Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 18599392 | Comparative studies on the interplay of testosterone, estrogen and progesterone in collage | 2008 Oct | Rheumatoid arthritis (RA) is a sexually dimorphic autoimmune disorder exhibiting a higher disease prevalence and severity among females. This study was carried out to understand the role of the major sex hormones viz., testosterone, estrogen and progesterone on the severity in arthritis. The interplay of the sex hormones was studied in a rat model of collagen induced arthritis (CIA). The parameters used for analyzing the disease severity included paw volume, radiology, histopathology of joint, markers for bone turnover, cytokine profile, levels of pain mediator (prostaglandin E(2)) and immune response to type II collagen. Arthritis induction to castrated and ovariectomised rats resulted in enhanced inflammation thereby indicating the importance of sex hormones. Treatment with physiological doses of dihydrotestosterone and estrogen attenuated the inflammation, with estrogen exhibiting higher potency. Progesterone was not shown to have any significance in disease modification; however, when progesterone was administered in combination with estrogen, the protective effects of estrogen were noticed to decrease. | |
| 17986412 | Elbow arthroscopy: where are we now? | 2007 Nov | Elbow arthroscopy has developed over the past several years. Indications have evolved from simple loose body removal to the treatment of rheumatoid arthritis. There have been few published reports of elbow arthroscopy compared to reports of knee or shoulder arthroscopy. Complications are more frequently reported after elbow arthroscopy than after arthroscopy of larger joints; therefore, careful attention to detail is necessary to help prevent neurovascular complications. Elbow arthroscopy can be a useful technique for the orthopaedic surgeon. This review will describe the operative setup and appropriate portal placement. Currently, several different pathologies have been addressed arthroscopically, including loose bodies, arthritis, fracture, instability, and osteochondritis dissecans. | |
| 18097817 | Cyclotronic ion resonance therapy and arthralgia. | 2007 | A total of 143 patients suffering various musculoskeletal disorders including rheumatoid arthritis, arthritis, osteoporosis, and post-surgical discomfort were subjected to ELF magnetic treatments using the Seqex device. A clear trend in pain reduction was observed over the 10 treatment regimen as well as a stabilization of relevant lab tests, including cholesterol level and blood pressure. Improvements were also noted in posturometric footboard tests. An additional 20 patients with various neuromuscular difficulties were treated with Seqex as well as magentic "concentrators" for periods ranging from 3 to 10 treatments. Similar improvements in pain reduction were observed in this smaller group. | |
| 18592243 | Bronchus-associated lymphoid tissue lymphoma in a patient with primary Sjögren's syndrome | 2008 Dec | Despite its infrequent occurrence, the possible development of lymphoma or lymphoid lung disease in patients with Sjögren's syndrome should always be borne in mind. We describe a case of bronchus-associated lymphoid tissue (BALT) lymphoma in a patient with Sjögren's syndrome that clearly exemplifies the wide-ranging problems of diagnosing, treating and following such patients. This difficulty is due to the fact that the clinical and radiological findings suggest interstitial lung disease, and histological assays are required for a correct diagnosis. A precise knowledge of the various histological and radiological patterns of lung involvement can aid patient management. | |
| 18302677 | Sjögren's syndrome sufferers have increased oral yeast levels despite regular dental care | 2008 Mar | AIM: To investigate the prevalence and quantity of oral yeasts and their association with oral candidiasis in Sjögren's syndrome (SS) patients receiving regular dental care. MATERIALS AND METHODS: Yeasts in oral rinse and full-mouth supra-gingival plaque samples from 25 primary SS, 27 secondary SS and 29 control subjects were selectively cultured. All yeasts except single-species isolates were genotyped using pulsed field gel electrophoresis (PFGE). RESULTS: Ten (19%) SS sufferers had symptomless candidiasis. SS subjects had a higher prevalence (73%vs 7%) and quantity of yeasts than controls in both oral rinse and plaque samples (P < 0.05). The prevalence of yeasts in plaque was associated with candidiasis regardless of denture wearing (P < or = 0.04). Candida albicans was the predominant yeast isolated. PFGE showed 20 (66% of total) C. albicans isolate pairs, i.e. C. albicans species isolated from plaque and oral rinse samples of the same individual, were of closely related genetic clonal types (P < 0.01). CONCLUSIONS: Despite effective oral hygiene, more SS subjects than controls had detectable levels of oral yeasts and their presence in supra-gingival plaque was associated with candidiasis. Candida albicans colonized supra-gingival biofilm even in well-maintained SS individuals, posing a challenge to the control of oral candidiasis. | |
| 17162248 | Mechanisms of autoantibody production and the relationship between autoantibodies and the | 2006 Dec | The major target organs of Sjögren's syndrome (SS) are lacrimal glands and salivary glands where prominent lymphocytic infiltration occurs, which may induce varying levels of autoantibody production. Multiple factors, including environmental stress, viral infection, hormonal imbalance, and apoptosis, are thought to be involved in the pathogenesis of SS. Production of anti-SS-A/Ro and anti-SS-B/La antibodies is thought to be regulated by the presentation of autoantigens in context with an aberrant expression pattern of human leukocyte antigen (HLA) in situ. Molecular mimicry with some viral sequences is also hypothesized. The apoptosis-resistance phenotype of B cells in labial salivary glands (LSGs) of SS is important in autoantibody production. CD40/CD40L (CD40 ligand) and Bcl-2 family proteins, in tandem with B cell-activating factor (BAFF), are supposed to protect infiltrating lymphocytes from apoptosis. Anti-muscarinic3 receptor antibody plays an important role in cholinergic hyperresponsiveness in SS. Fragmentation of autoantigens such as SS-B/La or alfa-fodrin during the process of apoptosis causes the redistribution of these autoantigens, leading to the production of autoantibodies in SS. In this review, the role of autoantibodies found in SS, corresponding to clinical aspects of each antibody as well as the mechanisms of production, is discussed. | |
| 17075579 | Early pathogenic events associated with Sjögren's syndrome (SjS)-like disease of the NOD | 2006 Dec | Recently, we reported development of the C57BL/6.NOD-Aec1Aec2 mouse carrying two genetic intervals derived from the NOD mouse. These two genetic regions confer full Sjögren's syndrome (SjS)-like disease in SjS-non-susceptible C57BL/6 mice. The current study was undertaken to apply microarray technology to define the molecular basis underlying onset of SjS-disease in C57BL/6.NOD-Aec1Aec2 mice. Using oligonucleotide microarrays, gene expression profiles of submandibular glands derived from 8- to 12-week-old C57BL/6.NOD-Aec1Aec2 mice and 8-week-old C57BL/6 mice were performed for comparison. Significant differential expressions were determined using the Mann-Whitney U test. Hybridizations using submandibular cDNA probes revealed 75 differentially expressed genes at 8 weeks and 105 differentially expressed genes at 12 weeks of age in C57BL/6.NOD-Aec1Aec2 mice compared to 8-week-old C57BL/6 mice. These genes were related generally to basic cellular activities such as transcription, translation, DNA replication, and protein folding. During the predisease phase, genes upregulated encode proteins associated with the IFN-gamma signal-transduction-pathway (Jak/Stat1), TLR-3 (Irf3 and Traf6) and apoptosis (casp11 and casp3), indicative of chronic proinflammatory stimuli, especially IL-1. Between 8 and 12 weeks of age, sets of clustered genes were upregulated that are associated with adaptive immune responses, especially B cell activation, proliferation and differentiation (Baffr, Taci, Bcma, Blys, April, CD70, CD40L, Traf1, Traf3, Pax5, c-Jun, Elk1 and Nf-kB), and neural receptors (Taj/Troy). Altered gene expressions of TLR3 and TNF-superfamily-receptors and ligands during this early phase of SjS suggest a possible viral etiology in the altered glandular homeostasis with an upregulated, possibly overstimulated, B-lymphocyte activation in the early autoimmune response present in the submandibular glands. The importance of NF-kappaB as a critical signal transduction pathway is also suggested but its link is not yet clear. | |
| 16370920 | Pharmacological management of transient synovitis. | 2006 Jan | Synovitis is a painful and, occasionally, disabling disease. Patients with synovitis, especially new onset synovitis, should be referred to a rheumatologist urgently so that they can be assed and treated as quickly as possible. Clinical assessment and investigations are required to help differentiate between transient (< 3 months) and persistent (> 3 months) synovitis. This differentiation is important, as persistent synovitis can lead to joint damage and disability. Septic arthritis is a rheumatological emergency requiring immediate assessment and specific treatment. The earlier synovitis is treated, the more effective treatment is likely to be. If treated very early, there is potential to prevent the move from transient to persistent synovitis. Transient synovitis can be treated with painkillers, NSAIDs and/or corticosteroids, depending on severity. Persistent synovitis may also require disease-modifying drugs. Clinical indicators of persistence include symptom duration at first visit, early morning stiffness for > 1 h, arthritis in more than three joints, bilateral compression pain in metatarsophalangeal joints, rheumatoid factor positivity, anti-cyclic citrullinated peptide antibody positivity, erosions on hand or feet X-rays and a family history of rheumatoid arthritis. Disease-modifying drugs need to be considered early to achieve clinical remission before damage and disability occur. Despite emerging new treatments for synovitis, especially persistent synovitis, full clinical remission is still not achieved in most patients, and more research into disease processes and targeted therapies is required. | |
| 16435022 | Susceptibility to JRA/JIA: complementing general autoimmune and arthritis traits. | 2006 Jan | Juvenile rheumatoid arthritis (JRA), also known as juvenile idiopathic arthritis (JIA), includes the most common chronic autoimmune arthropathies of childhood. These two nomenclatures for classification include components representing the major subclasses of disease. The chromosomal regions and the genes involved in these complex genetic traits are being elucidated, with findings often specific for a particular disease subtype. With the advent of new SNP technologies, progress is being made at an ever-increasing pace. This review discusses the difficulties of deciphering the genetic components in complex disorders, while demonstrating the similarities that JRA shares with other autoimmune disorders. Particular emphasis has been placed on positive findings either for candidate genes that have been replicated independently in JRA/JIA, or findings in JRA for which consistent results have been reported in other forms of autoimmunity. | |
| 19050807 | Sjögren's syndrome associated with chronic hepatitis C - the benefit of the antiviral tre | 2008 | Chronic hepatitis C virus infection (CHCV) has high prevalence of immunological abnormalities. Extrahepatic manifestations (EHM) have been reported in association with CHCV infection, whose heterogeneity makes difficult any correlation between the two disorders. Among extrahepatic symptoms of C virus hepatitis, sicca syndrome is also registered. Sjögren's or sicca syndrome (SS) is a chronic, slowly progressive disease, with inflammatory-immune mediation characterized by lymphocytic infiltration of the lachrymal and salivary glands. A distinct primary form and a secondary one, occurring when presented in the context of an autoimmune or hepatic disease have been described. We present a case of SS in a patient with CHCV, commenting a possible link between primary SS and the CHCV, as well as the similarities and the distinctions among these conditions. Our conclusion is that CHCV can induce SS with some clinical particularities like presence of pericapillary and not pericanalicular lymphocytic infiltrate without destroying the salivary glands, in the absence of SS-A/SS-B antibodies. The favorable evolution of SS under IFN therapy is an argument for an authentic relation. Further studies are necessary to determine if CHCV is an etiological agent of SS or of it can induce a pseudo-sicca syndrome, characterized by a simple glandular inflammation consisting mainly in a simple lymphocytic adenitis. | |
| 18984414 | Patient-reported outcomes including fatigue in primary Sjögren's syndrome. | 2008 Nov | The hallmark of Sjögren's syndrome is focal lymphocytic infiltration of exocrine glands leading to mucosal dryness, particularly of the eyes and mouth. In addition, approximately 70% of patients report fatigue as a particularly prominent and disabling feature associated with reduced health-related quality of life. Other key patient-reported extraglandular symptoms include arthralgia, myalgia, and Raynaud's phenomenon. This article reviews these patient-reported features, their relationships with objective assessment of the disease, potential therapies for these symptoms, and how measurements of these symptoms are relevant to outcome assessment in clinical therapeutic trials. | |
| 18984409 | Hepatitis C virus and Sjögren's syndrome: trigger or mimic? | 2008 Nov | Patients who have chronic hepatitis C virus infection present some extrahepatic manifestations that may mimic the clinical, immunologic, and histologic manifestations of primary Sjögren's syndrome (SS). Various demographic, clinical, and immunologic features may aid differentiation between the two processes. Chronic hepatitis C virus infection should be considered an exclusion criterion for the classification of primary SS, not because it mimics primary SS, but because the virus may be implicated in the development of SS in a specific subset of patients. | |
| 17894008 | Sjögren's syndrome--a plethora of clinical and immunological phenotypes with a complex ge | 2007 Jun | Primary Sjögren's syndrome is a complex autoimmune disorder, considered to represent an ideal disease with which to study the mechanisms underlying autoimmunity because its manifestations are both organ specific and systemic in nature. The characteristic histologic finding in target organs is a progressive focal infiltration of mononuclear lymphoid cells, replacing glandular epithelium (lymphoepithelial lesion). This involvement has been re-emphasized in the 2002 revised EU criteria for Sjögren's syndrome. Moreover, ectopic secondary lymphoid follicles in Sjögren's syndrome contain all elements of relevance for driving an autoimmune response. A number of cytokines and chemokines are involved and particularly B cell activating factor seems to direct the lifespan of infiltrating B cells by enhancing their proliferation and maturation. The recent discovery of clinical benefit after B cell depletion also highlights the pivotal role of B cells in Sjögren's syndrome. A major challenge in Sjögren's syndrome will be to stratify the disease process including genetic and environmental triggers. Identification of novel genetic and molecular markers may lead to the development of better diagnostic and prognostic tools in Sjögren's syndrome including its systemic complications. This minor review will cover the current knowledge on classification, pathogenesis, multiplex findings, potential candidate genes, gene profiling results, and novel therapy approaches. New hypotheses behind the complexity of Sjögren's syndrome are expected to follow. | |
| 17179174 | Reversal of Sjogren's-like syndrome in non-obese diabetic mice. | 2007 Jun | BACKGROUND: Non-obese diabetic (NOD) mice exhibit autoimmune diabetes and Sjögren's-like syndrome. OBJECTIVE: To test whether a treatment that reverses end-stage diabetes in the NOD mouse would affect their Sjögren's-like syndrome. METHODS: NOD mice have a proteasome defect. Improperly selected naive T cells escape, but can be killed by reintroducing major histocompatibility complex class I self-peptides on matched normal splenocytes. The proteasome defect also impairs nuclear factor kB, a transcription factor in pathogenic memory T cells, increasing their susceptibility to tumour necrosis factor-induced apoptosis stimulated through complete Freund's adjuvant (CFA). The impact of this two-limb therapy (injections of matched normal splenocytes and CFA) on the autoimmune salivary gland disease of the NOD mice was studied. RESULTS: All NOD mice receiving the above treatment had a complete recovery of salivary flow and were protected from diabetes. Restoration of salivary flow could be the result of a combination of rescue and regeneration of the gland, as confirmed by immunohistochemical analysis. All untreated NOD mice showed a continuous decline in salivary flow, followed by hyperglycaemia and death. CONCLUSION: This study establishes that a brief intervention in NOD mice with Sjögren's-like syndrome can reverse salivary gland dysfunction. | |
| 16646031 | Tissue-specific up-regulation of the proteasome subunit beta5i (LMP7) in Sjögren's syndro | 2006 May | OBJECTIVE: Sjögren's syndrome (SS) is characterized by autoimmune infiltration and focal accumulation of lymphocytes in the exocrine glands, with a predominance of CD4-positive T cells. Since these histologic findings are nonspecific, determination of clinical and serologic abnormalities contribute to the diagnosis. The aim of this study was to identify a novel, disease-specific, immunologically relevant marker for SS. METHODS: To analyze disease-related and tissue-specific expression of candidate markers, we examined biopsied minor salivary glands and peripheral blood mononuclear cells from patients with primary and secondary SS (n = 26) as well as from patients with sicca symptoms without autoimmune sialadenitis (n = 15). Expression of the Th1/Th2-related chemokines CCL3 (macrophage inflammatory protein 1alpha) and CCL2 (monocyte chemoattractant protein 1), CXCL7 (neutrophil-activating peptide 2 [NAP-2]), interleukin-1beta, inducible costimulator, and the proteasome subunits alpha3 (C9) and beta5i (LMP7) was analyzed at the messenger RNA (mRNA) level using real-time polymerase chain reaction techniques. Immunohistochemical analysis was used to identify the beta5i (LMP7)-expressing cell populations in minor salivary glands. RESULTS: The expression profiles revealed a significant up-regulation of beta5i (LMP7) exclusively in the salivary glands of SS patients. Immunohistochemistry confirmed expression of the immunoproteasome subunit beta5i (LMP7) within the acinar and ductal epithelial cells. No significant difference in the distinct histologic focus scores was evident for the expression of the markers investigated. In the peripheral blood compartment, the expression of CXCL7 was up-regulated both in primary and in secondary SS. CONCLUSION: Tissue-specific up-regulation of beta5i (LMP7) mRNA was shown to be characteristic of SS, indicating a disease-specific modulation of the proteasome system. Expression of beta5i (LMP7) represents an independent parameter that can be used in addition to the focus score to distinguish SS in biopsied labial salivary glands. | |
| 16249826 | Circulating auto-antibodies against nuclear and non-nuclear antigens in primary Sjögren's | 2006 May | The aim of this study was to analyze the prevalence and clinical significance of circulating auto-antibodies against nuclear and non-nuclear antigens in a large cohort of Spanish patients with primary Sjögren's syndrome (SS). We studied 335 patients diagnosed with primary SS seen consecutively in our department since 1994 and tested for anti-nuclear antibodies (ANA), anti-Ro/SS-A, anti-La/SS-B, anti-Sm, anti-ribonucleoprotein (anti-RNP), anti-smooth muscle antibodies (anti-SMA), anti-parietal cell antibodies (anti-PCA), anti-liver-kidney microsome type-1 (anti-LKM-1) antibodies and anti-mitochondrial antibodies (AMA). ANA were detected in 278 (83%) patients. The association of positive ANA with the presence of anti-Ro/SS-A and anti-La/SS-B antibodies reached statistical significance at a titre of ANA >1/80 (p<0.001), while the presence of anti-Sm and anti-RNP was associated with positive ANA at a titre > or =1/320 (p=0.037 for Sm and p=0.016 for RNP). ANA titres correlated with the number of positive antibodies against specific nuclear antigens (p<0.001) but not with the number of positive antibodies against non-nuclear antigens. We found positive anti-Ro/SS-A antibodies in 111 (33%) patients, anti-La/SS-B in 78 (23%), anti-RNP in 8 (2%) and anti-Sm in 4 (1%). Anti-SMA antibodies were detected in 208 (62%) patients, with no significant associations with clinical or analytical SS features, while anti-PCA antibodies were found in 90 (27%) patients and were associated with a higher prevalence of thyroiditis and liver involvement. AMA were detected in 28 (8%) patients, although only 14 presented clinical and/or analytical evidence of liver involvement. No patient presented anti-LKM antibodies. ANA play a central role in the immunological expression of primary SS, due to their frequency and close association with the underlying presence of one or more anti-ENA antibodies. Positivity for antibodies against non-nuclear antigens such as anti-PCA and AMA suggests an association with some organ-specific autoimmune diseases (thyroiditis and primary biliary cirrhosis), while the presence of anti-SMA, in spite of their high prevalence, has no clinical significance in primary SS. | |
| 16551571 | Enhanced intraarticular free radical reactions in adjuvant arthritis rats. | 2006 May | One of the reasons of rheumatoid arthritis (RA) development is widely recognized the relation of free radical reactions in tissue injuries. The aim of this study was to evaluate the location where in vivo free radical reactions was enhanced in adjuvant arthritis (AA) model rats using in vivo electron spin resonance (ESR)/nitroxyl spin probe technique. The signal decay after intravenous injection of spin probe was enhanced in AA than that in control and suppressed by the pre-treatment of dexamethasone (DXT). Interestingly, the decay in joint cavity occurred prior to paw swelling of AA and suppressed by a simultaneous injection of free radical scavengers, indicating that the enhancement of free radical reactions in joint cavity of AA rats. This technique would be useful tool to determine the location of the enhanced free radical reactions and evaluate the activity of antioxidant medicine with non-invasive real-time measurement. | |
| 18084697 | Efficacy and safety of mizoribine for the treatment of Sjögren's syndrome: a multicenter | 2007 | This multicenter clinical trial was performed to evaluate the efficacy and safety of mizoribine for the treatment of Sjögren's syndrome. Fifty-nine patients with a definite diagnosis of Sjögren's syndrome received 150;Smg of mizoribine daily for 16 weeks. The salivary secretion volume was determined at baseline, at weeks 8 and 16 after the start of the study treatment by the Saxon test, and clinical manifestations were assessed by the investigator and the patients using a 10-cm visual analog scale (VAS). Adverse drug reactions were reported in 18 patients, of whom 6 patients had to discontinue the study due to such adverse reactions; however, no serious adverse drug reactions definitely related to the study drug were noted. The salivary secretion volume, the rate of change in salivary secretion, the patients' own assessments of dry mouth and dry eyes, the investigators' assessment of oral sicca symptoms, and the investigators' overall assessment improved following the treatment regimen with statistical significance at week 16 after the start of treatment in comparison to the baseline values. These results suggested that mizoribine may be effective in producing a subjective and objective amelioration of the glandular symptoms in patients with Sjögren's syndrome, without observing any serious adverse effects related to this drug. | |
| 17286904 | [Serum IL-21 level in patients with primary Sjogren's syndrome and clinical significance o | 2007 Feb | AIM: To investigate the relation between the change of serum IL-21 level and other laboratory indexes by detecting serum IL-21 level from patients with primary Sjogren's syndrome (pSS) and explore the role of IL-21 in pSS. METHODS: The level of serum IL-21 from 40 pSS patients diagnosed according to 2002 revised international classification criteria for pSS and 30 healthy persons were detected by enzyme-linked immunosorbent assay(ELISA) respectively. Meanwhile, FT3, FT4, TSH, TgAb, TPOAb were detected by Immunochemiluminescent technique. Double diffusion method, Westergren and automatic gel method detected ant-SSA and ant-SSB antibody, ESR and serum protein electrophoresis respectively. The relationship between serum IL-21 level and other clinical symptom of the patients was analyzed. RESULTS: The level of serum IL-21 in patients with pSS (1051+/-335) ng/L was obviously higher than that in healthy control (466+/-90 ng/L), (P<0.05). The levels of serum IL-21 in the self-antibody positive group, parotid gland swelling pain group, rash group and incorporating hypothyroidism group were higher than those in their negative control groups, and there were significant differences(P<0.05). In addition, The level of serum IL-21 level in pSS patients showed positive correlation with gamma-globulin (r=0.719, P<0.05) and ESR level(r=0.745, P<0.05). CONCLUSION: The evident increase of serum IL-21 level in pSS patients has positive correlation with the levels of gamma-globulin and ESR, which suggests that IL-21 may play a critical role in the pathogenesis of pSS. | |
| 17087349 | [Small cell lung cancer with Sjögren's syndrome and Lambert-Eaton myasthenic syndrome]. | 2006 Oct | A 72-year-old man was admitted to our hospital with complaints of dry mouth, muscle weakness of the lower limbs and gait disturbance. The patient had dry mouth, dry eyes, positive anti-SS-B antibody and salivary gland inflammation. Sjögren's syndrome was diagnosed. Since muscle weakness of the lower limbs and gait disturbance were not compatible with Sjögren's syndrome, we considered the possibility of paraneoplastic syndrome. Serum levels of CEA, NSE and ProGRP were elevated. Chest roentgenogram and CT showed a nodular lesion in the right upper lobe of the lung and swollen lymph nodes in the hilum and mediastinum. Small cell lung cancer was diagnosed by bronchoscopy. Anti-P/Q-type Ca2+ channel antibody was positive. Electromyogram showed a reduction in the amplitude of the evoked muscle action potential response after slow repetitive stimulation and did not show a reduction after rapid repetitive stimulation. Based on these findings, we made a diagnosis of Lambert-Eaton myasthenic syndrome (LEMS). Concurrent chemoradiotherapy induced an improvement of muscle weakness of the lower limbs. LEMS is frequently associated with a malignant tumor and an autoimmune disorder. We thought that in this patient, the presentation of LEMS was apparent because he had both Sjögren's syndrome and small cell lung cancer. |