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ID PMID Title PublicationDate abstract
23344020 Immunological effects of Oenothein B, an ellagitannin dimer, on dendritic cells. 2012 Dec 20 Oenothein B is a unique macrocyclic ellagitannin dimer that has been found in various medicinal plants belonging to Onagraceae, Lythraceae, and Myrtaceae, with diverse biological activities. The immunological effects of tannins in terms of cytokine-release from macrophages and monocytes have been discussed, while the effects on other immunocompetent cells have been the subject of minimal investigation. We evaluated the immunomodulatory effects induced by tannin treatment in human dendritic cells (DCs), which play a critical role in the initial immune response, by measuring the changes in cytokine production, cell differentiation, and cell viability. Oenothein B showed significant down-regulation of the expression of cell surface molecules, CD1a and CD83, suggesting the inhibition of DC differentiation and/or maturation. The suppressive effect on DCs was associated with the induction of apoptosis without the activation of caspase-3/7, 8, and 9, and this was supported by the morphological features indicating significant nuclear condensation. Oenothein B also markedly suppressed the production of inflammatory cytokines, such as IL-1β and IL-6, in a dose-dependent manner. These data may, in part, be able to explain the traditional use of tannin-containing medicinal plants for the treatment of a variety of inflammatory diseases, including inflammatory bowel disease, celiac disease, and rheumatoid arthritis.
23295687 Inflammatory bowel disease: dysfunction of autophagy? 2012 Recent genome-wide association studies identified single nucleotide polymorphisms within gene loci, encoding autophagy genes, e.g. the autophagy-related 16-like 1 (ATG16L1) and the immunity-related GTPase family M (IRGM), as an important risk factor for the onset of chronic inflammatory diseases such as Crohn's disease (CD) or rheumatoid arthritis. CD is characterized by a breakdown of the intestinal epithelial barrier function leading to an overwhelming and uncontrolled immune response to bacterial antigens. Autophagy, and therefore ATG16L1 and IRGM, are critically involved in the innate immune response to invading pathogens. Dysfunction of these molecules results in the increased survival of intracellular bacteria, defective antigen presentation and proinflammatory cytokine secretion. Interestingly, autophagy can also be regulated by other CD susceptibility genes, such as nucleotide oligomerization domain 2 or protein tyrosine phosphatase nonreceptor type 2, and the presence of the CD-associated variations within these genes results in comparable effects. ATG16L1 also plays a crucial role in maintaining Paneth cell function and morphology, while IRGM seems to be associated with mitochondrial function and apoptosis. Dysfunction of these molecules, i.e. of autophagy in vivo, is clearly associated with the increased bacterial infection and the onset of colitis. Interestingly, the phenotype of aberrant Paneth cells and dextran sodium sulphate-induced colitis in ATG16L1 hypomorphic mice closely resembles human CD. Taken together, the available data strongly suggest an important role for autophagy in maintaining intestinal homeostasis, and dysfunction of autophagy seems to be a major risk factor for the onset of chronic intestinal inflammation.
23205339 Rituximab in the treatment of pemphigus vulgaris. 2012 Dec INTRODUCTION: Rituximab is increasingly used in patients with pemphigus vulgaris (PV) who are nonresponders to conventional therapy. METHODS: A PubMed search was conducted using the words pemphigus vulgaris and rituximab therapy from papers published between 2000 and 2012. Two protocols were used. In the lymphoma protocol, patients received four weekly infusions of rituximab (dose 375 mg/m(2)). The rheumatoid arthritis (RA) protocol consisted of two infusions of 1,000 mg each 15 days apart. The variables recorded from each study included clinical remission off or on therapy, relapse rate, incidence of serious adverse events, concomitant therapies, duration of follow-up, and when available, levels of B cells and autoantibodies. RESULTS: Forty-two studies were found, which reported 272 patients; 180 were treated by the lymphoma protocol and 92 by the RA protocol. Both protocols were effective in treating recalcitrant PV. The lymphoma protocol had a lower response rate, relapse rate and serious infections, but higher mortality, and there were nonresponders. The RA protocol produced a higher response rate, relapse rate, number of infections, but lower mortality rate, and lacked nonresponders. The cumulative follow-up for patients treated with the lymphoma protocol was 15.44 months (range 1-41) and 21.04 months (range 8.35-29) for the RA protocol. A major concern in both protocols was the high infection rates, some of which were fatal. A different protocol using a combination of rituximab with intravenous immunoglobulin in a defined manner with a definitive endpoint, used in a limited cohort of patients, showed promising results. CONCLUSION: Neither protocol produced a sustained clinical remission and both required continued systemic therapy. Before initiation of treatment, physicians should have a specific goal and endpoint and be aware of its potential side effects and lack of information on its long-term effects. Patients should be carefully monitored during and after therapy.
23164158 Aquaporin 1 (AQP1) expression in experimentally induced osteoarthritic knee menisci: an in 2013 Apr Osteoarthritis (OA) of the knee is a major problem in our society. The development of new treatment options for OA is limited, because the pathophysiological mechanisms are not clearly understood, especially on the molecular level. Aquaporin 1 (AQP1) is a specific protein channels for water transport; it is expressed in articular chondrocytes, human synovitis, in chondrocytes of patients with rheumatoid arthritis or OA and in chondrocyte-like cells of human intervertebral disc. The aim of this study was to investigate the expression of AQP1, through immunohistochemistry, immunocytochemistry and Western blot, in experimentally induced OA knee menisci. AQP1 was studied in vivo in knee OA menisci from 36 rats that underwent medial or lateral meniscectomy, and in vitro on fibrochondrocytes derived from knee OA menisci rats. OA in rats was experimentally induced and tested by histomorphometric analysis. Histological results demonstrated structural alterations in OA menisci accompanied by a very strong AQP1 immunohistochemical and immunocytochemical staining. The Western blot analysis confirmed a strong expression of AQP1 in OA fibrochondrocytes cells. The results of the present research suggest that an activation of AQP1, induced by the OA process, may represent an endogenous mechanism, which can be used to control the tissue degeneration within OA articular joints.
23125954 Connective Tissue Disease-associated Interstitial Lung Disease: A review. 2012 Sep 21 Interstitial lung disease (ILD) is commonly encountered in patients with connective tissue diseases (CTD). Besides the lung parenchyma, the airways, pulmonary vasculature and structures of the chest wall may all be involved, depending on the type of CTD. As a result of this so-called multi-compartment involvement, airflow limitation, pulmonary hypertension, vasculitis and extrapulmonary restriction can occur alongside fibro-inflammatory parenchymal abnormalities in CTD. Rheumatoid arthritis (RA), systemic sclerosis (SSc), poly-/dermatomyositis (PM/DM), Sjögren's syndrome (SjS), systemic lupus erythematosus (SLE), and undifferentiated (UCTD) as well as mixed connective tissue disease (MCTD) can all be associated with the development of ILD. Non-specific interstitial pneumonia (NSIP) is the most commonly observed histopathological pattern in CTD-ILD, but other patterns including usual interstitial pneumonia (UIP), organizing pneumonia (OP), diffuse alveolar damage (DAD) and lymphocytic interstitial pneumonia (LIP) may occur. Although the majority of patients with CTD-ILD experience stable or slowly advancing ILD, a small yet significant group exhibits a more severe and progressive course. Randomized placebo-controlled trials evaluating the efficacy of immunomodulatory treatments have been conducted only in SSc-associated ILD. However, clinical experience suggests that a handful of immunosuppressive medications are potentially effective in a sizeable portion of patients with ILD caused by other CTDs. In this manuscript, we review the clinical characteristics and management of the most common CTD-ILDs.
23001806 Diffuse lung diseases in cigarette smokers. 2012 Oct Cigarette smoking is a recognized causative agent or precipitant of specific diffuse lung diseases characterized by bronchiolar and interstitial lung inflammation. Respiratory bronchiolitis-associated interstitial lung disease and pulmonary Langerhans cell histiocytosis are now considered smoking-induced diffuse lung diseases. Desquamative interstitial pneumonia is also recognized as a smoking-induced interstitial pneumonia in most cases. These disorders affect relatively young adult smokers and may be progressive. Although distinguishable by histopathological and radiographic features, significant overlap occurs in many cases with chest radiography and lung histology showing overlapping features of smoking-related bronchiolar and interstitial lung injury. Cigarette smoking is also recognized as an important precipitant of many acute eosinophilic pneumonia cases. Smokers are at higher risk of developing fibrotic interstitial lung diseases such as idiopathic pulmonary fibrosis and rheumatoid arthritis-associated interstitial lung disease. Certain smokers also develop combined emphysema and lung fibrosis. The avoidance of primary and second-hand cigarette smoke is a critical component of management for patients afflicted with these smoking-induced diffuse lung diseases. The role of corticosteroids and other immunosuppressive treatments in the management of smoking-related interstitial lung diseases remains poorly defined and should be reserved for individuals with progressive disease despite smoking cessation. Understanding mechanisms by which tobacco induces diffuse lung pathology is critical in the pursuit of novel therapeutic approaches for these diseases.
22899963 Inhibition of Neurotoxic Secretory Phospholipases A(2) Enzymatic, Edematogenic, and Myotox 2012 Secretory phospholipases A(2) (sPLA(2)) exert proinflammatory actions through lipid mediators. These enzymes have been found to be elevated in many inflammatory disorders such as rheumatoid arthritis, sepsis, and atherosclerosis. The aim of this study was to evaluate the effect of harpalycin 2 (Har2), an isoflavone isolated from Harpalyce brasiliana Benth., in the enzymatic, edematogenic, and myotoxic activities of sPLA(2) from Bothrops pirajai, Crotalus durissus terrificus, Apis mellifera, and Naja naja venoms. Har2 inhibits all sPLA(2) tested. PrTX-III (B. pirajai venom) was inhibited at about 58.7%, Cdt F15 (C. d. terrificus venom) at 78.8%, Apis (from bee venom) at 87.7%, and Naja (N. naja venom) at 88.1%. Edema induced by exogenous sPLA(2) administration performed in mice paws showed significant inhibition by Har2 at the initial step. In addition, Har2 also inhibited the myotoxic activity of these sPLA(2)s. In order to understand how Har2 interacts with these enzymes, docking calculations were made, indicating that the residues His48 and Asp49 in the active site of these enzymes interacted powerfully with Har2 through hydrogen bonds. These data pointed to a possible anti-inflammatory activity of Har2 through sPLA(2) inhibition.
22842297 The role of illness perception and emotions on quality of life in fibromyalgia compared wi 2012 Jul 19 OBJECTIVE: Fibromyalgia syndrome (FMs) is a chronic widespread pain condition that can negatively impact on all aspects of patient's life. The purpose of this study was: first, to evaluate illness perception (IP), quality of life (QoL) and affective-emotive variables (EAV) of patients with FM; and second, to compare these variables to different pain conditions. METHODS: Consecutive 34 women (mean age 47.4±8.3 years) affected by FM were enrolled for the study from December 2009 to May 2011. IP was evaluated by means of the Revised Illness Perception Questionnaire, QoL through Nottigham Health Profile and EAV through the Beck Depression Inventory. Scores were compared with rheumatoid arthritis (RA) (n=20; mean age 53±12.8 years) and low back pain (LBP) (n=20; 51.3±7.8 years) groups. RESULTS: FM patients scored higher than RA and LBP groups on IP (Identity scale mean: FM=8.8±2.3, AR=5.5±3.3, LBP=4.1±2.9; Kruskal-Wallis=24.42). Moreover FM patients show higher EAV (mean FM=21±9.6, AR=8.9±5.6, LBP=14.9±6.5; Kolmogorov-Smirnov Z=2.17) and QoL (Pain scale mean: FM=74.2±24.1; AR=35.7±19.9; LBP=56.5±20.4; Kolmogorov-Smirnov Z=2.27; Energy scale mean: FM=86.2±28.5; AR=46.8±35.4; LBP=61.6 ±63.7; Kolmogorov-Smirnov Z=1.98) than RA group. CONCLUSIONS: Our study highlighted dysfunctional IP, low QoL, high EAV scores in FM patients and the significant relations between these variables. Research results provided support for relevance of a multidisciplinary approach to the management of FM, including psychological interventions, according to a biopsychosocial perspective.
22840916 Are patients with inflammatory bowel disease at increased risk of coronary artery disease? 2012 Oct The inflammatory state of atherosclerosis has been established as those with chronic inflammatory diseases, such as rheumatoid arthritis and systemic lupus erythematosus, who are at increased risk of coronary artery disease. A systematic search was conducted to retrieve high-quality, peer-reviewed studies of inflammatory bowel disease and coronary artery disease. Recent literature supports an association between inflammatory bowel disease and coronary artery disease. While hypertension increases the risk of coronary artery disease in inflammatory bowel disease patients, other typical risk factors have not been confirmed, and markers of inflammation may predict coronary artery disease risk in this population. Common cardiovascular drugs such as statins and angiotensin-converting enzyme inhibitors may have dual potential for controlling inflammatory bowel disease and preventing or treating coronary artery disease. Large, prospective, longitudinal studies can help to determine the true prevalence of coronary artery disease in this population and confirm risk factors. In the absence of such evidence, physicians should be cognizant of increased coronary artery disease risk in inflammatory bowel disease patients without traditional risk factors and consider primary preventive strategies.
22762008 IL-18 Serum Level in Adult Onset Still's Disease: A Marker of Disease Activity. 2012 Introduction. Immunological factors seem to play a pivotal role in Adult Onset Still's Disease (AOSD). Among all, IL-18 cytokine is overexpressed and drives the inflammatory process. Objective. We aimed to investigate the levels of IL-18 in sera of Italian patients with AOSD and to assess its possible role as a marker of disease activity. Methods. IL-18 serum levels were determined by ELISA in 26 Italian patients with AOSD. Disease activity was assessed using Pouchot's criteria. As controls, 21 patients with Rheumatoid Arthritis (RA), 21 patients with Sjogren's Syndrome (SS), 20 patients with Systemic Lupus Erythematosus (SLE), and 21 healthy subjects (normal human sera, NHS) were evaluated. Results. IL-18 serum levels were significantly higher in patients with active AOSD than in non-active (P = 0.001) and control groups (RA P = 0.0070, SS P = 0.0029, SLE P = 0.0032, NHS P = 0.0004). A significant correlation between IL-18 serum levels and disease activity (P < 0.0001), and laboratory parameters as ferritin (P = 0.0127) and C-reactive protein (P = 0.0032) was demonstrated. Conclusions. Higher levels of IL-18 are detected in active AODS patients and correlate with disease activity and inflammatory laboratory features. ROC-AUC analysis of the serum concentration of IL-18 suggests that it can be considered a diagnostic marker of AOSD. This paper supports the targeting of this cytokine as a possible therapeutic option in AOSD.
22650374 TNF-α inhibitors with anti-oxidative stress activity from natural products. 2012 Tumor necrosis factor-α (TNF-α) is a major cytokine involved in the inflammatory response. Elevated TNF-α expression has been found to be associated with the development of diabetes, septic shock, tumorigenesis, cardiovascular diseases, rheumatoid arthritis and inflammatory bowel disease. In the past decade, the success of anti-TNF-α biologics has valuated the importance of the blockade of TNF-α production in the treatment of patients with various inflammatory diseases. Oxidative stress is another important element in oxidative/inflammatory responses that directly linked to oxidation of proteins, DNA and lipids. The increased oxidant levels could activate nuclear factor-kappaB (NFκ-B), signal transduction and gene expression of TNF-α, interleukin-1 (IL-1) and other pro-inflammatory cytokines. Therefore, TNF-α inhibitors with anti-oxidative stress activity may have multiple target effect that could exhibit excellent anti-inflammatory activities. The review briefly highlights the pathological roles of TNF-α and oxidative stress in inflammation, and covers those natural products as TNF-α inhibitors capable of anti-oxidative stress activity.
22552601 Impact of human granulocyte and monocyte isolation procedures on functional studies. 2012 Jul One of the first lines of defense against infection is the activation of the innate immune system. It is becoming clear that autoimmune diseases, such as rheumatoid arthritis and Crohn's disease, may be caused by disturbed innate immunity, and relating granulocyte and monocyte functions to the patient genotype has become an important part of contemporary research. Although it is essential to move this field forward, a systematic study comparing the efficacy and suitability for functional studies of the various available protocols for the isolation of these immune cells has not been performed. Here, we compare human granulocyte functionality under three enrichment protocols: (i) Ficoll density gradient centrifugation, (ii) anti-CD15 antibody-conjugated microbeads (positive selection), and (iii) Polymorphoprep. Primary monocytes were isolated in parallel using (i) anti-CD14 magnetic microbeads, (ii) non-monocyte depletion by antibody-conjugated magnetic microbeads (negative selection), (iii) RosetteSep antibody cocktail, and (iv) the classical adherence protocol. The best results in terms of purity and cell functionality were obtained with positive selection by magnetic microbeads for both human granulocytes and monocytes. Whereas phagocytosis of Escherichia coli bacteria was identical in all isolation procedures tested, the granulocyte respiratory burst was higher in positively selected cells. In addition, different granulocyte enrichment procedures affect cell surface receptor expression to different extents. In toto, we propose that positive selection of granulocytes and monocytes be adopted as the procedure of choice for studies of human granulocyte and monocyte functions but caution investigators to be aware of possible alterations in cell phenotypes with different isolation procedures.
22469470 Sirtuin inhibition attenuates the production of inflammatory cytokines in lipopolysacchari 2012 Apr 20 In several inflammatory conditions such as rheumatoid arthritis or sepsis, the regulatory mechanisms of inflammation are inefficient and the excessive inflammatory response leads to damage to the host. Sirtuins are class III histone deacetylases that modulate the activity of several transcription factors that are implicated in immune responses. In this study, we evaluated the impact of sirtuin inhibition on the activation of lipopolysaccharide (LPS)-stimulated J774 macrophages by assessing the production of inflammatory cytokines. The pharmacologic inhibition of sirtuins decreased the production of tumour necrosis factor-alpha (TNF-α) interleukin 6 (IL-6) and Rantes. The reduction of cytokine production was associated with decreased nuclear factor kappa B (NF-κB) activity and inhibitor kappa B alpha (IκBα) phosphorylation while no impact was observed on the phosphorylation status of p38 mitogen-activated kinase (p38 MAPK). This work shows that sirtuin pharmacologic inhibitors are a promising tool for the treatment of inflammatory conditions.
22393540 Collagen IV in Normal Skin and in Pathological Processes. 2012 Jan CONTEXT: Type IV collagen is a type of collagen found primarily in the skin within the basement membrane zone. The type IV collagen C4 domain at the C-terminus is not removed in post-translational processing, and the fibers are thus link head-to-head, rather than in a parallel fashion. Also, type IV collagen lacks a glycine in every third amino-acid residue necessary for the tight collagen helix. Thus, the overall collagen-IV conformation is structurally more pliable and kinked, relative to other collagen subtypes. These structural features allow collagen IV to form sheets, which is the primary structural form found in the cutaneous basal lamina. There are six human genes associated with collagen IV, specifically COL4A1, COL4A2, COL4A3, COL4A4, COL4A5 and COL4A6. The aim of this review is to highlight the significance of this protein in normal skin, and in selected diseases. RESULTS: The alpha 3 protein constituent of type IV collagen is thought to be the antigen implicated in Goodpasture's syndrome, wherein the immune system attacks the basement membranes of the renal glomeruli and pulmonary alveoli. In addition, mutations to the genes coding for type IV collagen lead to the Alport syndrome. Furthermore, autoantibodies directed against denatured human type IV collagen have been described in rheumatoid arthritis, scleroderma, and SLE. Structural studies of collagen IV have been utilized to differentiate between subepidermal blistering diseases, including bullous pemphigoid, acquired epidermolysis bullosa, anti-epiligrin cicatricial pemphigoid, and bullous lupus erythematosus. Collagen IV is also of importance in wound healing and in embryogenesis. CONCLUSIONS: Pathological studies have demonstrated that minor structural differences in collagen IV can lead to distinct, clinically different diseases.
22313234 Pathogenesis and treatment of leukemia: an Asian perspective. 2012 Mar INTRODUCTION: Leukemias occur worldwide, but there are important geographic differences in incidences. AREAS COVERED: Three leukemias with special Asian perspectives, acute promyelocytic leukemia (APL), T-cell large granular lymphocyte (T-LGL) leukemia and NK-cell leukemia. EXPERT OPINION: In APL, China has made contributions in discovering the efficacy of all-trans retinoic acid (ATRA) and arsenic trioxide. Some APL patients are potentially curable after treatment with ATRA or arsenic trioxide as a single agent. Combined treatment of APL with ATRA and arsenic trioxide induces remission with deeper molecular response. An oral formulation of arsenic trioxide is available, making outpatient treatment feasible. Future regimens for APL should examine how ATRA and arsenic trioxide can be optimally combined with other synergistic drugs. Asian patients with T-LGL leukemia present more frequently with pure red cell aplasia, but less frequently with neutropenia, recurrent infection, splenomegaly and rheumatoid arthritis as compared with Western patients. These differences have potential effects on treatment and disease pathogenesis. NK-cell leukemia is rapidly fatal and occurs almost exclusively in Asian and South American patients. Conventional anthracycline-based chemotherapy designed for B-cell lymphomas do not work in NK-cell leukemias. Novel therapeutic approaches targeting cellular signaling pathways or preferentially upregulated genes are needed to improve outcome.
22274560 Increased expression of alpha 1-anti-trypsin in the synovial tissues of patients with anky 2012 Jan OBJECTIVES: Evidence indicates that the hyperplasia and inflammation of synovial tissues are significantly related to the pathogenic process of ankylosing spondylitis (AS). Using a proteomics approach, we detected a significantly increased expression of alpha 1-anti-trypsin (ATA1) in synovial membranes of patients with AS. METHODS: We continued to investigate the expression level and location of ATA1 in synovial tissue of AS. We also investigated the genetic effect of the gene encoding ATA1 on AS. Western blot analysis was applied to determine the expression of ATA1 in synovial tissues by comparing the expression profiles of AS (n=8), rheumatoid arthritis (RA, n=9) and osteoarthritis (OA, n=9) samples. Immunohistochemistry was used to localise the expression of ATA1 in the synovial membrane. Taqman method was used to genotype tag SNPs (rs2753934, rs2749531 and rs6575424) with 56 AS cases, 260 RA cases and 160 healthy controls. RESULTS: We detected an increased expression of ATA1 in synovial membranes of AS as compared with samples from RA and OA. We immuno-localised the significant expression of ATA1 in AS tissues. No significant association was found between the ATA1 polymorphism and AS or RA. Haplotype analysis did not reveal a haplotype to be associated with AS or RA. CONCLUSIONS: It has been reported that ATA1 is related with inflammation and new bone formation, two important features of AS. The current findings suggest that ATA1 contributes to the pathogenesis of AS by up-regulating the gene expression in the synovial tissues.
22230480 Targeting the Apo2L/TRAIL system for the therapy of autoimmune diseases and cancer. 2012 Jun 1 Apo 2 ligand/tumor necrosis factor (TNF)-related apoptosis-inducing ligand (Apo2L/TRAIL), is a member of the TNF family of cytokines, which can induce apoptotic cell death in cells expressing at least one of their specific death receptors, DR4 (TRAIL-R1) or DR5 (TRAIL-R2). In the last decade, the Apo2L/TRAIL system of apoptosis has attracted significant interest as a potential drug-targeting pathway for human therapy, due to the ability of that cytokine to trigger apoptosis in various types of cancer cells while displaying low or no toxicity to normal cells. Recent results suggest that manipulating the Apo2L/TRAIL system may be also useful for the treatment of inflammatory disorders such as rheumatoid arthritis. For its possible therapeutic use, a number of receptor-specific Apo2L/TRAIL molecular variants and agonistic monoclonal antibodies have been developed, and some of them are in clinical trials. In addition, Apo2L/TRAIL-resistant tumors can be sensitized to Apo2L/TRAIL by selected novel or classical chemotherapeutic agents, opening new possibilities for combined therapies. We will briefly review the current status of Apo2L/TRAIL-based therapies for human disease, their promises and limitations.
22228448 Effect of autoimmune diseases on mortality and survival in subsequent digestive tract canc 2012 Aug BACKGROUND: Patients with some autoimmune diseases (AIDs) are at increased risk of cancer, possibly a result of an underlying dysregulation of the immune system, medication, treatment or, probably, surveillance bias. Data on cancer mortality and survival in patients previously diagnosed with AIDs would provide novel information on these comorbidities and their clinical implications. PATIENTS AND METHODS: Standardized mortality ratios (SMRs) and hazard ratios (HRs) were calculated for subsequent deaths from seven digestive tract cancers between 1964 and 2008 in patients hospitalized for any of 33 AIDs. RESULTS: There were 33 increased SMRs for specific cancers after a defined AID; similarly, 21 HRs were increased. Both the SMR and HR were increased after 10 autoimmune disorders, including pernicious anemia, systemic lupus erythematosus and psoriasis. Increased SMRs and unchanged HRs were noted for 23 cancers. Myasthenia gravis was associated with SMRs for five cancers but no increases in HRs. For nine cancers, including esophageal cancer after ulcerative colitis and rheumatoid arthritis, the SMR was unchanged but the HR increased. CONCLUSIONS: The increases in SMRs provide evidence that cancer risks were truly increased and largely unaffected by surveillance bias. The prognostic survival data should contribute to clinical evaluation and therapeutic planning.
22177232 Twin studies in autoimmune disease: genetics, gender and environment. 2012 May Twin studies are powerful tools to discriminate whether a complex disease is due to genetic or environmental factors. High concordance rates among monozygotic (MZ) twins support genetic factors being predominantly involved, whilst low rates are suggestive of environmental factors. Twin studies have often been utilised in the study of systemic and organ specific autoimmune diseases. As an example, type I diabetes mellitus has been investigated to establish that that disease is largely affected by genetic factors, compared to rheumatoid arthritis or scleroderma, which have a weaker genetic association. However, large twin studies are scarce or virtually non-existent in other autoimmune diseases which have been limited to few sets of twins and individual case reports. In addition to the study of the genetic and environmental contributions to disease, it is likely that twin studies will also provide data in regards to the clinical course of disease, as well as risk for development in related individuals. More importantly, genome-wide association studies have thus far reported genomic variants that only account for a minority of autoimmunity cases, and cannot explain disease discordance in MZ twins. Future research is therefore encouraged not only in the analysis of twins with autoimmune disease, but also in regards to epigenetic factors or rare variants that may be discovered with next-generation sequencing. This review will examine the literature surrounding twin studies in autoimmune disease including discussions of genetics and gender.
22097097 Association of Pap smear abnormalities with autoimmune disorders. 2011 May 15 Recently, it is hypothesized that there might be an association between immunological disorders and cervical premalignant and malignant abnormalities. Related studies have been generally focused on some particular autoimmune disease, specially the Systemic Lupus Erythematosus (SLE). This study aimed at comparing the rate of Pap smear abnormalities in female patients with autoimmune diseases and normal counterparts. In a case-control setting, 118 female patients with various autoimmune diseases (the case group) and 118 healthy female counterparts (the control group) were recruited in Tabriz Imam Reza Teaching Centre in a 24 months period of time. The two groups were matched for demographics and known risk factors of cervical malignancy. Frequencies of abnormal Pap smear testing were compared between the two groups. The autoimmune disorders were SLE (74 patients), rheumatoid arthritis or RA (32 patients), systcmic sclerosis or SS (7 patients) and ankylosing spondylitis or AS (5 patients) in the case group. Frequency of abnormal Pap smear testing was significantly higher in the case group comparing with that in the controls (7.6% vs. 1.7%; p = 0.03). Frequency of abnormal Pap smear testing was higher in the patients with SLE (8.1%) and RA (9.3%) comparing with that in the controls; However, these differences were marginally nonsignificant (p = 0.06 and p = 0.07, respectively). Frequency of cases with abnormal Pap smear testing was not statistically different between the autoimmune disorders (p = 0.99). Based on these findings and in conclusion, there might be an association between the autoimmune disorders and occurrence of premalignant or malignant lesions in cervix. Further studies with larger samples sizes are recommended.