSKELETAL CONDITIONS. NEARLY ALL DISEASES WITHIN THIS FAMILY, INCLUDING OSTEOARTHRITIS, RHEUMATOID ARTHRITIS, AND JUVENILE IDIOPATHIC ARTHRITIS, ARE CHRONIC CONDITIONS WITH FEW OR NO DISEASE-MODIFYING THERAPEUTICS AVAILABLE. ADVANCES IN GENOME ENGINEERING TECHNOLOGY, MOST RECENTLY WITH CRISPR-CAS9, HAVE REVOLUTIONIZED OUR ABILITY TO INTERROGATE AND VALIDATE GENETIC AND EPIGENETIC ELEMENTS ASSOCIATED WITH CHRONIC DISEASES SUCH AS ARTHRITIS. THESE TECHNOLOGIES, TOGETHER WITH CELL REPROGRAMMING METHODS, INCLUDING THE USE OF INDUCED PLURIPOTENT STEM CELLS, PROVIDE A PLATFORM FOR HUMAN DISEASE MODELING. WE SUMMARIZE NEW EVIDENCE FROM GENOME-WIDE ASSOCIATION STUDIES AND GENOMICS THAT SUBSTANTIATES A GENETIC BASIS FOR ARTHRITIS PATHOGENESIS. WE ALSO REVIEW THE POTENTIAL CONTRIBUTIONS OF GENOME ENGINEERING IN THE DEVELOPMENT OF NEW ARTHRITIS THERAPEUTICS. 2017