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ID PMID Title PublicationDate abstract
9082927 Meaningful improvement criteria sets in a rheumatoid arthritis clinical trial. MIRA Trial 1997 Mar OBJECTIVE: To compare 3 sets of criteria for meaningful improvement in a rheumatoid arthritis (RA) clinical trial, and to evaluate the implications of these criteria sets for RA trial design. METHODS: Data were obtained from the Minocycline in Rheumatoid Arthritis (MIRA) trial (primary outcome measures: 50% improvement in joint tenderness and 50% improvement in joint swelling, based on joint scores). These MIRA data were evaluated against 1) the Paulus criteria (20% improvement in 4 of 6 measures: joint tenderness scores, joint swelling scores, physician's and patient's global assessments, erythrocyte sedimentation rate [ESR], and morning stiffness); and 2) the American College of Rheumatology (ACR) criteria (20% improvement in joint tenderness and joint swelling counts, and in 3 of 5 other measures: physician's and patient's global assessments, ESR, modified Health Assessment Questionnaire, and patient's pain assessment). The ACR criteria were modified using 3 of 4 remaining measures, since baseline pain assessment data were not available. RESULTS: Percentages of minocycline-treated patients versus placebo-treated patients showing meaningful improvement were as follows: by MIRA criteria, for joint tenderness, 56% versus 41% (P = 0.021), and for joint swelling, 54% versus 39% (P = 0.023); by Paulus criteria, 41% versus 28% (P = 0.040); and by ACR criteria, 44% versus 26% (P = 0.004). Both the modified ACR criteria and the Paulus criteria demonstrated a reduced placebo response rate. Compared with the MIRA criteria, the ACR criteria increased, and the Paulus criteria decreased, absolute between-group differences in improvement; however, both criteria sets increased relative percentages of patients showing improvement in the minocycline group versus the placebo group. Study design considerations indicated that application of the ACR criteria would reduce the required sample size. CONCLUSION: Different placebo response rates and treatment group differences were found using the 3 RA improvement criteria sets. These findings support the use of the ACR criteria for defining improvement in RA clinical trials.
10467022 Elevation of anti-cytokeratin 19 antibody in sera of the patients with idiopathic pulmonar 1999 It has been suggested that cytokeratin 19 is expressed in regenerated bronchoepithelial cells in patients with pulmonary fibrosis, and serum cytokeratin 19 fragment is elevated in patients with pulmonary fibrosis. We hypothesized that serum antibodies to cytokeratin 19 may be formed in patients with pulmonary fibrosis. To prove the existence of anti-cytokeratin 19 antibodies in patients' sera, human recombinant cytokeratin 19 was stained with patients' sera by a Western immunoblot. Then, we tried to establish an enzyme-linked immunosorbent assay to quantitate anti-cytokeratin 19 antibody in the sera of patients with idiopathic pulmonary fibrosis (IPF) and pulmonary fibrosis associated with collagen vascular disorders (PF-CVD). We demonstrated the anti-cytokeratin 19 antibody in patient' sera by a Western immunoblot. In patients with IPF and PF-CVD, significantly high anti-cytokeratin 19 antibody was demonstrated compared with normal volunteers, patients with chronic bronchitis, and patients with pneumonia. These results suggest that anti-cytokeratin 19 antibody may have played a role in the process of lung injury in pulmonary fibrosis.
9458201 Effect of rheumatoid arthritis on work status and social and leisure time activities in pa 1998 Jan OBJECTIVE: To evaluate the development of handicap in patients with rheumatoid arthritis (RA) followed 8 years from onset. METHODS: The study group consisted of 106 patients participating in a prospective early RA study. The mean duration of joint symptoms at inclusion was one year. The patients were assessed at least once annually. Disability was measured with the Health Assessment Questionnaire (HAQ) and emotional distress with a self-administered test (Symptom Checklist). Work status and different social measures were registered. A structured interview regarding work capacity, leisure time, and social activities was performed about 8 years after disease onset. RESULTS: Compared to study start, disease activity had decreased, emotional distress was unchanged, disability had increased somewhat, and radiographic changes had increased markedly. The prevalence of work disability at the end of the study was 37%. The majority of patients that eventually got disability pension had stopped working the first year after onset. Seventy-eight percent of the patients who continued to work had to adjust their work conditions to stay employed. The 3 most important predictors for work disability were higher HAQ at study start, lower educational level, and older age. Three-quarters of the patients had to alter leisure time activities and half of them were not satisfied with their recreation. Many patients experienced difficulties in their roles as spouse and parent. Higher levels of emotional distress were associated with these handicaps. CONCLUSION: In this cohort of patients with RA we found a high frequency of different types of handicaps at an early stage. Slightly more than 1/3 were work disabled. The majority had stopped working during the first year. Patients perceived handicaps in terms of changed leisure time activities, and difficulties performing different social roles were frequent. Patients with these handicaps felt more emotional distress.
10531077 A randomised trial of differentiated prednisolone treatment in active rheumatoid arthritis 1999 Nov OBJECTIVES: To study benefits and skeletal side effects of carefully monitored prednisolone treatment in patients with active rheumatoid arthritis. METHODS: One hundred and two patients with active rheumatoid arthritis were randomly allocated to treatment with disease modifying anti-inflammatory drug (DMARD) alone or DMARD and prednisolone in a one year follow up study. Prednisolone was given in a dose regimen adapted to the disease activity of the individual patient. The mean dose was 6 mg and the mean cumulated dose was 2160 mg. Patients were followed up with disease activity parameters, radiograph of the hands (Larsen score), and bone mineral density (BMD) of the lumbar spine, distal forearm and hand. At one year 26 patients had withdrawn from the investigation leaving 76 patients for evaluation. RESULTS: The results showed that disease activity in the prednisolone treated group was reduced within two weeks. In the DMARD alone group disease activity was gradually reduced over months. At six months there was no difference between the groups as evaluated by an improvement score using a number of ACR criteria. Prednisolone in the present set up was not able to protect significantly against radiological disease progression, although there was a trend towards less progression in Larsen score in the prednisolone group, a matter that was further underlined in an intention to treat analysis. BMD data revealed a significant reduction in spinal BMD in the prednisolone group, whereas prednisolone seemed to have a protective effect against bone loss in the hand and distal forearm. CONCLUSIONS: This study does not allow any firm conclusions for or against the treatment of rheumatoid arthritis with prednisolone. The data suggest that the beneficial effects of prednisolone are not as clear cut in established rheumatoid arthritis as in early disease. Furthermore the data indicate that treatment in the chosen relatively low dose does not provide sufficient control of disease. On the other hand the spinal bone loss observed in the prednisolone group does invite considerations about using higher doses.
10204353 [The mineral density of the bone tissue in patients with rheumatic diseases of the joints 1998 Dec Manifestations were studied of systemic osteoporosis in patients with rheumatoid arthritis, primary osteoarthrosis, and ankylosing spondylarthritis. There have been disclosed differently directed changes in mineral density of lumbar spine and thigh bone segments related to phase of the illness as well as to the treatments administered, patient age, and impact of the post-menopausal period (in female patients). A conclusion has been reached that it is necessary that the above-mentioned studies be made in order that we might choose relevant therapeutic alternatives for patients with rheumatic afflictions of the joints.
9103969 Development of performance measures for seven chronic diseases. Health Outcomes Work Group 1997 Mar BACKGROUND: In 1994 the Washington, DC-based Pharmaceutical Research and Manufacturers of America (PhRMA) initiated a project to develop performance measures for seven chronic diseases-chronic obstructive pulmonary disease, chronic stable angina, depression, diabetes mellitus, hypercholesterolemia, hypertension, and rheumatoid arthritis-that are commonly treated with pharmaceuticals. The project was coordinated by PhRMA's Health Outcomes Work Group (HOWG), an ad hoc committee that addresses issues concerning health outcomes research. METHODOLOGY: For each of the seven diseases, HOWG assembled a panel of clinical experts from the pharmaceutical industry to develop the quality-of-care performance measures. HOWG wanted the measures to be ones that health plans could use to improve the quality of care, that were based on reliable data that could be standardized to account for patient population differences, and that were practical to institute (not cost prohibitive). By the end of a 1 1/2-day working session, each panel had developed at least one preliminary performance measure. Following the panels' meeting, background literature searches were conducted and supporting documentation was obtained. The panels then sent the revised performance measures to appropriate professional organizations for informal review. Another round of revisions was then completed. CHALLENGES AND NEXT STEPS: HOWG's experience in developing these measures, which contain either or both the important clinical processes and outcomes for the respective diseases, has highlighted current challenges in the performance measure arena, such as the availability, validity, and varying sources of data. The PhRMA performance measures should be subjected to further external review and pilot tests before implementation.
10402068 Amyloidosis in a nationwide series of 1666 subjects with rheumatoid arthritis who died dur 1999 Jun OBJECTIVES: Virtually all studies dealing with the occurrence of amyloidosis in subjects with rheumatoid arthritis (RA) have been based on selected series collected from university clinics. The purpose of the study was to obtain information on the true prevalence of amyloidosis and the role of amyloidosis as a cause of death. METHODS: The study included all 1666 subjects (480 men and 1186 women) who had died in 1989 and had been entitled under the national sickness insurance scheme to receive specially reimbursed medication for RA. RESULTS: Amyloidosis was regarded as an immediate cause or an intervening antecedent cause of death in 64 cases (3.8%) and as a contributory cause of death in 33 cases (2%), corresponding to a prevalence of 5.8%. Amyloidosis had been diagnosed during life in 89 instances and was detected at autopsy in eight instances. Twenty-three (4.8%) of the subjects were men and 74 (6.2%) were women (P = 0.25). Compared with the remaining subjects in the study series, the lifespan of the subjects with amyloidosis was shortened by 7.7 yr. CONCLUSIONS: The prevalence of amyloidosis was lower than apparent from most earlier studies. Monitoring information derived from the Finnish sickness insurance system is a useful way of following trends in the occurrence of amyloidosis complicating RA.
10648015 Influence of blood and synovial fluid immune complexes of patients with rheumatoid arthrit 2000 Jan OBJECTIVE: To determine whether blood and synovial fluid (SF) immune complexes (IC) of patients with rheumatoid arthritis (RA) influence the production of nitric oxide (NO) and growth and viability of chondrocytes. METHODS: IC were precipitated and IgM and IgG were determined in the precipitates by ELISA and nephelometry, respectively. Primary cultures of bovine articular chondrocytes were incubated with the IC precipitates. After 48 h NO was determined as nitrite. After 7 days, growth was determined by incorporation of tritiated thymidine and viability was detected by neutral red uptake. RESULTS: Patient sera were positive in 8/12 for IgM IC and 9/12 for IgG IC, and 1/8 control sera was slightly positive for IgM IC. Seven of 12 SF samples were IgM IC and 10/12 IgG IC positive. With and without additional interleukin 1alpha (IL-1alpha) stimulation, NO production by chondrocytes was significantly higher with SF IC precipitates than with control serum precipitates (p = 0.03, p = 0.04, respectively). NO production by chondrocytes that were not stimulated with IL-1alpha was significantly increased with SF IC precipitates compared to RA serum IC precipitates (p = 0.03). SF IC significantly inhibited growth compared to control serum precipitates (p = 0.04) and RA serum IC (p = 0.012). Neutral red uptake by chondrocytes was significantly decreased when incubated with RA serum IC in comparison with control serum IC (p = 0.012) and SF IC (p = 0.006). With and without additional IL-1alpha stimulation, NO production by chondrocytes after incubation with SF derived IC was positively correlated to the Ritchie score (r = 0.8, r = 0.7, respectively) and the number of swollen joints (r = 0.8, r = 0.6, respectively). CONCLUSION: These results support the hypothesis that, especially in active RA, SF derived IC stimulate NO production and inhibit chondrocyte growth.
9797555 Involvement of simultaneous multiple transcription factor expression, including cAMP respo 1998 Aug OBJECTIVE: To elucidate possible roles of several transcription factors in the pathogenesis of rheumatoid arthritis (RA), the transcription factor expression in RA synovial tissue and their contribution to RA synovial cell functions were studied. METHODS: Single cell suspension of dissociated synovial tissue was cultured to induce in vitro tissue outgrowth of RA synovial cells. Transcription factors were immunohistochemically identified in RA synovial tissue obtained by joint surgery and in the in vitro tissue outgrowth, and confirmed by western blotting and gel shift assays. RESULTS: Immunohistochemical examination of RA synovial tissue revealed simultaneous expression of various transcription factors (NF-kappa B, c-Jun (a component of AP-1), cAMP responsive element binding protein (CREB), and OCT-1). The same set of transcription factors was expressed in the in vitro tissue outgrowth of RA patients. The early passage RA synovial cells were treated with interleukin 1 beta (IL1 beta) and confirmed translocation of transcription factors into the nucleus by western blotting, and their DNA binding activity by gel shift assays. CONCLUSION: This study emphasises the importance of the simultaneous expression of several transcription factors for the hyperactivity of RA synovial cells that leads to tissue outgrowth.
11735079 Predictors of pain catastrophizing in women with rheumatoid arthritis. 2001 Dec Catastrophizing has been conceptualized as an appraisal, a cognitive distortion, and a coping mechanism in the psychosocial literature. Regardless of its conceptualization, catastrophizing has been associated with negative psychological and physical outcomes in numerous studies, including our intervention study with 90 women with rheumatoid arthritis. Because of catastrophizing's robust relationship with negative outcomes, predictors of catastrophizing as a pain coping behavior were investigated in this sample, using data collected from two points in time before the intervention. Using Lazarus and Folkman's stress and coping theoretical framework to guide the analyses, variables with a proximal relationship to catastrophizing in the framework were examined for significant associations with pain catastrophizing using correlational analyses. Subsequent stepwise regression involving all variables from Time 1 with significant associations resulted in a model that explained 63% of the variance in Time 2 pain catastrophizing scores. The four predictors in this model were dispositional pessimism, passive pain coping, venting (as a pain coping behavior), and arthritis helplessness. Potential clinical implications related to these predictors are also discussed. Knowledge about predictors of catastrophizing may enhance efforts to address this maladaptive pattern through educational and therapeutic approaches.
9517760 Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia 1998 Mar OBJECTIVE: To determine the effect of longterm methotrexate (MTX) therapy and folic acid supplementation on folate nutriture and homocysteine levels in patients with rheumatoid arthritis. METHODS: A double blind, placebo controlled trial lasting one year was conducted at one academic medical center. A total of 79 patients taking low dose MTX were followed up to one year. The patients were randomized to receive placebo or 5 or 27.5 mg folic acid supplementation per week. RESULTS: Plasma and erythrocyte folate levels and plasma homocysteine levels were determined. The folate nutriture of patients taking low dose MTX declined without folic acid supplementation. Plasma homocysteine levels increased significantly over a one year period in the placebo group. Low folate nutriture and hyperhomocysteinemia occurred with greater frequency in the placebo group than in the folic acid supplemented groups. CONCLUSION: For longterm, low dose MTX therapy, there are now at least 3 reasons to consider supplementation with folic acid (a low cost prescription): (1) to prevent MTX toxicity, (2) to prevent or treat folate deficiency, and (3) to prevent hyperhomocysteinemia, considered by many investigators to be a risk factor for cardiovascular disease.
9733449 Cross cultural adaptation and validation of the Chinese Health Assessment Questionnaire fo 1998 Sep OBJECTIVE: The Health Assessment Questionnaire - Disability Index (HAQ), used as a disability and outcome measurement in rheumatoid arthritis (RA), has been validated in several languages, but not in Chinese. Our aim was to validate the Chinese version of HAQ (Chinese-HAQ) to suit the needs of Chinese speaking patients with RA in an Asian setting. METHODS: The original HAQ was modified in the context of Chinese culture and translated into Chinese by 2 translators aware of the objective of the questionnaire. The Chinese HAQ was self-administered by 42 patients with RA during their routine followup visit and one week later. RESULTS: The test-retest reliability assessed using Spearman's correlation coefficient was 0.84. Between dimensions measured in the HAQ, the highest test-retest reliability was observed for walking (Spearman correlation coefficient rs=0.80) and the lowest was for eating (rs=0.54). The internal consistency of the scale using Cronbach's alpha was high at 0.86. In terms of criterion validity, the Chinese-HAQ score was found to correlate well with American College of Rheumatology functional status (rs=0.501, p=0.01). The Chinese-HAQ scores also correlated well with markers of disease activity such as patient's perception of pain measured on a visual analog scale (rs=0.55, p < 0.001), grip strength in mm Hg (rs=-0.55. p < 0.001 ), and physician's assessment of disease activity (rs=0.59, p < 0.001). CONCLUSION: The Chinese HAQ is a reliable and valid instrument for studies measuring disability of patients with RA in Singapore.
10643712 The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrulli 2000 Jan OBJECTIVE: Since modern treatment of rheumatoid arthritis (RA) is shifting toward aggressive antirheumatic therapy in an early phase of the disease, diagnostic tests with high specificity are desirable. A new serologic test (anti-cyclic citrullinated peptide [anti-CCP] enzyme-linked immunosorbent assay [ELISA]) was developed to determine the presence of antibodies directed toward citrullinated peptides, using a synthetic peptide designed for this purpose. METHODS: A cyclic peptide variant that contains deiminated arginine (citrulline) was designed and used as antigenic substrate in ELISA. Test parameters and diagnostic characteristics of the test were studied in patients with and without RA, in patients with various infectious diseases, and in a group of patients from an early arthritis clinic (EAC). RESULTS: Using prevalent RA and non-RA sera, the anti-CCP ELISA proved to be extremely specific (98%), with a reasonable sensitivity (68%). Also, in the EAC study group, the anti-CCP ELISA appeared to be highly specific for RA (96%). In comparison with the IgM rheumatoid factor (IgM-RF) ELISA, the anti-CCP ELISA had a significantly higher specificity (96% for CCP versus 91% for IgM-RF; P = 0.016) at optimal cut-off values. The sensitivity of both tests for RA was moderate: 48% and 54% for the anti-CCP ELISA and the IgM-RF ELISA, respectively (P = 0.36). Combination of the anti-CCP and the IgM-RF ELISAs resulted in a significantly higher positive predictive value of 91% (P = 0.013) and a slightly lower negative predictive value of 78% (P = 0.35) as compared with the use of the IgM-RF ELISA alone. The ability of the 2 tests performed at the first visit to predict erosive disease at 2 years of followup in RA patients was comparable (positive predictive value 91%). CONCLUSION: The anti-CCP ELISA might be very useful for diagnostic and therapeutic strategies in RA of recent onset.
10963123 Histopathology and molecular pathology of synovial B-lymphocytes in rheumatoid arthritis. 2000 Jul B-cells of the rheumatoid synovial tissue are a constant part of and, in some histopathological subtypes, the dominant population of the inflammatory infiltrate, located in the region of tissue destruction. The pattern of B-cell distribution and the relationship to the corresponding antigen-presenting cells (follicular dendritic reticulum cells: FDCs) show a great variety. B-cells may exhibit (i) a follicular organization forming secondary follicles; (ii) follicle-like patterns with irregularly formed FDC networks, and (iii) a diffuse pattern of isolated FDCs. Molecular analysis of immunoglobulin VH and VL genes from human synovial B-cell hybridomas and synovial tissue demonstrates somatic mutations due to antigen activation. The FDC formations in the synovial tissue may therefore serve as an environment for B-cell maturation, which is involved in the generation of autoantibodies. An autoantibody is defined as "pathogenic" if it fulfills the Witebsky-Rose-Koch criteria for classical autoimmune diseases: definition of the autoantibody; induction of the disease by transfer of the autoantibody; and isolation of the autoantibody from the disease-specific lesion. B-cells from rheumatoid synovial tissue show specificity for FcIgG, type II collagen, COMP, sDNA, tetanus toxoid, mitochondrial antigens (M2), filaggrin and bacterial HSPs. The contributions of these antigens to the pathogenesis of RA are still hypothetical. A possible contribution could derive from crossreactivity and epitope mimicry: due to crossreaction, an antibody directed originally against a foreign infectious agent could react with epitopes from articular tissues, perpetuating the local inflammatory process. The characteristic distribution pattern, the localisation within the area of tissue destruction, the hypermutated IgVH and IgVL genes, and their exclusive function to recognize conformation-dependent antigens suggest a central role for B-cells in the inflammatory process of rheumatoid arthritis. Therefore, the analysis of synovial B-cell hybridomas and experimental expression of synovial IgVH and IgVL genes will help to characterise the antigens responsible for the pathogenesis of rheumatoid arthritis.
9629752 [Effects of bromocriptine in patients with active rheumatoid arthritis]. 1998 Jan BACKGROUND: Neuroendocrine factors play an important role in the expression of autoimmune diseases. Prolactin (PRL) can induce T-cell proliferation and macrophage activation. Elevated PRL levels have been described in patients with rheumatoid arthritis (RA). AIM AND METHODS: We studied immunological and clinical effects of PRL suppression in 9 RA patients with active disease, treated for 3 months with bromocriptine (BRC), an inhibitor of PRL secretion. RESULTS: BRC induced a significant depression of the peripheral blood mononuclear cells response to antigen (p = 0.008) and mitogen (p = 0.008) which was significantly correlated with improvements in the HAQ disability index (r = 0.68; p = 0.04) and grip strength (r = 0.7; p = 0.02). Also, the in-vitro production of IL-2, nitric oxide and poliamines--that are critical for the proliferative response of lymphoid cells--decreased significantly. The group experienced significant improvement of grip strength (p = 0.028) and the HAQ disability index (p = 0.025), whereas 4 individuals achieved clinical improvement according to the American College of Rheumatology preliminary definition. We conclude that BRC treatment induces a significant depression of in-vitro immune function in RA patients and that these changes are related to parameters of disease activity. The effects of BRC on immune function and disease activity in RA patients warrant further investigation.
9150069 Response to therapy in rheumatoid arthritis is influenced by immediately prior therapy. 1997 May OBJECTIVE: Clinicians do not often employ washout periods before prescribing a change in therapy for rheumatoid arthritis (RA). As a result, the observed effectiveness or lack of effectiveness of a new drug actually represents the effectiveness of that drug had the patient been taking placebo minus the residual effectiveness of the old drug. METHODS: We studied new starts of selected disease modifying antirheumatic drugs (DMARD) and prednisone in 2,898 patients with RA from 8 ARAMIS data bank centers, broken into subgroups on the basis of immediately prior therapy. Therefore, we examined the hypothesis that the chances of a treatment being observed effective depend upon the immediately preceding treatment. Using intent-to-treat analysis, we analyzed the effects upon Health Assessment Questionnaire (HAQ) disability and pain scores an average of 9 months after the new drug start. RESULTS: Methotrexate reduced disability significantly except after intramuscular gold or hydroxychloroquine and it reduced pain significantly after all prior therapies. Hydroxychloroquine reduced disability significantly after nonsteroidal antiinflammatory drugs (NSAID) only, but disability increased after intramuscular gold; pain was decreased only after NSAID only. Prednisone had no consistent effect upon disability but was consistently associated with decreased pain. Greatest effectiveness was always seen with a new drug start after NSAID only treatment versus after DMARD treatment. CONCLUSION: The effectiveness of a newly started RA treatment after 9 months may be substantially influenced by immediately prior treatment. This finding provides an additional reason for concern about direct extrapolation of clinical trial data into clinical practice.
9035016 Double blind evaluation of the long-term effects of etodolac versus ibuprofen in patients 1997 Feb We compared the longterm efficacy and safety of 2 dosages of etodolac with that of ibuprofen in the treatment of active rheumatoid arthritis (RA). The ability of etodolac to retard, arrest, reverse, or heal joint damage due to RA was also evaluated. Patients in the early stages of RA were assigned randomly to 3 parallel groups for up to 3 years of therapy: etodolac at 150 mg bid, etodolac at 500 mg bid, and ibuprofen 600 mg qid. Concurrent disease modifying antirheumatic drugs were not permitted; established low dosage corticosteroid therapy could be continued. A total of 1446 patients was enrolled. About 50% of patients completed one year; dropout rates were comparable between groups. Both etodolac dosages provided comparable efficacy to that of ibuprofen during the first 2 months; longterm assessment showed that 1000 mg/day of etodolac produced superior improvement as assessed by patients' opinions and number of swollen joints. About 2% of patients in each group achieved remission, and radiographs showed no difference in disease progression between treatments. The incidences of adverse events were comparable, although dyspepsia and rash occurred less frequently with 300 mg/day of etodolac than with 2400 mg/day ibuprofen. A higher incidence of gastrointestinal ulcers and bleeding was seen with ibuprofen. Changes in hepatic and renal function were of minor clinical significance and were similar between the 3 groups. Both dosages of etodolac were comparable to 2400 mg/day ibuprofen in treating RA. All 3 treatment regimens were well tolerated.
9177930 Glucocorticoids and Th-1, Th-2 type cytokines in rheumatoid arthritis, osteoarthritis, ast 1997 May Endogenous or exogenous glucocorticoids play a key role in the control of the immune and inflammatory network. Regulation of the effects of the glucocorticoids depends on changes in therapeutic levels, but also, as recently discovered, on modifications of the binding characteristics of the glucocorticoid receptors of target cells. In rheumatoid arthritis (RA), chronic bronchial asthma, atopic dermatitis, in chondrocytes from osteoarthritic patients, and in advanced stages of HIV infection, there is a down-regulation of the glucocorticoid receptors. As a consequence, B cell immune proliferation is stimulated in RA, proteolysis is enhanced in osteoarthritis, the glucocorticoids' therapeutic effect is reduced in asthma and atopic dermatitis, and a chronic persistent increase of interferon alpha is seen in HIV. Finally, glucocorticoids are also capable of switching CD4 cells from a Th-1 to a Th-2 pattern. A decreased affinity of lymphocyte glucocorticoid receptors could hinder such a switch, with obvious clinical implications.
9779838 Circulating levels of interleukin 10 and other cytokines in rheumatoid arthritis treated w 1998 Oct OBJECTIVE: To assess longitudinally over a 12 month period circulating serum levels of interleukin 10 (IL-10) and cytokines IL-3, IL-4, IL-6, and IL-12 in a cohort of patients with early onset rheumatoid arthritis (RA) treated with either cyclosporin A (CyA) or with combination therapy of CyA plus hydroxychloroquine as disease modifying antirheumatic drugs. METHODS: We studied 8 patients receiving CyA and 12 patients receiving CyA plus hydroxychloroquine. IL-3, IL-4, IL-6, IL-10, and IL-12 were determined by ELISA at entry, after 2 weeks, after one month, after 6 months, and after 12 months. Rheumatoid factor levels and the possible appearance of monoclonal gammopathies over time were studied by immunofixation and immunoblotting techniques. RESULTS: The pooled data show that at entry only the median baseline levels of IL-10 (3.9 vs 1.6 pg/ml; p < 0.01) and IL-6 (16.9 vs 1.4 pg/ml, p < 0.001) were higher in patients than in controls. IL-4 was not detectable. Some patients at entry (those with the longest disease duration) had detectable levels of IL-3. Only levels of IL-10 decreased significantly between entry and final values, in monotherapy and combination therapy as well. A single transient monoclonal band was observed after 6 months of treatment, which disappeared afterwards. No difference was seen in any of the cytokines between the CyA and the CyA plus hydroxychloroquine treated patients. CONCLUSION: During treatment with either CyA or CyA plus hydroxychloroquine, IL-10 levels decreased significantly. No additive effect of the 2 drugs was detected.
10825588 Analysis of CIITA encoding AIR-1 gene promoters in insulin-dependent diabetes mellitus and 2000 Jun Qualitative and/or quantitative alterations in the expression of the MHC class II molecules affect the onset and maintenance of the immune response and may be the basis of a wide variety of disease states, such as autoimmunity and immunodeficiency.CIITA is a major physiological regulator of the expression of MHC class II genes. The availability of CIITA ap- pears generally essential for MHC class II gene expression, and hence its own transcriptional regulatory mechanisms result of fundamental importance for a correct homeostasis of the immune response. Therefore, it is possible to hypothesize that variability at the CIITA-encoding locus, AIR-1, could constitute an additional source of susceptible traits to autoimmune diseases. Mutations at AIR-1/CIITA promoters could modulate expression of CIITA. Variations in CIITA expression could influence the qualitative and quantitative expression of MHC class II molecules at cell surface. We have analyzed sequence variation at AIR-1/CIITA promoters by PCR-SSCP in 23 IDDM and 30 RA patients compared to a sample of 19 unaffected normal controls and 16 unaffected IDDM family members, for a total of 88 Caucasian subjects from the Northeast of Italy. No sequence difference was found at the four AIR-1/CIITA promoters between autoimmune patients and normal controls. Moreover, the promoters resulted invariant within the entire group of 88 subjects analyzed, comprising patients and controls. This finding suggests a possible selective advantage in maintaining CIITA upstream regulatory sequences invariant.