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ID PMID Title PublicationDate abstract
18328154 In etanercept-treated psoriatic arthritis patients clinical improvement correlated with an 2008 Jan OBJECTIVE: In patients with rheumatoid arthritis (RA), long-term therapy with anti-tumor necrosis factor (TNF) antibodies sensitizes the pituitary gland and improves adrenal androgen secretion in prednisolone-naïve patients. However, whether this is similar in psoriatic arthritis (PsA) is not known. The aim of this study was to assess the effect of 12 weeks of etanercept treatment upon the function of the HPA axis in patients with PsA. METHODS: Eleven prednisolone-naïve patients (mean age 47.3+/-8.9 years) with PsA were included. We measured serum levels of adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17OHP), cortisol, and androstenedione (ASD), at baseline and at 4 and 12 weeks after initiation of anti-TNF therapy (etanercept, 50 mg every week as a single dose by sc. injection). Clinical improvement was assessed using the Disease Activity Score-28 (DAS-28). RESULTS: Mean levels of serum ACTH, serum cortisol, serum 17OHP and serum ASD did not markedly change during 12 weeks of etanercept treatment. Similarly, the ratio of serum cortisol divided by serum ACTH did not change during 12 weeks of anti-TNF treatment. However, an increase of serum cortisol relative to serum 17OHP or ASD was related to clinical improvement. This indicates that improvement was linked to higher serum cortisol levels relative to others adrenal hormones. CONCLUSION: This is the first study to demonstrate baseline serum levels and the course of HPA axis-related hormones in patients with PsA. An increase of serum cortisol relative to others adrenocortical hormones (i.e., androstenedione and ACTH) was accompanied by clinical improvement.
17113740 Immunomodulatory activity of the rhizomes of Impatiens pritzellii var. hupehensis on colla 2007 Feb 12 Impatiens pritzellii Hook. f. var. hupehensis Hook. f. (Balsaminaceae) has been well-known and widely used in China as an anti-rheumatoid arthritis (anti-RA) herb. In this present study, mice with collagen-induced arthritis (CIA) have been treated with the methanol (MeOH) extract (0.56, 1.12, 1.68 and 2.24 g/kg body weight) and the n-butanol (BuOH) fraction (0.13, 0.27, 0.40 and 0.53 g/kg body weight) of the rhizomes of Impatiens pritzellii orally for 3 weeks. The progression of CIA was evaluated by macroscopic scoring. Administration of the MeOH extract at dose of 1.12 g/kg and the BuOH fraction at 0.53 g/kg suppressed the development of CIA in mice significantly. The spleen and thymus indexes were measured and the levels of IgG, IL-10, INF-gamma and IL-18 in the serum of CIA mice were examined after the treatment of the MeOH extract (1.12 and 1.68 g/kg body weight) and the BuOH fraction (0.40 and 0.53 g/kg body weight). Administration of the MeOH extract and the BuOH fraction of Impatiens pritzellii decreased the spleen and thymus indexes, down-regulated the levels of IgG, INF-gamma, IL-18, and up-regulated the concentration of IL-10 in the serum of mice with CIA. From the results, it was concluded that administration of Impatiens pritzellii had obviously therapeutic effects on RA including immunomodulatory activity. Moreover, the BuOH fraction exerted the activity of anti-RA of Impatiens pritzellii.
18438856 Predominance of cyclooxygenase 1 over cyclooxygenase 2 in the generation of proinflammator 2008 May OBJECTIVE: Prostaglandins (PGs) are found in high levels in the synovial fluid of patients with rheumatoid arthritis, and nonsteroidal blockade of these bioactive lipids plays a role in patient care. The aim of this study was to explore the relative contribution of cyclooxygenase (COX) isoforms and PG species in the autoantibody-driven K/BxN serum-transfer arthritis. METHODS: The prostanoid content of arthritic ankles was assessed in ankle homogenates, and the importance of this pathway was confirmed with pharmacologic blockade. The presence of COX isoforms was assessed by Western blotting and their functional contribution was compared using COX-1-/- and COX-2-/- mice as well as isoform-specific inhibitors. The relative importance of PGE2 and PGI2 (prostacyclin) was determined using mice deficient in microsomal PGE synthase 1 (mPGES-1) and in the receptors for PGI2. RESULTS: High levels of PGE2 and 6-keto-PGF1alpha (a stable metabolite of PGI2) were detected in arthritic joint tissues, correlating strongly with the intensity of synovitis. Pharmacologic inhibition of PG synthesis prevented arthritis and ameliorated active disease. While both COX isoforms were found in inflamed joint tissues, only COX-1 contributed substantially to clinical disease; COX-1-/- mice were fully resistant to disease, whereas COX-2-/- mice remained susceptible. These findings were confirmed by isoform-specific pharmacologic inhibition. Mice lacking mPGES-1 (and therefore PGE2) developed arthritis normally, whereas mice incapable of responding to PGI2 exhibited a significantly attenuated arthritis course, confirming a role of PGI2 in this arthritis model. CONCLUSION: These findings challenge previous paradigms of distinct "housekeeping" versus inflammatory functions of the COX isoforms and highlight the potential pathogenic contribution of prostanoids synthesized via COX-1, in particular PGI2, to inflammatory arthritis.
18721667 [What are the risks of not intensively treating a chronic inflammatory disease?]. 2008 Jul With more than 10 years of experience in rheumatology and thousands of patients treated, the infectious and oncological risks of TNF-alpha blocking agents are well known. The efficacy of biotherapies in rheumatismal diseases has been largely demonstrated. The recent review of publications and communications shows that biotherapies benefit the comorbidities associated with inflammatory rheumatisms (uveitis, Crohn disease, hemorrhagic rectocolitis, stroke, myocardial infarction). They can even reduce the excess mortality of chronic rheumatoid inflammatory diseases.
16729293 Efficient new cationic liposome formulation for systemic delivery of small interfering RNA 2006 Jun OBJECTIVE: Tumor necrosis factor alpha (TNFalpha) is among the most prominent cytokines in rheumatoid arthritis (RA) and is secreted mainly by macrophages. A direct method for restoring the immunologic balance in RA is use of small interfering RNA (siRNA) for silencing the TNFalpha transcript. The aim of this study was to determine the therapeutic effect of systemic administration of TNFalpha siRNA in an experimental model of RA, optimizing its delivery using new liposome formulations. METHODS: Murine macrophages were transfected with siRNA targeting TNFalpha, and expression was measured. The therapeutic effect in collagen-induced arthritis (CIA) was assessed after intravenous delivery of TNFalpha siRNA. Delivery was optimized using a carrier DNA for complexation with the cationic liposome RPR209120/DOPE. Levels of TNFalpha and other cytokines were measured in sera and joint tissue-conditioned media. Biodistribution was determined using a fluorescent siRNA. RESULTS: In vitro, TNFalpha siRNA efficiently and specifically modulated the expression of TNFalpha at both the messenger RNA and protein levels. In vivo, complete cure of CIA was observed when TNFalpha siRNA was administered weekly, complexed with the liposome and combined with carrier DNA. Inhibition (50-70%) of articular and systemic TNFalpha secretion was detected in the siRNA-injected groups, which correlated with a decrease in the levels of interleukin-6 and monocyte chemotactic protein 1. The main organs targeted by siRNA were the liver and spleen; the addition of liposome RPR209120 and carrier DNA significantly increased organ uptake. CONCLUSION: We demonstrated the efficiency of systemic delivery of siRNA designed to silence TNFalpha in CIA, using a liposome carrier system as a way to address the methodologic limitations in vivo.
16412693 Anti-inflammatory effect of all-trans-retinoic acid in inflammatory arthritis. 2006 Jun OBJECTIVE: To determine whether all-trans-retinoic acid (ATRA) improves the destruction of joints and the effect of cytokines on DBA/1J mice with collagen-induced arthritis (CIA). METHODS: Starting from the time of type II collagen injection, DBA/1J mice were injected intraperitoneally with PBS or 0.5 mg of ATRA 3 times per week for 35 days. The effects of treatment were monitored by determining arthritis and histological scores and measuring cellular proliferation, production of cytokines (IL-2, IL-10, IL-12, IL-6, IFN-gamma, and TNF-alpha) and IgG, and the expression of mRNAs for inducible nitric oxide synthase (iNOS), monocyte chemoattractant protein-1 (MCP-1), and CXCR3. RESULTS: The arthritis score and incidence of arthritis were lower in the mice treated with ATRA than in those treated with PBS. Histopathologic evidence of joint damage was 34% lower, and the infiltrations of macrophages were reduced in the mice treated with ATRA compared with those treated with PBS. Type II collagen- and ConA-stimulated proliferation of spleen cells, the production of cytokines (IL-6, IL-12, and TNF-alpha), the serum levels of total IgG and IgG1 anti-collagen antibodies, and the expression of mRNAs for MCP-1 were significantly reduced in the mice treated with ATRA than in those treated with PBS. CONCLUSION: ATRA improved the clinical course and reduced the production of inflammatory cytokines, immunoglobulin, and chemokines in murine CIA. These data suggest that ATRA might be also effective for the treatment of inflammatory arthritis like human rheumatoid arthritis.
17933705 Inguinal hernia vs. arthritis of the hip in sporting adolescents--case report and review o 2007 Jul 26 Chronic pain in the hip, groin or thigh can be caused by a wide spectrum of diseases posing extended diagnostic problems. We describe the case of a 10-years old child with chronic pain in the groin with gait restriction for more than six months without successful classification and treatment. The girl suffered from heavy pain in the groin after a sporting contest which forced her to walk with walking sticks and to avoid climbing stairs. Within six months she was examined by pediatric, orthopedic, pediatric surgery, pediatric orthopedic, radiology, pediatric rheumatology specialists. Working diagnoses were transient synovitis (coxitis fugax), arthritis, streptococcal arthritis, Morbus Perthes, rheumatic fever, rheumatoid arthritis. She was treated with antibiotics and ibuprofen in high dosage. Repeated laboratory tests and imaging studies (ultrasound, x-rays, magnetic resonance imaging) of the hip and pelvis did not support any of these diagnoses. Six months after beginning of the complaints the girl was presented by her mother to our institution. The physical examination showed a sharp localized pain in the groin, just in the region of the inguinal ligament with otherwise free hip movement. There was no visible inguinal hernia. The family history for hernia was positive. After infiltration of the ilioinguinal nerve the girl had a complete long-lasting disappearance of pain and gait disturbance. This led to the diagnosis of inguinal hernia with nerve entrapment. After hernia repair and neurolysis/neurectomy there was a continuous state of disappearance of pain and gait disturbances. CONCLUSION: To avoid such a diagnostic dilemma one should always discuss all possible causes. Non-visible inguinal hernia may be more common in females than previously thought. Nerve entrapment as a cause of groin pain has been well described. The relationship of the start of complaints with sporting activity, a positive family history for inguinal hernia, a lack of signs of inflammation and bone involvement in the laboratory and imaging studies together with a localized pain in the groin, almost immediate long-lasting disappearance of pain after infiltration of the ilioinguinal nerve allowing free motion leads to the diagnosis of inguinal hernia with nerve entrapment. Hernia repair and neurolysis are the adequate treatment avoiding unnecessary radiation.
18653379 Persistent parvovirus B19 infection and arthralgia in a patient mistakenly treated for Lym 2008 Oct We report a case of a 37-year-old woman with persistent parvovirus B19 infection and arthralgia mistakenly treated for Lyme disease. This case indicates that poor standardization of both screening and confirmatory assays for Lyme disease can lead to an incorrect diagnosis of Lyme disease. Before making a final diagnosis of Lyme arthritis in an endemic region, other causative agents of arthritis, such as parvovirus B19, should be excluded to avoid unnecessary treatment or to add appropriate therapy in the case of co-infections. Since parvovirus B19 is often associated with arthralgia and can mimic rheumatoid arthritis and autoimmune diseases, it should be included in the differential diagnosis of arthralgia.
17663929 [Psoriasis, a systemic disease?]. 2007 Jul It has long been recognized the epidemiological association of psoriasis, especially the most severe forms, with several diseases that share a common pathogenic substrate involving TNF-alpha and different target organs (arthritis and Crohn's disease, for example), as well as an increased risk of coronary heart disease and occlusive cardiovascular disease. In the patient with severe psoriasis there is also an increased prevalence of obesity, dyslipemia, adult diabetes mellitus, alcohol abuse and tobacco habit which contribute to the increased risk of mortality associated with atherosclerosis. Recently it has been identified the so-called metabolic syndrome, characterized by the association of abdominal obesity, atherogenic dyslipemia, hypertension, insulin resistance with or without glucose intolerance and a proinflammatory and prothrombotic state as a risk factor for cardiovascular disease. There is evidence that in rheumatoid arthritis as well as in psoriasis, chronic inflammation has a pathogenic role in the metabolic syndrome and associated comorbidities, and its adequate treatment may contribute to revert it. The dermatologist should recognize the elements of the metabolic syndrome and propose the patient with psoriasis, in addition to the optimal dermatologic treatment, changes in life habits and appropriate drug therapy to reduce the risk of cardiovascular morbi-mortality.
17224293 Engraftment of cutaneous fibroblasts within synovial membrane in a nonhuman primate: short 2007 Jan OBJECTIVES: Gene therapy using cells as vectors to achieve secretion of therapeutic proteins may hold promise in the treatment of chronic diseases. Cell-based gene therapy with xenogeneic cells secreting antiinflammatory cytokines (IL-4, IL-13, or IL-1 receptor type II) has been found effective in mice with collagen-induced arthritis (CIA), a model for human rheumatoid arthritis. Autologous cells engineered to produce antiinflammatory cytokines were also effective in the mouse CIA model. In all these experiments, the cells were grafted into the subcutaneous tissue of the back, resulting in systemic treatment. To evaluate the feasibility of cell-based gene therapy confined to the joints, we performed intraarticular injections of autologous cells in a rhesus monkey with CIA, a model more similar to human RA. METHODS: We prepared ex vivo cultures of skin fibroblasts from the animal then transfected the cells with a plasmid carrying the lacZ gene. We injected these marker cells into metacarpophalangeal, metatarsophalangeal, and interphalangeal joints. RESULTS: Kinetic evaluation of synovial tissue X-gal labeling, which reflected reported gene expression by skin fibroblasts present within the synovium, showed significant labeling by transfected cells up to 6 days after intraarticular injection. Xenogeneic fibroblasts (Chinese hamster ovary cells) injected intraarticularly were also detected within synovial specimens; however, labeling intensity was less marked than with autologous cells. Our findings establish the feasibility of skin fibroblast grafting into the synovium. CONCLUSION: This preliminary study opens the door to studies of heterotopic autologous transfected cells for the treatment of CIA in monkeys by direct gene transfer within joints.
16835702 Allelic frequency of the MCP-1 promoter -2518 polymorphism in the Turkish population and i 2007 Apr Although genetic and environmental factors contribute to the pathogenesis of juvenile rheumathoid arthritis (JRA), the etiology and pathogenesis remain controversial. The objective of this study was to investigate genotypic and allelic frequencies of monocyte chemoattractant protein-1 (MCP-1) gene -2518 (G/A) polymorphism in the healthy Turkish population and patients with JRA. Genomic DNA was collected from 66 JRA patients and 150 healthy individuals. To evaluate the association of the -2518 (G/A) MCP-1 gene polymorphism with the outcome of JRA, we analyzed the types of JRA and the score on the childhood health assessment questionnaire (C-HAQ score). In the healthy Turkish population, the frequencies of A and G alleles were 71 and 29%, respectively. No significant difference was observed between the JRA patients and healthy subjects in the distribution allelic and genotypic frequencies of the -2518 (G/A) MCP-1 gene polymorphism (p>0.05). However, the AG genotype was found to be higher and the AA genotype was found to be lower in the patients with systemic type JRA compared to those with the other types of JRA (p=0.019). When the JRA patients were evaluated according to the C-HAQ score, we found that the -2518 (G/A) MCP-1 gene polymorphism did not relate the prognosis (p>0.05). AG genotype was found to be higher in the systemic type of JRA. The results indicate that MCP-1 gene polymorphism might slightly associate with patients with systemic JRA. Further studies are needed to elucidate the role of this polymorphism in the pathogenesis of JRA in various populations because this polymorphism has a functional significance and an ethnic difference.
16886561 [Serological markers of arthritis in patients with chronic viral hepatitis]. 2006 Apr Wide range of different autoantibodies (e.g. rheumatoid factor, antinuclear antibodies, smooth muscle antibodies, anticardiolipin antibodies) can be detected in low titres in more than 70% of patients with chronic hepatitis. THE AIM OF THE STUDY: Prevalence of serological markers typical for rheumatic diseases in patients with chronic viral hepatitis was examined and the correlation between those markers and serum activity of liver enzymes was evaluated. MATERIAL AND METHODS: 80 patients (30 female and 50 male aged 43.5 +/- 10 years) with chronic viral hepatitis hospitalized in Department of Internal Diseases and Rheumatology of Medical Military Institute in Warsaw were included in the study. 16 of patients were infected with hepatitis virus B, 60 with hepatitis virus C, 4 suffered from both infections. Blood morphology, ESR, CRP aminotransferases activity, protein and bilirubin levels were measured in every patient. Serological examination included levels of antinuclear antibodies (ANA), smooth muscle antibodies (SMA), LKM-1, antineutrophil antibodies (ANCA), anticardiolipin antibodies (aCL), antimitochondrial antibodies (AMA), circulating immunological complexes (CIC), cryoglobulins and rheumatoid factor. RESULTS: At least one serological marker was found in 60 (75%) patients. Latex fixation reaction was positive in 42 (54%), rheumatoid factor was present in 25 (31%), aCL in 28 (34%), pANCA in 22 (27%) and CIC in 16 (20%). Antibodies ANA, AMA, LKM-1 and cryoglobulins were less frequently observed (6%, 5.5% and 7% respectively). The presence of autoantibodies was more frequent in patients with hepatitis C (77% vs. 62%). AMA, LKM-1 and cryoglobulins were detected only in that group of patients. There was no correlation between liver enzymes activity and presence of serological markers of rheumatic diseases. CONCLUSIONS: Serological markers considered to be typical for rheumatic disorders were detected in 75% patients (especially in patients with HCV). There is no correlation between aminotransferases activity and tested serological.
29319954 2007 Feb Objectives Metaanalysis of randomised controlled trials has shown that TNF-inhibitors are effective in RA. These trials however are undertaken in highly selective populations; under an experimental setting that may differ from that of clinical practice, and follow up rarely extend beyond 1 year. In addition all trials were sponsored by the manufacturer. We were asked to extend the review and meta-analysis of RCTs with a review of data from registries to evaluate efficacy and safety of TNF-inhibitors when used in clinical practice (real world). We focused particularly on the following questions: What is the efficacy of TNF-inhibitors when used outside clinical trials? What is the efficacy of TNF-inhibitors after long term use? What adverse events are reported in these studies? What is the risk of malignancies following long term use? What are the experiences concerning use of medication, treatment compliance and change of medication? Methods We searched Medline and Embase June 2006 by combining search terms for registries, cohort studies and databases with terms for TNF-inhibitors and rheumatoid arthritis (RA). We included publications from registries or databases on adalimumab, etanercept and infliximab for treatment of rheumatoid arthritis (RA), ankylosing spondylitis, psoriatic arthritis or juvenile idiopathic arthritis. Manufacturers were also invited to submit data. Outcomes considered were efficacy, safety and medication use. Results The search gave 290 hits, 64 references were retrieved and assessed in full text, and 23 publications finally included. These studies covered patients with RA, in addition we found one study on juvenile idiopathic arthritis. We did not identify relevant studies on ankylosing spondylitis or psoriatic arthritis. The summary of the results from the studies are as follows: Effectiveness: We included seven studies from registries and databases reporting clinical effects of TNF-inhibitors. In summary these studies showed that TNFinhibitors were effective also when used in clinical practice. The effect however appeared to be lower compared with RCTs. This could be explained by a more heterogeneous patient population. In addition patients in clinical practice often continued with existing medication, opposed to most clinical trials where patients often discontinued existing medications before enrolling. Although we aimed to 9 assess long-term effectiveness, few patients have been followed beyond 2-3 years of treatment. One study assessed patients with JIA, in this study treatment with TNF-inhibitor (etanercept) led to a significant reduction of the disease activity in most of the patients. Combination therapy: Two randomised controlled trials and data from registries evaluated the combination of TNF and MTX treatment. Treatment with TNFinhibitors and methotrexate (MTX) appeared more effective than treatment with TNFinhibitor alone in reducing the disease activity in patients with RA. . Cancer: We included six publications that assessed cancer risk following TNFtreatment. A general comments to these studies is that patients have not been followed sufficiently long to allow for conclusions regarding cancer risk. Four studies analysed risk of lymphoma or leukaemia, with inconsistent results. Two studies analysed risk of solid cancer, with inconcistent results. Experiences from transplantation patients shows that cancer usually develops 10-15 years after immunosuppressive medication. Hence, these studies does not give any further information about the risk of developing cancer following treatment with TNF-inhibitors than reported in the randomized controlled trials. Infections: Treatment with TNF-inhibitors were associated with increase the risk of infections. In particular, the risk of reactivation of latent tuberculosis. However, routine screening and treatment of tuberculosis prior to TNF-treatment have reduced this risk considerably. Compliance: Continuation of treatment with TNF-inhibitors (etanercept og infliximab) after one year was between 62-73 %. This number is lower than compared with RCTs . The reasons for ceasing TNF-treatment were in most cases adverse events or lack of effect. However, it was found that the compliance to TNF-inhibitors was higher then for traditional DMARDs. Conclusion: In conclusion, results from clinical trials and registries show that TNF-inhibitors are effective, also when used on a broader patient population outside the setting of clinical trials. Treatment with TNF-inhibitors is associated with increased risk of infections, in particular tuberculosis. Included studies does not allow for conclusion regarding risk of cancer. Thus, the issue of long term safety is at time being incomplete, with a follow up of 2-3 years in most studies. A national registry for treatment with TNF-inhibitors (and other biologics) in Norway would be a very helpful tool to identify the effect and adverse events after longtreatment with TNF-inhibitors.
18307273 Characterization of fibroblasts responsible for cartilage destruction in arthritis. 2008 Apr In the pathogenesis of rheumatoid arthritis (RA), synovial fibroblasts (SF) play a key role as they secrete distinct patterns of cytokines and express variable levels of costimulatory and adhesion molecules. The murine fibroblast cell line LS48 has been shown to be invasive in the cartilage destruction models in vivo and in vitro. The purpose of this study was to examine in detail the LS48 phenotype, to obtain a better understanding of the SF-mediated cartilage destruction in RA. The destructive fibroblasts line LS48 and the nondestructive 3T3 cells were cultured and characterized with slide-based and flow cytometry, using antibodies against several adhesion molecules, immunological acting molecules, and marker proteins. The invasive LS48 fibroblasts are characterized by significantly higher expression of adhesion molecules such as CD47 (IAP), CD51 (integrin alpha V), CD61 (GPIIIa), and CD147 (EMMPRIN), and immunological acting molecules such as CD40 (Bp50), CD55 (DAF), and TLR-2. The results from the slide-based and flow cytometry analyses were exactly the same, except for the selected CD147 and TLR-2. This study demonstrated that the destructive fibroblast cell line LS48 has the characteristics of RA SFs. The high expression of specific costimulatory and adhesion molecules underlines the aberrant phenotype of these cells when compared with noninvasive fibroblasts. Furthermore, slide-based and flow cytometry complement each other in fibroblast phenotyping. Overall, this study shows that LS48 is an excellent tool to gain a deeper understanding of SF in RA.
17584980 Stress, heat shock proteins, and autoimmunity: how immune responses to heat shock proteins 2007 Oct Especially since the (re-)discovery of T cell subpopulations with specialized regulatory activities, mechanisms of anti-inflammatory T cell regulation are studied very actively and are expected to lead to the development of novel immunotherapeutic approaches, especially in chronic inflammatory diseases. Heat shock proteins (Hsp) are possible targets for regulatory T cells due to their enhanced expression in inflamed (stressed) tissues and the evidence that Hsp induce anti-inflammatory immunoregulatory T cell responses. Initial evidence for an immunoregulatory role of Hsp in chronic inflammation was obtained through analysis of T cell responses in the rat model of adjuvant arthritis and the findings that Hsp immunizations protected against the induction of various forms of autoimmune arthritis in rat and mouse models. Since then, immune reactivity to Hsp was found to result from inflammation in various disease models and human inflammatory conditions, such as rheumatoid arthritis (RA), type 1 diabetes, and atherosclerosis. Now, also in the light of a growing interest in T cell regulation, it is of interest to further explore the mechanisms through which Hsp can be utilized to trigger immunoregulatory pathways, capable of suppressing such a wide and diversified spectrum of inflammatory diseases.
16855145 Microsomal prostaglandin E synthase-1, ephrins, and ephrin kinases as suspected therapeuti 2006 Jun Feeding information obtained in one criminal case into the profile of another crime often helps to solve the latter. The literature on two different "crimes," namely, acute systemic inflammation and arthritis (including osteoarthritis [OA] and rheumatoid arthritis [RA] deals largely with the same "gang" of inflammatory mediators, such as prostaglandin (PG) E2. Early investigations suggested that microsomal PGE synthase-1 (mPGES-1; a terminal PGE2-synthesizing enzyme) plays a pivotal role in bacterial lipopolysaccharide (LPS)-induced systemic inflammation, but overlooked the possibility that the same enzyme could be involved in OA or RA. Later studies showed that mPGES-1 is indeed a key perpetrator in arthritic diseases, a fact that could have been predicted earlier by pooling the new knowledge about mPGES-1 into the profile of arthritic diseases. In this review, we analyze our recent study on the expression of erythropoietin-producing hepatocellular (Eph) receptor kinases and their ligands, ephrins, in LPS-induced systemic inflammation. By pooling these results together with literature data into the profile of RA, we conclude that Eph kinases and ephrins are prime suspects for being involved in the pathogenesis of RA. We further conjecture that the involvement of Eph kinases and ephrins may be realized via the induction of angiogenesis in the inflamed joint, promotion of leukocyte infiltration, and activation of the infiltrated cells. Studies to test this new hypothesis seem warranted, and our prediction is that the "smoking gun" will be found.
17552056 Differential expression of Ro/SSA 60 kDa and La/SSB, but not Ro/SSA 52 kDa, mRNA and prote 2007 Jun OBJECTIVE: To analyze the protein and messenger RNA (mRNA) expression of La/SSB, Ro/SSA 60, and Ro/SSA 52 antigens in minor salivary glands (MSG) from patients with primary Sjögren's syndrome (pSS). METHODS: La/SSB, Ro/SSA 60, and Ro/SSA 52 protein expression was studied by immunohistochemistry in MSG from 26 patients with pSS and 16 controls. mRNA expression was determined by real-time polymerase chain reaction in MSG of 10 patients with pSS and 7 controls. RESULTS: La/SSB and Ro/SSA 60, but not Ro/SSA 52, mRNA expression was higher in samples from patients with pSS compared to controls (p < 0.05). La/SSB protein had higher expression in the cytoplasm of ductal cells than in the cytoplasm of mucous acinar cells in patients with pSS (p = 0.013) but not in controls. Ro/SSA 60 had higher expression in the cytoplasm of ductal cells than in the cytoplasm of serous acinar cells in patients with pSS (p = 0.006) but not in controls. The Ro/SSA 52 expression pattern was similar in patients and controls. There was no association between circulating autoantibodies to Ro/SSA or La/SSB and the aberrant expression of the cognate autoantigens. CONCLUSION: The increased Ro/SSA 60 and La/SSB mRNA expression in MSG of patients with pSS as well as the differential Ro/SSA 60 and La/SSB protein expression in ductal cells of MSG in patients with pSS suggest that these these 2 autoantigens, but not Ro/SSA 52, are probably involved in triggering and maintaining the tissue-specific autoimmune response in pSS MSG and may contribute to the antigen-driven immune response and local autoantibody production in pSS.
18480584 A fulminant case of renal vein thrombosis in a patient with autoimmune disorder and membra 2008 A previously healthy middle-aged woman noted a rapid onset of flank pain with gross hematuria. Enhanced CT scan showed thrombosis of the inferior vena cava and right renal vein. Laboratory findings revealed nephrotic proteinuria, Sjogren's syndrome (SjS), and Graves' disease (GD). A right nephrectomy was performed because of progressive and refractory renal necrosis. Renal specimens showed venous infarction with diffuse hemorrhagic and severe congestive renal necrosis, and membranous nephropathy (MN). The present case was diagnosed as acute renal necrosis due to catastrophic thrombosis in a patient with SjS, GD, and MN. It was thought that sudden development of thrombosis may have been caused by the status of the autoimmune disorders, and the associated MN.
18189198 Can sulfasalazine therapy induce or exacerbate Wegener's granulomatosis? 2008 Jan Sulfasalazine (SSZ) can induce serological and clinical autoimmune reactions but the occurrence of SSZ-related Wegener's granulomatosis (WG) has not been reported before. We describe two patients with rheumatoid factor (RF)-positive rheumatoid arthritis (RA) who developed biopsy-proven WG with serious organ involvement during SSZ therapy. The pathogenetic mechanism that explains the relationship between SSZ and the occurrence of a de novo anti-neutrophil cytoplasmic antibody (ANCA)-related vasculitis or a flare is discussed. We propose that WG can be a rare complication of SSZ therapy and that this, like other autoimmune adverse events of this drug, is mediated by SSZ-induced apoptosis.
18984420 Therapeutic potential for B-cell modulation in Sjögren's syndrome. 2008 Nov B-cell hyperactivity has been recognized for a long time in Sjögren's syndrome. This B-cell activation is firstly polyclonal but can progress to monoclonal B-cell lymphoproliferation. This article addresses the therapeutic potential of B-cell modulation in Sjögren's syndrome.