Browse

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

ID PMID Title PublicationDate abstract
12022346 Enhanced expression of a peanut agglutinin reactive O linked oligosaccharide on fibronecti 2002 May OBJECTIVE: To characterize the domain localization, quantitation, and functional binding consequences of an O linked oligosaccharide expressed on synovial fluid (SF) fibronectin (Fn). METHODS: Identification and localization of the O linked oligosaccharide was performed by limited digestion of isolated SF Fn with a series of proteolytic enzymes followed by Western blotting with peroxidase labeled peanut agglutinin. Binding affinity to denatured collagen was performed utilizing a solid phase gelatin-binding assay. Quantitation was performed by measuring purified Fn in an antibody-lectin sandwich binding assay. RESULTS: A desialyated O linked oligosaccharide was identified on the C-terminal 18 kDa segment of the SF Fn collagen-binding domain. These SF collagen-binding Fn fragments were more basic and had higher gelatin-binding affinities than corresponding plasma fibronectin fragments. Expression of this O linked oligosaccharide was highest on Fn isolated from osteoarthritic SF, followed by Fn isolated from rheumatoid arthritis SF, and finally normal human plasma. CONCLUSION: Fn isolated from SF have glycosylation alterations that may influence their biologic properties in the diseased joint.
15370717 Tumour necrosis factor-alpha (TNF-alpha) levels and influence of -308 TNF-alpha promoter p 2004 OBJECTIVE: To investigate the influence of -308 tumour necrosis factor-alpha (TNF-alpha) promoter polymorphism and circulating TNF-alpha levels in the clinical response to the infliximab treatment in patients with rheumatoid arthritis (RA). METHODS: One hundred and thirty-two RA patients were genotyped for TNF-alpha promoter by polymerase-chain reaction restriction fragment-length polymorphism (PCR-RFLP) analysis. Ten patients with the -308 TNF-alpha gene promoter genotype G/A, and 10 with the G/G genotype were selected and received 3 mg/kg of infliximab at Weeks 0, 2, 6, and 14. RESULTS: Both groups showed a significant improvement with treatment in all variables studied. Total mean TNF-alpha levels increased significantly with respect to basal levels in most of patients after treatment [probability (p)=0.04]. Only patients from G/A showed a statistically significant correlation between ACR 50 and the increase of TNF-alpha levels (p<0.03). CONCLUSION: A relationship was detected between ACR criteria of improvement and increased circulating TNF-alpha levels in RA patients subjected to anti-TNF-alpha therapy.
12739820 Demonstration of species-specific and cross-reactive components of hydatid cyst fluid anti 2003 Apr ELISA-hydatid cyst fluid antigen (HCF-Ag-ELISA) and conventional echinococcosis IHAT were assessed for cystic hydatid disease (CHD), confirmed by HCF-Ag immunoblotting assay. The sensitivity of the tests was 94.4% and 83.3% for HCF-Ag-ELISA and IHA respectively. HCF-Ag-ELISA showed some cross-reaction in tumor cases (5.5%), but no cross-reaction was observed in Rheumatoid arthritis patients. IHA showed 100% specificity. To confirm this data SDS-PAGE immunoblotting using HCF-Ag was applied. Echinococcus specific reactions were reported with 44Kda, 34Kda, 29Kda and 8Kda HCF-Ag resolved bands. Cross-reaction was found with 27Kda, 21Kda, 16Kda and 13Kda bands in tumor patients. Moreover, cross-reaction was found with 200Kda, 175Kda, 62Kda, 52Kda and 40Kda in serological anti-Schistosoma antibodies positive cases. So, using specific HCF-Ag components, immunoblotting provided 100% sensitivity and specificity in CHD.
15334456 Effects of hypoxia on the expression and activity of cyclooxygenase 2 in fibroblast-like s 2004 Aug OBJECTIVE: Rheumatoid synovium is characterized by hyperplasia of fibroblast-like (type B) synoviocytes (FLS), infiltration with mononuclear leukocytes, and tissue hypoxia. Although the latter is well documented, it has received little attention in dissection of the biochemical events that mediate the inflammatory lesion in rheumatoid arthritis (RA). Therefore, this study was designed to assess the effect of hypoxia on FLS responses to the monokine interleukin-1beta (IL-1beta) and to monocyte conditioned medium. METHODS: FLS obtained from serial cultures of synovial fluid aspirates were treated with IL-1beta or monocyte conditioned medium, under normoxia and hypoxia. RESULTS: In hypoxia, transcription of cyclooxygenase 2 (COX-2), expression of COX-2 protein, and production of COX-2-derived eicosanoids and matrix metalloproteinase (MMP) activity by FLS were all increased in response to IL-1beta. In contrast to our recent observations concerning monocytes, there was no change in COX-2 message stability and cytosolic phospholipase A2 activity in the FLS under hypoxia. Treatment of monocyte conditioned medium with an IL-1beta blocking antibody showed that most of the effect of the conditioned medium was attributable to IL-1beta. CONCLUSION: The findings suggest that hypoxia is an important factor in aggravating the inflammatory lesion in RA, through increased production of COX-2-derived nociceptive eicosanoids and increased release of tissue-damaging MMPs.
14663290 Increased prevalence of severe subclinical atherosclerotic findings in long-term treated r 2003 Nov We conducted the current study to search for subclinical atherosclerosis in patients with rheumatoid arthritis (RA) without clinically evident atherosclerosis or its complications who had been treated for a long duration, and to assess whether demographic or clinical factors affect the development of atherosclerotic disease. Forty-seven white patients fulfilling the 1987 American College of Rheumatology classification criteria for RA were recruited from Hospital Xeral-Calde, Lugo, Spain. Patients were required to have been treated for at least 5 years, including current treatment with 1 or more disease-modifying antirheumatic drugs. Patients with diabetes mellitus, renal insufficiency, hypertension, cardiovascular or cerebrovascular disease, and smokers were excluded. Forty-seven matched controls were also studied. Carotid intima-media wall thickness (IMT) and carotid plaques were measured in the right common carotid artery. The study was performed using high-resolution B-mode ultrasound. Patients had greater carotid IMT (0.779 +/- 0.164 mm) than did controls (0.699 +/- 0.129 mm); (p = 0.010). Sixteen (34%) patients showed carotid plaques compared with only 7 (15%) controls (p = 0.031). There was a positive correlation between the age at the time of study and the carotid IMT. Patients with carotid plaques had significantly greater carotid IMT (0.859 +/- 0.116 mm) than those without plaques (0.739 +/- 0.171 mm) (p = 0.014). Also, RA patients with carotid plaques had a significantly longer disease duration (mean, 21.0 yr) and more extraarticular manifestations (63%) than those without plaques (mean, 12.7 yr and 26%, respectively). Age at the time of the study and disease duration were the best predictive factors for the development of severe morphologic expression of atherosclerotic disease. The present study confirms an increased frequency of severe subclinical atherosclerotic findings in long-term actively treated RA patients from northwest Spain.
15564310 Soluble TRAIL concentrations are raised in patients with systemic lupus erythematosus. 2005 Jun BACKGROUND: Increased apoptosis may induce autoimmune conditions. Apoptosis is induced by binding of death receptor ligands, members of the tumour necrosis factor (TNF) superfamily, to their cognate receptors. The Fas-Fas ligand pathway has been studied extensively in relation to systemic lupus erythematosus (SLE). However, other death pathways are also considered important. TNF related apoptosis inducing ligand (TRAIL), another ligand of the TNF superfamily, induces apoptosis in sensitive cells. OBJECTIVE: To assess soluble (s) TRAIL concentrations in sera of SLE patients. METHODS: 40 SLE patients were studied (20 with active and 20 with inactive disease). Serum sTRAIL concentrations were measured by a solid phase sandwich enzyme linked immunosorbent assay. Levels in SLE patients were compared with those in patients with rheumatoid arthritis (n = 20), Wegener's granulomatosis (n = 20), and healthy controls (n = 20). RESULTS: Mean (SEM) serum sTRAIL concentration in SLE patients (936.0 (108.2) pg/ml) was higher than in healthy controls (509.4 (33.8) pg/ml; p<0.01) or in disease control patients with rheumatoid arthritis (443.8 (36.1) pg/ml, p<0.001) or Wegener's granulomatosis (357.1 (32.2) pg/ml; p<0.001). The mean serum sTRAIL concentration was 1010.2 (168.0) pg/ml for patients with inactive disease and 861.8 (138.7) pg/ml for those with active disease. sTRAIL values were not correlated with specific manifestations of the disease, such as leucopenia or lymphopenia, or with SLE disease activity index. CONCLUSIONS: Serum sTRAIL concentrations are increased SLE patients. This seems to be disease specific and could indicate a role for TRAIL in SLE pathophysiology.
12774626 [Chemical and pharmacological advances of the study on zushima]. 2002 Jun OBJECTIVE: To review the progress in the research of the active ingredients of Zushima and their pharmacological activities. METHOD: Base on the articles of the chemical constituents and pharmacological activities of Zushima. RESULT: Traditional Chinese drug, Zushima contains coumarins, diteropenoids, lignans, flavonoids, anthraquinones and sterols. Pharmacological investigation concludes that it has actions of painkilling, antiinflammation, inhibiting bacteria, antithrombus, antitumer and antifertility. CONCLUSION: Zushima has extensive actions in pharmacology. And plant resources are very rich. It is a meaning job to study the chemical ingredients and pharmacological activities of Zushima further.
12070679 Soluble HLA in saliva of patients with autoimmune rheumatic diseases. 2002 Jun OBJECTIVES: The limited number of studies addressing the presence of soluble human leukocyte antigen (HLA) in body fluids such as tears, urine, sweat, and saliva are restricted to healthy subjects. In this study, we applied solid-phase enzyme-linked immunoassay to quantify soluble HLA class I (sHLA-I) and class II (sHLA-II) molecules in saliva and in selected serum samples obtained from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome (SS). RESULTS: While saliva from normal subjects (n=35) contained levels of sHLA-I that were undetectable (n=7) or ranged from 9 ng/ml to 70 ng/ml (30+/-3.7 ng/ml, n=28), sHLA-I among 38 patients with moderately active RA ( n=24) or SLE (n=14) were significantly elevated (222+/-81.4 ng/ml and 120+/-27.3 ng/ml, respectively, P<0.0001). Intriguingly, sHLA-I levels were even higher in patients whose disease was regarded as active. Specifically, sHLA-I averaged 683+/-189 ng/ml in patients with active RA (n=13) and 230+/-24.5 ng/ml in patients with active SLE (n=7). This was significantly higher than in patients with milder forms of these diseases (P<0.0001). All five subjects with SS had severe disease with high levels of sHLA-I (mean 486+/-86 ng/ml). The concentrations of saliva sHLA-II in the disease groups studied were comparable with levels found in normal controls. The sHLA-I in severe and mild states was investigated in purified serum and saliva from a patient with SS. While 44-kDa fragments of serum HLA-I were detectable in severe SS, they were undetectable in saliva HLA at any time; 35-37-kDa fragments of serum or saliva HLA-I were detected during both mild and severe disease. Interestingly, the 39-kDa fragment was detected in both body fluids during severe but not mild forms of SS. Similarly, the isoforms with the molecular masses 39 kDa and 44 kDa were mainly identified in the purified material obtained from serum of SLE patients. CONCLUSIONS: Collectively, our data suggest that the measurement of soluble HLA in body fluids can be of both diagnostic and prognostic value in the assessment of patients with autoimmune rheumatic disorders. The mechanism by which sHLA enters saliva is unclear, but they probably are not acquired from serum.
12399645 A case of SIADH induced by mizoribin administration. 2002 Dec We describe a 74-year-old man with rheumatoid arthritis (RA) who developed syndrome of inappropriate secretion of antidiuretic hormone (SIADH) 1.5 months after commencement of mizoribin prescription when his arthritis was improved. He noticed nausea and headache and serum Na fell as low as 118 mEq/l. Normal urinary Na excretion without hypotension or hemoconcentration negated the possibility of dehydration resulting from urinary Na loss. Serum antidiuretic hormone (ADH) remained elevated at 0.59 pg/ml in spite of a significant reduction in serum osmolality to 254 mosm/kg. He had no organic disease likely to cause SIADH. Despite infusion of hypertonic saline, his serum Na was not restored to normal. Shortly after mizoribin withdrawal, his serum Na increased significantly from 128 to 139 mEq/l and plasma osmolality from 265 to 287 mosm/kg. ADH hypersecretion in relation to plasma osmolality was reversed by mizoribin withdrawal, suggesting that bredinin might adversely induce SIADH. Additional predisposing factors were the patient's age and difficulty in urination due to benign prostatic hypertrophy. In summary, we report herein the first case of SIADH believed to be an adverse effect of mizoribin, which may therefore needed to be added to the list of drugs which can induce SIADH.
15500137 [Secondary nephrotic syndrome due to collagen disease and vasculitis]. 2004 Oct The most frequent and representative nephrotic syndrome associated with collagen disease is encountered in patients suffering from lupus nephritis. Lupus nephritis is a glomerulonephritis, which discloses various localizations of immune complexes in the endothelium, mesangium and subepithelium. In addition, vasculitides complicated by nephrotic syndrome also show the deposition of immune complexes in their glomeruli, such as Henoch-Schönlein nephritis and cryoglobulinemic nephritis. The pathogenetic mechanisms of these nephrotic syndromes are explained as follows. The depositions of immune complexes in glomeruli causes proteinuria through a variety of mechanisms. Namely, subendothelial and mesangial immune deposits give capillary and mesangial injuries as well as inflammation that are mediated through activation of complements and cytokines, and subsequently leads to nephrotic-range proteinuria and impairment of renal function. On the other hand, subepithelial and intramembranous deposits disrupt the regulated arrangement of epithelial cells and slit diaphragms, and then disturb the slit diaphragms. The eventual dysfunction of slit diaphragms accordingly progresses to massive proteinuria even without capillary injury. Therefore, nephrotic syndrome associated with collagen disease or vasculitis is usually observed in lupus nephritis or vasculitis related to immune complex depositions, but is not observed in non-immune complex glomerulopathy or vasculopathy.
15642131 MMP-3 expression and release by rheumatoid arthritis fibroblast-like synoviocytes induced 2005 Fibroblast-like synoviocytes (FLSs) play a major role in the pathogenesis of rheumatoid arthritis (RA) by secreting effector molecules that promote inflammation and joint destruction. How these cells become and remain activated is still elusive. Both genetic and environmental factors probably play a role in transforming FLSs into inflammatory matrix-degrading cells. As bacterial products have been detected in the joint and shown to trigger joint inflammation, this study was undertaken to investigate whether a bacterial ligand of integrin alpha5beta1, protein I/II, could contribute to the aggressive behavior of RA FLSs. Protein I/II is a pathogen-associated molecular pattern (PAMP) isolated from oral streptococci that have been identified in the joints of RA patients. The response of RA and osteoarthritis FLSs to protein I/II was analyzed using human cancer cDNA expression arrays. RT-PCR and pro-MMP-3 (pro-matrix metalloproteinase) assays were then performed to confirm the up-regulation of gene expression. Protein I/II modulated about 6% of all profiled genes. Three of these, those encoding IL-6, leukemia inhibitory factor, and MMP-3, showed a high expression level in all RA FLSs tested, whereas the expression of genes encoding other members of the cytokine or MMP-family was not affected. Furthermore, the up-regulation of MMP-3 gene expression was followed by an increase of pro-MMP-3 release. The expression of interferon regulatory factor 1 and fibroblast growth factor-5 was also up-regulated, although the expression levels were lower. Only one gene, that for insulin-like growth factor binding protein-4, was down-regulated in all RA FLSs. In contrast, in osteoarthritis FLSs only one gene, that for IL-6, was modulated. These results suggest that a bacterial ligand of integrin alpha5beta1 may contribute to the aggressive behavior of RA FLSs by inducing the release of pro-inflammatory cytokines and a cartilage-degrading enzyme, such as IL-6 and MMP-3, respectively.
14508072 Detection of antibodies against glucose 6-phosphate isomerase in synovial fluid of rheumat 2003 Aug 31 We have used a surface plasmon resonance biosensor (SPR, BIACORE 2000) to detect antibodies against glucose 6-phosphate isomerase (GPI) in synovial fluids of rheumatoid arthritis (RA) and osteoarthritis (OA). Recombinant human GPI proteins fused with or without NusA were expressed in E. coli, purified to homogeneity and immobilized in flow cells of CM5 sensor chips. The flow cells immobilized with NusA protein or bovine serum albumin were used to monitor non-specific binding. Synovial fluid samples from RA patients showed a significantly higher level of binding to recombinant GPI proteins than samples from OA patients. Proteins which bound to the recombinant GPI proteins were confirmed to be immunoglobulin through the administration of anti-human immunoglobulin. NusA fusion protein was excellent for this assay because of a low background binding activity in the SPR analysis and its advantage of increased solubility in recombinant protein production. These results suggested a useful utilization of recombinant NusA-GPI fusion protein for the detection of autoantibodies against GPI in RA patients.
12709536 Serious bacterial infections in patients with rheumatoid arthritis under anti-TNF-alpha th 2003 May OBJECTIVE: With rising numbers of anti-tumour necrosis factor alpha (TNF-alpha) treatments for rheumatoid arthritis (RA), Crohn's disease and other conditions, physicians unaware of potential pitfalls are increasingly likely to encounter associated severe infections. Our purpose was to assess the incidence and nature of severe infections in our RA patients under anti-TNF-alpha therapy. METHODS: We reviewed patient charts and records of the Infectious Disease Unit for serious infections in patients with RA in the 2 yr preceding anti-TNF-alpha therapy and during therapy. RESULTS: Serious infections affected 18.3% of patients treated with infliximab or etanercept. The incidence was 0.181 per anti-TNF-alpha treatment year vs 0.008 in the 2 yr preceding anti-TNF-alpha therapy. In several cases, only a few signs or symptoms indicated the severity of developing infections, including sepsis. CONCLUSIONS: A high level of suspicion of infection is necessary in patients under anti-TNF-alpha therapy. We suggest additional strategies for the prevention, rapid identification and pre-emptive therapy of such infections.
12538717 A novel anti-inflammatory role for simvastatin in inflammatory arthritis. 2003 Feb 1 3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) exert favorable effects on lipoprotein metabolism, but may also possess anti-inflammatory properties. Therefore, we explored the activities of simvastatin, a lipophilic statin, in a Th1-driven model of murine inflammatory arthritis. We report in this study that simvastatin markedly inhibited not only developing but also clinically evident collagen-induced arthritis in doses that were unable to significantly alter cholesterol concentrations in vivo. Ex vivo analysis demonstrated significant suppression of collagen-specific Th1 humoral and cellular immune responses. Moreover, simvastatin reduced anti-CD3/anti-CD28 proliferation and IFN-gamma release from mononuclear cells derived from peripheral blood and synovial fluid. Proinflammatory cytokine production in vitro by T cell contact-activated macrophages was suppressed by simvastatin, suggesting that such observations have direct clinical relevance. These data clearly illustrate the therapeutic potential of statin-sensitive pathways in inflammatory arthritis.
12640890 Percutaneous arthrodesis. 2003 Feb It has been generally accepted that residual cartilage and subchondral bone has to be removed in order to get bony fusion in arthrodeses. In 1998 we reported successful fusion of 11 rheumatoid ankles, all treated with percutaneous fixation only. In at least one of these ankle joint there was cartilage left. This was confirmed by arthrotomy in order to remove an osteophyte, which hindered dorsiflexion. More than 25 rheumatoid patients with functional alignment in the ankle joint have subsequently been operated on with the percutaneous technique, and so far we have had only one failure. Patients with rheumatoid arthritis are known to sometimes fuse at least their subtalar joints spontaneously, and the destructive effect of the synovitis on the cartilage could contribute to fusion when using the percutaneous technique. In a rabbit study we therefore tested the hypothesis that even a normal joint can fuse merely by percutaneous fixation. The patella was fixated to the femur with lag screw technique without removal of cartilage, and in 5 of 6 arthrodeses with stable fixation bony fusion followed. Depletion of synovial fluid seemed to be the mechanism behind cartilage disappearance. The stability of the fixation achieved at arthrodesis surgery is an important factor in determining success or failure. Dowel arthrodesis without additional fixation proved to be deleterious. A good fit of the bone surfaces appears necessary. In the ankle joint, it would be technically demanding to retain the arch-shaped geometry of the joint after resection of the cartilage. Normally the joint surfaces are resected to produce flat osteotomy surfaces that are thus easier to fit together, encouraging healing to occur. On the other hand it is considered an advantage to preserve as much subchondral bone as possible, as the strong subchondral bone plate can contribute to the stability of the arthrodesis. Ankle arthrodesis can be successfully performed in patients with rheumatoid arthritis by percutaneous screw fixation without resection of the joint surfaces. This procedure has two advantages: first, it is less surgically traumatic, second, both the arch-shaped geometry and the subchondral bone are preserved, and thus both could contribute to the postoperative stability of the construct. Intuitively, preservation of the arch-shape should increase rotational stability. The results of our experimental sawbone study indicate that the arch shape and the subchondral bone should be preserved when ankle arthrodesis is performed. The importance of this is likely to increase in weak rheumatoid bone. In a finite element study the initial stability provided by two different methods of joint preparation and different screw configurations in ankle arthrodesis, was compared. Better initial stability is predicted for ankle arthrodesis when joint contours are preserved rather than resected. Overall, inserting the two screws at a 30-degree angle with respect to the long axis of the tibia and crossing them above the fusion site improved stability for both joint preparation techniques. The question rose as to whether patients with osteoarthritis could also be operated on solely by percutaneous fixation technique. The first metatarsophalangeal joint in patients with hallux rigidus was chosen as an appropriate joint to test the percutaneous technique. In this small series we have shown that it is possible to achieve bony fusion with a percutaneous technique in an osteoarthrotic joint in humans, but failed to say anything about the fusion rate.
15334455 The rise and decline of nonsteroidal antiinflammatory drug-associated gastropathy in rheum 2004 Aug OBJECTIVE: Nonsteroidal antiinflammatory drug (NSAID)-associated gastropathy is a major cause of hospitalization and death. This study was undertaken to examine whether recent preventive approaches have been associated with a declining incidence of NSAID gastropathy, and, if so, what measures may have caused the decline. METHODS: We studied 5,598 patients with rheumatoid arthritis (RA) over 31,262 patient-years at 8 sites. We obtained standardized longitudinal information on the patients that had been previously used to establish the incidence of NSAID gastropathy, and also information on patient risk factors and differences in toxicity between NSAIDs. Consecutive patients were followed up with biannual Health Assessment Questionnaires and medical record audits between 1981 and 2000. The major outcome measure was the annual rate of hospitalization involving bleeding, obstruction, or perforation of the gastrointestinal (GI) tract and related conditions. RESULTS: Rates of GI-related hospitalizations rose from 0.6% in 1981 to 1.5% in 1992 (P < 0.001), and then declined to 0.5% in 2000 (P < 0.001). The fitted spline curve fit the data well (R2 = 0.70). The period of rise was mainly associated with increasing patient age and the GI risk propensity score. The period of decline was associated with lower doses of ibuprofen and aspirin, a decline in the use of "more toxic" NSAIDs from 52% to 42% of patients, a rise in the use of "safer" NSAIDs from 19% to 48% of patients, and increasing use of proton-pump inhibitors, but not with change in age, NSAID exposure, or GI risk propensity score. CONCLUSION: The risk of serious NSAID gastropathy has declined by 67% in these cohorts since 1992. We estimate that 24% of this decline was the result of lower doses of NSAIDs, while 18% was associated with the use of proton-pump inhibitors and 14% with the use of less toxic NSAIDs. These declines in the incidence of NSAID gastropathy are likely to continue.
12089323 Predominant selection of T cells specific for the glycosylated collagen type II epitope (2 2002 Jul 23 Rheumatoid arthritis (RA) is associated with certain MHC class II alleles and is characterized by a chronic autoimmune response in the joints. Using transgenic mice expressing human DR4 (DRB1*0401) and human CD4, but lacking endogenous MHC class II, we show that posttranslational glycosylation of type II collagen (CII) influences the level of T cell tolerance to this candidate cartilage-specific autoantigen. In such mice, the expression of human CII resulted in a tolerized murine T cell response to human CII. However, tolerance induction remained incomplete, preferentially deleting responses to the nonmodified CII 263-270 epitope, whereas T cell recognition of a glycosylated variant of this epitope was affected to a lesser degree. A similar dominance of T cell responses to CII-glycopeptides was recorded in a cohort of severely affected RA-patients (n = 14). Thus, RA T cells predominantly recognize the immunodominant CII peptide in its glycosylated form and may explain why previously it has been difficult to detect T cell responses to CII in RA patients.
15077294 Decreases in rates of hospitalizations for manifestations of severe rheumatoid arthritis, 2004 Apr OBJECTIVE: To determine whether the rates of hospitalization for 4 manifestations of severe rheumatoid arthritis (RA), which are used as indicators of long-term health outcomes, have changed from 1983 to 2001. METHODS: Data on all patients with RA who were hospitalized with rheumatoid vasculitis or to undergo splenectomy for Felty's syndrome, cervical spine fusion for myelopathy, or total knee arthroplasty at hospitals in California were abstracted from a state hospitalization database. Changes in rates of hospitalization from 1983 to 2001 were examined in this serial cross-sectional study. RESULTS: Rates of hospitalization for rheumatoid vasculitis and splenectomy in Felty's syndrome decreased progressively over time. The risk of hospitalization for rheumatoid vasculitis was one-third lower in 1998-2001 than in 1983-1987. The risk of hospitalization for splenectomy in Felty's syndrome was 71% lower in 1998-2001 than in 1983-1987. There were no significant decreases in the rates of hospitalization for cervical spine surgery or total knee arthroplasty (primary and revision), although in 1998-2001 there was a reversal of the trend of increasing rates of total knee arthroplasty. The risk of hospitalization for primary total knee arthroplasty was significantly lower in 1998-2001 than in 1990-1993 (rate ratio 0.90, 95% confidence interval 0.86-0.95; P < 0.0001). CONCLUSION: Rates of hospitalization for rheumatoid vasculitis and splenectomy in Felty's syndrome have decreased over the past 19 years, and there has been a recent decrease in the rates of primary total knee arthroplasty in patients with RA. Although several factors may account for these decreases, these findings suggest that since the early 1980s, the long-term health outcomes of patients with RA have improved.
12135181 Detection and monitoring of methotrexate-associated lung injury using serum markers KL-6 a 2002 Jun The applicability of monitoring concentrations of serum KL-6 and serum surfactant protein-D (SP-D) in the detection of methotrexate-associated lung injury (MTX pneumonitis) in patients with rheumatoid arthritis (RA) was investigated. The concentrations of these markers, sequentially measured in two patients with RA complicated with MTX pneumonitis, were increased in accordance with the severity of MTX pneumonitis. Conversely, the concentrations of these markers were decreased with the improvement of MTX pneumonitis, suggesting that the monitoring of these markers could be applicable not only for detecting the onset of MTX pneumonitis, but also for detecting the therapeutic response of MTX pneumonitis.
14584907 Disease-specific expression of tartrate-resistant acid phosphatase isoforms. 2003 Oct The association between elevated serum type 5 TRACP activity and metabolic bone diseases has been recognized for many years. However, serum type 5 TRACP exists as two related isoforms: 5a and 5b. Only isoform 5b is osteoclast-derived; the origin and significance of isoform 5a has hardly been explored. We have used simultaneous immunoassays for type-5 TRACP activity and total type-5 TRACP protein in conjunction with non-denaturing gel electrophoresis and column chromatography to investigate the nature and significance of TRACP isoforms 5a and 5b in end-stage renal disease (ESRD) and rheumatoid arthritis (RA). Our studies have shown that TRACP activity and protein are elevated in approximately 50% of sera from ESRD patients, which is caused by osteoclastic isoform 5b. We have also shown that total TRACP protein, but not TRACP activity, is elevated in approximately 30% of sera from RA patients, which is caused by non-osteoclastic isoform 5a. When macrophages or dendritic cells (DC) were cultured in vitro, abundant TRACP 5a was secreted into the culture medium, whereas TRACP 5b was retained intracellularly by both cell types. This implicates macrophages and DC as potential sources of elevated TRACP 5a in RA. Because TRACP isoform expression may be disease-specific, it is important to be able to distinguish TRACP 5a from 5b. There are four criteria by which to do so: (1) TRACP 5a bears sialic acid residues while TRACP 5b does not; (2) the pH optimum for TRACP 5a is 5.2 while that for TRACP 5b is 5.8; (3) the specific activity of TRACP 5a is significantly lower than that of TRACP 5b; and (4) TRACP 5a is as an uncleaved polypeptide, whereas TRACP 5b is a proteolytically nicked disulfide-linked "heterodimer." The differences in biochemical properties and disease-specific expression of TRACP isoforms 5a and 5b suggest that they are regulated differently and perform separate functions in a tissue-specific manner.