1 555 98 AXIAL SPONDYLOARTHRITIS: RESHAPE THE FUTURE-FROM THE "2022 GISEA INTERNATIONAL SYMPOSIUM". THE TERM "AXIAL SPONDYLOARTHRITIS" (AXSPA) REFERS TO A GROUP OF CHRONIC RHEUMATIC DISEASES THAT PREDOMINANTLY INVOLVE THE AXIAL SKELETON AND CONSIST OF ANKYLOSING SPONDYLITIS, REACTIVE ARTHRITIS, ARTHRITIS/SPONDYLITIS ASSOCIATED WITH PSORIASIS (PSA) AND ARTHRITIS/SPONDYLITIS ASSOCIATED WITH INFLAMMATORY BOWEL DISEASES (IBD). MOREOVER, PAIN IS AN IMPORTANT AND COMMON SYMPTOM OF AXSPA. IT MAY PROGRESS TO CHRONIC PAIN, A MORE COMPLICATED BIO-PSYCHOSOCIAL PHENOMENA, LEADING TO A SIGNIFICANT WORSENING OF QUALITY OF LIFE. THE DEVELOPMENT OF THE AXSPA INFLAMMATORY PROCESS IS GROUNDED IN THE COMPLEX INTERACTION BETWEEN GENETIC (SUCH AS HLA B27), EPIGENETIC, AND ENVIRONMENTAL FACTORS ASSOCIATED WITH A DYSREGULATED IMMUNE RESPONSE. CONSIDERING THE PIVOTAL CONTRIBUTION OF IL-23 AND IL-17 IN AXSPA INFLAMMATION, THE INHIBITION OF THESE CYTOKINES HAS BEEN EVALUATED AS A POTENTIAL THERAPEUTIC STRATEGY. WITH THIS CONTEXT, HERE WE DISCUSS THE MAIN PATHOGENETIC MECHANISMS, THERAPEUTIC APPROACHES AND THE ROLE OF PAIN IN AXSPA FROM THE 2022 INTERNATIONAL GISEA/OEG SYMPOSIUM. 2022 2 3173 33 GUT MICROBIOTA-MICRORNA INTERACTIONS IN ANKYLOSING SPONDYLITIS. ANKYLOSING SPONDYLITIS (AS) IS A CHRONIC AUTOIMMUNE INFLAMMATORY DISABILITY THAT IS PART OF THE RHEUMATIC DISEASE GROUP OF SPONDYLOARTHROPATHIES. AS COMMONLY INFLUENCES THE JOINTS OF THE AXIAL SKELETON. THE CONTRIBUTIONS TO AS PATHOGENESIS OF GENETIC SUSCEPTIBILITY (PARTICULARLY HLA-B27 AND ERAP-1) AND EPIGENETIC MODIFICATIONS, LIKE NON-CODING RNAS, AS WELL AS ENVIRONMENTAL FACTORS, HAVE BEEN INVESTIGATED OVER THE LAST FEW YEARS. BUT THE FUNDAMENTAL ETIOLOGY OF AS REMAINS ELUSIVE TO DATE. THE EVIDENCE SUMMARIZED HERE INDICATES THAT IN THE IMMUNOPATHOGENESIS OF AS, MICRORNAS AND THE GUT MICROBIOME PERFORM CRITICAL FUNCTIONS. WE DISCUSS SIGNIFICANT ADVANCES IN THE IMMUNOLOGICAL MECHANISMS UNDERLYING AS AND ADDRESS POTENTIAL CROSS-TALK BETWEEN THE GUT MICROBIOME AND HOST MICRORNAS. THIS CRITICAL INTERACTION IMPLICATES A CO-EVOLUTIONARY SYMBIOTIC LINK BETWEEN HOST IMMUNITY AND THE GUT MICROBIOME. 2021 3 6289 38 THE POTENTIAL ROLE OF GENETICS, ENVIRONMENTAL FACTORS, AND GUT DYSBIOSIS IN THE ABERRANT NON-CODING RNA EXPRESSION TO MEDIATE INFLAMMATION AND OSTEOCLASTOGENIC/OSTEOGENIC DIFFERENTIATION IN ANKYLOSING SPONDYLITIS. ANKYLOSING SPONDYLITIS (AS) OR RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS IS A CHRONIC IMMUNE-MEDIATED RHEUMATIC DISORDER CHARACTERIZED BY THE INFLAMMATION IN THE AXIAL SKELETON, PERIPHERAL JOINTS, AND SOFT TISSUES (ENTHESIS, FASCIA, AND LIGAMENT). IN ADDITION, THE EXTRA-SKELETAL COMPLICATIONS INCLUDING ANTERIOR UVEITIS, INTERSTITIAL LUNG DISEASES AND AORTITIS ARE FOUND. THE PATHOGENESIS OF AS IMPLICATES AN INTRICATE INTERACTION AMONG HLA (HLA-B27) AND NON-HLA LOCI [ENDOPLASMIC RETICULUM AMINOPEPTIDASE 1 (ERAP1), AND INTERLEUKIN-23 RECEPTOR (IL23R), GUT DYSBIOSIS, IMMUNE PLASTICITY, AND NUMEROUS ENVIRONMENTAL FACTORS (INFECTIONS, HEAVY METALS, STRESS, CIGARETTE SMOKING, ETC.) THE LATTER MULTIPLE NON-GENETIC FACTORS MAY EXERT A POWERFUL STRESS ON EPIGENETIC REGULATIONS. THESE EPIGENETIC REGULATIONS OF GENE EXPRESSION CONTAIN DNA METHYLATION/DEMETHYLATION, HISTONE MODIFICATIONS AND ABERRANT NON-CODING RNAS (NCRNAS) EXPRESSION, LEADING TO INFLAMMATION AND IMMUNE DYSFUNCTIONS. IN THE PRESENT REVIEW, WE SHALL DISCUSS THESE CONTRIBUTORY FACTORS THAT ARE INVOLVED IN AS PATHOGENESIS, ESPECIALLY THE ABERRANT NCRNA EXPRESSION AND ITS EFFECTS ON THE PROINFLAMMATORY CYTOKINE PRODUCTIONS (TNF-ALPHA, IL-17 AND IL-23), T CELL SKEWING TO TH1/TH17, AND OSTEOCLASTOGENIC/OSTEOGENIC DIFFERENTIATION. FINALLY, SOME POTENTIAL INVESTIGATORY APPROACHES ARE RAISED FOR SOLVING THE PUZZLES IN AS PATHOGENESIS. 2021 4 4676 34 NEW INSIGHTS TOWARD THE PATHOGENESIS OF ANKYLOSING SPONDYLITIS; GENETIC VARIATIONS AND EPIGENETIC MODIFICATIONS. ANKYLOSING SPONDYLITIS (AS) IS A CHRONIC INFLAMMATORY AUTOIMMUNE DISEASE, CHARACTERIZED BY TYPICALLY AN AXIAL ARTHRITIS. AS IS THE PROTOTYPE OF A GROUP OF DISORDERS CALLED SPONDYLOARTHROPATHIES, WHICH IS BELIEVED TO HAVE COMMON CLINICAL MANIFESTATIONS AND GENETIC PREDISPOSITION. TO DATE, THE EXACT ETIOLOGY OF AS REMAINS UNCLEAR. OVER THE PAST FEW YEARS, HOWEVER, THE ROLE OF GENETIC SUSCEPTIBILITY AND EPIGENETIC MODIFICATIONS CAUSED THROUGH ENVIRONMENTAL FACTORS HAVE BEEN EXTENSIVELY SURVEYED WITH RESPECT TO THE PATHOGENESIS OF AS, RESULTED IN IMPORTANT ADVANCES. THIS REVIEW ARTICLE FOCUSES ON THE RECENT ADVANCES IN THE FIELD OF AS RESEARCH, INCLUDING HLA AND NON-HLA SUSCEPTIBILITY GENES IDENTIFIED IN GENOME-WIDE ASSOCIATION STUDIES (GWAS), AND ABERRANT EPIGENETIC MODIFICATIONS OF GENE LOCI ASSOCIATED WITH AS. HLA GENES MOST SIGNIFICANTLY LINKED WITH AS SUSCEPTIBILITY INCLUDE HLA-B27 AND ITS SUBTYPES. NUMEROUS NON-HLA GENES SUCH AS THOSE IN UBIQUITINATION, AMINOPEPTIDASES AND MHC CLASS I PRESENTATION MOLECULES LIKE ERAP-1 WERE ALSO REPORTED. MOREOVER, EPIGENETIC MODIFICATIONS OCCURRED IN AS HAS BEEN SUMMARIZED. TAKEN TOGETHER, THE FINDINGS PRESENTED IN THIS REVIEW ATTEMPT TO EXPLAIN THE CIRCUMSTANCE BY WHICH BOTH GENETIC VARIATIONS AND EPIGENETIC MODIFICATIONS ARE INVOLVED IN TRIGGERING AND DEVELOPMENT OF AS. NONETHELESS, SEVERAL UNANSWERED DARK SIDES CONTINUE TO CLOG OUR EXHAUSTIVE UNDERSTANDING OF AS. FUTURE RESEARCHES IN THE FIELD OF EPIGENETICS SHOULD BE CARRIED OUT TO EXTEND OUR VISION OF AS ETIOPATHOGENESIS. 2017 5 3033 39 GENETICS, EPIGENETICS, AND GENDER IMPACT IN AXIAL-SPONDYLOARTHRITIS SUSCEPTIBILITY: AN UPDATE ON GENETIC POLYMORPHISMS AND THEIR SEX RELATED ASSOCIATIONS. SPONDYLOARTHRITIS (SPA) IS A GROUP OF CHRONIC INFLAMMATORY RHEUMATIC DISEASE THAT CAN BE DIVIDED INTO PREDOMINANTLY AXIAL OR PREDOMINANTLY PERIPHERAL INVOLVEMENT, WITH OR WITHOUT ASSOCIATED PSORIASIS, INFLAMMATORY BOWEL DISEASE OR PREVIOUS INFECTION. AXIAL SPA (AXSPA) ENCOMPASSES ANKYLOSING SPONDYLITIS (AS) WITH RADIOLOGICAL SACROILIITIS, AND A TYPE WITHOUT RADIOGRAPHIC SACROILIITIS, CALLED "NON-RADIOGRAPHIC AXIAL SPA" (NR-AXSPA). MALES AND FEMALES SHOW LARGE DIFFERENCES IN THEIR SUSCEPTIBILITY TO SPA, SUCH AS DISTINCTIONS IN CLINICAL PATTERNS, PHENOTYPES AND IN THERAPEUTICAL RESPONSE, PARTICULARLY TO TNF INHIBITORS (TNFI). SEVERAL STUDIES INDICATE THAT AS WOMEN HAVE DOUBLED RISK TO FAILURE TNFI COMPARED WITH MALES. THIS DIVERSITY IN DRUGS' EFFICACY AMONG WOMEN AND MEN MAY BE CAUSED BY DIFFERENCES IN THE BALANCE OF SEX HORMONES AND IN GENE-SPECIFIC EXPRESSION LIKELY TRIGGERED BY X-CHROMOSOME INSTABILITY AND GENE-SPECIFIC EPIGENETIC MODIFICATIONS. EVIDENCE REPORTED THAT POLYMORPHISMS IN MICRORNAS ON X- AND OTHER CHROMOSOMES, SUCH AS MIR-146A, MIR-155, MIR-125A-5P, MIR-151A-3P AND MIR-22-3P, MIR-199A-5P COULD BE INVOLVED IN THE DIFFERENT CLINICAL PRESENTATION OF SPA, AS WELL AS DISEASE ACTIVITY. IN ADDITION, ASSOCIATION WITH NON-RESPONSE TO TNFI TREATMENT AND PRESENCE OF IRAK3 AND CHUCK GENES IN SPA PATIENTS WAS RECENTLY DETECTED. FINALLY, POLYMORPHISMS IN GENES INVOLVED IN IL-23/IL-17 PATHWAY, SUCH AS IN DRUG PHARMACODYNAMICS AND PHARMACOKINETICS MAY HAVE A ROLE IN RESPONSE TO TNFI, IL17I, AND IL23I. A MAJOR UNDERSTANDING OF GENOMIC VARIABILITY COULD HELP IN THE DEVELOPMENT OF NEW THERAPEUTIC TARGETS OR IN TAKING ADVANTAGES OF DIFFERENT MECHANISMS OF ACTION OF BIOLOGICAL DRUGS. MOVING FROM THE MULTIFACTORIAL ETIOLOGY OF DISEASE, THE PRESENT REVIEW AIMS AT EVALUATING GENETIC AND EPIGENETIC FACTORS AND THEIR RELATIONSHIP WITH SEX AND BDMARDS RESPONSE, HELPING TO INVESTIGATE THE DIFFERENT EXPRESSION AMONG MALES AND FEMALES OF GENES ON X- AND OTHER CHROMOSOMES, AS WELL AS MI-RNA, TO HIGHLIGHT RELATIONSHIPS BETWEEN SEX AND OCCURRENCE OF SPECIFIC PHENOTYPES AND SYMPTOMS OF THE DISEASE. MOREOVER, THE ROLE OF THE EPIGENETIC MODIFICATION IN RELATION TO IMMUNE-REGULATORY MECHANISMS WILL BE EVALUATED. 2021 6 4319 25 MICRORNAS IN AXIAL SPONDYLARTHRITIS: AN OVERVIEW OF THE RECENT PROGRESSES IN THE FIELD WITH A FOCUS ON ANKYLOSING SPONDYLITIS AND PSORIATIC ARTHRITIS. PURPOSE OF REVIEW: TO HIGHLIGHT THE RECENT DISCOVERIES AND LINES OF EVIDENCE ON THE ROLE OF MICRORNAS IN ANKYLOSING SPONDYLITIS (AS) AND PSORIATIC ARTHRITIS (PSA), FOCUSING ON THEIR EXPRESSION PROFILING AND MECHANISMS OF ACTION. RECENT FINDINGS: AS AND PSA ARE CHRONIC INFLAMMATORY MUSCULOSKELETAL DISEASES WITH AXIAL MANIFESTATIONS AND REPRESENT AN EXCELLENT MODEL FOR STUDYING MICRORNAS CONTRIBUTION TO THE DISEASE PATHOGENESIS, PARTICULARLY THROUGH IMMUNOMODULATION, INFLAMMATION, AND BONE REMODELLING, OR THEIR VALUE AS CANDIDATE DIAGNOSTIC AND PROGNOSTIC BIOMARKERS. MICRORNAS ARE SINGLE-STRANDED NUCLEOTIDES ABLE TO REGULATE GENE EXPRESSION. THEY ARE A KEY COMPONENT OF THE EPIGENETIC MACHINERY, INVOLVED IN PHYSIOLOGICAL AND PATHOLOGICAL PROCESSES. THE CONTRIBUTION OF MICRORNAS IN AS AND PSA (SUCH AS MIR-29A IN REGULATING BONE METABOLISM) IS HIGHLIGHTED BY SEVERAL WORKS IN THE FIELD BUT THEIR UTILITY AS POSSIBLE MARKERS MUST BE STILL CONFIRMED, PARTICULARLY IN LARGER PATIENTS' COHORTS. 2021 7 2989 35 GENETIC FACTORS INVOLVED IN THE CO?OCCURRENCE OF ENDOMETRIOSIS WITH ANKYLOSING SPONDYLITIS (REVIEW). PREVIOUS RESEARCH HAS REVEALED AN ASSOCIATION BETWEEN ENDOMETRIOSIS AND VARIOUS AUTOIMMUNE DISEASES, WHILE RECENT DATA SUGGEST, FOR THE FIRST TIME, AN ASSOCIATION BETWEEN ENDOMETRIOSIS AND THE RISK OF DEVELOPING ANKYLOSING SPONDYLITIS (AS). AS, THE PROTOTYPE OF SPONDYLOARTHRITIDES DISEASES, IS A SYSTEMIC, CHRONIC, IMMUNE?MEDIATED INFLAMMATORY ARTHRITIS, WHICH PRIMARILY AFFECTS THE SPINE AND SACROILIAC JOINTS, AS WELL AS THE AXIAL SKELETON WITH OR WITHOUT EXTRASPINAL MANIFESTATIONS. AS IS OF POLYGENIC INHERITANCE AND NUMEROUS IMMUNOLOGICALLY RELEVANT GENES CONTRIBUTE TO ITS DEVELOPMENT. ENDOMETRIOSIS IS AN ENIGMATIC, RELATIVELY COMMON, BENIGN, ESTROGEN?DEPENDENT, HETEROGENEOUS GYNECOLOGICAL DISEASE, INFLUENCED BY MULTIPLE GENETIC, EPIGENETIC AND ENVIRONMENTAL FACTORS. IT IS CHARACTERIZED BY THE GROWTH OF ENDOMETRIAL TISSUE OCCURRING IN SITES OTHER THAN THE UTERINE CAVITY, MOST COMMONLY IN THE PELVIC CAVITY, INCLUDING THE OVARIES AND THE UTEROSACRAL LIGAMENTS, AFFECTING UP TO 10% OF THE FEMALE POPULATION OF CHILDBEARING AGE, CAUSING PAIN AND INFERTILITY. THE PRESENT REVIEW DISCUSSES WHETHER A PARTIALLY SHARED GENETIC BACKGROUND MAY EXPLAIN THE CO?OCCURRENCE OF THESE DISORDERS, AS WELL AS POTENTIAL SIMILARITIES REGARDING THE UNDERLYING PATHOGENETIC MECHANISMS AND SPECIFIC MOLECULAR AND CELLULAR PATHWAYS. 2023 8 4962 34 PATHOGENESIS OF PSORIATIC ARTHRITIS. PSORIATIC ARTHRITIS (PSA) IS A CHRONIC INFLAMMATORY ARTHROPATHY INVOLVING SYNOVIAL AND ENTHESEAL STRUCTURES, ASSOCIATED WITH PSORIASIS OR SIMILAR CONDITIONS. THE ETIOPATHOGENETIC MECHANISMS UNDERLYING PSA REMAIN UNCLARIFIED. THE MOST ACCREDITED HYPOTHESIS INVOLVES A COMPLEX INTERACTION AMONG GENETIC, ENVIRONMENTAL, AND IMMUNOLOGICAL FACTORS. ENVIRONMENTAL AGENTS, PARTICULARLY TRAUMA, MECHANICAL STRESS, AND SMOKE HAVE BEEN CITED AS POSSIBLE FACTORS IN TRIGGERING THE DISEASE IN GENETICALLY PREDISPOSED SUBJECTS. LIKE OTHER FORMS OF SPONDYLOARTHROPATHIES, PSA SHOWS SEVERAL GENETIC ASSOCIATIONS WITH THE MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) CLASS I ALLELES LOCATED ON CHROMOSOME 6P21.3, PARTICULARLY THE HUMAN LEUKOCYTE ANTIGEN (HLA)-B27 IN AXIAL PHENOTYPES. RECENT STUDIES HAVE DEMONSTRATED THAT THE MOST COMMON EPIGENETIC MECHANISMS THAT REGULATE GENE EXPRESSION IN PSA ARE REPRESENTED BY DNA METHYLATION, PARENT OF ORIGIN EFFECT OR GENOMIC IMPRINTING, EXPRESSION OR ACTIVITY OF EPIGENETIC MODIFYING ENZYMES, AND RNA INTERFERENCE (RNAI) BY MICRORNAS (MIRNAS). THE MECHANISMS UNDERLYING PSA PATHOGENESIS ACTIVATE THE INNATE AND ADAPTIVE IMMUNE SYSTEM AND OVEREXPRESSION OF TNF ASSOCIATED WITH AMPLIFICATION OF THE IL-23/IL-17 AXIS. IN RECENT YEARS, MORE PSA SUSCEPTIBILITY GENES AND EPIGENETIC MECHANISMS HAVE BEEN IDENTIFIED. ADVANCES IN THE KNOWLEDGE OF INNATE AND ADAPTIVE IMMUNE MECHANISMS UNDERLYING PSA HAVE CONTRIBUTED TO A BETTER UNDERSTANDING OF THE HETEROGENEOUS CLINICAL EXPRESSION OF THE DISEASE AND, THUS, TO THERAPY STRATEGIES. THE COMPLEXITY OF THE PATHOGENETIC ASPECTS INVOLVING MULTIPLE CYTOKINES, CELL LINES, AND MOLECULES NEEDS TO BE FURTHER INVESTIGATED TO ADVANCE PERSONALIZED THERAPEUTIC STRATEGIES AND TO IMPROVE OUTCOMES OF PATIENTS AFFECTED BY PSA. 2019 9 2569 30 EPIGENETICS OF ANKYLOSING SPONDYLITIS: RECENT DEVELOPMENTS. ANKYLOSING SPONDYLITIS (AS) IS A CHRONIC INFLAMMATORY AUTOIMMUNE DISEASE WHICH MAINLY AFFECTS THE SPINE, SACROILIAC JOINT AND PERIPHERAL JOINTS. TO DATE, THE EXACT CAUSES AND PATHOGENESIS OF AS STILL REMAIN UNKNOWN. IT IS CONSIDERED THAT THE PATHOGENESIS OF AS IS ASSOCIATED WITH GENETIC, INFECTION, ENVIRONMENT, IMMUNITY AND OTHER FACTORS. AMONG THEM, THE ROLE OF GENETIC FACTORS IN THE PATHOGENESIS OF AS HAS BEEN STUDIED MOST DEEPLY. HOWEVER, OVER THE PAST FEW YEARS, THE FUNCTION OF ENVIRONMENTAL PREDISPOSITION AND EPIGENETIC MODIFICATION IN THE PATHOGENESIS OF AS HAS RECEIVED EXTENSIVE ATTENTION. THIS PAPER SUMMARIZES THE RECENT PROGRESS IN THE EPIGENETICS OF AS, INCLUDING ABNORMAL EPIGENETIC MODIFICATIONS AT AS-ASSOCIATED GENOMIC LOCI, SUCH AS DNA METHYLATION, HISTONE MODIFICATION, MICRORNA, AND SO ON. IN SUMMARY, THE FINDINGS OF THIS REVIEW ATTEMPT TO EXPLAIN THE ROLE OF EPIGENETIC MODIFICATION IN THE OCCURRENCE AND DEVELOPMENT OF AS. NEVERTHELESS, THERE ARE STILL UNKNOWN AND COMPLICATED ASPECTS WORTH EXPLORING TO DEEPEN OUR UNDERSTANDING OF THE PATHOGENESIS OF AS. 2021 10 3057 29 GENOME-WIDE DNA METHYLATION ANALYSIS IN ANKYLOSING SPONDYLITIS IDENTIFIES HLA-B*27 DEPENDENT AND INDEPENDENT DNA METHYLATION CHANGES IN WHOLE BLOOD. BACKGROUND AND OBJECTIVE: ANKYLOSING SPONDYLITIS IS A CHRONIC INFLAMMATORY DISEASE CHARACTERIZED BY INFLAMMATION OF THE SACROILIAC JOINTS AND THE SPINE THAT CAN LEAD TO SIGNIFICANT PAIN, IMMOBILITY, AND DISABILITY. THE ETIOLOGY AND PATHOGENESIS OF ANKYLOSING SPONDYLITIS ARE INCOMPLETELY UNDERSTOOD, THOUGH MOST PATIENTS CARRY THE HLA-B*27 ALLELE. THE OBJECTIVE OF THIS STUDY WAS TO EVALUATE DNA METHYLATION CHANGES IN ANKYLOSING SPONDYLITIS WITH THE GOAL OF REVEALING NOVEL MECHANISTIC INSIGHTS INTO THIS DISEASE. METHODS: GENOME-WIDE DNA METHYLATION ANALYSIS WAS PERFORMED IN WHOLE BLOOD DNA SAMPLES USING THE INFINIUM METHYLATIONEPIC ARRAY IN PATIENTS WITH ANKYLOSING SPONDYLITIS COMPARED TO AGE, SEX, AND RACE MATCHED PATIENTS WITH OSTEOARTHRITIS AS A NON-INFLAMMATORY DISEASE CONTROL. WE STUDIED 24 PATIENTS WITH ANKYLOSING SPONDYLITIS, INCLUDING 12 PATIENTS WHO CARRY HLA-B*27 AND 12 PATIENTS WHO ARE HLA-B*27 NEGATIVE. DNA METHYLATION ANALYSIS WAS PERFORMED WITH ADJUSTMENT FOR BLOOD CELL COMPOSITION IN EACH SAMPLE. RESULTS: WE IDENTIFIED A TOTAL OF 67 DIFFERENTIALLY METHYLATED SITES BETWEEN ANKYLOSING SPONDYLITIS PATIENTS AND OSTEOARTHRITIS CONTROLS. HYPERMETHYLATED GENES FOUND INCLUDED GTPASE-RELATED GENES, WHILE HYPOMETHYLATED GENES INCLUDED HCP5, WHICH ENCODES A LNCRNA WITHIN THE MHC REGION, PREVIOUSLY ASSOCIATED WITH GENETIC RISK FOR PSORIASIS AND TOXIC EPIDERMAL NECROLYSIS. CARRYING HLA-B*27 WAS ASSOCIATED WITH ROBUST HYPOMETHYLATION OF HCP5, TUBULIN FOLDING COFACTOR A (TBCA) AND PHOSPHOLIPASE D FAMILY MEMBER 6 (PLD6) IN ANKYLOSING SPONDYLITIS PATIENTS. HYPOMETHYLATION WITHIN HCP5 INVOLVES A CPG SITE THAT CONTAINS A SINGLE NUCLEOTIDE POLYMORPHISM IN LINKAGE DISEQUILIBRIUM WITH HLA-B*27 AND THAT CONTROLS DNA METHYLATION AT THIS LOCUS IN AN ALLELE-SPECIFIC MANNER. CONCLUSIONS: A GENOME-WIDE DNA METHYLATION ANALYSIS IN ANKYLOSING SPONDYLITIS IDENTIFIED DNA METHYLATION PATTERNS THAT COULD PROVIDE POTENTIAL NOVEL INSIGHTS INTO THIS DISEASE. OUR FINDINGS SUGGEST THAT HLA-B*27 MIGHT PLAY A ROLE IN ANKYLOSING SPONDYLITIS IN PART THROUGH INDUCING EPIGENETIC DYSREGULATION. 2019 11 6152 24 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 12 986 31 CHRONIC RECURRENT MULTIFOCAL OSTEOMYELITIS (CRMO) AND JUVENILE SPONDYLOARTHRITIS (JSPA): TO WHAT EXTENT ARE THEY RELATED? CHRONIC RECURRENT MULTIFOCAL OSTEOMYELITIS (CRMO) IS AN AUTOINFLAMMATORY DISEASE OCCURRING MAINLY IN THE PEDIATRIC AGE GROUP (BEFORE 16 YEARS) AND GENERALLY PRESENTS AS A SEPARATE ENTITY. SYNOVITIS, ACNE, PUSTULOSIS, HYPEROSTOSIS AND OSTEITIS (SAPHO) SYNDROME COMBINES OSTEOARTICULAR AND CUTANEOUS INVOLVEMENT, SIMILAR TO CRMO, AND FALLS INTO THE SPECTRUM OF SPONDYLOARTHRITIS (SPA). THE FACT THAT A PATIENT CAN PROGRESS FROM ONE DISEASE TO ANOTHER RAISES THE QUESTION OF WHETHER CRMO, LIKE SAPHO, COULD FALL WITHIN THE SPECTRUM OF SPA, RANGING FROM A PREDOMINANTLY OSTEOARTICULAR FORM TO AN ENTHESITIC FORM WITH MORE OR LESS MARKED SKIN INVOLVEMENT. IN THIS REVIEW, WE SET OUT TO DISCUSS THIS HYPOTHESIS BY HIGHLIGHTING THE DIFFERENCES AND SIMILARITIES BETWEEN CRMO AND JUVENILE SPA IN CLINICAL, RADIOLOGICAL AND PATHOPHYSIOLOGICAL ASPECTS. A COMMON HYPOTHESIS COULD POTENTIALLY CONSIDER INTESTINAL DYSBIOSIS AS THE ORIGIN OF THESE DIFFERENT INFLAMMATORY DISEASES. INTERINDIVIDUAL FACTORS SUCH AS GENDER, ENVIRONMENT, GENETICS AND/OR EPIGENETIC BACKGROUND COULD ACT AS COMBINED DISEASE MODIFIERS. THIS IS WHY WE SUGGEST THAT PATHOPHYSIOLOGY, RATHER THAN CLINICAL PHENOTYPE, BE USED TO RECLASSIFY THESE DISEASES. 2023 13 2556 20 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 14 4318 27 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 15 631 26 BIOLOGICAL AND SYNTHETIC TARGET DMARDS IN PSORIATIC ARTHRITIS. PSORIATIC ARTHRITIS (PSA) IS A CHRONIC MULTI-FACETED IMMUNE-MEDIATED SYSTEMIC DISORDER, CHARACTERIZED BY ARTICULAR, CUTANEOUS, ENTHESIS, NAIL AND SPINE INVOLVEMENT. ARTICULAR MANIFESTATIONS OF PSA ARE PARTICULARLY COMMON AND HIGHLY DISABLING FOR PATIENTS, WHILE THE HETEROGENEOUS CLINICAL SUBSETS OF THE DISEASE ARE CHALLENGING FOR CLINICIANS. IN RECENT YEARS, RESEARCH HAS MADE MANY ADVANCES IN UNDERSTANDING THE PATHOGENESIS OF THE DISEASE FROM GENETIC, EPIGENETIC AND MOLECULAR POINTS OF VIEW. NEW DRUGS ARE NOW AVAILABLE FOR THE TREATMENT OF THIS CONDITION, AND, IN PARTICULAR, TNF-ALFA INHIBITORS, HISTORICALLY THE FIRST BIOLOGICALS APPROVED IN PSA, ARE NOW JUXTAPOSED BY NEW BIOLOGICAL DISEASE MODIFYING ANTI-RHEUMATIC DRUGS (BDMARDS) WITH DIFFERENT MODES OF ACTION. TARGETING IL-12/IL-23 P40 COMMON SUBUNIT WITH USTEKINUMAB, IL-17A WITH SECUKINUMAB AND IXEKIZUMAB, T CELLS CO-STIMULATION WITH ABATACEPT, IS NOW POSSIBLE, SAFE AND EFFECTIVE. MOREOVER, TARGETED SYNTHETIC MOLECULES WITH ORAL ADMINISTRATION ARE AVAILABLE, WITH THE POSSIBILITY TO INTERFERE WITH PHOSPHODIESTERASE-4 AND JAK/STAT PATHWAYS. INDEED, NEW DRUGS ARE UNDER DEVELOPMENT, WITH THE POSSIBILITY TO TARGET SELECTIVELY IL-17 RECEPTOR, IL-23, AND OTHER KEY MOLECULAR TARGETS IN THE PATHOGENESIS OF THIS CONDITION. IN THIS NARRATIVE REVIEW, WE PROVIDE AN UP-TO-DATE OVERVIEW OF THE CURRENT APPLICATION OF BIOLOGICAL AND TARGETED SYNTHETIC DMARDS IN THE FIELD OF PSA, WITH PARTICULAR REGARD TO THE CLINICAL SIGNIFICANCE OF THIS POSSIBILITY TO TARGET A HIGHER NUMBER OF DISTINCT IMMUNE-PATHWAYS. 2019 16 6787 24 [CONTRIBUTION OF NON-HLA GENES TO JUVENILE IDIOPATHIC ARTHRITIS SUSCEPTIBILITY]. JUVENILE IDIOPATHIC ARTHRITIS (JAL4) IS THE MOST COMMON CHRONIC RHEUMATOLOGIC DISEASE IN CHILDREN. JIA IS A GROUP OF DISORDERS THAT SHARE THE CLINICAL MANIFESTATION OF CHRONIC JOINT INFLAMMATION. THE HUMAN LEUKOCYTE ANTIGEN REGION (HLA) SEEMS TO BE A MAJOR SUSCEPTIBILITY LOCUS FOR JIA THAT IS ESTIMATED TO ACCOUNT FOR 17% OF FAMILIAL SEGREGATION OF THE DISEASE. GENOME-WIDE ASSOCIATION STUDIES (GWAS), CASE-CONTROL STUDIES AND META-ANALYSES OF THE POST-GWAS ERA REVEALED OVER 20 NON-HLA LOCI CONFERRING SUSCEPTIBILITY TO JIA. AT LEAST A HALF OF THOSE ARE SHARED BETWEEN JIA AND RHEUMATOID ARTHRITIS, AN ADULT RHEUMATIC DISEASE, THEREBY SUGGESTING FOR SIMILARITY OF PATHOGENIC MECHANISMS OF BOTH DISEASES. NEW FINDINGS ALSO SUGGEST FOR A LIKELY ROLE OF EPIGENETIC ALTERATIONS IN THE PATHOGENESIS OF JIA THAT SHOULD BE INVESTIGATED IN THE FUTURE. 2014 17 6218 29 THE JOINT SYNOVIUM: A CRITICAL DETERMINANT OF ARTICULAR CARTILAGE FATE IN INFLAMMATORY JOINT DISEASES. THE SYNOVIUM CONSTITUTES THE ENVELOPE OF ARTICULAR JOINTS AND IS A CRITICAL PROVIDER OF SYNOVIAL FLUID COMPONENTS AND ARTICULAR CARTILAGE NUTRIENTS. ITS INFLAMMATION IS A PREDOMINANT FEATURE AND CAUSE OF JOINT DEGENERATION IN DISEASES AS DIVERSE AS RHEUMATOID, PSORIATIC, JUVENILE AND IDIOPATHIC ARTHRITIS, AND LUPUS, GOUT AND LYME DISEASE. THESE INFLAMMATORY JOINT DISEASES (IJDS) ARE DUE TO A WIDE VARIETY OF GENETIC, EPIGENETIC AND ENVIRONMENTAL FACTORS THAT TRIGGER, PROMOTE, AND PERPETUATE JOINT DESTABILIZATION. IN SPITE OF THIS VARIETY OF CAUSES, IJDS SHARE MAIN PATHOLOGICAL FEATURES, NAMELY INFLAMMATION OF THE JOINT SYNOVIUM (SYNOVITIS) AND PROGRESSIVE DEGENERATION OF ARTICULAR CARTILAGE. IN ADDITION TO BEING A DRIVING FORCE BEHIND THE DESTRUCTION OF ARTICULAR CARTILAGE IN IJD, SYNOVITIS IS ALSO INCREASINGLY BEING RECOGNIZED AS A SIGNIFICANT CONTRIBUTOR OF ARTICULAR CARTILAGE DEGENERATION IN OSTEOARTHRITIS, A DISEASE PRIMARILY DUE TO AGING- OR TRAUMA-RELATED WEAR AND TEAR OF CARTILAGE SURFACES. IN VIEW OF THIS IMPORTANT ROLE OF THE SYNOVIUM IN DETERMINING THE FATE OF ARTICULAR CARTILAGE, THIS REVIEW FOCUSES ON ITS UNDERLYING MECHANISMS IN THE PATHOLOGY OF IJD. WE ADDRESS THE ROLES OF SYNOVIAL FIBROBLASTS, MACROPHAGES AND ENDOTHELIAL CELLS IN THE MAINTENANCE OF JOINT HEALTH AND IN THE DESTRUCTION OF ARTICULAR CARTILAGE INTEGRITY DURING IJD. MOLECULAR MECHANISMS THAT HAVE BEEN RECENTLY SHOWN TO GOVERN THE PATHOLOGICAL ACTIVITIES OF THE RESIDENT SYNOVIAL CELLS ARE HIGHLIGHTED. FINALLY, ADVANTAGES AND DISADVANTAGES OF TARGETING THESE NEW MOLECULAR MECHANISMS FOR PREVENTING CARTILAGE DEGENERATION DUE TO CHRONIC INFLAMMATION ARE ALSO DISCUSSED. 2017 18 2979 23 GENETIC BACKGROUND OF JUVENILE IDIOPATHIC ARTHRITIS. JUVENILE IDIOPATHIC ARTHRITIS (JIA) IS THE MOST COMMON CHRONIC RHEUMATOLOGIC DISEASE IN CHILDREN. JIA IS A GROUP OF DISORDERS THAT SHARE THE CLINICAL MANIFESTATION OF CHRONIC JOINT INFLAMMATION. THE HUMAN LEUKOCYTE ANTIGEN REGION (HLA) SEEMS TO BE A MAJOR SUSCEPTIBILITY LOCUS FOR JIA THAT IS ESTIMATED TO ACCOUNT FOR 17% OF FAMILIAL SEGREGATION OF THE DISEASE. TO DATE, AROUND 20 NON-HLA LOCI CONFERRING SUSCEPTIBILITY TO JIA WERE FOUND. AT LEAST A HALF OF THOSE ARE SHARED BETWEEN JIA AND RHEUMATOID ARTHRITIS (RA), AN ADULT RHEUMATIC DISEASE, THEREBY SUGGESTING FOR SIMILARITY OF PATHOGENIC MECHANISMS OF BOTH DISEASES. NEW FINDINGS ALSO SUGGEST FOR A LIKELY ROLE OF EPIGENETIC ALTERATIONS IN THE PATHOGENESIS OF JIA THAT SHOULD BE INVESTIGATED IN THE FUTURE. 2014 19 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 20 4452 25 MOLECULAR MECHANISMS AND MANAGEMENT OF A CUTANEOUS INFLAMMATORY DISORDER: PSORIASIS. PSORIASIS IS A COMPLEX CHRONIC INFLAMMATORY CUTANEOUS DISORDER. TO DATE, ROBUST MOLECULAR MECHANISMS OF PSORIASIS HAVE BEEN REPORTED. AMONG DIVERSE ABERRANT IMMUNOPATHOGENETIC MECHANISMS, THE CURRENT MODEL EMPHASIZES THE ROLE OF TH1 AND THE IL-23/TH17 AXIS, SKIN-RESIDENT IMMUNE CELLS AND MAJOR SIGNAL TRANSDUCTION PATHWAYS INVOLVED IN PSORIASIS. THE MULTIPLE GENETIC RISK LOCI FOR PSORIASIS HAVE BEEN RAPIDLY REVEALED WITH THE ADVENT OF A NOVEL TECHNOLOGY. MOREOVER, IDENTIFYING EPIGENETIC MODIFICATIONS COULD BRIDGE THE GAP BETWEEN GENETIC AND ENVIRONMENTAL RISK FACTORS IN PSORIASIS. THIS REVIEW WILL PROVIDE A BETTER UNDERSTANDING OF THE PATHOGENESIS OF PSORIASIS BY UNRAVELING THE COMPLICATED INTERPLAY AMONG IMMUNOLOGICAL ABNORMALITIES, GENETIC RISK FOCI, EPIGENETIC MODIFICATION AND ENVIRONMENTAL FACTORS OF PSORIASIS. WITH ADVANCES IN MOLECULAR BIOLOGY, DIVERSE NEW TARGETS ARE UNDER INVESTIGATION TO MANAGE PSORIASIS. THE RECENT ADVANCES IN TREATMENT MODALITIES FOR PSORIASIS BASED ON TARGETED MOLECULES ARE ALSO DISCUSSED. 2017