1 986 122 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 2 4667 34 NEW INSIGHTS INTO ADULT AND PAEDIATRIC CHRONIC NON-BACTERIAL OSTEOMYELITIS CNO. PURPOSE OF REVIEW: TO DESCRIBE IN DETAIL THE CLINICAL SYNOPSIS AND PATHOPHYSIOLOGY OF CHRONIC NON-BACTERIAL OSTEOMYELITIS AND SAPHO SYNDROME. RECENT FINDINGS: CHRONIC NON-BACTERIAL OSTEOMYELITIS (CNO) HAS BEEN IDENTIFIED AS A DISEASE ENTITY FOR ALMOST 50 YEARS. THIS INFLAMMATORY BONE DISORDER IS CHARACTERIZED BY OSTEOLYTIC AS WELL AS HYPEROSTOTIC/OSTEOSCLEROTIC LESIONS. IT IS CHRONIC IN NATURE, BUT IT CAN PRESENT WITH EPISODIC FLAIRS AND PHASES OF REMISSION, WHICH HAVE LED TO THE DENOMINATION "CHRONIC RECURRENT OSTEOMYELITIS", WITH ITS SEVERE MULTIFOCAL FORM "CHRONIC RECURRENT MULTIFOCAL OSTEOMYELITIS" (CRMO). FOR ALMOST THREE DECADES, AN INFECTIOUS AETIOLOGY HAD BEEN CONSIDERED, SINCE ESPECIALLY PROPIONIBACTERIUM ACNES HAD BEEN ISOLATED FROM BONE LESIONS OF INDIVIDUAL PATIENTS. HOWEVER, THIS CONCEPT HAS BEEN CHALLENGED SINCE LONG-TERM ANTIBIOTIC THERAPY DID NOT ALTER THE COURSE OF DISEASE AND MODERN MICROBIOLOGICAL TECHNIQUES (INCLUDING PCR) FAILED TO CONFIRM BONE INFECTION AS AN UNDERLYING CAUSE. OVER RECENT YEARS, A PROFOUND DYSREGULATION OF CYTOKINE EXPRESSION PROFILES HAS BEEN DEMONSTRATED IN INNATE IMMUNE CELLS OF CNO PATIENTS. A HALLMARK OF MONOCYTES FROM CNO PATIENTS IS THE FAILURE TO PRODUCE IMMUNE REGULATORY CYTOKINES INTERLEUKIN-10 (IL-10) AND IL-19, WHICH HAVE BEEN LINKED WITH GENETIC AND EPIGENETIC ALTERATIONS. SUBSEQUENTLY, A SIGNIFICANT UPREGULATION OF PRO-INFLAMMATORY, NLRP3 INFLAMMASOME-DEPENDENT CYTOKINES (IL-1BETA AND TNF-ALPHA), HAS BEEN DEMONSTRATED. THE CURRENT KNOWLEDGE ON CNO, THE UNDERLYING MOLECULAR PATHOPHYSIOLOGY, AND MODERN IMAGING STRATEGIES ARE SUMMARIZED; DIFFERENTIAL DIAGNOSES, TREATMENT OPTIONS, OUTCOME MEASURES, AS WELL AS QUALITY OF LIFE STUDIES ARE DISCUSSED. 2020 3 6345 35 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 4 2027 39 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 5 1935 29 ENVIRONMENTAL RISK FACTORS AND EPIGENETIC ALTERNATIONS IN PSORIASIS. INTRODUCTION AND OBJECTIVE: PSORIASIS ISA QUITE COMMON, CHRONIC AND IMMUNE-MEDIATED SKIN DISORDER. THE PREVALENCE OF PSORIASIS DIFFERS IN VARIOUS COUNTRIES, BUT IT IS SAID TO AFFECT 2% OF THE WORLD'S POPULATION IN GENERAL. PSORIASIS HAS MANY DIFFERENT CLINICAL FEATURES BUT ALL LESIONS HAVE THE SAME CHARACTERISTIC: ERYTHEMA, THICKENING AND SCALE, ALTHOUGH OTHER CLINICAL FEATURES ARE ALSO CONNECTED, SUCH AS PSORIATIC ARTHRITIS, OBESITY AND METABOLIC SYNDROME. ALL OF THESE MAY LEAD TO CONDITIONS IMPAIRING THE QUALITY OF LIFE. THIS REVIEW IS AN ATTEMPT TO SUMMARIZE RECENT DATA REGARDING ENVIRONMENTAL FACTORS, TOGETHER WITH EPIGENETIC MARKERS AND PROCESSES PLAYING AN IMPORTANT ROLE IN PSORIASIS. STATE OF KNOWLEDGE: MANY DIFFERENT ENVIRONMENTAL FACTORS PLAY A ROLE IN GENETICALLY PREDISPOSED PATIENTS. THIS IS CAUSES EPIGENETIC ALTERNATIONS WHICH MAY BE A LINKING PART IN THE WHOLE PROCESS. MANY STUDIES HAVE INDICATED A CONNECTION BETWEEN PSORIASIS AND VARIOUS GENES AND ANTIGENS. THE PRESENCE OF HLA-CW6 IS COMMON AS WELL A STRONG LINK BETWEEN ITS PRESENCE AND THE ONSET OF PSORIASIS BEING OBSERVED. THE MAIN ALTERNATIONS ARE DNA METHYLATION, HISTONE'S MODIFICATIONS AND THE ROLE OF MICRORNA. EXCESSIVE REACTION IS USUALLY NOT PRESENT WITHOUT A TRIGGERING FACTOR. ENVIRONMENTAL FACTORS ARE MOSTLY RATED, SUCH AS DRUGS, LIFE STYLE AND HABITS (SMOKING, ALCOHOL), DIET, PHYSICAL TRAUMA (SKIN INJURY PROVOKING KOEBNER PHENOMENON), STRESS, MICROORGANISM AND INFECTIONS. CONCLUSIONS: THE CORRELATION BETWEEN PATHOGENESIS OF PSORIASIS AND ENVIRONMENTAL RISK FACTORS, TOGETHER WITH EPIGENETIC ALTERNATIONS STILL REQUIRE MORE INVESTIGATION. EDUCATION ABOUT DIET HABITS, NUTRITION, WEIGHT LOSS AND HEALTHY LIFESTYLE SEEMS TO BE IMPORTANT DURING THE TREATMENT OF PSORIASIS. 2020 6 6821 33 [GASTROINTESTINAL MANIFESTATIONS IN IMMUNODEFICIENCIES WITH MONOGENIC ORIGIN]. ALTHOUGH VERY EARLY ONSET INFLAMMATORY BOWEL DISEASE THAT DEVELOPS IN EARLY CHILDHOOD (BEFORE THE AGE OF 6 YEARS) HAS A DIFFERENT ETIOLOGY FROM CROHN'S DISEASE AND ULCERATIVE COLITIS, IT IS ALSO CHARACTERIZED BY CHRONIC INFLAMMATION OF THE GASTROINTESTINAL TRACT. BASICALLY, VERY EARLY ONSET INFLAMMATORY BOWEL DISEASE SHOULD BE CONSIDERED AS AN IMMUNODEFICIENCY WITH MONOGENIC ORIGIN WHERE BOTH GASTROINTESTINAL MANIFESTATIONS AND SYMPTOMS OF IMMUNODEFICIENCIES MAY DEVELOP IN VARIABLE COMBINATIONS. HOWEVER, IN THE FUTURE, THE EVALUATION OF GENETIC ALTERATIONS IN THE BACKGROUND OF THE DISEASE WILL PROBABLY BE PERFORMED BY NEXT-GENERATION SEQUENCING TECHNOLOGY; ONE SHOULD ALSO CONSIDER THAT THE SEQUENCE OF THE DNA STANDS IN CONTINUOUS INTERACTION WITH A WIDE VARIETY OF ENVIRONMENTAL EFFECTS, AMONG WHICH NUTRITION SHOULD BE EMPHASIZED BY ALL MEANS. EPIGENETIC ALTERATIONS THAT ARE INDUCED BY ENVIRONMENTAL FACTORS, COULD CONTRIBUTE TO THE PATHOGENESIS OF INFLAMMATORY BOWEL DISEASES THAT DEVELOP DURING CHILDHOOD, THEREFORE, THEY SHOULD ALSO BE IDENTIFIED DURING FURTHER RESEARCH. IT HAS A KEY SIGNIFICANCE TO ESTABLISH THE DIAGNOSIS OF VERY EARLY ONSET INFLAMMATORY BOWEL DISEASE AS EARLY AS POSSIBLE, BECAUSE THIS COULD GIVE THE OPPORTUNITY TO START THE ADEQUATE TREATMENT WHICH IS BONE MARROW TRANSPLANTATION IN THE CASE OF MONOGENIC IMMUNODEFICIENCIES. ORV HETIL. 2018; 159(49): 2050-2056. 2018 7 3016 26 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 8 2989 33 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 9 395 32 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 10 5905 24 TACKLING THE HETEROGENEITY OF CVID. PURPOSE OF REVIEW: COMMON VARIABLE IMMUNODEFICIENCY IS CLINICALLY THE MOST RELEVANT PRIMARY IMMUNODEFICIENCY OF THE ADULT. ITS HETEROGENEITY HAS HINDERED PROGRESS IN THE PATHOGENETIC UNDERSTANDING OF THE MAJORITY OF COMMON VARIABLE IMMUNODEFICIENCY PATIENTS. THIS ABSTRACT SUMMARIZES RECENT ASPECTS OF THE FIELD AND EMPHASIZES THE NEED FOR A COMMONLY ACCEPTED APPROACH TO CLASSIFY COMMON VARIABLE IMMUNODEFICIENCY. RECENT FINDINGS: IN THE LAST 2 YEARS, THE FIRST GENETIC DEFECTS UNDERLYING COMMON VARIABLE IMMUNODEFICIENCY, INCLUDING ICOS, TACI, BAFF-R AND CD19, HAVE BEEN IDENTIFIED. THE ANALYSIS OF DENDRITIC CELLS DEMONSTRATED ALTERATIONS IN A MAJORITY OF PATIENTS IN ADDITION TO THE DISTURBED T AND B-CELL FUNCTION. SEVERAL CHANGES OF THE ADAPTIVE IMMUNE SYSTEM MIGHT BE SECONDARY TO AN UNDERLYING CHRONIC INFLAMMATORY SETTING POSSIBLY DUE TO A HHV8 INFECTION IN A SUBGROUP OF PATIENTS WITH GRANULOMATOUS DISEASE, AUTOIMMUNE PHENOMENA AND T-CELL DYSFUNCTION. THE OCCURRENCE OF GRANULOMATOUS INFLAMMATION IS ASSOCIATED WITH A WORSE PROGNOSIS COMPARED WITH COMMON VARIABLE IMMUNODEFICIENCY PATIENTS WITHOUT GRANULOMA. SUMMARY: THE PATHOGENESIS OF COMMON VARIABLE IMMUNODEFICIENCY INCLUDES DISTURBANCES OF THE ADAPTIVE AS WELL AS INNATE IMMUNE SYSTEM. IDENTIFIED MONOGENIC DEFECTS ACCOUNT FOR ABOUT 10% OF CASES, LEAVING THE MAJORITY OF DEFECTS UNDEFINED AND CERTAINLY IN PART EPIGENETIC. TO COMBINE THE KNOWN ASPECTS OF THE PATHOGENESIS OF COMMON VARIABLE IMMUNODEFICIENCY TO A CONCLUSIVE PICTURE, THE CLINICAL AND IMMUNOLOGIC PHENOTYPING OF PATIENTS NEEDS TO BE STANDARDIZED. 2005 11 845 22 CHILDHOOD ATOPIC DERMATITIS: CURRENT DEVELOPMENTS, TREATMENT APPROACHES, AND FUTURE EXPECTATIONS. ATOPIC DERMATITIS (AD) IS THE MOST COMMON CHRONIC INFLAMMATORY SKIN DISORDER OF CHILDHOOD. UNDERLYING FACTORS THAT CONTRIBUTE TO AD ARE IMPAIRED EPITHELIAL BARRIER, ALTERATIONS IN THE LIPID COMPOSITION OF THE SKIN, IMMUNOLOGICAL IMBALANCE INCLUDING INCREASED TH2/TH1 RATIO, PROINFLAMMATORY CYTOKINES, DECREASED T REGULATORY CELLS, GENETIC MUTATIONS, AND EPIGENETIC ALTERATIONS. ATOPIC DERMATITIS IS A MULTIFACTORIAL DISEASE WITH A PARTICULARLY COMPLICATED PATHOPHYSIOLOGY. DISCOVERIES TO DATE MAY BE CONSIDERED THE TIP OF THE ICEBERG, AND THE INCREASING NUMBER OF STUDIES IN THIS FIELD INDICATE THAT THERE ARE MANY POINTS TO BE ELUCIDATED IN AD PATHOPHYSIOLOGY. IN THIS REVIEW, WE AIMED TO ILLUSTRATE THE CURRENT UNDERSTANDING OF THE UNDERLYING PATHOGENIC MECHANISMS IN AD, TO EVALUATE AVAILABLE TREATMENT OPTIONS WITH A FOCUS ON RECENTLY DISCOVERED THERAPEUTIC AGENTS, AND TO DETERMINE THE PERSONAL, FAMILIAL, AND ECONOMIC BURDENS OF THE DISEASE, WHICH ARE FREQUENTLY NEGLECTED ISSUES IN AD. CURRENTLY AVAILABLE THERAPIES ONLY PROVIDE TRANSIENT SOLUTIONS AND CANNOT FULLY CURE THE DISEASE. HOWEVER, ADVANCES IN THE UNDERSTANDING OF THE PATHOGENIC MECHANISMS OF THE DISEASE HAVE LED TO THE PRODUCTION OF NEW TREATMENT OPTIONS, WHILE ONGOING DRUG TRIALS ALSO HAVE HAD PROMISING RESULTS. 2019 12 3020 31 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 13 6276 26 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 14 3033 44 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 15 3802 33 INTERSTITIAL LUNG DISEASE IN CONNECTIVE TISSUE DISEASE: A COMMON LESION WITH HETEROGENEOUS MECHANISMS AND TREATMENT CONSIDERATIONS. CONNECTIVE TISSUE DISEASE (CTD) RELATED INTERSTITIAL LUNG DISEASE (CTD-ILD) IS ONE OF THE LEADING CAUSES OF MORBIDITY AND MORTALITY OF CTD. CLINICALLY, CTD-ILD IS HIGHLY HETEROGENOUS AND INVOLVES RHEUMATIC IMMUNITY AND MULTIPLE MANIFESTATIONS OF RESPIRATORY COMPLICATIONS AFFECTING THE AIRWAYS, VESSELS, LUNG PARENCHYMA, PLEURA, AND RESPIRATORY MUSCLES. THE MAJOR PATHOLOGICAL FEATURES OF CTD ARE CHRONIC INFLAMMATION OF BLOOD VESSELS AND CONNECTIVE TISSUES, WHICH CAN AFFECT ANY ORGAN LEADING TO MULTI-SYSTEM DAMAGE. THE HUMAN LUNG IS PARTICULARLY VULNERABLE TO SUCH DAMAGE BECAUSE ANATOMICALLY IT IS ABUNDANT WITH COLLAGEN AND BLOOD VESSELS. THE COMPLEX ETIOLOGY OF CTD-ILD INCLUDES GENETIC RISKS, EPIGENETIC CHANGES, AND DYSREGULATED IMMUNITY, WHICH INTERACT LEADING TO DISEASE UNDER VARIOUS ILL-DEFINED ENVIRONMENTAL TRIGGERS. CTD-ILD EXHIBITS A BROAD SPECTRA OF CLINICAL MANIFESTATIONS: FROM ASYMPTOMATIC TO SEVERE DYSPNEA; FROM SINGLE-ORGAN RESPIRATORY SYSTEM INVOLVEMENT TO MULTI-ORGAN INVOLVEMENT. THE DISEASE COURSE IS ALSO FEATURED BY REMISSIONS AND RELAPSES. IT CAN RANGE FROM STABILITY OR SLOW PROGRESSION OVER SEVERAL YEARS TO RAPID DETERIORATION. IT CAN ALSO PRESENT CLINICALLY AS HIGHLY PROGRESSIVE FROM THE INITIAL ONSET OF DISEASE. CURRENTLY, THE DIAGNOSIS OF CTD-ILD IS PRIMARILY BASED ON DISTINCT PATHOLOGY SUBTYPE(S), IMAGING, AS WELL AS RELATED CTD AND AUTOANTIBODIES PROFILES. METICULOUS COMPREHENSIVE CLINICAL AND LABORATORY ASSESSMENT TO IMPROVE THE DIAGNOSTIC PROCESS AND MANAGEMENT STRATEGIES ARE MUCH NEEDED. IN THIS REVIEW, WE FOCUS ON EXAMINING THE PATHOGENESIS OF CTD-ILD WITH RESPECT TO GENETICS, ENVIRONMENTAL FACTORS, AND IMMUNOLOGICAL FACTORS. WE ALSO DISCUSS THE CURRENT STATE OF KNOWLEDGE AND ELABORATE ON THE CLINICAL CHARACTERISTICS OF CTD-ILD, DISTINCT PATHOHISTOLOGICAL SUBTYPES, IMAGING FEATURES, AND RELATED AUTOANTIBODIES. FURTHERMORE, WE COMMENT ON THE IDENTIFICATION OF HIGH-RISK PATIENTS AND ADDRESS HOW TO STRATIFY PATIENTS FOR PRECISION MEDICINE MANAGEMENT APPROACHES. 2021 16 3286 41 HIDRADENITIS SUPPURATIVA: DETANGLING PHENOTYPES AND IDENTIFYING COMMON DENOMINATORS. HIDRADENITIS SUPPURATIVA (HS) IS A CHRONIC INFLAMMATORY SKIN DISEASE WITH A SEVERE IMPACT ON PATIENTS' QUALITY OF LIFE THROUGH ITS RECURRENT AND PAINFUL NATURE, AS WELL AS ITS COMORBIDITY BURDEN. THE SHIFT IN THE PATHOGENIC PARADIGM FROM A CONDITION OF THE APOCRINE GLANDS TO AN AUTOINFLAMMATORY DISEASE ASSOCIATED WITH FOLLICULAR DESTRUCTION HAS RENDERED ITS UNDERSTANDING DIFFICULT, AS THERE ARE STILL LARGE GAPS IN PINPOINTING THE UNDERLYING MECHANISMS, WHICH CANNOT CURRENTLY EXPLAIN THE EXISTING CLINICAL VARIATION AND AS A RESULT, TRANSLATE INTO SUBOPTIMAL THERAPY. MULTIFACTORIAL INVOLVEMENT IS HYPOTHESIZED, WITH AN IMPLICATION OF GENETIC MUTATIONS, MICROBIOME DYSBIOSIS, CYTOKINE UPREGULATION, AND ENVIRONMENTAL FACTORS. CLINICAL OBSERVATION IS FUNDAMENTAL FOR DIAGNOSIS, HOWEVER, THE MARKED HETEROGENEITY IN PRESENTATION LEADS TO DELAYS IN DETECTION AND CHALLENGES IN TREATMENT SELECTION, SHOWCASING CLEAR LIMITS IN DEFINING THE LINK BETWEEN GENETIC ASPECTS OF HS, THE ROLE OF EPIGENETIC FACTORS, AND ITS PATHOGENIC PATHWAYS. THERE HAVE BEEN ATTEMPTS TO FORMULATE PHENOTYPES THAT COULD AID IN PROGNOSTICATION AND MANAGEMENT, HOWEVER, CURRENT CLASSIFICATION SCHEMATA SHOW SIGNIFICANT OVERLAP AND NO VALIDATION THROUGH LONGITUDINAL STUDIES. IN THIS CONTEXT, NOMENCLATURE POSES A GREAT CHALLENGE DUE TO THE LACK OF GLOBAL AGREEMENT IN THE DEFINITION OF LESIONS, WHICH SHOULD BE ADDRESSED BY FUTURE RESEARCH TO ENABLE SIMPLIFIED RECOGNITION AND ALLOW FOR MORE PRECISE SEVERITY SCORING. THIS COULD BE COMPLEMENTED BY THE ADDITION OF EXTRA DERMATOLOGIC FINDINGS OR PARACLINICAL ASSESSMENT IN CONSTRUCTING PHENOTYPES. THE DEVELOPMENT OF VALID, PREDICTIVE, AND RELIABLE CLASSIFICATIONS OF HS MAY LEAD TO AN IMPROVEMENT IN COMPREHENDING ITS PATHOPHYSIOLOGY, FAVORING A MORE PERSONALIZED APPROACH IN MANAGEMENT. THIS COULD BE ACHIEVED THROUGH CONSENSUS IN THE CHARACTERIZATION OF CLINICAL FEATURES AND DATA GATHERING, AS WELL AS VALIDATION ATTEMPTS FOR DESCRIBED PHENOTYPES. ULTIMATELY, THE GENOTYPE-ENDOTYPE-PHENOTYPE CORRELATION IN HS REQUIRES TARGETED, SYSTEMATIC INQUIRIES AND SHOULD BE ADDRESSED MORE LARGELY TO BROADEN THE PERSPECTIVE ON THIS DEBILITATING ENTITY. 2023 17 728 33 CAN WE IDENTIFY PATIENTS WITH HIGH RISK OF OSTEOARTHRITIS PROGRESSION WHO WILL RESPOND TO TREATMENT? A FOCUS ON BIOMARKERS AND FRAILTY. OSTEOARTHRITIS (OA), A DISEASE AFFECTING DIFFERENT PATIENT PHENOTYPES, APPEARS AS AN OPTIMAL CANDIDATE FOR PERSONALIZED HEALTHCARE. THE AIM OF THE DISCUSSIONS OF THE EUROPEAN SOCIETY FOR CLINICAL AND ECONOMIC ASPECTS OF OSTEOPOROSIS AND OSTEOARTHRITIS (ESCEO) WORKING GROUP WAS TO EXPLORE THE VALUE OF MARKERS OF DIFFERENT SOURCES IN DEFINING DIFFERENT PHENOTYPES OF PATIENTS WITH OA. THE ESCEO ORGANIZED A SERIES OF MEETINGS TO EXPLORE THE POSSIBILITY OF IDENTIFYING PATIENTS WHO WOULD MOST BENEFIT FROM TREATMENT FOR OA, ON THE BASIS OF RECENT DATA AND EXPERT OPINION. IN THE FIRST MEETING, PATIENT PHENOTYPES WERE IDENTIFIED ACCORDING TO THE NUMBER OF AFFECTED JOINTS, BIOMECHANICAL FACTORS, AND THE PRESENCE OF LESIONS IN THE SUBCHONDRAL BONE. IN THE SECOND MEETING, SUMMARIZED IN THE PRESENT ARTICLE, THE WORKING GROUP EXPLORED OTHER MARKERS INVOLVED IN OA. PROFILES OF PATIENTS MAY BE DEFINED ACCORDING TO THEIR LEVEL OF PAIN, FUNCTIONAL LIMITATION, AND PRESENCE OF COEXISTENT CHRONIC CONDITIONS INCLUDING FRAILTY STATUS. A CONSIDERABLE AMOUNT OF DATA SUGGESTS THAT MAGNETIC RESONANCE IMAGING MAY ALSO ASSIST IN DELINEATING DIFFERENT PHENOTYPES OF PATIENTS WITH OA. AMONG MULTIPLE BIOCHEMICAL BIOMARKERS IDENTIFIED, NONE IS SUFFICIENTLY VALIDATED AND RECOGNIZED TO IDENTIFY PATIENTS WHO SHOULD BE TREATED. CONSIDERABLE EFFORTS ARE ALSO BEING MADE TO IDENTIFY GENETIC AND EPIGENETIC FACTORS INVOLVED IN OA, BUT RESULTS ARE STILL LIMITED. THE MANY POTENTIAL BIOMARKERS THAT COULD BE USED AS POTENTIAL STRATIFIERS ARE PROMISING, BUT MORE RESEARCH IS NEEDED TO CHARACTERIZE AND QUALIFY THE EXISTING BIOMARKERS AND TO IDENTIFY NEW CANDIDATES. 2015 18 6884 23 [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 19 6791 28 [DOES THE NUMBER OF PATIENTS WITH AUTOIMMUNE DISORDERS AND THE FREQUENCY OF AUTOIMMUNE DISEASES INCREASE?]. AUTOIMMUNE DISEASES GENERALLY BELONG TO THE RARE DISEASES, HOWEVER, SOME OF THEM ARE FREQUENT IN THE POPULATION. IN THE PRESENT WORK THE AUTHORS ANALYSE WHETHER CAN ANY INCREASE BE OBSERVED IN THE NUMBER OF PATIENTS SUFFERING FROM AUTOIMMUNE DISEASES AND WHETHER DO THE FREQUENCY OF CERTAIN AUTOIMMUNE DISORDERS INCREASE. DUE MAINLY TO EPIGENETIC FACTORS THE INCIDENCE OF AUTOIMMUNE DISEASES ARE INCREASING, THEREFORE THERE ARE MORE PATIENTS RECOGNISED WITH PARTICULAR DISORDERS. ON THE OTHER HAND THE INCIDENCE IS INCREASED BY IMPROVING DIAGNOSTIC POSSIBILITIES, BY THE USE OF MORE SPECIFIC AND SENSITIVE CLASSIFICATION CRITERIA AND MORE SOPHISTICATED LABORATORY TESTS, RESULTED IN THE RECOGNITION OF MILDER AND ATYPICAL DISEASE VARIANTS AS WELL. THE PREVALENCE IS ALSO INCREASING IN CONSEQUENCE OF NOVEL IMMUNE SUPPRESSIVE THERAPEUTIC POSSIBILITIES AND THE CONSEQUENT IMPROVEMENT OF SURVIVAL IN THE MOST OF THESE DISEASES. BESIDES, MORE AND MORE DISEASES HAVE BEEN REVEALED TO HAVE AUTOIMMUNE BACKGROUND, AND LOT OF NEW AUTOIMMUNE SYNDROMES, DISEASES HAVE BEEN CHARACTERISED RECENTLY. THIS INCREASES THE NUMBER OF THE KNOWN AUTOIMMUNE RHEUMATIC DISORDERS WITH A CONSEQUENT INCREASE IN THE NUMBER OF AUTOIMMUNE PATIENTS. ASSIGNED TO THE INCREASING NUMBER OF VARIABLE CHRONIC AUTOIMMUNE DISORDERS, AND THE INCREASING NUMBER OF DISABLED PATIENTS WITH SUCH DISEASES INCREASING MEDICAL AND SOCIAL ATTENTION HAS TO BE FOCUSED ON. 2007 20 4685 25 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