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ID PMID Title PublicationDate abstract
17573576 Chronic rhinosinusitis and psoriasis: do mutually exclusive systemic Th1 and Th2 disease p 2007 Jul CONCLUSION: Our results support the theory that chronic rhinosinusitis (CRS) is a systemic Th alteration, the relevance of which is discussed in detail. OBJECTIVE: CRS imposes a heavy burden on society; however, a reliable CRS therapy has not been found. Developing a better understanding of this pathology will help us in our search for more effective therapies. One question, which is rarely examined, is the possibility of CRS existing as a systemic immune alteration in Th response. Thus, the goal of this study was to examine the occurrence of CRS, a Th2 pathology, with Th1 pathologies such as psoriasis. PATIENTS AND METHODS: This study was performed via a retrospective electronic query of our medical center in regards to patients coded with the respective diagnosis. RESULTS: Analysis of the data showed that occurrence of CRS rarely coincided with the occurrence of psoriasis and other such Th1 pathologies.
16700888 CD4+CD25+ regulatory T cells in health and disease. 2006 May 1. Over the past 5 years, tremendous progress has been made in understanding the suppressive mechanisms of T regulatory (Treg) cells. The Treg cells, a subpopulation of T cells, have been shown to play an important role in maintaining peripheral tolerance and the prevention of autoimmunity. 2. Various populations of Treg cells have been described, including thymically derived CD4(+)CD25(+) Treg cells. These naturally occurring Treg cells are present in the periphery and are capable of suppressing proliferation and effector T cell responses both in vitro and in vivo. 3. In addition, a second subset of Treg cells, type 1 T regulatoary (Tr1) and Th3 cells, exert their suppressive capacity via cytokines such as interleukin-10 and transforming growth factor-beta and are contact independent. 4. The present review summarizes the characteristics and molecular basis of CD4(+)CD25(+) Treg cells, as well as their therapeutic potential in modulating inflammatory diseases, such as inflammatory bowel disease and rheumatoid arthritis.
16368150 Interleukin-18 induces the production of vascular endothelial growth factor (VEGF) in rheu 2006 Mar 15 Interleukin-18 (IL-18) is a novel pro-inflammatory cytokine which has been implicated to play a pathogenic role in rheumatoid arthritis (RA). Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis in rheumatoid synoviocytes. In present study, we examined the effect of IL-18 on VEGF production in fibroblast-like synoviocytes (FLS) isolated from the patients with RA. FLS were prepared from the synovial tissues of patients with RA and osteoarthritis (OA) and cultured in the presence of IL-18. The production of VEGF from FLS was measured in culture supernatants by enzyme-linked immunosorbent assay (ELISA). The VEGF messenger RNA (mRNA) expression and AP-1 binding activity of VEGF transcript were determined by reverse transcription-polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assay (EMSA). IL-18 and VEGF levels of sera and synovial fluids (SF) of RA patients (n=30) were significantly higher than those of OA patients (n=20). IL-18 dose-dependently increased the production of VEGF. The effect of IL-18 on VEGF production appeared to be as potent as IL-1beta, whereas tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma showed little effects on VEGF production. AP-1-specific inhibitor Curcumin dose-dependently abrogated the effect of IL-18 on VEGF production. The VEGF enhancement of IL-18 was associated with increased AP-1 binding activity to the VEGF promoter site. These findings suggest IL-18 as an angiogenic factor in RA and down-regulation of IL-18 activity or AP-1 signal pathway can be potential therapeutic targets for RA.
19026123 Serum levels of free heat shock protein 70 and anti-HSP70 are elevated in Behçet's diseas 2008 Jul OBJECTIVES: As heat shock proteins (HSPs) are described as candidate self-antigens in Behçet's disease (BD), free HSP70 and anti-HSP70 levels were measured in the sera of patients to investigate their role in the pathogenesis of BD. METHODS: Free human HSP70 levels were measured in the sera of patients with BD and compared to disease controls [patients with rheumatoid arthritis (RA) or recurrent oral ulcerations (ROU)] and healthy controls (HC) using ELISA. Anti-HSP70 antibody levels were also determined. RESULTS: Free human HSP70 levels were significantly elevated in BD sera (1.12+/-0.86 ng/ml) compared to HC (0.67+/-0.46 ng/ml, BD vs. HC: p<0.001). However similarly elevated levels were also present in ROU (0.95+/-1.01 ng/ml, p<0.05) and RA (1.1+/-23.3 ng/ml, p<0.01). Anti-HSP70 antibody levels were also significantly higher in BD (668+/-658 microg/ml) compared to HC (490+/-742.05 microg/ml, p<0.05). However no significant anti-HSP70 antibody responses were observed in ROU (634.7+/-548.21 microg/ml) and RA (431.8+/-840.98 microg/ml). No association of any organ manifestation, the disease duration, or treatment with HSP70 or anti-HSP70 antibody levels were observed in BD. A correlation between HSP70 and anti-HSP70 levels was only found in HC (p=0.007). CONCLUSION: Free human HSP70 and anti-HSP70 antibodies are both elevated in patients with BD. HSP70-mediated innate and adaptive immune responses may participate in proinflammatory cytokine activation and tissue destruction in BD.
18592989 [Case of chronic necrotizing pulmonary aspergillosis successfully treated with a combinati 2008 Jun A 58-year-old Japanese man was admitted with high fever, productive cough, marked leukocytosis, and chest X-ray findings of infiltration and fluid levels within lung cysts. He had been treated for pulmonary tuberculosis for 6 months. He was also receiving home oxygen therapy for chronic obstructive pulmonary disease and 10 mg prednisolone daily for rheumatoid arthritis. Aspergillus fumigatus was cultured from bronchial washing fluid and we diagnosed chronic necrotizing pulmonary aspergillosis (CNPA). Micafungin was initially effective but 9 weeks later the symptoms recurred. Micafungin was stopped and after combination therapy of intravenous liposomal amphotericin B and oral itraconazole capsule was started his symptoms and laboratory data markedly improved. Fifteen weeks later his medication was switched to oral voriconazole and he was discharged. CNPA is a chronic infectious disease with poor prognostic and no standard therapy has been confirmed. Each antifungal drug has different mechanisms and sites of action. In the case of treatment failure with several drugs, combination therapy to achieve drug interaction can be a treatment option.
17611987 Good clinical response, remission, and predictors of remission in rheumatoid arthritis pat 2007 Aug OBJECTIVE: To assess the prevalence of good clinical response and remission in rheumatoid arthritis (RA) patients with longstanding disease treated with anti-tumor necrosis factor-alpha (TNF-alpha) drugs at outpatient clinics. METHODS: Retrospective national study of 14 academic tertiary referral rheumatology medical centers. RA patients with a Disease Activity Score (DAS28) > 3.2 were defined as having active disease and could start TNF-alpha blockers. All patients received one TNF-alpha blocker plus methotrexate (10-20 mg/wk). At the third month the patients were categorized as responders or nonresponders, based on improvement of at least 0.25 of the Health Assessment Questionnaire (HAQ). Those who had improved by at least 0.25 HAQ were analyzed for possible predictors of DAS28 remission at the sixth month. RESULTS: A total of 1257 patients started TNF-alpha blockers. Of these, 591 (46.7%) reached the sixth month with an improvement of HAQ of 0.25 at the third month. In the cohort of patients reaching HAQ of 0.25, DAS28 remission was seen in 24% of rheumatoid factor (RF)-positive and 36% of RF-negative patients (p = 0.03). Logistic regression analysis for predictors of remission identified age at baseline, HAQ < 1.63, and RF negativity as positive predictors of remission at 6 months along with sex (male). CONCLUSION: We show that only a minority of patients with longstanding RA achieve a good clinical response or remission at the outpatient community level. Predictors of remission identify characteristics commonly observed in subsets with less severe RA.
17469100 The effect of methotrexate and anti-tumor necrosis factor therapy on the risk of lymphoma 2007 May OBJECTIVE: To ascertain the relationship between anti-tumor necrosis factor (anti-TNF) therapy, methotrexate (MTX), and the risk of lymphoma in patients with rheumatoid arthritis (RA). This report updates our previous report during 29,314 person-years of followup. METHODS: Participants in the National Data Bank for Rheumatic Diseases (NDB) longitudinal study of long-term outcomes of RA completed semiannual questionnaires from 1998 through 2005, during 89,710 person-years of followup. Lymphoma reports were validated by medical records. The association between lymphoma and treatment was investigated using conditional logistic regression, adjusted for severity and demographic covariates. RESULTS: Of the 19,591 participants, 55.3% received biologic agents and 68.0% received MTX while enrolled in the NDB. The lymphoma incidence rate was 105.9 (95% confidence interval [95% CI] 86.6-129.5) per 100,000 person-years of exposure. Compared with the SEER (Surveillance, Epidemiology, and End-Results) lymphoma database, the standardized incidence ratio was 1.8 (95% CI 1.5-2.2). The odds ratio (OR) for lymphoma in patients who received anti-TNF therapy compared with patients who did not receive anti-TNF therapy was 1.0 (95% CI 0.6-1.8 [P = 0.875]). The OR for lymphoma in patients who received anti-TNF plus MTX therapy compared with patients who received MTX treatment alone was 1.1 (95% CI 0.6-2.0 [P = 0.710]). Infliximab and etanercept considered individually also were not associated with a risk of lymphoma. CONCLUSION: In a study of lymphoma in 19,591 RA patients over 89,710 person-years of followup, which included exposure to anti-TNF therapy in 10,815 patients, we did not observe evidence for an increase in the incidence of lymphoma among patients who received anti-TNF therapy.
17278785 [New possibilities of making the diagnosis of Caplan syndrome]. 2006 Jan We describe a 56-year old man with rheumatoid arthritis and pulmonary nodules detected by HRCT. Needle biopsy confirmed the diagnosis of Caplan syndrome.
17239366 Effect of interleukin-6 neutralization on CYP3A11 and metallothionein-1/2 expressions in a 2007 Mar 8 Rheumatoid arthritis is characterized by chronic inflammation of the synovial tissue. We examined the effect of interleukin (IL)-6 neutralization on the expression of cytochrome P450 or metallothionein-1/2 (metallothionein) during chronic phase inflammatory disease using rheumatoid arthritis model mice, human T-cell leukemia virus type I (HTLV-I) transgenic mice. Serum IL-6 concentrations of arthritis-developed HTLV-I transgenic mice were 129.9+/-26.1 pg/ml. Moreover, signal transducer and activator of transcription (STAT) 1/3 phosphorylations was observed in arthritic HTLV-I transgenic mouse livers. CYP3A11 mRNA was more strongly reduced by the development of arthritis in HTLV-I transgenic mouse livers as compared with CYP2C29 or CYP2E1 mRNAs. CYP3A protein and testosterone 6beta-hydroxylation activity also changed in a similar manner to the corresponding CYP3A11 mRNA level. On the other hand, metallothionein mRNA was significantly induced as compared with that of wild-type or non-arthritic mice. CYP3A suppression and metallothionein mRNA overexpression activity seen in the developed arthritic mice returned to the gene conditions of the non-arthritic HTLV-I transgenic mice by IL-6 antibody at 48 h after treatment. The present study has revealed that CYP3A11 and metallothionein expressions are affected by the release of IL-6 by arthritis and its systemic circulation, and neutralization of IL-6 recovered from the down-regulation of CYP3A11 mRNA and the induction of metallothionein mRNA in arthritic HTLV-I transgenic mice.
18709695 Arrhythmic risk during acute infusion of infliximab: a prospective, single-blind, placebo- 2008 Oct OBJECTIVE: Reports suggest that infliximab (IFX) may be associated with life-threatening tachyarrhythmias and bradyarrhythmias. We evaluated the prevalence of cardiac rhythm disorders during acute infusion of IFX in a prospective, single-blind, placebo-controlled crossover study of patients with chronic arthritis. Effects of the drug on measures of arrhythmia risk such as QT interval and heart rate variability (HRV) were evaluated. METHODS: Seventy-five patients with spondyloarthritis (SpA; n=55) or rheumatoid arthritis (RA) underwent an ambulatory 12-channel electrocardiogram (ECG) recording to monitor cardiac arrhythmias, QT interval, and HRV during the infusion of IFX and saline (placebo). RESULTS: The occurrence of both tachyarrhythmias and bradyarrhythmias was not statistically different during IFX or placebo infusion. During IFX infusion, new-onset ventricular tachyarrhythmias had an 8% incidence (2.7% with placebo; OR 3.17, 95% CI 0.61-16.26) and were more severe. In these patients, mainly with RA, baseline-corrected QT interval and HRV values were significantly prolonged and depressed, respectively, in comparison with subjects without such arrhythmias. IFX acutely produced a significant shift toward a relative vagal prevalence without affecting QT interval measurements. CONCLUSION: New-onset cardiac arrhythmias, particularly ventricular tachyarrhythmias, developed during IFX infusion, but their incidence did not achieve statistical significance. We identified some specific risk factors possibly characteristic of the small subset of patients with a higher risk for ventricular arrhythmias. The acute effects of IFX on autonomic balance may substantiate the role of the complex interaction between autonomic nervous system and inflammation during chronic arthritis.
16508972 Obstetric hospitalizations in the United States for women with systemic lupus erythematosu 2006 Mar OBJECTIVE: To estimate the national occurrence of pregnancies in women with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and to compare pregnancy outcomes in these patients with those in women with pregestational diabetes mellitus (DM) and with the general obstetric population. METHODS: We studied the 2002 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project to estimate the number of obstetric hospitalizations, deliveries, and cesarean deliveries in women with SLE, RA, pregestational DM, and the general obstetric population. Pregnancy outcomes included length of hospital stay, hypertensive disorders including preeclampsia, premature rupture of membranes, and intrauterine growth restriction. RESULTS: Of an estimated 4.04 million deliveries, 3,264 occurred in women with SLE, 1,425 in women with RA, and 13,574 in women with pregestational DM. Women with SLE, RA, and pregestational DM had significantly increased rates of hypertensive disorders compared with the general obstetric population (23.2%, 11.1%, 27.4%, and 7.8%, respectively), longer hospital stays, and significantly higher risk of cesarean delivery. Although women with SLE, RA, and pregestational DM were significantly older than women in the general obstetric population, disparities in the risk of adverse outcomes of pregnancy remained statistically significant after adjustment for maternal age. CONCLUSION: To our knowledge, this is the first study to examine national data on pregnancy outcomes in women with common rheumatic diseases. As with underlying pregestational DM, women with SLE and RA appear to have a higher age-adjusted risk of adverse outcomes of pregnancy and longer hospital stays than do pregnant women in the general population, and careful antenatal monitoring should be performed.
16606651 Etanercept and sulfasalazine, alone and combined, in patients with active rheumatoid arthr 2006 Oct OBJECTIVE: To compare the efficacy and safety of etanercept and sulfasalazine, alone and in combination, in patients with active rheumatoid arthritis despite sulfasalazine treatment. METHODS: A double-blind, randomised study in adult patients with active rheumatoid arthritis despite stable sulfasalazine (2-3 g/day) treatment. The primary end point was a 20% response by the American College of Rheumatology (ACR) criteria at 24 weeks. RESULTS: At baseline, the three treatment groups (sulfasalazine, n = 50; etanercept, n = 103; etanercept and sulfasalazine, n = 101) were comparable for demographic variables and disease activity. Lack of efficacy was the primary reason for discontinuation (sulfasalazine, n = 12; etanercept, n = 1; etanercept and sulfasalazine, n = 4; p<0.001). Significantly more patients receiving etanercept, alone or in combination (74% for each), achieved ACR 20 responses at 24 weeks than those receiving sulfasalazine (28%; p<0.01). Similarly, more patients in the etanercept groups achieved ACR 50 and ACR 70 responses than those in the sulfasalazine group (p<0.01). In the groups receiving etanercept, significant differences in the ACR core components were observed by week 2 compared with those receiving sulfasalazine alone (p<0.01). The incidences of several common adverse events (headache, nausea, asthenia) were lower with etanercept alone than with the combination (p<0.05), but infections and injection site reactions were higher with etanercept alone (p<0.05). The safety profiles of both etanercept treatment groups were comparable with previous experience of etanercept. CONCLUSIONS: For all efficacy variables assessed, etanercept alone or in combination with sulfasalazine resulted in substantial and similar improvement in disease activity from baseline to week 24 compared with sulfasalazine alone in patients with active rheumatoid arthritis despite their sulfasalazine treatment. All three treatments were generally well tolerated.
16792676 Suspects in the tale of lupus-associated thrombocytopenia. 2006 Jul Immunologically mediated thrombocytopenia is a frequent clinical manifestation in patients with systemic lupus erythematosus (SLE). Autoantibodies targeting platelet membrane glucoproteins have a central role in peripheral platelet destruction. Autoantibodies against thrombopoietin are also present in about one-third of patients, but their pathogenetic role is obscure. Thirty-eight serum samples from SLE patients were tested for anti-platelet antibodies, anti-thrombopoietin antibodies and levels of circulating thrombopoietin. Bone marrow histology was also assessed. Thirty-nine per cent of sera displayed anti-thrombopoietin antibodies and 29% had circulating anti-platelet antibodies. Anti-thrombopoietin antibodies were associated with lower thrombopoietin concentrations, and lower mean platelet values in long-term follow-up. Anti-platelet antibodies were present in about 40% of thrombocytopenic and non-thrombocytopenic individuals but were absent in patients who had recovered from thrombocytopenia, supporting their pathogenetic role. Both autoantibodies were absent in control sera from patients with rheumatoid arthritis and primary Sjögren's syndrome. Decreased bone marrow cellularity, normal or low number of hypolobulated, pyknotic megakaryocytes and stromal alterations were prominent findings in thrombocytopenic SLE patients, suggesting a defect in megakaryopoiesis. These findings were not evident in specimens from patients with idiopathic thrombocytopenic purpura who had increased megakaryocytes, normal cellularity and absence of stromal alterations. In conclusion, peripheral destruction due to platelet autoantibodies, anti-thrombopoetin antibodies, lower effective circulating thrombopoetin and impaired compensatory response due to bone marrow damage interact in SLE and thrombocytopenia ensues.
18975323 Analysis of apoptosis in peripheral blood and synovial tissue very early after initiation 2008 Nov OBJECTIVE: Infliximab treatment results in a decrease in synovial cellularity as early as 48 hours after initiation of therapy in patients with rheumatoid arthritis (RA). This study was undertaken to investigate whether infliximab induces apoptosis within the first 24 hours after infusion. METHODS: The percentage of apoptotic cells was determined by flow cytometry in blood drawn from 21 patients directly before, 1 hour after, and 24 hours after infliximab infusion. Synovial tissue samples obtained before, 1 hour after (n = 5), or 24 hours after (n = 5) initiation of therapy were subjected to immunohistochemistry to detect active caspase 3 and to TUNEL assay and electron microscopy to detect apoptosis. In addition, plasma levels of nucleosomes (generated during apoptosis) and C4b/c (an indicator of complement activation) were measured. RESULTS: There were no signs of apoptosis induction in peripheral blood monocytes or lymphocytes after infliximab treatment. Circulating lymphocyte counts were increased within 1 hour after infusion (P < 0.05). There was no definite evidence of apoptosis induction in the synovium, except in 1 patient 24 hours after the infliximab infusion. Consistent with these results, there was no increase in nucleosome levels nor were there signs of complement activation. CONCLUSION: Our findings indicate that the rapid decrease in synovial cellularity observed after initiation of anti-tumor necrosis factor antibody therapy cannot be explained by apoptosis induction at the site of inflammation. It is tempting to speculate that the striking effects on synovial inflammation may be explained by other mechanisms, such as decreased migration toward the synovial compartment and reduced retention in the inflamed synovium.
17562353 Dendritic cells and interferon-mediated autoimmunity. 2007 Jun Dendritic cells (DCs) are central cells of the immune responses. They can be considered as the most influential antigen-presenting cells in the body because of their unique role in initiating immunity against most types of antigens. Recent studies have clearly established that the state of maturation of DC can be crucial for the ability of these antigen-presenting cells to inhibit or induce T-cell-mediated autoimmune diseases. Type I interferon has been shown to be produced at very high amounts by a specific type of DC (pDC). In recent years, the study of multiple autoimmune diseases has pointed to a central role for type I interferon (IFN-I) in disease pathogenesis, in particular through the IFN-molecular signature deciphered in some of these diseases. One hypothesis would be that IFN directly affects multiple actors of the immune reaction such as T cells and B cells and that it can induce the unabated activation of peripheral dendritic cells. On the other hand, type II IFN has been considered as pathogenic in multiple autoimmune diseases leading to the paradigm of TH-1 type autoimmune diseases. The discovery of the TH-17 type of cells and the protective role IFN-gamma can exert on particular phases of these diseases urge one to re-evaluate this assumption.
16680388 Treatment with anti-TNF-alpha antibody infliximab reduces serum IL-15 levels in patients w 2007 Apr The aim of this study was to analyze the change of serum cytokines and pentosidine levels in patients with rheumatoid arthritis (RA) by infliximab treatment. Twenty-three patients with RA were studied for 30 weeks on the effects of infliximab treatment. Serum levels of IL-15, IL-16, IL-17, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured with ELISA methods and pentosidine levels were determined using high-performance liquid chromatography, both at baseline and at 14 and 30 weeks after the initial treatment with infliximab. In addition, the patients also underwent physical and routine blood examinations. The higher levels of serum IL-15 in RA patients before treatment with infliximab significantly decreased at 14 and 30 weeks after the initial treatment with infliximab, but serum IL-16, IL-17, GM-CSF, and pentosidine levels did not decrease. The serum IL-17 and GM-CSF levels remained to be a limited detectable level at the pre- and posttreatment with infliximab. Infliximab treatment significantly lowered the serum levels of IL-15 in patients with RA. IL-15 is one of the crucial cytokines affected by infliximab.
17952386 Assessment of minerals in obesity-related diseases in the Chandigarh (India) population. 2008 Feb Excessive Zn but normal Cu and Mg in the staple food consumed by the people of Chandigarh (Union territory and capital of Punjab and Haryana States of India) has been considered to be the major risk factor for the prevalence of obesity (33.15%) and obesity-related diseases in this region. Therefore, in the present investigations, in obesity-related diseases, the status of these minerals was estimated in their tissues, including hair, nails, and blood serum and urine, and compared with those of normal subjects. They were grouped as: normal subjects in control Group A, middle-aged diabetics in Group D(M), older diabetics in Group D(O), and diabetics with osteoarthritis in Group D+ OA, osteoarthritis in Group OA and rheumatoid arthritis in Group RA, respectively. The results evaluated in the order as: hair Zn, group D+OA>D(M)>OA>A (control)>RA>D(O) (p < 0.001); hair Cu, group A (control)>D(M)>OA>D+OA>D(O)>RA (p < 0.001); hair Mg, group A (control)>D(M)>OA>D+OA>RA>D(O) (p < 0.001, 0.01); hair Mn, group A (control)>RA>OA>D-OA>D(M)>D(O) (p < 0.001); nail Zn, group D(M)>D+OA>OA>A (control)>RA>D(O) (p < 0.001, 0.05); nail Cu, group A (control)>OA>D(M)>D+OA>RA>D(O) (p < 0.001); nail Mg, group A (control)>OA>D(M)>D(O)>D+OA >RA (p < 0.001); nail Mn, group A (control) >RA>OA>D+OA>D(M)>D(O) (p < 0.01); urine Zn, group D(O)>D(M)>D+OA>A (control)>RA>OA (p < 0.01); urine Cu, group RA>D+OA>D(O)>OA> D(M)>A (control) (p<0.001); urine Mg, group RA>OA>D+OA>D(O)>D(M)>A (control; p < 0.001); urine Mn, group D(O)>D(M)>OA>D+OA>RA>A (control; p < 0.001), respectively. The analysis of the mineral status in serum of diabetics further showed their highly significant rise from lower mean age subgroup to higher mean age subgroup than their control counter parts (p < 0.001, 0.01, and 0.05) with coincident deficiencies of Cu, Mg, and Mn in their tissues. This study would be helpful considering the status of minerals in these obesity-related diseases depending on the choice of the food consumed to improve the quality of life and prognosis for the diseases.
17469112 Presentation of arthritogenic peptide to antigen-specific T cells by fibroblast-like synov 2007 May OBJECTIVE: To assess the ability of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) to function as antigen-presenting cells (APCs) for arthritogenic autoantigens found within inflamed joint tissues. METHODS: Human class II major histocompatibility complex (MHC)-typed FLS were used as APCs for murine class II MHC-restricted CD4 T cell hybridomas. Interferon-gamma (IFNgamma)-treated, antigen-loaded FLS were cocultured with T cell hybridomas specific for immunodominant portions of human cartilage gp-39 (HC gp-39) or human type II collagen (CII). T cell hybridoma activation was measured by enzyme-linked immunosorbent assay of culture supernatants for interleukin-2. Both synthetic peptide and synovial fluid (SF) were used as sources of antigen. APC function in cocultures was inhibited by using blocking antibodies to human class II MHC, CD54, or CD58, or to murine CD4, CD11a, or CD2. RESULTS: Human FLS could present peptides from the autoantigens HC gp-39 and human CII to antigen-specific MHC-restricted T cell hybridomas. This response required pretreatment of FLS with IFNgamma, showed MHC restriction, and was dependent on human class II MHC and murine CD4 for effective antigen presentation. Furthermore, FLS were able to extract and present antigens found within human SF to both the HC gp-39 and human CII T cell hybridomas in an IFNgamma-dependent and MHC-restricted manner. CONCLUSION: RA FLS can function as APCs and are able to present peptides derived from autoantigens found within joint tissues to activated T cells in vitro. In the context of inflamed synovial tissues, FLS may be an important and hitherto overlooked subset of APCs that could contribute to autoreactive immune responses.
18237382 Rheumatic diseases in China. 2008 INTRODUCTION: Epidemiological studies of rheumatic diseases have been conducted during the past 20 years in China. The aim of this study was to clarify prevalence rates of common rheumatic diseases in China. METHODS: Relevant reports of population-based surveys conducted from 1980 to 2006 were retrieved. Studies using the World Health Organization-International League of Associations for Rheumatology COPCORD (Community Oriented Program for Control of Rheumatic Diseases) protocol and those that did not employ this protocol but were published in recognized journals were identified and analyzed. RESULTS: Thirty-eight surveys including 241,169 adults from 25 provinces/cities were pooled for analysis. The prevalence of rheumatic complaints ranged from 11.6% to 46.4%, varying by locality, study protocol and age of the people surveyed. Prevalence of symptomatic osteoarthritis (OA) varied from 5.1% to 20.8%, with common sites of involvement being the lumbar spine, knee joint and cervical spine. Compared with rates of radiographic and symptomatic knee OA in the USA, elderly men in Beijing exhibited similar prevalence rates and elderly women exhibited a higher prevalence. The prevalence of hip OA and hand OA was much lower in Chinese than in Caucasian populations, but both kinds of OA were more common in coal miners. The prevalence of ankylosing spondylitis ranged from 0.2% to 0.54% among Han ethnic Chinese and were lower among mixed ethnic populations. The prevalence of psoriatic arthritis ranged from 0.01% to 0.1%, and that of reactive arthritis was 0.02%; undifferentiated spondyloarthropathy was identified in 0.64% to 1.2% of the individuals included in the surveys. The prevalence of rheumatoid arthritis (RA) ranged from 0.2% to 0.93%, with the highest rate being reported from a Taiwan urban area. In mainland China there were no significant differences in prevalence of RA between the northern and southern parts of China, or between different ethnic groups. The prevalence of hyperuricemia increased after the 1980s. The prevalence of gout was found to have increased in recent decades from 0.15% to 1.98%, apart from in the Taiwan aborigines, among whom the highest prevalence rate of 11.7% was recorded. The prevalence of primary Sjögren's syndrome in Beijing was 0.77% by the Copenhagen criteria and 0.33% by the San Diego criteria. The prevalence of soft tissue rheumatism was 2.5% to 5.7%. Fibromyalgia was seldom observed in China. CONCLUSION: Rheumatic diseases are common in China. The prevalence of rheumatic complaints varied with the locality surveyed. The prevalence of OA is comparable with that in Western countries but varies in terms of joint involvement. The prevalence of ankylosing spondylitis is similar to that in Caucasians. Except in Taiwan, the prevalence of RA in China is lower than that in developed countries. The prevalence of hyperuricemia and gout increased after the 1980s, but it remains lower than that in developed countries. More studies are required to evaluate prevalence rates among minority groups in the west and northwest parts of China, and further study is needed to address fibromyalgia in China.
18412314 Low-dose prednisolone in rheumatoid arthritis: adverse effects of various disease modifyin 2008 Jun OBJECTIVE: To assess the incidence and severity of disease modifying antirheumatic drug (DMARD)-induced adverse effects (AE) in patients with rheumatoid arthritis (RA) taking/not taking glucocorticoids (GC). More specifically, we tested whether GC can prolong the survival time of DMARD in patients receiving combination therapy. METHODS: In a retrospective study of 154 patients with RA, data were examined for DMARD therapy and duration of low-dose GC ((3/4) 7.5 mg prednisone equivalent/day). Patients were followed for 2-62 months, and AE were graded following WHO criteria. RESULTS: GC therapy significantly increased the duration of therapy with sulfasalazine (SSZ) from 10.4 +/- 2.3 to 22.5 +/- 1.9 months and for methotrexate (MTX) from 21.8 +/- 2.9 to 43.3 +/- 2.7 months. Stratifying the withdrawal of DMARD for occurrence of AE and loss of efficacy revealed that GC comedication significantly increased the time until AE for users of MTX (3.0 +/- 0.6 vs 18.8 +/- 1.3 mo; p < 0.05), hydroxychloroquine (HCQ; 34.5 +/- 4.6 vs 54.4 +/- 5.1 mo; p < 0.05), and gold (6.6 +/- 0.9 vs 10.5 +/- 0.9 mo; p < 0.05). In patients taking SSZ the time until cessation due to loss of efficacy increased significantly under GC comedication (16.8 +/- 1.2 vs 31.3 +/- 2.9 mo; p < 0.05). However, in patients taking azathioprine (AZA) the duration of therapy decreased from 44.4 +/- 2.6 to 22.3 +/- 1.6 months under GC due to both time until AE and loss of efficacy. Patients under comedication of MTX + GC, HCQ + GC, and AZA + GC experienced significantly more AE compared to the respective DMARD monotherapy. A highly significant reduction was observed in the frequency of erosive RA in patients with GC comedication (n = 30; 49.1%) compared to patients without low-dose GC (n = 81, 80.4%; OR 4.05, 95% CI 1.91-8.66, p < 0.0001). CONCLUSION: Low-dose GC retard radiological progression of RA and exhibit a differential effect on survival of DMARD and degree of AE due to DMARD. Further studies are warranted to address safety and interactions of chronic low-dose GC in RA patients treated with DMARD.