1 395 136 AN UPDATE ON EPIGENETIC REGULATION IN AUTOIMMUNE DISEASES. AUTOIMMUNE DISEASES (AIDS) GENERALLY MANIFEST AS CHRONIC IMMUNE DISORDERS CHARACTERIZED BY SIGNIFICANT HETEROGENEITY AND COMPLEX SYMPTOMS. THE DISCORDANT INCIDENCE OF AIDS BETWEEN MONOZYGOTIC TWINS GUIDED PEOPLE TO ATTACH IMPORTANCE TO ENVIRONMENTAL FACTORS. EPIGENETICS IS ONE OF THE MAJOR WAYS TO BE INFLUENCED, SOME OF THEM CAN EVEN OCCUR YEARS BEFORE CLINICAL DIAGNOSIS. WITH THE ADVENT OF HIGH-THROUGHPUT OMICS TIMES, THE MYSTERIOUS VEIL OF EPIGENETIC MODIFICATION IN AIDS HAS BEEN GRADUALLY UNRAVELED, AND SOME PROGRESS HAS BEEN MADE IN UTILIZING IT AS INDICATORS OF DIAGNOSIS AND DISEASE ACTIVITY. FOR EXAMPLE, THE HYPOMETHYLATED IFI44L PROMOTER IN DIAGNOSING SYSTEMATIC LUPUS ERYTHEMATOSUS (SLE). MORE RECENTLY, NEWLY IDENTIFIED NONCODING RNAS (NCRNAS), INCLUDING LONG NONCODING RNAS (LNCRNAS) AND CIRCULAR RNAS (CIRCRNAS), ARE ALSO BELIEVED TO BE INVOLVED IN THE ETIOLOGY OF AIDS WHILE THE INITIAL FACTOR BEHIND THOSE EPIGENETIC ALTERATIONS CAN BE DIVERSE FROM METABOLISM TO MICROBIOTA. UPDATE AND COMPREHENSIVE INSIGHTS INTO EPIGENETICS IN AIDS CAN HELP US UNDERSTAND THE PATHOGENESIS AND FURTHER ORCHESTRATE IT TO BENEFIT PATIENTS IN THE FUTURE. THEREFORE, WE REVIEWED THE LATEST EPIGENETIC FINDINGS IN SLE, RHEUMATOID ARTHRITIS (RA), TYPE 1 DIABETES (T1D), SYSTEMIC SCLEROSIS (SSC) PRIMARILY FROM CELLULAR LEVELS. 2022 2 6276 48 THE PATHOGENIC ROLE OF DYSREGULATED EPIGENETIC MODIFICATIONS IN AUTOIMMUNE DISEASES. AUTOIMMUNE DISEASES CAN BE CHRONIC WITH RELAPSE OF INFLAMMATORY SYMPTOMS, BUT IT CAN BE ALSO ACUTE AND LIFE-THREATENING IF IMMUNE CELLS DESTROY LIFE-SUPPORTING ORGANS, SUCH AS LUPUS NEPHRITIS. THE ETIOPATHOGENESIS OF AUTOIMMUNE DISEASES HAS BEEN REVEALED AS THAT GENETICS AND ENVIRONMENTAL FACTORS-MEDIATED DYSREGULATED IMMUNE RESPONSES CONTRIBUTE TO THE INITIATION AND DEVELOPMENT OF AUTOIMMUNE DISORDERS. HOWEVER, THE CURRENT UNDERSTANDING OF PATHOGENESIS IS LIMITED AND THE UNDERLYING MECHANISM HAS NOT BEEN WELL DEFINED, WHICH LOWS THE DEVELOPMENT OF NOVEL BIOMARKERS AND NEW THERAPEUTIC STRATEGIES FOR AUTOIMMUNE DISEASES. TO IMPROVE THIS, BROADENING AND DEEPENING OUR UNDERSTANDING OF PATHOGENESIS IS AN UNMET NEED. AS GENETIC SUSCEPTIBILITY CANNOT EXPLAIN THE LOW ACCORDANCE RATE OF INCIDENCE IN HOMOZYGOUS TWINS, EPIGENETIC REGULATIONS MIGHT BE AN ADDITIONAL EXPLANATION. THEREFORE, THIS REVIEW WILL SUMMARIZE CURRENT PROGRESS OF STUDIES ON EPIGENETIC DYSREGULATIONS CONTRIBUTING TO AUTOIMMUNE DISEASES, INCLUDING SLE, RHEUMATOID ARTHRITIS (RA), PSORIASIS, TYPE 1 DIABETES (T1D), AND SYSTEMIC SCLEROSIS (SSC), HOPEFULLY PROVIDING OPINIONS ON ORIENTATION OF FUTURE RESEARCH, AS WELL AS DISCUSSING THE CLINICAL UTILIZATION OF POTENTIAL BIOMARKERS AND THERAPEUTIC STRATEGIES FOR THESE DISEASES. 2019 3 6107 44 THE EMERGING ROLE OF NONCODING RNAS IN SYSTEMIC LUPUS ERYTHEMATOSUS: NEW INSIGHTS INTO THE MASTER REGULATORS OF DISEASE PATHOGENESIS. AUTO-IMMUNE DISEASES ARE A FORM OF CHRONIC DISORDERS IN WHICH THE IMMUNE SYSTEM DESTROYS THE BODY'S CELLS DUE TO A LOSS OF TOLERANCE TO SELF-ANTIGENS. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE), IDENTIFIED BY THE PRODUCTION OF AUTOANTIBODIES IN DIFFERENT BODY PARTS, IS ONE OF THE MOST WELL-KNOWN EXAMPLES OF THESE DISEASES. ALTHOUGH THE ETIOLOGY OF SLE IS UNCLEAR, THE DISEASE'S PROGRESSION MAY BE AFFECTED BY GENETIC AND ENVIRONMENTAL FACTORS. AS STUDIES IN TWINS PROVIDE ADEQUATE EVIDENCE FOR GENETIC INVOLVEMENT IN THE SLE, OTHER PHENOMENA SUCH AS METALLIZATION, HISTONE MODIFICATIONS, AND ALTERATIONS IN THE EXPRESSION OF NONCODING RNAS (NCRNAS) ALSO INDICATE THE INVOLVEMENT OF EPIGENETIC FACTORS IN THIS DISEASE. AMONG ALL THE EPIGENETIC ALTERATIONS, NCRNAS APPEAR TO HAVE THE MOST CRUCIAL CONTRIBUTION TO THE PATHOGENESIS OF SLE. THE NCRNAS' LENGTH AND SIZE ARE DIVIDED INTO THREE MAIN CLASSES: MICRO RNAS, LONG NONCODING RNAS (LNCRNA), AND CIRCULAR RNAS (CIRCRNAS). ACCUMULATING EVIDENCE SUGGESTS THAT DYSREGULATIONS IN THESE NCRNAS CONTRIBUTED TO THE PATHOGENESIS OF SLE. HENCE, CLARIFYING THE FUNCTION OF THESE GROUPS OF NCRNAS IN THE PATHOPHYSIOLOGY OF SLE PROVIDES A DEEPER UNDERSTANDING OF THE DISEASE. IT ALSO OPENS UP NEW OPPORTUNITIES TO DEVELOP TARGETED THERAPIES FOR THIS DISEASE. 2023 4 6345 44 THE ROLE OF EPIGENETICS IN AUTOIMMUNE/INFLAMMATORY DISEASE. HISTORICALLY, SYSTEMIC SELF-INFLAMMATORY CONDITIONS WERE CLASSIFIED AS EITHER AUTOINFLAMMATORY AND CAUSED BY THE INNATE IMMUNE SYSTEM OR AUTOIMMUNE AND DRIVEN BY ADAPTIVE IMMUNE RESPONSES. HOWEVER, IT BECAME CLEAR THAT REALITY IS MUCH MORE COMPLEX AND THAT AUTOIMMUNE/INFLAMMATORY CONDITIONS RANGE ALONG AN "INFLAMMATORY SPECTRUM" WITH PRIMARILY AUTOINFLAMMATORY VS. AUTOIMMUNE CONDITIONS RESEMBLING EXTREMES AT EITHER END. EPIGENETIC MODIFICATIONS INFLUENCE GENE EXPRESSION AND ALTER CELLULAR FUNCTIONS WITHOUT MODIFYING THE GENOMIC SEQUENCE. METHYLATION OF CPG DNA DINUCLEOTIDES AND/OR THEIR HYDROXYMETHYLATION, POST-TRANSLATIONAL MODIFICATIONS TO AMINO TERMINI OF HISTONE PROTEINS, AND NON-CODING RNA EXPRESSION ARE MAIN EPIGENETIC EVENTS. THE PATHOPHYSIOLOGY OF AUTOIMMUNE/INFLAMMATORY DISEASES HAS BEEN CLOSELY LINKED WITH DISEASE CAUSING GENE MUTATIONS (RARE) OR A COMBINATION OF GENETIC SUSCEPTIBILITY AND EPIGENETIC MODIFICATIONS ARISING FROM EXPOSURE TO THE ENVIRONMENT (MORE COMMON). OVER RECENT YEARS, PROGRESS HAS BEEN MADE IN UNDERSTANDING MOLECULAR MECHANISMS INVOLVED IN SYSTEMIC INFLAMMATION AND THE CONTRIBUTION OF INNATE AND ADAPTIVE IMMUNE RESPONSES. EPIGENETIC EVENTS HAVE BEEN IDENTIFIED AS (I) CENTRAL PATHOPHYSIOLOGICAL FACTORS IN ADDITION TO GENETIC DISEASE PREDISPOSITION AND (II) AS CO-FACTORS DETERMINING CLINICAL PICTURES AND OUTCOMES IN INDIVIDUALS WITH MONOGENIC DISEASE. THUS, A COMPLETE UNDERSTANDING OF EPIGENETIC CONTRIBUTORS TO AUTOIMMUNE/INFLAMMATORY DISEASE WILL RESULT IN APPROACHES TO PREDICT INDIVIDUAL DISEASE OUTCOMES AND THE INTRODUCTION OF EFFECTIVE, TARGET-DIRECTED, AND TOLERABLE THERAPIES. HERE, WE SUMMARIZE RECENT FINDINGS THAT SIGNIFY THE IMPORTANCE OF EPIGENETIC MODIFICATIONS IN AUTOIMMUNE/INFLAMMATORY DISORDERS ALONG THE INFLAMMATORY SPECTRUM CHOOSING THREE EXAMPLES: THE AUTOINFLAMMATORY BONE CONDITION CHRONIC NONBACTERIAL OSTEOMYELITIS (CNO), THE "MIXED PATTERN" DISORDER PSORIASIS, AND THE AUTOIMMUNE DISEASE SYSTEMIC LUPUS ERYTHEMATOSUS (SLE). 2019 5 2224 30 EPIGENETIC MODIFICATIONS IN THE PATHOGENESIS OF SYSTEMIC SCLEROSIS. SYSTEMIC SCLEROSIS IS A RARE CHRONIC AUTOIMMUNE DISEASE, WHICH MAINLY MANIFESTS AS IMMUNE DISORDERS, VASCULAR DAMAGE, AND PROGRESSIVE FIBROSIS. THE ETIOLOGY OF SSC IS COMPLEX AND INVOLVES MULTIPLE FACTORS. BOTH GENETIC AND ENVIRONMENTAL FACTORS ARE INVOLVED IN ITS PATHOGENESIS. AS ONE OF THE MOLECULAR MECHANISMS OF ENVIRONMENTAL FACTORS, EPIGENETIC REGULATION PLAYS AN IMPORTANT ROLE IN THE OCCURRENCE AND DEVELOPMENT OF SYSTEMIC SCLEROSIS, WHICH INVOLVES DNA METHYLATION, HISTONE MODIFICATION AND NON-CODING RNA REGULATION. THIS REVIEW SUMMARIZES RESEARCH ADVANCES IN EPIGENETICS, INCLUDING EXOSOMES, LNCRNA, AND MENTIONS POSSIBLE BIOMARKERS AND THERAPEUTIC TARGETS AMONG THEM. 2022 6 4153 36 MECHANISTIC INSIGHTS OF CHEMICALS AND DRUGS AS RISK FACTORS FOR SYSTEMIC LUPUS ERYTHEMATOSUS. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IS A CHRONIC AND RELAPSING HETEROGENOUS AUTOIMMUNE DISEASE THAT PRIMARILY AFFECTS WOMEN OF REPRODUCTIVE AGE. GENETIC AND ENVIRONMENTAL RISK FACTORS ARE INVOLVED IN THE PATHOGENESIS OF SLE, AND SUSCEPTIBILITY GENES HAVE RECENTLY BEEN IDENTIFIED. HOWEVER, AS GENE THERAPY IS FAR FROM CLINICAL APPLICATION, FURTHER INVESTIGATION OF ENVIRONMENTAL RISK FACTORS COULD REVEAL IMPORTANT THERAPEUTIC APPROACHES. WE SYSTEMATICALLY EXPLORED TWO GROUPS OF ENVIRONMENTAL RISK FACTORS: CHEMICALS (INCLUDING SILICA, SOLVENTS, PESTICIDES, HYDROCARBONS, HEAVY METALS, AND PARTICULATE MATTER) AND DRUGS (INCLUDING PROCAINAMIDE, HYDRALAZINE, QUINIDINE, DPENICILLAMINE, ISONIAZID, AND METHYLDOPA). FURTHERMORE, THE MECHANISMS UNDERLYING RISK FACTORS, SUCH AS GENETIC FACTORS, EPIGENETIC CHANGE, AND DISRUPTED IMMUNE TOLERANCE, WERE EXPLORED. THIS REVIEW IDENTIFIES NOVEL RISK FACTORS AND THEIR UNDERLYING MECHANISMS. PRACTICABLE MEASURES FOR THE MANAGEMENT OF THESE RISK FACTORS WILL BENEFIT SLE PATIENTS AND PROVIDE POTENTIAL THERAPEUTIC STRATEGIES. 2020 7 5886 40 SYSTEMIC LUPUS ERYTHEMATOSUS. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IS A CHRONIC MULTISYSTEM AUTOIMMUNE DISEASE THAT IS HIGHLY HETEROGENEOUS IN ITS PRESENTATION. THIS CAN POSE SIGNIFICANT CHALLENGES FOR PHYSICIANS RESPONSIBLE FOR THE DIAGNOSIS AND TREATMENT OF SUCH PATIENTS. SLE ARISES FROM A COMBINATION OF GENETIC, EPIGENETIC AND ENVIRONMENTAL FACTORS. PATHOLOGICALLY, THE DISEASE IS PRIMARILY DRIVEN BY LOSS OF IMMUNE TOLERANCE AND ABNORMAL B- AND T-CELL FUNCTION. MAJOR ORGAN INVOLVEMENT MAY LEAD TO SIGNIFICANT MORBIDITY AND MORTALITY. CLASSIFICATION CRITERIA FOR SLE HAVE BEEN DEVELOPED LARGELY FOR RESEARCH PURPOSES; HOWEVER, THESE ARE ALSO WIDELY USED IN CLINICAL PRACTICE. ANTINUCLEAR ANTIBODIES ARE THE HALLMARK SEROLOGICAL FEATURE, OCCURRING IN OVER 95% OF PATIENTS WITH SLE AT SOME POINT DURING THEIR DISEASE. THE MAINSTAY OF TREATMENT IS ANTIMALARIAL DRUGS SUCH AS HYDROXYCHLOROQUINE, COMBINED WITH CORTICOSTEROIDS AND CONVENTIONAL IMMUNOSUPPRESSIVE DRUGS. AN INCREASING UNDERSTANDING OF PATHOGENESIS HAS FACILITATED A MOVE TOWARDS THE DEVELOPMENT OF TARGETED BIOLOGIC THERAPIES, WITH THE INTRODUCTION OF RITUXIMAB AND BELIMUMAB INTO CLINICAL PRACTICE. 2017 8 2533 41 EPIGENETICS IN AUTOIMMUNE CONNECTIVE TISSUE DISEASES. BACKGROUND. AUTOIMMUNE CONNECTIVE TISSUE DISEASES (ACTDS) ENCOMPASS A HETEROGENEOUS GROUP OF CHRONIC IMMUNE-MEDIATED INFLAMMATORY DISORDERS, PRIMARILY AFFECTING CONNECTIVE TISSUES AND CLINICALLY CHARACTERIZED BY VARIABLE MULTISYSTEM MANIFESTATIONS, FREQUENTLY OVERLAPPING. ENVIRONMENTAL FACTORS ARE THOUGHT TO PROMOTE ACTD DEVELOPMENT IN GENETIC PREDISPOSING/ENDOCRINE PERMISSIVE BACKGROUND THROUGH THE INDUCTION OF EPIGENETIC MODIFICATIONS, CONSISTING OF STABLE, HERITABLE, BUT POTENTIALLY REVERSIBLE CHANGES IN GENE EXPRESSION, OCCURRING WITHOUT ALTERATIONS OF THE DNA SEQUENCE. ACTUALLY, EPIGENETIC MECHANISMS (SUCH AS HISTONE MODIFICATIONS, DNA METHYLATION, NUCLEOSOME POSITIONING, AND RNA INTERFERENCE) LINK GENOTYPE UPSTREAM AND PHENOTYPE DOWNSTREAM, AND, IF PERSISTENTLY ABERRANT, MAY CAUSE A VARIETY OF HUMAN DISEASES, INCLUDING ACTDS. WE AIMED TO REVIEW THE RECENT ADVANCES IN THE KNOWLEDGE OF THE ACTD EPIGENETIC ALTERATIONS. METHODS: A DETAILED SEARCH OF THE AVAILABLE LITERATURE WAS PERFORMED IN THE PUBMED (U.S. NATIONAL LIBRARY OF MEDICINE) DATABASE. RESULTS: GROWING EVIDENCE UNDERLINES THE RELEVANT ROLE OF EPIGENETIC DEFECTS IN THE ACTD PATHOGENESIS, AND SPECIFIC EPIGENETIC PATTERNS CAN REPRESENT DISEASE BIOMARKERS. IN PATIENTS WITH RHEUMATOID ARTHRITIS (RA), EPIGENETIC VARIATIONS INTERACT DETERMINING THE TYPICAL "AGGRESSIVE" PHENOTYPE DISPLAYED BY RA SYNOVIAL FIBROBLASTS. EPIGENETIC MODIFICATIONS ARE INVOLVED IN THE PROFIBROTIC PROCESS THAT CHARACTERIZES SYSTEMIC SCLEROSIS. IN SYSTEMIC LUPUS ERYTHEMATOSUS AND SJOGREN'S SYNDROME, COMPLEX EPIGENETIC CHANGES ALTERING GENE EXPRESSION HAVE BEEN DEMONSTRATED. CONCLUSIONS: COMPREHENSIVE STUDIES WILL CONTRIBUTE TO FURTHER DEFINE THE ABERRANT EPIGENETIC MECHANISMS INVOLVED IN THE ACTDS ETIOPATHOGENESIS. MOREOVER, BEING EPIGENETIC CHANGES POTENTIALLY REVERSIBLE, THE IDENTIFICATION OF ACTDS EPIGENETIC BIOMARKERS WILL ALLOW THE DEVELOPMENT OF THERAPEUTIC STRATEGIES ADDRESSED TO TARGET DYSREGULATED GENES AND CORRECT ABERRANT EPIGENOMIC ALTERATIONS. 2014 9 6194 37 THE IMPACT OF PROTEIN ACETYLATION/DEACETYLATION ON SYSTEMIC LUPUS ERYTHEMATOSUS. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IS A CHRONIC INFLAMMATORY AUTOIMMUNE DISEASE IN WHICH THE BODY'S IMMUNE SYSTEM MISTAKENLY ATTACKS HEALTHY CELLS. ALTHOUGH THE EXACT CAUSE OF SLE HAS NOT BEEN IDENTIFIED, IT IS CLEAR THAT BOTH GENETICS AND ENVIRONMENTAL FACTORS TRIGGER THE DISEASE. IDENTICAL TWINS HAVE A 24% CHANCE OF GETTING LUPUS DISEASE IF THE OTHER ONE IS AFFECTED. INTERNAL FACTORS SUCH AS FEMALE GENDER AND SEX HORMONES, THE MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) LOCUS AND OTHER GENETIC POLYMORPHISMS HAVE BEEN SHOWN TO AFFECT SLE, AS WELL AS EXTERNAL, ENVIRONMENTAL INFLUENCES SUCH AS SUNLIGHT EXPOSURE, SMOKING, VITAMIN D DEFICIENCY, AND CERTAIN INFECTIONS. SEVERAL STUDIES HAVE REPORTED AND PROPOSED MULTIPLE ASSOCIATIONS BETWEEN THE ALTERATION OF THE EPIGENOME AND THE PATHOGENESIS OF AUTOIMMUNE DISEASE. EPIGENETIC FACTORS CONTRIBUTING TO SLE INCLUDE MICRORNAS, DNA METHYLATION STATUS, AND THE ACETYLATION/DEACETYLATION OF HISTONE PROTEINS. ADDITIONALLY, THE ACETYLATION OF NON-HISTONE PROTEINS CAN ALSO INFLUENCE CELLULAR FUNCTION. A BETTER UNDERSTANDING OF NON-GENOMIC FACTORS THAT REGULATE SLE WILL PROVIDE INSIGHT INTO THE MECHANISMS THAT INITIATE AND FACILITATE DISEASE AND ALSO CONTRIBUTE TO THE DEVELOPMENT OF NOVEL THERAPEUTICS THAT CAN SPECIFICALLY TARGET PATHOGENIC MOLECULAR PATHWAYS. 2018 10 2027 45 EPIGENETIC CHANGES IN CHRONIC INFLAMMATORY DISEASES. THE NUMBER OF PEOPLE DIAGNOSED WITH CHRONIC INFLAMMATORY DISEASES HAS INCREASED NOTEWORTHY IN THE LAST 40 YEARS. SPONDYLOARTHRITIS (SPA), INFLAMMATORY BOWEL DISEASES (IBD), AND PSORIASIS ARE THE MOST FREQUENT CHRONIC INFLAMMATORY DISEASES, RESULTING FROM A COMBINATION OF GENETIC PREDISPOSITION AND ENVIRONMENTAL FACTORS. EPIGENETIC MODIFICATIONS INCLUDE DNA METHYLATION, HISTONE MODIFICATIONS, AND SMALL AND LONG NONCODING RNAS. THEY ARE INFLUENCED BY ENVIRONMENTAL EXPOSURE, LIFE-STYLE, AND AGING AND HAVE RECENTLY BEEN SHOWN TO BE ALTERED IN MANY COMPLEX DISEASES INCLUDING INFLAMMATORY DISEASES. WHILE EPIGENETIC MODIFICATIONS HAVE BEEN WELL CHARACTERIZED IN OTHER DISEASES SUCH AS CANCER AND AUTOIMMUNE DISEASES, KNOWLEDGE ON CHANGES IN INFLAMMATORY DISEASES IS LAGGING BEHIND WITH SOME DISEASE-SPECIFIC DIFFERENCES. WHILE THE DNA METHYLATION PROFILE OF DIFFERENT CELL TYPES IN PATIENTS WITH IBD HAS BEEN RELATIVELY WELL DESCRIBED, LESS IS KNOWN ON CHANGES IMPLICATED IN PSORIASIS, AND NO SYSTEMATIC GENOME-WIDE STUDIES HAVE SO FAR BEEN PERFORMED IN SPA. IN THIS CHAPTER, WE REVIEW IN DETAIL THE REPORTED CHANGES IN PATTERNS OF DNA METHYLATION AND POSTTRANSLATIONAL HISTONE MODIFICATIONS IN CHRONIC INFLAMMATORY DISEASES HIGHLIGHTING POTENTIAL CONNECTIONS BETWEEN DISEASE-ASSOCIATED PATHOPHYSIOLOGICAL CHANGES SUCH AS THE DYSBIOSIS OF THE MICROBIOME OR GENETIC VARIATIONS ASSOCIATED WITH DISEASE SUSCEPTIBILITY AND THE EPIGENOME. WE ALSO DISCUSS IMPORTANT PARAMETERS OF MEANINGFUL EPIGENETIC STUDIES SUCH AS THE USE OF WELL DEFINED, DISEASE-RELEVANT CELL POPULATIONS, AND ELUDE ON THE POTENTIAL FUTURE OF ENGINEERING OF THE EPIGENOME IN INFLAMMATORY DISEASES. 2017 11 3020 33 GENETICS AND EPIGENETICS OF OSTEOARTHRITIS. OSTEOARTHRITIS (OA) IS A COMMON AGE-RELATED DISEASE THAT AFFECTS THE TISSUES OF THE SYNOVIAL JOINT, LEADING TO LOSS OF FUNCTION AND PAIN. IT IMPACTS ON BOTH PATIENT MORBIDITY AND MORTALITY. IT IS A COMPLEX, POLYGENIC DISEASE THAT LACKS ANY LARGE-EFFECT SUSCEPTIBILITY LOCI. INSTEAD, OA SUSCEPTIBILITY ALLELES INDIVIDUALLY CONTRIBUTE ONLY MODESTLY TO THE OVERALL DISEASE RISK, MAKING THEIR IDENTIFICATION CHALLENGING. DESPITE THIS, BREAKTHROUGHS HAVE OCCURRED WITH COMPELLING ASSOCIATIONS SO FAR REPORTED TO POLYMORPHISMS WITHIN THE GENES GDF5 AND MCF2L AND TO THE GENOMIC REGION 7Q22. THE LATTER TWO HAVE EMERGED FROM GENOME-WIDE ASSOCIATION SCANS, WHICH ARE LIKELY TO YIELD MORE HITS IN THE NEAR FUTURE. AS FOR MANY COMPLEX DISEASES, IT IS NOW APPARENT THAT EPIGENETIC EFFECTS ARE ALSO IMPORTANT MEDIATORS OF DISEASE BIOLOGY, WITH DNA METHYLATION, HISTONE MODIFICATIONS AND NON-CODING RNAS ALL HAVING A ROLE. AT PRESENT, MUCH OF THE EPIGENETIC FOCUS HAS BEEN ON CARTILAGE, THE TISSUE AT THE CENTER OF THE OA DISEASE PROCESS. IF WE ARE TO GET CLOSE TO A QUALITATIVE AND QUANTITATIVE UNDERSTANDING OF THE IMPACT OF EPIGENETICS ON OA, THEN IN FUTURE THE OTHER TISSUES OF THE JOINT WILL ALSO NEED TO BE INVESTIGATED. ONE OF THE MORE EXCITING INSIGHTS TO HAVE EMERGED RECENTLY IS THE FACT THAT EPIGENETIC EFFECTS CAN IMPACT ON OA GENETIC EFFECTS AND THIS MAY BE A PARTICULARLY FRUITFUL AVENUE FOR INTEGRATING BOTH AS WE MOVE TOWARD A CLEARER UNDERSTANDING OF THE PATHOPHYSIOLOGY OF THIS INTRIGUING DISEASE. 2012 12 4844 38 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 13 2591 41 EPIGENETICS OF PSORIASIS. PSORIASIS IS A CHRONIC AND RECURRENT INFLAMMATORY SKIN DISEASE, INVOLVING THE RAPID PROLIFERATION AND ABNORMAL DIFFERENTIATION OF KERATINOCYTES AND ACTIVATION OF T CELLS. IT IS GENERALLY ACCEPTED THAT THE CENTRAL PATHOGENESIS OF PSORIASIS IS A T CELL-DOMINANT IMMUNE DISORDER AFFECTED BY MULTIPLE FACTORS INCLUDING GENETIC SUSCEPTIBILITY, ENVIRONMENTAL FACTORS, INNATE AND ADAPTIVE IMMUNE RESPONSES, ETC. HOWEVER, THE EXACT ETIOLOGY IS LARGELY UNKNOWN. IN RECENT YEARS, EPIGENETIC INVOLVEMENTS, SUCH AS THE DNA METHYLATION, CHROMATIN MODIFICATIONS, AND NONCODING RNA REGULATION ARE REPORTED TO BE CRITICAL FOR THE PATHOGENESIS OF PSORIASIS. HOWEVER, THE INTERPLAY BETWEEN THESE FACTORS HAS ONLY RECENTLY BEEN STARTED TO BE UNRAVELED. NOTABLY, INHIBITORS OF ENZYMES THAT WORK IN EPIGENETIC MODIFICATIONS, SUCH AS DNA METHYLTRANSFERASES AND HISTONE DEACETYLASES, ARE BEGINNING TO APPEAR IN THE CLINICAL SETTING TO RESTORE NORMAL EPIGENETIC PATTERNS (GENERALI ET AL. IN J AUTOIMMUN 83:51-61, 2017), PROVIDING NOVEL THERAPEUTIC POTENTIAL AS NOVEL TREATMENT TARGETS FOR PSORIASIS. INDEED, MEDICATIONS PREVIOUSLY USED TO TREAT AUTOIMMUNE DISEASES HAVE LATER BEEN DISCOVERED TO EXERT THEIR ACTION VIA EPIGENETIC MECHANISMS. HEREIN, WE REVIEW THE FINDINGS ON EPIGENETICS ASSOCIATED WITH PSORIASIS, AND DISCUSS FUTURE PERSPECTIVES IN THIS FIELD. 2020 14 2553 35 EPIGENETICS IN PSORIASIS: PERSPECTIVE OF DNA METHYLATION. PSORIASIS IS A CHRONIC INFLAMMATORY SKIN DISEASE CHARACTERIZED BY EXCESSIVE PROLIFERATION OF KERATINOCYTES (KCS). ONSET OF PSORIASIS IS RELATED TO GENETIC, IMMUNE AND ENVIRONMENTAL FACTORS. THE ENVIRONMENT CAN INTERACT WITH THE GENOME THROUGH EPIGENETIC MODIFICATIONS, INCLUDING DNA METHYLATION, AND THIS MODIFICATION IS INVOLVED IN THE PATHOGENESIS OF PSORIASIS. IN ADDITION TO A SKIN DISEASE, PSORIASIS IS ALSO CONSIDERED A SYSTEMIC DISEASE. WE REVIEWED THE CURRENT LITERATURE OF PSORIATIC DNA METHYLATION FOR STUDIES FROM SEVERAL ASPECTS ON THE DNA METHYLATION DISTRIBUTION PATTERNS IN DIFFERENT TISSUES/CELLS, SINGLE-NUCLEOTIDE POLYMORPHISMS, AND CANDIDATE DISEASE GENES AND IDENTIFIED TARGET GENES REGULATED BY DNA METHYLATION THAT HAVE BEEN DIRECTLY/INDIRECTLY VALIDATED. THIS REVIEW CONTRIBUTES TO A COMPREHENSIVE UNDERSTANDING OF THE IMPORTANT A ROLE THAT DNA METHYLATION PLAYS IN PSORIASIS FROM A HOLISTIC PERSPECTIVE AND WILL PROMOTE THE IMPLEMENTATION OF DNA METHYLATION IN DIAGNOSTIC AND THERAPEUTIC STRATEGIES FOR PSORIATIC PATIENTS. 2021 15 6152 30 THE FUNCTION OF NCRNAS IN RHEUMATIC DISEASES. RHEUMATIC DISEASES ARE A GROUP OF CHRONIC HETEROGENEOUS AUTOIMMUNE DISORDERS CHARACTERIZED BY ABNORMAL REGULATION OF THE INNATE AND ADAPTIVE IMMUNE SYSTEMS. DESPITE EXTENSIVE EFFORTS, THE FULL SPECTRUM OF MOLECULAR FACTORS THAT CONTRIBUTE TO THE PATHOGENESIS OF RHEUMATIC DISEASES REMAINS UNCLEAR. NCRNAS CAN GOVERN GENE EXPRESSION AT THE TRANSCRIPTIONAL AND POST-TRANSCRIPTIONAL LEVELS IN MULTIPLE DISEASES. RECENT STUDIES HAVE DEMONSTRATED AN IMPORTANT ROLE FOR NCRNAS, SUCH AS MIRNAS AND LNCRNAS, IN THE DEVELOPMENT OF IMMUNE CELLS AND RHEUMATIC DISEASES. HERE, WE FOCUS ON THE EPIGENETIC REGULATORY ROLES OF NCRNAS IN THE PATHOGENESIS OF RHEUMATIC DISEASES AND AS BIOMARKERS OF DISEASE STATE. 2019 16 2988 25 GENETIC FACTORS AND SYSTEMIC SCLEROSIS. SYSTEMIC SCLEROSIS (SSC) IS A RARE CONNECTIVE TISSUE DISEASE OF UNKNOWN ETIOLOGY CHARACTERIZED BY CHRONIC INFLAMMATION AND FIBROSIS OF THE SKIN, VASCULAR ABNORMALITIES, AND VARIABLE INVOLVEMENT OF ORGANS INCLUDING KIDNEYS, GASTROINTESTINAL TRACT, HEART, AND LUNGS. SSC SHOWS A COMPLEX ETIOLOGY IN WHICH BOTH ENVIRONMENTAL AND GENETIC FACTORS SEEM TO INFLUENCE THE ONSET AND OUTCOME OF THE DISEASE. WE PROVIDE AN EXTENSIVE OVERVIEW OF THE GENETIC FACTORS AND EPIGENETIC MODIFICATIONS AND WHAT THEIR KNOWLEDGE HAS REVEALED IN TERMS OF ETIOPATHOGENESIS OF SSC. 2016 17 6734 40 WHAT DO WE KNOW ABOUT THE ROLE OF LNCRNAS IN MULTIPLE SCLEROSIS? MULTIPLE SCLEROSIS IS A CHRONIC, INFLAMMATORY AND DEGENERATIVE DISEASE OF THE CENTRAL NERVOUS SYSTEM OF UNKNOWN AETIOLOGY ALTHOUGH WELL-DEFINED EVIDENCE SUPPORTS AN AUTOIMMUNE PATHOGENESIS. SO FAR, THE EXACT MECHANISMS LEADING TO AUTOIMMUNE DISEASES ARE STILL ONLY PARTIALLY UNDERSTOOD. WE KNOW THAT GENETIC, EPIGENETIC, MOLECULAR, AND CELLULAR FACTORS RESULTING IN PATHOGENIC INFLAMMATORY RESPONSES ARE CERTAINLY INVOLVED. LONG NON-CODING RNAS (LNCRNAS) ARE NON-PROTEIN CODING TRANSCRIPTS LONGER THAN 200 NUCLEOTIDES THAT PLAY AN IMPORTANT ROLE IN BOTH INNATE AND ACQUIRED IMMUNITY, SO THERE IS GREAT INTEREST IN LNCRNAS INVOLVED IN AUTOIMMUNE DISEASES. THE RESEARCH ON MULTIPLE SCLEROSIS HAS BEEN ENRICHED WITH MANY STUDIES ON THE MOLECULAR ROLE OF LNCRNAS IN THE PATHOGENESIS OF THE DISEASE AND THEIR POTENTIAL APPLICATION AS DIAGNOSTIC AND PROGNOSTIC BIOMARKERS. IN PARTICULAR, MANY MULTIPLE SCLEROSIS FIELDS OF RESEARCH ARE BASED ON THE IDENTIFICATION OF LNCRNAS AS POSSIBLE BIOMARKERS ABLE TO PREDICT THE ONSET OF THE DISEASE, ITS ACTIVITY DEGREE, ITS PROGRESSION PHASE AND THE RESPONSE TO DISEASE-MODIFYING DRUGS. LAST BUT NOT LEAST, STUDIES ON LNCRNAS CAN PROVIDE A NEW MOLECULAR TARGET FOR NEW THERAPIES, MISSING, SO FAR, A CURE FOR MULTIPLE SCLEROSIS. WHILE OUR KNOWLEDGE ON THE ROLE OF LNCRNA IN MULTIPLE SCLEROSIS HAS RECENTLY IMPROVED, FURTHER STUDIES ARE REQUIRED TO BETTER UNDERSTAND THE SPECIFIC ROLE OF LNCRNAS IN THIS NEUROLOGICAL DISEASE. IN THIS REVIEW, WE PRESENT THE MOST RECENT STUDIES ON MOLECULAR CHARACTERIZATION OF LNCRNAS IN MULTIPLE SCLEROSIS DISORDER DISCUSSING THEIR CLINICAL RELEVANCE AS BIOMARKERS FOR DIAGNOSIS AND TREATMENTS. 2021 18 4318 24 MICRORNAS IN ANKYLOSING SPONDYLITIS: FUNCTION, POTENTIAL AND CHALLENGES. EPIGENETIC MECHANISMS SUCH AS DNA METHYLATION, HISTONE MODIFICATIONS AND NON-CODING RNA, ARE CONSIDERED THE ESSENTIAL CONNECTION BETWEEN A DISORDER'S ONSET AND THE ENVIRONMENT, ON A PERMISSIVE GENETIC BACKGROUND. AMONG AUTOIMMUNE AND INFLAMMATORY-MEDIATED DISORDERS, ANKYLOSING SPONDYLITIS (AS), A CHRONIC ARTHRITIS OF THE SPINE, IS A VERY GOOD EXAMPLE FOR THE WEIGHT OF EPIGENETICS' CONTRIBUTION. MICRORNAS (MIRNAS) ARE SINGLE-STRANDED NUCLEOTIDES WHICH REGULATE GENE EXPRESSION AND ARE INVOLVED IN PATHOLOGICAL AND PHYSIOLOGICAL PROCESSES. IN THIS MANUSCRIPT WE PROVIDE A CLARIFICATION ON THE ROLE OF MICRORNAS IN AS, WITH A FOCUS ON THE MECHANISMS OF PATHOGENESIS. IN SPECIFIC, WE HAVE EXAMINED THE CONTRIBUTION OF MIRNAS IN THE PROCESSES OF INFLAMMATION, NEW BONE FORMATION AND T-CELL FUNCTION, AND THE PATHWAYS (I.E. WNT, BMP, TGFBETA SIGNALLING ETC.) THEY REGULATE. THE UTILITY OF MIRNAS IN BETTER UNDERSTANDING AS PATHOGENESIS IS UNDISPUTED AND THEIR UTILITY AS THERAPEUTIC OPPORTUNITY IS STRONGLY INCREASING. 2020 19 6624 32 UNDERSTANDING PSORIASIS: ROLE OF MIRNAS. PSORIASIS IS A CHRONIC, IMMUNE-MEDIATED INFLAMMATORY SKIN DISEASE, WITH A MULTIFACTORIAL ETIOLOGY AND IMPORTANT IMMUNOLOGIC, GENETIC AND ENVIRONMENTAL COMPONENTS. PSORIASIS VULGARIS REPRESENTS ITS MOST COMMON FORM, WITH A VARIABLE PREVALENCE ACROSS THE GLOBE. ALTHOUGH ITS PATHOGENESIS REMAINS TO BE FULLY ELUCIDATED, A LACK OF BALANCE IN THE EPIGENETIC NETWORK HAS BEEN SHOWN TO TRIGGER CERTAIN ELEMENTS OF THIS DISEASE, POSSIBLY ALTERING ITS OUTCOME. MICRORNAS ARE SMALL NON-CODING RNA MOLECULES INVOLVED IN RNA-SILENCING AND THE POST-TRANSCRIPTIONAL REGULATION OF GENE EXPRESSION, WHICH ALSO APPEAR TO MEDIATE THE IMMUNE DYSFUNCTION IN PSORIASIS. ALTHOUGH MICRORNA RESEARCH IS A NEW FIELD IN DERMATOLOGY AND PSORIASIS, THERE IS RAPIDLY ACCUMULATING EVIDENCE FOR ITS MAJOR CONTRIBUTION IN THE PATHOGENESIS OF CHRONIC INFLAMMATORY CONDITIONS, INCLUDING PSORIASIS AND OTHER DERMATOLOGICAL DISORDERS. FURTHERMORE, CIRCULATING MIRNAS IDENTIFIED IN PATIENTS' BLOOD SAMPLES HAVE BEEN IDENTIFIED AS PROMISING BIOMARKERS OF DIAGNOSIS, PROGNOSIS OR TREATMENT RESPONSE. EXTENDED INVESTIGATIONS IN THIS FIELD ARE REQUIRED, AS UNTIL NOW, THE EXACT INVOLVEMENT OF MIRNAS IN PSORIASIS HAVE REMAINED TO BE ENTIRELY ELUCIDATED. THIS SHORT REVIEW HIGHLIGHTS A NUMBER OF THE ROLES OF MIRNAS FOUND IN DIFFERENT STAGES OF PSORIASIS. 2018 20 3016 29 GENETICS AND EPIGENETICS OF IBD. INFLAMMATORY BOWEL DISEASES (IBD) ARE CHRONIC INTERMITTENT INFLAMMATORY DISORDERS OF THE GASTROINTESTINAL TRACT OF UNKNOWN ETIOLOGY BUT A CLEAR GENETIC PREDISPOSITION. PROMPTED BY THE FIRST INVESTIGATIONS ON IBD FAMILIES AND TWINS, THE GENETIC AND EPIGENETIC STUDIES HAVE PRODUCED AN UNPRECEDENTED AMOUNT OF INFORMATION IN COMPARISON WITH OTHER IMMUNE-MEDIATED OR COMPLEX DISEASES. NEW INFLAMMATORY PATHWAYS AND POSSIBLE MECHANISMS OF ACTION HAVE BEEN DISCLOSED, POTENTIALLY LEADING TO NEW-TARGETED THERAPY. HOWEVER, THE IDENTIFICATION OF GENETIC MARKERS DUE TO THE GREAT DISEASE HETEROGENEITY AND THE OVERWHELMING CONTRIBUTION OF ENVIRONMENTAL RISK FACTORS HAS NOT MODIFIED YET THE DISEASE MANAGEMENT. THE POSSIBILITY FOR THE FUTURE OF A BETTER PREDICTION OF DISEASE COURSE, RESPONSE TO THERAPY AND THERAPY-RELATED ADVERSE EVENTS MAY ALLOW A MORE EFFICIENT AND PERSONALIZED STRATEGY. THIS REVIEW WILL FOCUS ON MORE RECENT DISCOVERIES THAT MAY POTENTIALLY BE OF RELEVANCE IN DAILY CLINICAL PRACTICE. 2020