Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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17894007 | The influence of sex steroids on Sjögren's syndrome. | 2007 Jun | Sjögren's syndrome is an autoimmune disease affecting the exocrine glands, most typically salivary and lacrimal glands. In Sjögren's syndrome, the acinar cells of these glands are damaged and destroyed, leading to diminished secretion of saliva and tear fluid. Accordingly, the current American-European criteria of Sjögren's syndrome include xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). In addition to these sicca symptoms and signs, the diagnostic criteria require autoimmune features in the form of Sjögren's syndrome SS-A and/or SS-B autoantibodies and lymphocyte infiltrates in labial salivary glands. Majority of patients with Sjögren's syndrome are women and the diagnosis is usually done when they are 40-50 years old. The cause of Sjögren's syndrome is unknown, but taking into account the female dominance and the late onset, our hypothesis is that sex steroids play a key role in the etiology of Sjögren's syndrome. More specifically, we believe that the driving factor behind Sjögren's syndrome could be lack of androgens. It has been shown that patients with Sjögren's syndrome have low concentrations of circulating dehydroepiandrosterone sulfate (DHEA-S) compared to age-matched healthy controls. Our hypothesis is that patients with Sjögren's syndrome suffer from an insufficient local androgen effect in the exocrine target tissues of the disease because of low systemic levels and/or ineffective local intracrine handling of DHEA-S prohormone. To further clarify the role of sex steroids and the eventual deficiency of androgens, salivary glands are studied using protein markers regulated by androgens or estrogens. | |
17695193 | [Leukocytoclastic vasculitis in primary Sjögren syndrome: a case report]. | 2007 May | We report a case of primary Sjögren's syndrome (SSjö with cutaneous leukocytoclastic vasculitis. The accurate diagnosis of SSjö was established based on objective signs and symptoms of ocular and oral dryness and characteristic appearance of a biopsy sample from a minor salivary gland, and presence of anti-SS-A autoantibody. Another autoimmune disorder was not present, so diagnosis of primary SSjö was established. Histologic finding of skin biopsy of purpuric lesion was typical for leukocytoclastic vasculitis. The patient was treated with small doses of glucocorticoids and with local symptomatic therapy for ocular and oral dryness. SSjö is one of the most common autoimmune disorders and vasculitis is one of the most characteristic extraglandular manifestations, but wide spectrum of cutaneous involvement in primary SSjö has been little studied. | |
18984415 | Measurement of disease activity and damage in Sjögren's syndrome. | 2008 Nov | Sjögren's syndrome (SS) is a systemic autoimmune disease that is characterized by an aggressive autoimmune response to epithelia, with consequent reduction of their secretions accompanied by sicca complaints. Systemic features may also be present in a subset of patients and may require more aggressive therapies. Improvements in knowledge concerning disease pathophysiology, combined with the availability of specifically targeted therapies able to modulate or block some of the most important pathologic mechanisms of the disease, may open totally new perspectives in the therapeutic approach to SS. The absence of reliable and validated outcome measures for SS is a major obstacle in performing clinical trials of new therapies in SS but studies devoted to defining outcome measurement instruments for this disorder have been performed or are in an advanced phases of completion. | |
17559494 | Coexistence of Sjögren's syndrome and sarcoidosis: a report of five cases. | 2007 Jul | BACKGROUND: Sjögren's syndrome (SS) and sarcoidosis are diseases that can affect the salivary glands and result in the loss of salivary gland function. Most of the criteria used for the diagnosis of SS exclude sarcoidosis before establishing the diagnosis of SS. However, several reports have suggested the coexistence of both SS and sarcoidosis in the same patient. OBJECTIVE: The purpose of this study was to present five cases that support a true coexistence of sarcoidosis and SS. METHODS: Clinical and laboratory findings of patients with evidence of having both SS and sarcoidosis were reviewed. The diagnosis of SS was based on the European community criteria; the diagnosis of sarcoidosis was based on the presence of serological, radiographic and/or histopathologic findings that are consistent with sarcoidosis. RESULTS: All patients fulfilled the criteria for the diagnosis of both diseases. CONCLUSION: Our findings appear to support a true coexistence of sarcoidosis with SS. Therefore, it is reasonable to suggest removing the exclusion of sarcoidosis from the diagnostic criteria for SS. | |
16575363 | [Sjögren syndrome in Obstetric and Gynecology: literature review]. | 2006 Apr | Sjogren syndrome (SS) is an immune disease characterized by a progressive degeneration of exocrine glands. It leads to dryness of mucosa and conjunctivitis. Gynecologists and obstetricians may encounter this disease in women at any age, including during pregnancy. Knowledge of the main characteristics is required for early diagnosis and multidisciplinary program. In the event of secondary Sjögren syndrome occurring during pregnancy, treatment focuses on the associated disease, mainly systemic lupus erythematosus. In primary Sjögren syndrome, pregnancy does not appear to influence disease course. However, patients with both primary and secondary Sjögren syndrome must be monitored carefully. There is a risk of neonatal lupus and congenital atrioventricular bloc associated with high morbidity and mortality. These patients should benefit from multidisciplinary care in a hospital with a neonatal intensive care unit. | |
18575164 | Relevance of 99mTc-HYNIC-tir-octreotide scintigraphy in a patient affected by sarcoidosis | 2008 Mar | We report the case of a 59 years old woman affected by lung and joint sarcoidosis, secondary Sjogren's syndrome refractory to common disease-modifying antirheumatic drugs (DMARDs) that regressed with infliximab and methotrexate. 99mTc-HYNIC-TOC scintigraphy was useful in diagnosis, choice of treatment and follow-up. | |
18493768 | Encephalic large arteries narrowness and peripheral neuropathy in a patient with adult-ons | 2008 Oct | Adult-onset Still's disease (AOSD) is a rare, systemic inflammatory disorder, characterized by spiking high fever, fever-associated evanescent rash, arthritis, myalgia, serositis and hepatosplenomegaly. White blood cell count, neutrophilic cell count, and serum ferritin level are markedly elevated in the active stage of the disease. Neurological complications of AOSD commonly were cranial nerve palsies, seizures, aseptic meningoencephalitis, peripheral neuropathy and Miller-Fisher syndrome. We report a previously healthy 60-year-old Chinese man who fulfilled the criteria for AOSD and had a combination of focal and peripheral neurological symptoms. Magnetic resonance angiography (MRA) and transcranial Doppler ultrasonography (TCD) showed narrowness of cerebral blood vessel. Peripheral neuropathy was confirmed by electromyography and sural nerve biopsy. His generalized neuropathy and other symptoms were rapidly improved by receiving glucocorticoid therapy. We do a literature review about neurological manifestations observed in AOSD patients. | |
17921797 | Severe pulmonary hypertension in pediatric primary Sjögren syndrome: a case report. | 2007 Oct | A 9-year-old girl with a history of xerostomia and recurrent bilateral parotid gland enlargement presented with purpura of the lower limbs and exertional dyspnea. She had hyperglobulinemia, positive ANA, SSA, and SSB and an abnormal Shirmer test leading to a diagnosis of primary Sjögren syndrome. Cardiologic and imaging investigations revealed severe isolated pulmonary hypertension and ruled out pulmonary fibrosis. Prednisolone and cyclophosphamide, together with anticoagulant and vasodilatory drugs therapy, induced a significant improvement of exertional dyspnea and lowered pulmonary artery pressure. This case and reports from the literature suggest that immune mechanisms, not just vasospasm, can be factors in some pulmonary hypertension. | |
17308315 | Effects of exercise on aerobic capacity and fatigue in women with primary Sjogren's syndro | 2007 May | OBJECTIVE: To investigate the effect of a moderate to high intensive exercise program on two primary outcomes (aerobic capacity, fatigue), and three secondary outcomes [anxiety, depression and health-related quality of life (HRQoL)] in women with primary Sjögren's syndrome (primary SS). METHODS: Twenty-one women with primary SS were ranked according to degree of fatigue and allocated to an exercise group (TG; n = 11) or a control group (CG; n = 10). The exercise method was Nordic walking for 45 min three times a week for 12 weeks. Outcome measures assessed at baseline and after 12 weeks were aerobic capacity, fatigue, ratings of perceived exertion (RPE), anxiety, depression and HRQoL. RESULTS: Nine women in the TG and 10 women in the CG completed the study. Analysis showed significant differences between the groups regarding aerobic capacity (P = 0.03), fatigue (P = 0.03), RPE (P = 0.03), and depression (P = 0.02) with the better values for the TG. There were no differences in anxiety or HRQoL. CONCLUSION: Our findings support the use of appropriate aerobic exercise in the treatment of primary SS. | |
18779593 | Positional cloning of the Igl genes controlling rheumatoid factor production and allergic | 2008 Sep 16 | Rheumatoid factors (RF), autoantibodies that bind the Fc region of IgG, are one of the major diagnostic marker in rheumatoid arthritis (RA) but occur with lower frequency also in other infectious and inflammatory conditions. Through positional cloning of the previously described quantitative trait locus (QTL) Rf1 in congenic and advanced intercrossed rats, we identified the Ig lambda light chain locus as a locus that regulates the production of RF in rats. The congenic rats produce RF-Ig lambda and have significant higher levels of RF-IgG and RF-IgM in serum, while the DA rat has an impaired RF production and does not produces RF-Ig lambda. Thus, we could investigate the role of RF in pristane-induced arthritis (PIA) as well as ovalbumin-induced airway inflammation. We show that there was no difference in the development and severity of PIA between congenic and parental DA rats, suggesting that RF using lambda light chains have no impact on PIA. However, the RF producing congenic rats developed a more severe airway inflammation as indicated in the significantly increased number of eosinophils in bronchoalveolar lavage fluid as well as total IgE in serum. In addition, RF congenic rats had a significantly enhanced immune response toward OVA due to increased OVA-Igk but not OVA-Igl antibodies, suggesting a possible involvement of RF in the regulation of the humoral immune response. | |
17717915 | [Clinical observation on effect of total glucosides of paeony in treating patients with no | 2007 Jul | OBJECTIVE: To investigate the efficacy and adverse reaction of total glucosides of paeony (TGP) in treating patients with non-systemic involved Sjögren syndrom (NSI-SS). METHODS: Retrospective study was conducted on 27 patients with NSI-SS who received TGP treatment for over two years as the TGP group, and 20 patients received hydroxychloroquine sulfate (HCQs) for over two years in the HCQs group for positive control. Salivary flow, Schirmer's test and serum gamma-globulin at different time points, i.e. before treatment, and at the end of 1st, 3rd, 6th, 12th and 24th month respectively, were compared between groups, and adverse reactions associated with TGP and HCQ were also observed. RESULTS: In the TGP group, saliva secretion was significantly increased and serum gamma-globulin decreased significantly from the 6th month (P <0.01), Schirmer's test improved significantly after 12 months (P< 0.01). While in the HCQs group serum gamma-globulin was significantly decreased from the 3rd month (P <0.01), saliva secretion and Schirmer's test improved significantly after six months (P<0.01). However, the 3 indexes determined at the end of the 3rd month were insignificantly different from those before treatment. Mild diarrhea occurred in 4 cases in the TGP group, they were improved two weeks later, but one case with severe diarrhea was dropped. While in the HCQs group, 2 patients were dropped, one for the raising of alanine aminotransferase at the 6th month and the other for decreased vision at the 9th month. CONCLUSION: Efficacy of TGP is equivalent to that of HCQs in treating NSI-SS, but with higher safety and the effect initiating time being about 6 - 12 months. | |
16917562 | Evaluation of the concordance of sialometry and salivary glands scintigraphy in dry mouth | 2006 Jan | INTRODUCTION: Many diagnostic tests are used to evaluate dry mouth patients, especially the ones with Sjögren's Syndrome, to whom these tests are part of classification criteria for scientific studies. AIM: Thus, the concordance between results of sialometry and salivary glands scintigraphy was evaluated; if positive, it would enable the choice of one or the other for diagnosis. PATIENTS AND METHOD: Seventy-two dry mouth patients were divided into non-Sjögren's Syndrome group, primary Sjögren's Syndrome group and secondary Sjögren's Syndrome group. The concordance among sialometry and scintigraphy results was evaluated by Kappa test. RESULTS: It was observed that their concordance was equal or near to zero. CONCLUSION: It is not possible to make a choice between these tests and both should be performed. | |
18984407 | New concepts in the pathogenesis of Sjögren's syndrome. | 2008 Nov | Sjögren's syndrome (SS) is a rheumatic disease in which the salivary and lacrimal glands are the principal targets of a pathologic autoimmune reaction. SS is manifested by xerostemia and keratoconjunctivitis sicca and marked by persistent focal mononuclear cell infiltration within the salivary glands, often accompanied by glandular atrophy and fibrosis. A challenge is to clarify the roles of genetic backgrounds and environmental trigger. Advanced bioanalytic platforms have enabled identification of potential biomarkers with the intent to improve diagnosis, promote development of prognostic tools, and identify processes for therapeutic treatment. Such approaches allow a glimpse at the apparent complexity of SS. | |
16491762 | [Thinking and methods of treatment of Sjogren's syndrome based on syndrome differentiation | 2006 Jan | Sjogren's syndrome is one of clinical difficult and complicated diseases and there is no radical treatment for it at present. The authors summarize the thinking of clinical syndrome differentiation and treatment of acupuncture and moxibustion, 4 syndrome-differentiation methods and dredging the Triple Energizer channel, and needling three parts by long-term clinical practice and in combination with clinical study achievements of TCM in recent years, and put the important point of treatment on the Triple Energizer, with the points on the Triple Energizer channel as main points, combined with the points with functions of regulating functional activity of qi and regulating visceral functions, attaining better results. This provides a new method for acupuncture and moxibustion treatment of Sjogren's Syndrome. | |
17695197 | [Arthroscopic surgery of the ankle]. | 2007 May | Arthroscopic surgery of the ankle has become indispensable method in the armamentarium of the modern orthopaedic surgeon. Technological advancement and thorough understanding of the anatomy have resulted in improved ability to perform arthroscopy of the ankle. The method is minimally invasive and it allows the direct visualization of intra-articular structures without arthrotomy or malleolar osteotomy. Anterior or posterior approach may be used, and various indications have become generally accepted: anterior soft tissue or bony impingement, loose bodies, osteochondral defects, synovitis (rheumatoid arthritis, infective arthritis, and hemophilic arthropathy), posterior impingement syndrome, posttraumatic conditions, osteoarthritis (arthrosis), ankle arthrodesis, tumor-like lesions (synovial osteochondromatosis, pigmented villonodular synovitis) and many combinations of these pathological entities. In this paper we will discuss technique, indications, complications and future perspective of the ankle arthroscopy. In addition we will review the most recent literature data regarding this appealing technique. | |
17371654 | Outcome analysis of agility total ankle replacement with prior adjunctive procedures: two | 2007 Mar | BACKGROUND: A retrospective case review of 65 agility total ankle replacements (64 patients) was done between April, 1998, and March, 2002. The purpose of this study was to more closely identify factors that may be predictive of a favorable outcome, including a comparison of outcome measures between patients who had preoperative corrective procedures and those patients who did not. METHODS: The outcomes of this series of patients were examined with post-operative Short Form (SF)-36 scores as well as chart and radiographic review. Endpoints for this study were amputation, arthrodesis, osteochondral allograft, total ankle revision, or revision of either or both components. The Kaplan-Meier survivorship curve also was estimated including the 95% confidence intervals. RESULTS: Patients with rheumatoid arthritis (RA) were found to have a statistically significant lower rate of failure. Use of a size 1 prosthesis was associated with subsidence and the highest rate of subsequent failure, but fell short of statistical significance (because of the limited power of the study). Smoking, diabetes, and methotrexate use were not associated with an adverse outcome either clinically or statistically, but the number of patients in each group was small. The age of the patient was not a factor in predicting failure of the prosthesis in the posttraumatic arthritis group; however it trended toward significance in the osteoarthritis group. The mean time to failure in patients with osteoarthritis was shorter than in the patients with post-traumatic arthritis but fell just short of statistical significance. CONCLUSIONS: From this series we concluded that rheumatoid arthritis and use of a prosthesis larger than size 1 are predictive factors for better outcome. | |
18388517 | At the horizon of innovative therapy in rheumatology: new biologic agents. | 2008 May | PURPOSE OF REVIEW: To review the rational and the results regarding the use of novel biologic agents in inflammatory rheumatic diseases. RECENT FINDINGS: Recent findings show that excessive IL-1 processing and release contribute to different rheumatic conditions, including periodic fever syndromes, systemic-onset juvenile idiopathic arthritis, adult Still's disease, and crystal-induced arthritis. Preliminary results indicate that administration of IL-1 receptor antagonist and other IL-1 inhibitors improves these conditions. IL-6 also plays a major role in the control of inflammatory responses. Several clinical trials have shown that inhibition of IL-6 by a monoclonal antibody against its receptor is efficacious in rheumatoid arthritis and systemic-onset juvenile idiopathic arthritis patients. Accumulating evidence indicates that other cytokines, including IL-15, IL-18, and IL-21 may also play an important role in rheumatoid arthritis. Several signaling pathways involved in the immune and inflammatory responses may also constitute novel targets. Preliminary data on an agent targeting the Janus kinase/Signal transducer and activators of transcription pathway are encouraging. SUMMARY: Beyond tumor necrosis factor alpha targeting, the use of inhibitors against other cytokines and cytokine-induced intracellular responses is leading to a promising therapy in the future. | |
18367413 | Use of a portable thermal imaging unit as a rapid, quantitative method of evaluating infla | 2008 May | INTRODUCTION: Thermal imaging has been utilized, both preclinically and clinically, as a tool for assessing inflammation and arthritis. However, previous studies have employed large, relatively immobile devises to obtain the thermal signature of the tissue of interest. The present study describes the characterization of a hand-held thermal imaging device in a preclinical model of general inflammation and a model of rheumatoid arthritis (RA). METHODS: A hand-held ThermoView Ti30 portable thermal imager was utilized to detect the temporal changes in thermal signatures in rat model of carrageenan-induced paw edema (CFE) and a model of collagen-induced arthritis (CIA). In both in vivo models, the kinetics of the thermal changes were correlated to footpad swelling. In addition, the CFE model was utilized to examine the ability of this technology to delineate pharmacodynamic changes in thermal signature in response to the non-steroidal anti-inflammatory drug indomethacin (10 mg/kg; p.o.). RESULTS: Thermal analysis of rat paws in the CFE model demonstrated a significant increase in the mean temperature difference between the inflamed and contralateral control paw by two hours post-carrageenan (8.3 +/-0.5 degrees F). Indomethacin significantly decreased the mean temperature difference in treated animals as compared to vehicle. In the rat CIA model, increases in footpad temperature, as determined by thermal imaging, were significantly elevated by Day 11 and remained elevated throughout the duration of the 28 day protocol. Thermal changes were also found to precede increases in footpad edema (swelling). DISCUSSION: The results of this study demonstrate that the hand-held thermal imaging technology represents a rapid, highly-reproducible method by which to quantitate the degree of inflammation in rat models of general inflammation and rheumatoid arthritis. The ability to detect pharmacodynamic responses in paw temperature suggests that this technology may be a useful tool for the development of pharmacologic interventions for the treatment inflammation-related pathologies. | |
17157574 | FR177995, a novel vacuolar ATPase inhibitor, exerts not only an inhibitory effect on bone | 2007 Apr | There is considerable evidence that osteoclasts are involved in the pathogenesis of juxta-articular bone destruction in rheumatoid arthritis. Vacuolar ATPases (V-ATPases), which are highly expressed in the ruffled border membrane of osteoclasts, play a central role in the process of bone resorption, and V-ATPase inhibitors are effective in preventing bone destruction in several animal models of lytic bone diseases. Here, we evaluated for the first time the effects of V-ATPase inhibition in rats with adjuvant-induced arthritis (AIA) using FR177995, a novel V-ATPase inhibitor. FR177995 completely inhibited H(+) transport driven by V-ATPase, but exerted no effect on the H(+) transport activities of F- and P-ATPase, indicating that FR177995 is a specific inhibitor of V-ATPase. FR177995 acted directly on osteoclastic bone resorption and equally inhibited in vitro bone resorption stimulated by IL-1, IL-6 or PTH. In addition, FR177995 dose-dependently reduced retinoic acid-induced hypercalcemia in thyroparathyroidectomized-ovariectomized rats. When FR177995 was administered to AIA rats once a day, the loss of femoral bone mineral density was significantly improved. Moreover, indicators of cartilage damage (arthritis score and glycosaminoglycan content in the femoral condyles) and inflammation parameters (paw swelling volume, erythrocyte sedimentation rate and plasma sialic acid level) were found to be unexpectedly ameliorated. These results strongly suggest that V-ATPase may be an interesting drug target in the treatment of rheumatoid arthritis. | |
18334024 | Mannose-binding lectin deficiency is associated with early onset of polyarticular juvenile | 2008 | BACKGROUND: Mannose-binding lectin (MBL) is an innate immune protein. The aim of our study was to determine whether genetically determined MBL deficiency is associated with susceptibility to juvenile rheumatoid arthritis (JRA) and whether MBL2 genotypes are associated with JRA severity. METHODS: In a retrospective cohort study of 218 patients with polyarthritis (n = 67) and oligoarthritis (n = 151), clinical and laboratory disease variables were obtained by clinical examination and chart reviews. Healthy Caucasian adults (n = 194) served as control individuals. MBL2 gene mutations were determined by Taqman analysis to identify genotypes with high, medium and low expression of MBL. Functional MBL plasma concentrations were measured using enzyme-linked immunosorbent assay. Associations between clinical and laboratory variables and MBL2 genotypes were determined by Kruskal-Wallis and chi2 tests. RESULTS: MBL2 genotype frequencies were similar in polyarthritis and oligoarthritis patients as compared with control individuals. MBL plasma concentrations were associated with the high, medium and low MBL genotype expression groups (P < 0.01). In polyarthritis patients, the presence of low-expressing (deficient) MBL2 genotypes was associated with early age at onset of disease (P = 0.03). In oligoarthritis patients, patients with low-expressing MBL2 genotypes were more often in remission (81%) than patients in the medium (54%) and high (56%) genotype groups (P = 0.02). The remaining clinical and laboratory variables, such as arthritis severity index, presence of radiographic erosions and antinuclear antibody positivity, were not associated with MBL2 genotypes. CONCLUSION: Genetically determined MBL deficiency does not increase susceptibility to JRA, but MBL deficiency is associated with a younger age at onset of juvenile polyarthritis. On the other hand, MBL-deficient children with juvenile oligoarthritis are more often in remission. Therefore, MBL appears to play a dual role in JRA. |