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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12111623 | Alkaline phosphatase in rheumatoid arthritis patients: possible contribution of bone-type | 2002 Jun | Raised serum alkaline phosphatase (ALP) activity in rheumatoid arthritis (RA) has been reported, although its aetiology is not clear. In this paper we investigate whether synovial tissue is a possible source of raised ALP activity in RA. The activities and isozymes of ALP were determined in sera and synovial fluids from 22 RA and seven osteoarthritis (OA) patients. The expression of both protein and ALP mRNA in synovial tissue was investigated immunohistochemically and by reverse transcription (RT) PCR. ALP activity was higher in serum and synovial fluid from RA patients than in those from OA patients. In addition, the ratio of levels of bone-type ALP to those of liver-type ALP was significantly higher in synovial fluid than in serum from RA patients. Bone-type ALP was positive around the perivascular area and the subepithelial cells in the synovial tissue from RA patients. In contrast, the synovial tissue from OA patients exhibited no staining. The mRNA of bone-type ALP was detected in RA synoviocytes. In conclusion, ALP levels were elevated in both serum and synovial fluid from RA patients. Bone-type ALP derived from the synovial tissue may contribute to the raised activities of ALP in RA patients. | |
15067654 | A simple capsulorrhaphy in a posterior approach for total hip arthroplasty. | 2004 Apr | In an attempt to decrease a 4% incidence of posterior hip dislocation following a posterior approach, a simple capsulorrhaphy was utilized in 255 consecutive primary total hip arthroplasties performed by 1 surgeon. All patients were reviewed at a minimum of 2 years' postoperatively, and no patient was lost to follow-up. One patient sustained a posterior hip dislocation, whereas there were no anterior hip dislocations. The dislocation rate of 0.4% is equal to or less than the rates of dislocation reported in the literature using other posterior repairs. This technique differs from other reported methods because of its simplicity and ease of repair. Only the capsule (and not the rotators) is sutured to the medius tendon (not to bone), creating an elastic endpoint that is less likely to disrupt during the healing process. | |
11937537 | Formation of the killer Ig-like receptor repertoire on CD4+CD28null T cells. | 2002 Apr 15 | Killer Ig-like receptors (KIRs) are expressed on CD4(+)CD28(null) T cells, a highly oligoclonal subset of T cells that is expanded in patients with rheumatoid arthritis. It is unclear at what stage of development these T cells acquire KIR expression. To determine whether KIR expression is a consequence of clonal expansion and replicative senescence, multiple CD4(+)CD28(null) T cell clones expressing the in vivo dominant TCR beta-chain sequences were identified in three patients and analyzed for their KIR gene expression pattern. Based on sharing of TCR sequences, the clones were grouped into five clone families. The repertoire of KIRs was diverse, even within each clone family; however, the gene expression was not random. Three particular receptors, KIR2DS2, KIR2DL2, and KIR3DL2, had significant differences in gene expression frequencies between the clone families. These data suggest that KIRs are successively acquired after TCR rearrangement, with each clone family developing a dominant expression pattern. The patterns did not segregate with the individual from whom the clones were derived, indicating that peripheral selection in the host environment was not a major shaping force. Several models were examined using a computer algorithm that was designed to simulate the expression of KIRs at various times during T cell proliferation. The computer simulations favored a model in which KIR gene expression is inducible for a limited time during the initial stages of clonal expansion. | |
15361375 | Influence of guideline adherence on outcome in a randomised controlled trial on the effica | 2004 Oct | OBJECTIVE: To study the influence of rheumatologists' adherence to a methotrexate guideline on efficacy and toxicity in the treatment of rheumatoid arthritis. METHODS: In a 48 week randomised controlled trial of methotrexate, comparing folates with placebo, rheumatologists were advised on methotrexate dosage using a guideline reflecting daily practice. The influence of guideline non-adherence on outcome was analysed using generalised estimating equations and survival analysis. RESULTS: In 51% of the 411 study patients the guidelines were always followed. Non-adherence resulted in lower doses of methotrexate in 25% of cases, and higher doses in 24%. The reduction in the disease activity score was significantly greater (mean -0.4; p = 0.0085) in the adherent group than in the "low dose" group; the "high dose" group did not differ from the adherent group. Dropout caused by severe adverse events did not differ between the three groups. CONCLUSIONS: There is an indication that adherence to guidelines on methotrexate dosage may benefit patients with rheumatoid arthritis by improving disease activity without increasing toxicity. For definite proof, a randomised controlled trial comparing guideline supported dosing with usual care is needed. | |
11796404 | Increased matrix metalloproteinase-3 serum levels in rheumatic diseases: relationship with | 2002 Feb | OBJECTIVE: To determine matrix metalloproteinase-3 (MMP-3) serum levels in patients with rheumatic diseases and to study the relation between MMP-3 and C reactive protein (CRP) levels. METHODS: MMP-3 serum levels were determined by enzyme linked immunosorbent assay (ELISA) in (a) patients with active inflammatory rheumatic diseases: rheumatoid arthritis (RA), psoriatic arthritis, polymyalgia rheumatica, acute crystal arthritis, and ankylosing spondylitis; (b) patients with active inflammatory systemic diseases: cutaneo-articular or renal systemic lupus erythematosus (SLE), systemic sclerosis, and vasculitides; (c) patients with non-inflammatory rheumatic diseases: osteoarthritis and fibromyalgia; (d) critically ill patients without rheumatic diseases, representing an acute inflammatory control group; (e) healthy controls. RESULTS: MMP-3 serum levels were significantly increased in patients with active RA, psoriatic arthritis, and polymyalgia rheumatica, whether treated or not by corticosteroids, and in female patients with acute crystal arthritis. MMP-3 serum levels were normal in steroid-free patients with active cutaneo-articular or renal SLE, systemic sclerosis, and vasculitides but were significantly increased in steroid treated patients. MMP-3 levels were normal in fibromyalgia, osteoarthritis, ankylosing spondylitis, and acute inflammatory controls. MMP-3 was significantly correlated with CRP in RA (r=0.5, p=0.0004) but not in any of the other disease groups. CONCLUSIONS: MMP-3 serum levels are increased in inflammatory rheumatic diseases characterised by joint synovitis, such as RA, polymyalgia rheumatica, psoriatic arthritis, and acute crystal arthritis-that is, whether the diseases are acute or chronic, erosive or not. They are normal in SLE, systemic sclerosis, and vasculitides as well as in non-rheumatic inflammatory controls, but are significantly increased by steroids. These data strongly suggest that serum MMP-3 reflects synovial inflammation. | |
11904962 | [Infliximab(chimeric monoclonal antibody to tumor necrosis factor alpha)]. | 2002 Mar | In rheumatoid arthritis and inflammatory bowel disease, such as Crohn's disease, certain immunological abnormalities are considered as its cause, but the fundamental mechanism remains unclear. However, recent researches revealed that inflammatory cytokines, such as TNF-alpha, IL-1 and IL-6, are greatly involved in these immunological abnormalities. This led to the development of anti-cytokine therapy using monoclonal antibodies to these cytokines. Among them, Infliximab, a chimeric monoclonal antibodies to TNF-alpha, is most clinically applied and marked therapeutic effect is seen in various diseases. | |
12828565 | Modelling autoimmune rheumatic disease: a likelihood rationale. | 2003 Jul | Immunoglobulins (Igs) and autoantibodies are commonly tested in sera from patients with suspected rheumatic disease. To evaluate the clinical utility of the tests in combination, we investigated sera from 351 patients with autoimmune rheumatic disease (ARD) rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) and 96 patients with nonautoimmune rheumatic disease (NAD) (fibromyalgia, osteoarthritis, etc.). Antinuclear antibodies (ANA), rheumatoid factor (RF), antibodies against DNA and extractable nuclear antigens (anti-ENA), IgG, IgA and IgM were measured for all patients. Logistic regression analysis of test results was used to calculate each patient's probability for belonging to the ARD or NAD group as well as likelihood ratios for disease. Test accuracy was investigated using receiver-operating characteristic (ROC) plots and nonparametric ROC analysis. Neither concentrations of IgG, IgA, IgM, anti-DNA nor anti-ENA gave a significant effect on diagnostic outcome. Probabilities for disease and likelihood ratios calculated by combining RF and ANA performed significantly better at predicting ARD than utilization of the diagnostic tests in isolation (P < 0.001). At a cut-off level of P = 0.73 and likelihood ratio = 1, the logistic model gave a specificity of 93% and a sensitivity of 75% for the differentiation between ARD and NAD. When compared at the same level of specificity, ANA gave a sensitivity of 37% and RF gave a sensitivity of 56.6%. Dichotomizing ANA and RF as positive or negative did not reduce the performance characteristics of the model. Combining results obtained from serological analysis of ANA and RF according to this model will increase the diagnostic utility of the tests in rheumatological practice. | |
15058168 | [Thalidomide--a new prospective therapy in rheumatology and transplantation]. | 2003 | This review article discusses the thalidomide therapy of diseases such as systemic sclerosis, rheumatoid arthritis, Behçet syndrome, lupus erythematosus disseminatus and graft-versus-host disease. The main mechanism of action of thalidomide in these diseases is probably based on the suppression of tumor necrosis factor-alpha and the modulation of interleukins. | |
14598117 | Recent advances in therapeutic apheresis. | 2003 | Recent advances in therapeutic apheresis include technical improvements, new indications, and pathophysiological insights. A new device that adsorbs endotoxins onto immobilized human albumin from human whole blood was recently developed. In a prospective randomized controlled trial (endotoxin adsorber study EASY), apheresis-treated patients had more improved APACHE II scores than controls. In a prospective randomized trial, the Prosorba column containing immobilized staphylococcal protein A was tested against sham apheresis in patients with end-stage rheumatoid arthritis. A significant improvement occurred in 42% of the treated patients vs. 16% of the controls. Sudden hearing loss was treated in a prospective randomized trial by a single heparin-induced extracorporeal LDL precipitation (HELP) treatment in comparison with conservative therapy. In patients with elevated fibrinogen and/or low-density lipoprotein (LDL) cholesterol levels, HELP was significantly superior to 10 days of intravenous conventional treatment. Promising results were achieved in prospective randomized trials applying immunoadsorption in end-stage dilated cardiomyopathy and rheopheresis in age-related macular degeneration. In a noncontrolled trial, C4d-positive acute humoral rejection after kidney transplantation could be effectively treated by immunoadsorption. Finally, HELP apheresis was simplified by using new hardware (HELP-Futura). Direct adsorption of lipids (DALI)-LDL-apheresis was improved by testing DALI 1250 adsorbers with improved capacity. High-blood-flow DALI was shown to be safe and effective, with the advantage of reduced treatment time. Last but not least, a modification of dextran-sulfate cellulose LDL apheresis was developed for direct LDL hemoperfusion. | |
15142273 | Autoantibody profile in rheumatoid arthritis during long-term infliximab treatment. | 2004 | The aim of the present study was to investigate the effect of long-term infliximab treatment on various autoantibodies in patients with rheumatoid arthritis. Serum samples from 30 consecutive patients, who were prospectively followed during infliximab and methotrexate therapy for refractory rheumatoid arthritis, were tested at baseline and after 30, 54 and 78 weeks. At these points, median values of the Disease Activity Score were 6.38 (interquartile range 5.30-6.75), 3.69 (2.67-4.62), 2.9 (2.39-4.65) and 3.71 (2.62-5.06), respectively. Various autoantibodies were assessed by standard indirect immunofluorescence and/or ELISA. Initially, 50% of patients were positive for antinuclear antibodies, and this figure increased to 80% after 78 weeks (P = 0.029). A less marked, similar increase was found for IgG and IgM anticardiolipin antibody titre, whereas the frequency of anti-double-stranded DNA antibodies (by ELISA) exhibited a transient rise (up to 16.7%) at 54 weeks and dropped to 0% at 78 weeks. Antibodies to proteinase-3 and myeloperoxidase were not detected. The proportion of patients who were positive for rheumatoid factor (RF) was similar at baseline and at 78 weeks (87% and 80%, respectively). However, the median RF titre exhibited a progressive reduction from 128 IU/ml (interquartile range 47-290 IU/ml) to 53 IU/ml (18-106 IU/ml). Anti-cyclic citrullinated peptide (CCP) antibodies were found in 83% of patients before therapy; anti-CCP antibody titre significantly decreased at 30 weeks but returned to baseline thereafter. In conclusion, the presence of anti-double-stranded DNA antibodies is a transient phenomenon, despite a stable increase in antinuclear and anticardiolipin antibodies. Also, the evolution of RF titres and that of anti-CCP antibody titres differed during long-term infliximab therapy. | |
15552519 | Glucocorticoid use in rheumatoid arthritis: benefits, mechanisms, and risks. | 2004 Sep | Glucocorticoids have long been recognized to have beneficial effects in rheumatoid arthritis (RA) (1,2). Several clinical trials over the last decade have further documented the efficacy of glucocorticoids in relieving inflammation and in preventing radiographic erosions in early RA (3-5). Additionally, research has yielded new insights about the cellular mechanisms responsible for these perceived beneficial effects (6,7). Despite potential short term benefits, there is a lack of demonstrated long-term efficacy as well as concerns about short and long-term toxicity. Although these concerns have limited enthusiasm for glucocorticoids by many patients and practitioners, in the U.S. it is estimated that 44% to 75% of RA patients use glucocorticoids (8,9). Confusion and controversy may relate to the fact that toxicity reports are also limited by only modest data quality and quantity. Given growing clinical and basic science evidence supporting the efficacy of glucocorticoids for the treatment of rheumatoid arthritis, their use may further increase. In this review we will examine the latest data supporting the benefits and risks of glucocorticoid use in RA. | |
12508389 | Patient compliance in rheumatoid arthritis, polymyalgia rheumatica, and gout. | 2003 Jan | OBJECTIVE: (1) To explore patient compliance with prescribed drug regimens in the setting of usual care for outpatients with rheumatoid arthritis (RA), gout, and polymyalgia rheumatica (PMR) by utilizing electronic medication event monitors (MEMS(R)) to register openings of the medication package. (2) To examine the influence of disease, frequency of intake of the drug, and class of drug on compliance. (3) To explore the influence of demographic factors, quality of life measures, coping, health status, and functional ability as potential predictors of patient compliance. METHODS: A total of 127 consenting consecutive patients were enrolled: 81 patients with RA, 33 taking nonsteroidal antiinflammatory drugs (13 diclofenac TID and 20 naproxen BID) and 48 taking disease modifying antirheumatic drugs [25 sulfasalazine (SSZ) BID and 23 methotrexate (MTX) once weekly]; 17 patients with PMR starting with prednisolone QD; and 29 patients with gout starting with colchicine (12, QD) or starting with uric acid lowering agents (17, QD). All patients received first prescriptions and were instructed to take the medication as prescribed. Followup was 6 months (gout 12 mo). All patients were aware of the monitoring capability of the package. At baseline a series of questionnaires was completed. We summarized the dosing histories as "taking compliance" (percentage of total prescribed doses taken), "correct dosing" (percentage of doses taken as prescribed), and "timing compliance" (percentage of doses taken within +/- 25% of prescribed interdose intervals). RESULTS: A total of 26,685 days (> 73 patient-years) were monitored. Compliance expressed as "taking compliance," mean (95% CI), "correct dosing," mean (95% CI), and "timing compliance," mean (95% CI) are: naproxen: 82% (75-90), 68% (57-80), 48% (34-61); diclofenac: 77% (61-93), 67% (47-87), 39% (21-57); MTX: 107% (98-117), 81% (75-87), 83% (76-90); SSZ: 72% (60-84), 55% (44-67), 25% (18-33); prednisolone: 96% (89-102), 88% (83-92), 82% (74-89); colchicine: 65% (48-81), 44% (26-62), 32% (18-46); and uric acid lowering agents: 84% (76-92), 74% (63-85), 65% (52-79). Missed doses occurred more frequently than taking of extra doses: in RA, on 10% of all monitored days there was no evidence of dosing, while on 3% of all monitored days extra doses were taken. In PMR and gout these data are 10% and 4%, and 15% and 7%, respectively. We observed a decline of compliance over time in all study medication groups. Multiple regression analyses showed that the class of medication (symptom modifying or disease controlling), the dosing frequency, the patient's sex, coping pattern (avoidance, passive reaction pattern, and expression of emotions), and the overall health (total Nottingham Health Profile score) together explained 67% of the variance in taking compliance (adjusted R2) (p = 0.002). CONCLUSION: Studying patient compliance with prescribed drug regimens utilizing electronic medication event monitors in RA, gout, and PMR showed that large differences exist in compliance between the various medication groups. Compliance declines over time. A regression model shows that it is possible to relate differences in patient compliance to a number of medication and patient related factors. | |
12223112 | Regulation of CD154-induced interleukin-12 production in synovial fluid macrophages. | 2002 | Interleukin (IL)-12, being a major cytokine that induces T helper (Th) 1 differentiation and inflammatory response, has been postulated to be an important mediator of synovial inflammation in rheumatoid arthritis (RA). However, the regulation of IL-12 production in RA has not been elucidated. Our knowledge is mainly based on studies of the production of IL-12p40 and not the functional IL-12p70 heterodimer. We have studied the CD154-induced IL-12p40 and IL-12p70 production by synovial fluid (SF) macrophages from patients with RA. CD40 ligation induced the secretion of IL-12p40 but not IL-12p70. The observed increase in IL-10 and tumor necrosis factor (TNF)-alpha production indicated that SF macrophages responded to CD40 ligation. The expression of p40 mRNA was increased significantly and remained upregulated after CD40 ligation, whereas the increase of p35 transcript expression was observed only transiently and at a lower level. We further observed that dendritic cells (DCs) derived in vitro from SF macrophages produced IL-12p70. Most importantly, IL-4 and IL-13 primed SF macrophages to produce IL-12p70, whereas IFN-gamma was not observed to activate IL-12p70 production in these cells, in contrast with normal peripheral blood monocytes. These results provide novel information about the regulation of IL-12p70 production and the function of the cytokine network in RA. | |
12563693 | Enhanced lipid peroxidation in synoviocytes from patients with osteoarthritis. | 2003 Feb | OBJECTIVE: To evaluate the degree of lipid peroxidation of synoviocytes from patients with rheumatoid arthritis (RA), osteoarthitis (OA), and controls and to look at the production of nitric oxide (NO) and its involvement in this process. METHODS: Human synoviocytes were isolated from synovial tissues from patients with RA, OA, and from healthy controls. Cells were maintained in culture for up to 3 culture passages. Lipid peroxidation, verified by the production of malonaldehyde (MDA) and 4-hydroxy-2(E)-nonenal (4-HNE), was determined by colorimetric assay. NO was evaluated by estimating the stable NO metabolite nitrite by the Griess method in the supernatants of unstimulated and interleukin (IL)-1beta and tumor necrosis factor (TNF)-a stimulated cells. RESULTS: Increased levels of lipid peroxidation were observed for OA-derived synoviocytes compared to RA and controls. The cells in each experimental group produced low amounts of NO both in basal and in stimulated conditions. CONCLUSION: In OA, synovial cells underwent a lipid peroxidation process that did not occur in synoviocytes from RA or controls even in the absence of a detectable production of the reactive nitrogen intermediate NO. We can postulate that this peroxidation process might be due to the action of NO secreted by chondrocytes that are known to produce higher levels of this radical in OA compared to RA. | |
15498849 | Mechanism by which H-2g, a glucose analog of blood group H antigen, mediates angiogenesis. | 2005 Mar 15 | The 4A11 antigen is a unique cytokine-inducible antigen up-regulated on rheumatoid arthritis (RA) synovial endothelial cells (ECs) compared with normal ECs. Previously, we showed that in soluble form, this antigen, Lewis(y)-6/H-5-2 (Le(y)/H) or its glucose analog, 2-fucosyl lactose (H-2g), induced the expression of EC intercellular adhesion molecule-1 (ICAM-1) and leukocyte-endothelial adhesion through the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway. Currently, we show that H-2g induces release of EC angiogenic basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), an effect inhibited by decoy nuclear factor kappaB (NFkappaB) oligodeoxynucleotide (ODN). JAK2 and phosphoinositide-3 kinase (PI3K) are 2 upstream kinases of NFkappaB activated by H-2g, as confirmed by an inhibitor of kappa B kinase (IKKbeta) assay. In vitro, H-2g induces vascular sprouting in the rat aortic ring model, whereas blockade of JAK2, PI3K, or NFkappaB inhibits sprouting. Likewise, in the in vivo mouse Matrigel plug angiogenesis assay, chemical inhibitors and antisense or decoy ODNs of JAK2, PI3K, or NFkappaB decrease angiogenesis, confirming the importance of these pathways in H-2g-induced EC signaling. The critical role of Le(y)/H involvement in angiogenesis and its signaling pathways may provide new targets for therapy of diseases characterized by pathologic neovascularization. | |
15605672 | Disseminated tuberculosis complicating anti-TNF-alpha treatment. | 2004 Nov | An unusually large number of cases of tuberculosis, often of miliary or disseminated form, have been reported in patients receiving infliximab therapy for rheumatoid arthritis or Crohn's disease. We describe a patient with rheumatoid arthritis who was treated with infliximab and became systemically ill with Mycobacterium tuberculosis-disseminated infection. Patients who are candidates for treatment with tumour necrosis factor-alfa inhibitors should be evaluated for the presence of latent or active | |
15230130 | [Markov model of decision making for basic therapy of rheumatoid arthritis: oder of monoth | 2004 | AIM: To design Markov's model of decision making to study the role of order in the use of most usable basic antirheumatic drugs (methotrexate-MT, parenteral gold--PG and sulfasalasine--SS) in terms of the course duration and cost. MATERIAL AND METHODS: The model was based on metaanalysis made in 2000. The program TreeAge 3.0 was used. The prices for the drugs were taken as mean about Moscow for 2002 and prices presented by ACR for 2002. RESULTS: The sequence MT-PG-SS had the advantage over the other sequences in that less number of patients stopped treatment after 5 and 10 years of therapy. Mean cost of the drugs per patient is the lowest (for five years) if MT is prescribed first. In longer treatment SS-MT-PG is more cost-effective. CONCLUSION: It is feasible to design Markov's models for making decision on optimal therapy of rheumatoid arthritis both in terms of cost and clinical response. | |
12115159 | Physician treatment preferences in rheumatoid arthritis of differing disease severity and | 2002 Jun 15 | OBJECTIVE: To conduct a pilot study to identify rheumatologists' treatment preferences for first-line rheumatoid arthritis (RA) therapy and determine whether pharmacoeconomic variables modify physician choice(s). METHODS: A questionnaire describing 3 different RA scenarios was mailed to American College of Rheumatology members within 4 geographic regions of the US. Physicians were asked to identify their choice(s) of first-line therapy for each of the cases, first taking cost into consideration, second without considering the influence of cost, and third identifying the therapy that would be chosen for either themselves or a family member. RESULTS: Three hundred seventy-five questionnaires out of a total of 994 (37.7%) were returned between 3/12/00 and 4/25/00. Hydroxychloroquine was the most commonly cited medication for a mild disease activity/severity presentation, and methotrexate for a moderate-to-severe disease activity/severity presentation. For the severe disease activity/severity presentation, when cost was not considered, 217 (65%) rheumatologists included new disease-modifying antirheumatic drugs (leflunomide, etanercept, and infliximab) in their choice of first-line agents; this number decreased to 47 (14%) when cost was a consideration. CONCLUSION: Pharmacoeconomics appear to play a dominant role in rheumatologists' choice of treatment regimens, at times contrary to the physician's perception of the effectiveness of a drug. Future studies should address physician preferences in more depth with respect to cost and its various components. | |
12796204 | Methotrexate-induced pulmonary lymphoma. | 2003 Jun | Methotrexate has proven to be effective in treating rheumatoid arthritis (RA), and is believed to be nononcogenic in the low weekly dose typically employed in the patients with RA. We report, however, a patient with RA in whom a rapidly enlarging diffuse large B-cell lymphoma developed in the left upper lung after weekly treatment with methotrexate for 5 years. The patient had a positive serum IgG for Epstein-Barr virus but a negative in situ hybridization of the resected specimen. Methotrexate therapy was discontinued, and the patient elected for clinical observation instead of chemotherapy or radiation therapy. There has been no clinically detectable recurrence of the lymphoproliferative disorder for 2 years. We believe that methotrexate has an oncogenic potential even in low weekly dosing in a subset of patients with RA and latent Epstein-Barr virus infection. The strongest causal link is demonstrated by the persistent tumor remission after stopping treatment with methotrexate. | |
12734891 | Cytotoxicity responses to peptide antigens in rheumatoid arthritis and ankylosing spondyli | 2003 May | OBJECTIVE: To measure levels of IgG antibodies against structurally related synthetic peptides of HLA-DRB1*0404, type XI collagen, and Proteus mirabilis in patients with rheumatoid arthritis (RA) and HLA-B*2705 and Klebsiella pneumoniae in patients with ankylosing spondylitis (AS), and to determine whether sera from RA and AS patients are cytotoxic for sheep red blood cells (SRBC) coated with HLA-DRB1*0404, type XI collagen, or HLA-B*2705. METHODS: Sera from 51 patients with RA, 34 with AS, and 38 healthy controls were tested against synthetic EQRRAA, ESRRAL, LRREI, and IRRET peptides by ELISA. Sera from patients and controls were also tested for reactivity in complement mediated cytotoxicity with SRBC coated with EQRRAA and HLA-B*2705, LRREI peptides. RESULTS: Antibodies to synthetic peptides containing EQRRAA, ESRRAL, LRREI, and IRRET were significantly increased in RA patients compared with AS patients (p < 0.001) and controls (p < 0.001). The percentage lysis data for SRBC coated with EQRRAA and LRREI peptides were significantly higher for RA sera (p < 0.001) compared to control sera. Percentage lysis for SRBC coated with HLA-B*2705 peptide was significantly higher for AS sera (p < 0.001) compared to control sera. CONCLUSION: Our results suggest that antibodies against antigenic determinants of P. mirabilis in RA and K. pneumoniae in AS have cytotoxic properties on structurally related host proteins. These cytotoxic antibodies together with T cell interactions could be relevant in the etiopathogenesis of RA and AS. |