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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
25473153 Risk of infections associated with biological treatment in inflammatory bowel disease. 2014 Nov 21 Tumor necrosis factor-α (TNF-α) inhibitors are biological agents introduced in the late 1990s for the treatment of different immune-mediated diseases as inflammatory bowel disease, rheumatoid arthritis and psoriasis. The most commonly used TNF-α antagonists are infliximab, adalimumab, and certolizumab pegol, and though highly effective in lowering inflammation, the efficacy must be weighed against the potential for adverse events. The treatment-induced immunosuppression is suspected to increase the risk of infections, including the risk of reactivation of latent tuberculosis, as the TNF-α cytokine plays an important role in the immune function. In this topic highlight a short overview of the infection risk associated with TNF-α inhibiter therapy is outlined with a focus on the overall risk of serious infections, mycobacterial infection and latent viral infections.
25373087 The effect of omega-3 fatty acids on biomarkers of inflammation: a rapid evidence assessme 2014 Nov INTRODUCTION: Previous studies of omega-3 fatty acids report improved outcomes where inflammation is a key factor. The objective of this systematic review is to evaluate effects of omega-3s on inflammatory biomarkers. METHODS: Randomized clinical studies that measured the influence of omega-3 fatty acids on inflammatory biomarkers were identified using a comprehensive search. Eligible studies were rated with the American Dietetic Association Evidence Analysis Manual and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) process to examine study quality and risk/benefit. RESULTS: 112 studies were included. Over 65% reported statistically significant effects. The majority were scored as low risk of bias (high quality) and scored strong (cardiac populations and critically ill) to weak (Alzheimer's Disease, hypertriglyceridemia/diabetes, and obesity) on the risk/benefit ratio evidence for modulation of inflammatory biomarkers. There was inadequate data to determine a GRADE for inflammatory biomarker studies for some conditions (healthy individuals, rheumatoid arthritis, metabolic syndrome, renal disease, pregnancy, or children). CONCLUSION: Clinical literature on the effects of omega-3 fatty acids on inflammatory biomarkers contains mostly small sample sizes, is neutral to high quality, and report mixed effects. Larger studies examining dose and delivery are needed.
25337443 Receptor Tyrosine Kinase and Tyrosine Kinase Inhibitors: New Hope for Success in Multiple 2014 Jul Receptor tyrosine kinases (RTKs) are essential components of signal transduction pathways that mediate cell-to-cell communication and their function as relay points for signaling pathways. They have a key role in numerous processes that control cellular proliferation and differentiation, regulate cell growth and cellular metabolism, and promote cell survival and apoptosis. Recently, the role of RTKs including TCR, FLT-3, c-Kit, c-Fms, PDGFR, ephrin, neurotrophin receptor, and TAM receptor in autoimmune disorder, especially rheumatoid arthritis and multiple sclerosis has been suggested. In multiple sclerosis pathogenesis, RTKs and their tyrosine kinase enzymes are selective important targets for tyrosine kinase inhibitor (TKI) agents. TKIs, compete with the ATP binding site of the catalytic domain of several tyrosine kinases, and act as small molecules that have a favorable safety profile in disease treatment. Up to now, the efficacy of TKIs in numerous animal models of MS has been demonstrated, but application of these drugs in human diseases should be tested in future clinical trials.
25321605 Identification of the reactive metabolites of fenclozic acid in bile duct cannulated rats. 2014 Nov 18 Fenclozic acid (Myalex) was developed by ICI pharmaceuticals in the 1960s for the treatment of rheumatoid arthritis and was a promising compound with a good preclinical safety profile and efficacy. While it did not show adverse hepatic effects in preclinical animal tests or initial studies in man [ Chalmers et al. Ann. Rheum. Dis. 1969 , 28 , 595 and Chalmers et al. Ann. Rheum. Dis. 1969 , 28 , 590 ], it was later withdrawn from clinical development. Hepatotoxicity was observed in humans at daily doses of 400 mg but was not replicated in any of the animal species tested. Rodrigues et al. [ Arch. Toxicol. 2013 , 87 , 1569 ] published a mechanistic investigation using modern in vitro assays/techniques in order to investigate the hepatotoxicity; however, only the covalent binding in rat, dog, and human microsomes was identified as a potential indicator for hepatoxicity. Metabolites associated with or responsible for covalent binding could not be detected, likely due to the low in vitro metabolic turnover of fenclozic acid in microsomes. Foulkes [ J. Pharmacol. Exp. Ther. 1970 , 172 , 115 ] investigated the in vivo metabolism of fenclozic acid which included a rat bile duct cannulated (BDC) study characterizing the biliary and urinary metabolites; however, no reactive metabolites were identified. This study aimed to reinvestigate the in vivo metabolism of fenclozic acid in rat, with a focus on identifying any reactive metabolites that could explain the in vitro covalent binding in microsomes observed across the species. Using modern analytical techniques, we were successful in identifying an epoxide reactive metabolite, which upon conjugation with glutathione (GSH), formed up to 16 GSH-related products including positional and diastereoisomers. Not including the GSH related conjugates, 7 additional metabolites were identified compared to these previous metabolism studies.
25006519 Methotrexate induced pancytopenia. 2014 The well-reported methotrexate (MTX) toxicities are based on the duration and cumulative dosing of drug. The typical toxicities can be predicted by the timing of drug administration, where mucositis occurs as an earlier effect, while myelosuppression and the sequelae of pancytopenia occur later after MTX administration. Despite these well-known toxicities, low dose MTX therapy can become problematic, in particular with the elderly, who are at a greater risk for significant myelosuppression. We present a case of a 73-year-old female with pancytopenia causing severe neutropenia, mucocutaneous bleeding, and bruising and requiring intravenous antibiotic therapy and limited transfusion dependence as a result of low dose daily MTX for rheumatoid arthritis.
24927868 Risk factors for manipulation after total knee arthroplasty: a pooled electronic health re 2014 Oct A commercially available software platform, Explorys (Explorys, Inc., Cleveland, OH), was used to mine a pooled electronic healthcare database consisting of the medical records of more than 27 million patients. A total of 229,420 patients had undergone a total knee arthroplasty; 3470 (1.51%) patients were identified to have undergone manipulation under anesthesia. Individual risk factors of being female, African American race, age less than 60, BMI >30 and nicotine dependence were determined to have relative risk of 1.25, 2.20, 3.46, 1.33 and 1.32 respectively. Depressive disorder, diabetes mellitus, opioid abuse/dependence and rheumatoid arthritis were not significant risk factors. African Americans under the age of 60 at time of TKA had the greatest incidence of MUA (5.17%) and relative risk of 3.73 (CI: 3.36, 4.13).
24923340 Depression as a comorbidity in Behcet's syndrome. 2014 Behcet's syndrome (BD) is a controversial, chronic, and episodic condition that is autoimmune in origin and causes systemic vasculitis in the arteries and genital veins. BD is consistently associated with depression, with an incidence of 86% upon the first appearance of symptoms and disorders of the disease. However, few studies have looked at depression and other psychiatric disorders, such as anxiety, in the context of comorbidity with BD. The aim of this review is to identify articles that focus on the relation between BD and depression as a comorbidity. The studies found revealed a consistently high incidence of depression in the BD population, even when compared with other chronic pathologies including Rheumatoid Arthritis and Psoriasis, although there was a limitation in the use of scales and other tools for assessment and control of comorbid symptoms, moreover there are no studies linking the drugs used in the BD treatment of each patient and the symptoms present in each case. This review clearly shows the lack of research in which depression scores are analyzed in relation to the medications used by individual patients. Additionally, the use of additional scales is necessary to increase the knowledge about the nature and consequences of depression as comorbidity of BD.
24756550 Combined structure- and ligand-based pharmacophore modeling and molecular dynamics simulat 2014 May Matrix metalloproteinase-8 (MMP-8) is the key mediator in initiating type I collagen degradation and is associated with rheumatoid arthritis. In the present study, a pharmacophore hypothesis was developed based on selective non zinc binding inhibitors of MMP-8. The pharmacophore hypothesis was refined manually and validated by observing structures and the interactions of MMP-8 inhibitors. The refined pharmacophore model was able to discriminate the non-zinc binding inhibitors of MMP-8 with respect to other inhibitors. Hence this study proposes a combined structure- and ligand-based pharmacophore model that is suitable for retrieving the novel inhibitors of MMP-8. The pharmacophore hypothesis AADRH was used as query for retrieving potential compounds from the Zinc database and hits were selected based on the catalytic selective amino acid residues of Arg 222, and Tyr 227. We identified six compounds as potent inhibitors and their selectivity profile were checked against different subtypes of MMPs using the cross-docking method. Molecular dynamics results indicated that ZINC 00673680 forms a stable interaction with the key amino acid residues and avoids the zinc atom with a distance of 5.49 Å. Our computational study might be useful for further development of selective MMP-8 inhibitors.
24749538 Novel techniques in the development of osteoporosis drug therapy: the osteoclast ruffled-b 2014 May INTRODUCTION: Bone loss occurs in many diseases, including osteoporosis, rheumatoid arthritis and periodontal disease. For osteoporosis alone, it is estimated that 75 million people are afflicted worldwide, with high risks of fractures and increased morbidity and mortality. The demand for treatment consumes an ever-increasing share of healthcare resources. Successive generations of antiresorptive bisphosphonate drugs have reduced side effects, minimized frequency of dosing, and increased efficacy in halting osteoporotic bone loss, but their shortcomings have remained significant to the extent that a monoclonal antibody antiresorptive has recently taken a significant market share. Yet this latter, paradigm-shifting approach has its own drawbacks. AREAS COVERED: This review summarizes recent literature on bone-remodeling cell and molecular biology and the background for existing approaches and emerging therapeutics and targets for treating osteoporosis. The authors discuss vacuolar H(+)-ATPase (V-ATPase) molecular biology and the recent advances in targeting the osteoclast ruffled-border V-ATPase (ORV) for the development of novel antiresorptive drugs. They also cover examples from the V-ATPase-targeted drug discovery literature, including conventional molecular biology methods, in silico drug discovery, and gene therapy in more detail as proofs of concept. EXPERT OPINION: Existing therapeutic options for osteoporosis have limitations and inherent drawbacks. Thus, the search for novel approaches to osteoporosis drug discovery remains relevant. Targeting the ORV may be one of the more selective means of regulating bone resorption. Furthermore, this approach may be effective without removing active osteoclasts from the finely balanced osteoclast-osteoblast coupling required for normal bone remodeling.
24708914 Embitterment in patients with a rheumatic disease after a disability pension examination: 2014 May OBJECTIVES: Health care and vocational professionals regularly encounter patients with rheumatic diseases who are embittered after a disability pension examination. People who are embittered typically feel victimised, experience resentment and injustice, resist help, and have difficulty coping. Our objective was to examine the occurrence of embitterment in patients with rheumatic diseases after a disability pension examination and the association of embitterment with its possible determinants helplessness and illness invalidation at work. METHODS: The Illness Cognition Questionnaire (ICQ), Illness Invalidation Inventory (3*I), and Bern Embitterment Inventory were completed by patients who had 9 to 12 weeks earlier received the result of a disability pension examination. Diagnoses were fibromyalgia (n=103), rheumatoid arthritis (n=46), osteoarthritis (n=158), another rheumatic disease (n=62), and more than one rheumatic disease (n=187). Scores were compared to scores of reference groups. Hierarchical regression analyses were conducted. RESULTS: Eighteen to 27 percent of patients had high levels of embitterment with no differences between diagnostic groups (p=0.71). Helplessness (p<0.001), the two invalidation dimensions discounting and lack of understanding (p<0.001), and the combination of helplessness with these invalidation dimensions (p<0.01), were predictive of more embitterment. CONCLUSIONS: Our results suggest that, after a disability pension examination, embitterment is present in about one out of five patients with a rheumatic disease. This is problematic insofar as embitterment limits well-being, functioning, and the potential to reintegrate to work. To the extent that helplessness and invalidation at work are causal determinants of embitterment, interventions targeting these aspects may be key to reduce embitterment.
24697297 Role of MIF in myocardial ischaemia and infarction: insight from recent clinical and exper 2014 Aug First discovered in 1966 as an inflammatory cytokine, MIF (macrophage migration inhibitory factor) has been extensively studied for its pivotal role in a variety of inflammatory diseases, including rheumatoid arthritis and atherosclerosis. Although initial studies over a decade ago reported increases in circulating MIF levels following acute MI (myocardial infarction), the dynamic changes in MIF and its pathophysiological significance following MI have been unknown until recently. In the present review, we summarize recent experimental and clinical studies examining the diverse functions of MIF across the spectrum of acute MI from brief ischaemia to post-infarct healing. Following an acute ischaemic insult, MIF is rapidly released from jeopardized cardiomyocytes, followed by a persistent MIF production and release from activated immune cells, resulting in a sustained increase in circulating levels of MIF. Recent studies have documented two distinct actions of MIF following acute MI. In the supra-acute phase of ischaemia, MIF mediates cardioprotection via several distinct mechanisms, including metabolic activation, apoptosis suppression and antioxidative stress. In prolonged myocardial ischaemia, however, MIF promotes inflammatory responses with largely detrimental effects on cardiac function and remodelling. The pro-inflammatory properties of MIF are complex and involve MIF derived from cardiac and immune cells contributing sequentially to the innate immune response evoked by MI. Emerging evidence on the role of MIF in myocardial ischaemia and infarction highlights a significant potential for the clinical use of MIF agonists or antagonists and as a unique cardiac biomarker.
24649098 Twin studies on the effect of genetic factors on serum agalactosyl immunoglobulin G levels 2014 Mar The level of immunoglobulin G (IgG) lacking the terminal galactose, referred to as agalactosyl IgG, was found to be increased in chronic inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease (IBD), particularly in Crohn's disease, which is suggested to have a genetic component. This oligosaccharide modification of IgG is mainly regulated by the expression of glyco-genes; however, the association between genetic factors and changes in the IgG glycosylation has not been fully elucidated. The aim of the present study was to assess the role of genetics in this process by comparing the serum agalactosyl IgG levels between members of monozygotic and dizygotic twin pairs who underwent medical check-ups at the same time. The serum agalactosyl IgG level was assayed using high-performance liquid chromatography. Hematological and biochemical markers, including γ-glutamyltranspeptidase (γGTP), alanine aminotransferase (ALT) and white blood cell (WBC) count, were also measured. Although the serum γGTP levels (and, to a lesser extent, ALT and WBC levels) exhibited a correlation within monozygotic twin pairs, agalactosyl IgG levels were not found to be correlated between members of either type of twin pairs. Thus, the role of genetic factors in determining serum agalactosyl IgG levels may be less significant compared to the effect of environmental factors or the onset of inflammatory disease.
24551573 Protective effect of ethyl pyruvate on epididymal sperm characteristics, oxidative stress 2013 Oct BACKGROUND: Methotrexate (MTX) is an anti-metabolite drug widely used in treatment of neoplastic disorders, rheumatoid arthritis and psoriasis. The ester derivative, ethyl pyruvate (EP) is stable in solution and should function as an antioxidant and energy precursor. This study was conducted to evaluate the protective role of EP on sperm parameters, testosterone level and malondialdehyde (MDA) production in mice treated with MTX. METHODS: 32 adult male NMRI mice weighing 26±2 g were divided into 4 groups. Group 1 received 0.1 ml/mice/day of distilled water intraperitoneally for 30 days (ip). Group 2 was treated with methotrexate at a dose of 20 mg/kg once a week (ip) for 30 days. Group 3 was treated with ethyl pyruvate at a dose of 40 mg/kg/daily (ip) for 30 days. Group 4 was treated with methotrexate (20 mg/kg) once a week simultaneously with ethyl pyruvate 40 mg/kg for 30 days. The results were analyzed by oneway ANOVA. A p<0.05 was considered to be significant. RESULTS: The results showed significant (p<0.05) decrease in sperm count and sperm motility as well as testosterone concentration while sperm with damaged DNA and MDA concentration in mice treated with MTX in comparison with control and MX+EP groups increased significantly (p<0.05). Instead, MTX+EP group caused partial amelioration in all parameters mentioned above. CONCLUSION: Based on the present study, it can be concluded that MTX induced toxicity in sperm parameters and serum level of testosterone and increased MDA level. EP with its antioxidant properties could be administrated during treatment with MTX due to its protective effects on sperm parameters, plasma testosterone levels and lipid peroxidation.
24436785 Radiographic parameter analysis on modified sauvé-kapandji procedure. 2013 Feb Purpose The Sauvé-Kapandji (S-K) procedure is now an established treatment option for symptomatic distal radioulnar joint (DRUJ) dysfunction. However, for patients with poor bone quality (frequently as a result of advanced-stage rheumatoid arthritis [RA]), the conventional S-K procedure is difficult to perform without reducing the radioulnar diameter of the wrist, which may result in a loss of grip strength and pain over the proximal ulnar stump. The purpose of this study was to review the radiographic outcomes of patients who underwent a modified S-K procedure that involves rotating the resected ulnar segment 90 degrees and using it to bridge the gap between the sigmoid notch and the ulnar head. Methods The modified S-K procedure was performed in 29 wrists of 23 patients. Twenty-one patients had severe RA, while two had malunited radius fractures. The mean follow-up period was 43 months (range, 23 to 95). The radiographic evaluation included a measurement of the radioulnar width, the pseudarthrosis gap between the proximal and distal ulnar stump, the radioulnar distance, and the ulnar translation of the carpus. Results The radioulnar width of the wrist, pseudarthrosis gap, and radioulnar distance were well maintained throughout the period. A postoperative loss in the radioulnar width of the wrists appeared to correlate with a postoperative additional ulnar translocation of the carpus. Conclusion Narrowing of the radioulnar width of the wrist is a potential cause of progressive ulnar translocation of the carpus. The modified technique for the S-K procedure maintains the distal ulna in the proper position and provides sufficient ulnar support for the carpus. It is a useful reconstruction procedure in patients with severe RA with poor bone quality.
24300145 [Analyses of risk factors for deep vein thrombosis in lower extremities]. 2013 Aug 6 OBJECTIVE: To explore the risk factors of deep vein thrombosis (DVT) in lower extremities. METHODS: Retrospective data analyses were performed for a total of 1264 DVT patients at our department from January 2010 to December 2012. RESULTS: Among them, 984 cases (77.85%) were over 40 years old, no overt cause was found for 642 cases (50.79%), 142 cases (11.23%) had a clear history of trauma before onset (without surgery). Among 316 recurrent postoperative cases, there were the surgical histories of orthopedics (n = 142, 11.23%), gynecology (n = 90, 7.12%), general practice (n = 42, 3.32%), vascular (n = 23, 1.82%), urological (n = 12, 0.94%) and others (n = 7, 0.55%). Ten cases (0.79%) occurred after suffering bedridden chronic diseases. And 20 cases (1.58%) were caused by conditions during pregnancy or postpartum period.had Malignant tumors were found in 25 (1.98%) patients. After long-term uses of hormones, 10 patients (0.79%) of rheumatoid arthritis had a recurrence.Owing to varicose veins, 27 patients (2.14%) recurred. Eight patients (0.63%) had a history of drug abuse, 2 cases (0.16%) suffered depression and 62 cases (4.9%) were recurrent. CONCLUSION: There are many causative factors of DVT so that prevention is of great importance. We should pay more attention to the prevention and treatment of high-risk DVT patients.
24159346 Tai chi chuan in medicine and health promotion. 2013 Tai Chi Chuan (Tai Chi) is a Chinese traditional mind-body exercise and recently, it becomes popular worldwide. During the practice of Tai Chi, deep diaphragmatic breathing is integrated into body motions to achieve a harmonious balance between body and mind and to facilitate the flow of internal energy (Qi). Participants can choose to perform a complete set of Tai Chi or selected movements according to their needs. Previous research substantiates that Tai Chi has significant benefits to health promotion, and regularly practicing Tai Chi improves aerobic capacity, muscular strength, balance, health-related quality of life, and psychological well-being. Recent studies also prove that Tai Chi is safe and effective for patients with neurological diseases (e.g., stroke, Parkinson's disease, traumatic brain injury, multiple sclerosis, cognitive dysfunction), rheumatological disease (e.g., rheumatoid arthritis, ankylosing spondylitis, and fibromyalgia), orthopedic diseases (e.g., osteoarthritis, osteoporosis, low-back pain, and musculoskeletal disorder), cardiovascular diseases (e.g., acute myocardial infarction, coronary artery bypass grafting surgery, and heart failure), chronic obstructive pulmonary diseases, and breast cancers. Tai Chi is an aerobic exercise with mild-to-moderate intensity and is appropriate for implementation in the community. This paper reviews the existing literature on Tai Chi and introduces its health-promotion effect and the potential clinical applications.
24154764 Effects of mulberry ethanol extracts on hydrogen peroxide-induced oxidative stress in panc 2014 Jan Reactive oxygen species (ROS) are key mediators of mammalian cellular damage and are associated with diseases such as aging, arteriosclerosis, inflammation, rheumatoid arthritis and diabetes. Type 1 diabetes develops upon the destruction of pancreatic β-cells, which is partly due to ROS activity. In this study, we investigated the cytoprotective and anti-oxidative effects of fractionated mulberry extracts in mouse insulin-producing pancreatic β-cells (MIN6N cells). Treatment with hydrogen peroxide (H2O2) induced significant cell death and increased intracellular ROS levels, lipid peroxidation and DNA fragmentation in the MIN6N cells. Fractionated mulberry extracts significantly reduced the H2O2-dependent production of intracellular ROS, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and lipid peroxidation. In addition, mulberry extracts inhibited DNA fragmentation induced by H2O2. Thus, the antioxidant properties of mulberry extracts in pancreatic β-cells may be exploited for the prevention or treatment of type 1 diabetes.
24059223 Pharmacophore-based 3DQSAR and molecular docking studies to identify new non-peptidic inhi 2014 Cathepsin S (CatS) is one of the 11 cysteine protease cathepsins which are expressed predominantly in antigen presenting cells (APC) namely B cells, macrophages and dendritic cells. CatS has been implicated in a wide range of diseases such as rheumatoid arthritis, multiple sclerosis, neuropathic pain and allergic disorders. In the present study, pharmacophore mapping studies followed by 3D QSAR analysis was undertaken for a large set of 161 molecules reported to be non-covalent binding and non-peptidic inhibitors of CatS. The activity range (IC50) of these compounds was between 2 picomolar to 100 nanomolar. A five point pharmacophore model with three hydrogen bond acceptors (A), one hydrogen bond donor (D) and one hydrophobic (H) group as pharmacophoric features was developed. The generated model showed reasonable predictive power, with a correlation coefficient Q(2) of 0.607. The model was further confirmed by an external test-set validation that showed statistically significant parameters r(2) value of 0.840 with the R(2)p value of 0.812 and r(2)m value of 0.530. Validated model was then used to identify six diverse non-peptidic scaffolds from a commercial structure database by the analyses of parameters such as pharmacophore fitness, docking score, interacting amino acids and ADME properties to achieve prototypical lead compounds.
24021708 Biologics in relapsing polychondritis: a case series. 2013 Nov OBJECTIVES: To describe the effects of biologics in an unbiased series of relapsing polychondritis cases. METHODS: We extracted all the cases encoded 'polychondritis' from the computerized medical files of our department. The relapsing polychondritis diagnosis was confirmed using Damiani's criteria. Patients treated with biologics were evaluated for efficacy and adverse drugs reactions until October 2012. RESULTS: Nine patients were exposed to 22 biologics as corticosteroid-sparing drugs. Biologics were used at the same doses as in rheumatoid arthritis. Mean duration of exposure to biologics was 28 months. A TNF-antagonist was most frequently used as first-line biologic therapy (7/9), leading to partial or complete efficacy in six cases (85.7%). Loss of efficacy occurred in 5 cases. Abatacept (n=3) and tocilizumab (n=2) were effective as second-line biologic therapy while anakinra (n=2) and certolizumab (n=1) were not. Seven serious adverse drug reactions occurred, including 5 infections. CONCLUSIONS: TNF-α antagonists may be proposed earlier in relapsing polychondritis to spare corticosteroids. Switching to another biologic can be proposed in case of loss of efficacy. Tocilizumab or abatacept can be proposed as third-line therapy. The benefit-to-risk ratio of biologics in relapsing polychondritis should be evaluated prospectively.
23919214 Inflammatory bowel disease: An archetype disorder of outer environment sensor systems. 2013 Aug 6 The pathogenesis of the two inflammatory bowel diseases (IBDs) phenotypes ulcerative colitis (UC) and Crohn's disease (CD) has remained elusive, thus frustrating attempts at defining a cure. IBD often presents as a complex inflammatory process wherein colon lesions (UC) or widespread ulceration and fissure (CD) might be accompanied by ancillary extra-intestinal manifestations involving the eye, skin, joints or liver, but also by full-blown "autoimmune" disorders from psoriasis and multiple sclerosis to rheumatoid arthritis; attempts at unraveling a link or a hierarchical order in these entities have proven almost fruitless. More recently, the input of genetics has suggested that the IBDs might be multi-organ inflammatory processes, elicited by a large number of low-penetrance susceptibility genes, with environmental factors needed to induce full-blown disease. At a noteworthy exception to this rule, the description of the nucleotide-oligomerization domain (NOD) gene mutations in CD came at the beginning of the 2000s: the NOD-LRR are part of a highly conserved microbial sensor system which respond to bacterial peptidoglycans by mounting an inflammatory response. At least in Caucasian patients, the prevalently loss-of-function mutation of NOD permitted to unexpectedly define CD as an immune deficiency state, and upon its recent description in apparently unrelated disorders such as the Blau syndrome (a granulomatous pediatric syndrome), and perhaps in psoriasis and chronic obstructive pulmonary disorders, has contributed to revolutionize our view of IBD and CD in particular. The latter affection, together with psoriasis and chronic pulmonary disease can now be included into a newly identified category named "barrier organ disease", wherein a barrier organ is defined as a large mucosal or epithelial surface with an abundant metagenomic microbial population and an underneath reactive tissue, the whole structure being in contact with the outer environment and capable to react to it. Personalized treatments and empowerment of research across different disease phenotypes should be the advantages of this novel mindset.