Browse

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

ID PMID Title PublicationDate abstract
10792496 Decreased expression of FcgammaRIII (CD16) by gammadelta T cells in patients with rheumato 2000 Apr Some gammadelta T cells express a receptor for the Fc portion of immunoglobulin G (FcgammaRIII - CD16). The relevance of this Fc receptor to gammadelta T-cell function is at present unclear. Our previous studies have shown that gammadelta T cells express activation markers in patients with rheumatoid arthritis (RA). In this study we have examined the relative proportions of CD16+ gammadelta T cells in the blood and synovial fluid of these patients compared with control blood. CD16+ gammadelta T cells from RA patients were significantly reduced in synovial fluid compared with the circulation. That this was due to blocking of antibody binding to CD16 was unlikely as treatment of blood gammadelta T cells with RA synovial fluid (known to contain immune complexes) failed to alter expression of CD16. Treatment of blood gammadelta T cells with phytohaemagglutinin in vitro, resulted in a time-dependent decrease in expression of CD16, with a concomitant increase in expression of human leucocyte antigen-DR, at the single cell level. We conclude that expression of CD16 by gammadelta T cells is lost in the synovial compartment as the result of activation.
10527386 Tracking antigen-specific human T lymphocytes in rheumatoid arthritis by T cell receptor a 1999 Sep The aim of this study was to use TCR sequencing as a tool to address the frequency of antigen specific T cells in different T cell compartments from a rheumatoid arthritis patient. We have previously established a clear link between T cell recognition of a specific Mhsp60 epitope and the amino acid sequence in the CDR3 region of the TCRB chain. This information was used to determine the frequency of these characteristic sequences in unmanipulated synovial fluid (SF), peripheral blood (PB) and hyperplastic lymph node of the same patient by amplification and sequencing. TCRBV sequences identical to those seen in antigen-specific clones, and closely related sequences, were readily identified in SF, where they represented approximately 1% of all T cells, but were absent from PB or lymph node. The prevalence of putative Mhsp60 specific T cells within the SFMC is much greater than previously suggested by limiting dilution assays. Thus, amplification and sequencing may prove a superior technique for tracking the frequency of antigen-specific T cells in different tissues and in a longitudinal fashion.
17974357 [Sjogren's syndrome]. 1997 Jan Sjogren's syndrome is a chronic inflammatory disease of unknown aethiology. It is characterized by decreased secretion of salivary and lacrimal glands, which induces keratoconjunctivitis sicca and xerostomia. Sjogren's syndrome is a central autoimmune disease, and it has characteristics of both organ-specific and generalized autoimmune diseases. It can exist as a primary disease or is associated with other autoimmune diseases (most freyuently with systemic lupus erythematosus or rheumatoid arthritis) and is classified as a secondary Sjogren's syndrome. The aethiology is multifactorial, and it has not yet been completely explained. In the pathogenesis of the disease the important role have genetic predisposition, chronic oestrogen stimulation, end viral infections, especially of the herpes virus group (EBV, CMV, HHV6) and retroviruses. In the clinical picture xerostomia, xerophtalmia and non-erosive arthritis are the most common features, with the whole spectrum of extraglandular manifestations of respiratory, gastrointestinal, skin, and haematologic, neurologic and endocrinologic disturbances. Pathohistological findings of minor labial salivary gland lymphocyte infiltration is the most specific and the most sensitive diagnostic criterion of Sjogren's syndrome. The diagnosis of keratoconjunctivitis sicca is made by Schrimer's test, Rose bengal dye staining and by the "tear break up time". Differential diagnosis of Sjogren's syndrome includes an extremely large number of various pathologic states. The treatment of Sjogren's syndrome consists of symptomatic treatment of dry mucosas (artificial tears, etc.) and also of antiinflammatory drugs, glucocorticoids, immunosuppressive drugs. Plasmapheresis and intravenous administration of immunoglobulins are used for immunosuppression in these patients.
9201820 Immunosuppressant therapy during gestation. 1997 Apr Use of immunosuppressants during pregnancy is indicated for anti-rejection therapy in transplantation patients and treatment of autoimmune diseases. Maternal side effects include nephrotoxocity and hepatotoxicity. All immunosuppressant drugs cross the placenta. Immunosuppressant use during the first trimester is not strongly associated with an increased risk of congenital anomalies, although some agents (eg, azathioprine) may be associated with slightly increased frequencies of birth defects. Effects of exposure to this class of drugs during the second and third trimesters affects the fetus' immune system. The result is an infant with a transiently compromised immune system at an increased risk of slightly lower birth weight. Other direct toxic effects of the drugs on the infant's pancreas, liver, and lymphocytes are reported. Certain agents (eg, penicillamine, chloroquine) should be avoided during pregnancy, if possible. However, their use cannot be discontinued during pregnancy given the life-threatening nature of the indication for use of immunosuppressants.
9662188 Cell electrophoretic mobility and glycerol lysis of human erythrocytes in various diseases 1998 Jun Using an automated cell electrophoresis system equipped with an image processor, we studied electrophoretic mobilities of erythrocytes of healthy donors and of patients suffering from systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), hypergammaglobulinemia and diabetes mellitus (DM). On average, erythrocytes from SLE patients showed mean electrophoretic mobilities (EPM) which were significantly lower (p < 0.005) than the EPM of red blood cells of normal donors. Evaluation of mean EPM and standard deviations revealed that three groups of SLE patients could be distinguished regarding the electrophoretic behavior of their erythrocytes. Some patients had red blood cells with normal EPM, others had erythrocytes with significantly reduced EPM, and a third group appeared to have both kinds of erythrocytes. In addition, erythrocytes of various SLE patients showed enhanced resistance to lysis by glycerol and their membranes contained less quantities of band 3 proteins.
9375870 Renal stones in patients with rheumatoid arthritis. 1997 Nov OBJECTIVE: Renal stones are reported to be one of the causes of hematuria in patients with juvenile rheumatoid arthritis (RA). We performed abdominal ultrasonography on patients with RA to investigate the frequency of renal stones and whether renal stones are related to hematuria. METHODS: We conducted abdominal ultrasonography in 224 patients with RA (42 men, 182 women). Mean age was 61.4 years, and the mean duration of disease was 13.5 years. RESULTS: Renal stones were defined as hyperechoic spots with acoustic shadows, and they were observed in 37 patients. We also noticed hyperechoic spots without acoustic shadows in 50 patients. Five of these 50 patients also had renal stones. Twenty-one patients showing hyperechoic spots without acoustic shadows underwent computed tomographic scans, and apparent calcifications were observed in 10 patients. Age and sex matched controls had a significantly lower incidence of renal stones and hyperechoic spots without acoustic shadows than did patients with RA. Hematuria was more frequently observed in patients with RA with renal stones than in those without renal stones or hyperechoic spots without acoustic shadows. Urinary calcium/creatinine (Ca/Cr) ratios were elevated in patients compared to controls. Urinary Ca/Cr ratios in patients taking vitamin D3 were higher than those of patients not receiving the vitamin. Administration of vitamin D3 also was associated with increased incidence of renal stones. CONCLUSION: We observed a high incidence of renal stones in patients with RA. Hematuria was more prevalent in patients with RA with renal stones than in those without. These results suggest the importance of performing abdominal ultrasonography on patients with RA.
9645413 Low incidence of osteoporosis in a two year follow-up of early community based patients wi 1998 52 patients with early rheumatoid arthritis (RA) were followed with regular measurements of bone mineral density (BMD) and serum markers of type I collagen metabolism in order to determine whether they develop osteoporosis during the first two years of the disease course and if the changes in type I collagen metabolites reflect the alterations in BMD. The mean percentage BMD change over the first year of follow-up was -0.91 for lumbar spine (LS) and -0.76 for femoral neck (FN); the corresponding figures from 0 to 24 months was -1.3 and -0.8, respectively. During the follow-up, only five patients developed osteoporosis by the Z-score definition (<-1). If defined by T-score (<-2.5) none of the patients developed osteoporosis. The BMD change correlated neither with the clinical parameters of disease activity nor with the markers of collagen metabolism. However, the BMD change in FN was associated with the cumulative corticosteroid dose (r=-0.31, p <0.05, 95% CI -0.54 to -0.04). Reasons for the lack of accelerated bone loss in our series are open to various interpretations. This series was community based and most of the patients had mild RA. The patients were also actively treated and their physical function did not deteriorate.
9389223 Long-term persistent accumulation of CD8+ T cells in synovial fluid of rheumatoid arthriti 1997 Oct OBJECTIVE: To characterise the type and kinetics of T cell clones in synovial lesions of patients with rheumatoid arthritis (RA). METHODS: Mononuclear cells from serial samples of synovial fluid (SF) and peripheral blood from nine RA patients were separated phenotypically using antibody coated magnetic beads. After mRNA preparation, reverse transcription-polymerase chain reaction (RT-PCR) was performed to amplify V-D(N)-J (that is, the third complementarity determining, CDR3) regions of their T cell receptor beta chain genes. This was followed by single strand conformation polymorphism (SSCP) analysis to detect the clonotypes of accumulating T cells. Amino acid sequences of the dominant clones were also determined. RESULTS: Although peripheral T cells were heterogeneous, accumulation of oligoclonal T cells was detected in SF. The predominant accumulating clone was the CD8 subset, which was persistently present in serial samples obtained over almost one year of follow up. A proportion of these cells expressed CD25 or CD45RO, or both, suggesting they are 'memory' clones. CONCLUSION: The persistent presence of CD8+ T cell clones in RA joints indicates that they may be involved in the perpetuation of the chronic inflammatory process in RA joints.
10498563 Therapeutic plasma exchange: an update from the Canadian Apheresis Group. 1999 Sep 21 In 1997, the Canadian Apheresis Group reviewed data on 103,416 plasma exchange procedures that had been collected since 1980. Although the number of plasma exchanges gradually increased (from 3189 to 8208 per year), the pattern changed. In 1981, the five most frequent indications for plasma exchange resulted in 55% of all such procedures; by 1997, the five most frequent indications for plasma exchange resulted in 81.1% of all such procedures. During this period, three conditions that were originally among the most frequent indications for plasma exchange became among the least frequent. This paper reviews the published evidence that supports or refutes the use of plasma exchange in the category of the five most frequent indications from 1981 to 1997: thrombotic thrombocytopenic purpura, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, Waldenstrom macroglobulinemia, the Guillain-Barre syndrome, rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. For most disorders, use of plasma exchange procedures is correlated with published evidence, and the changing patterns of plasma exchange use by members of the Canadian Apheresis Group reflect published evidence. Annual center-by-center reviews of use of plasma exchange may also have influenced practice patterns.
10229399 Disability in patients with early inflammatory polyarthritis cannot be "tracked" from year 1999 Apr OBJECTIVE: To determine whether disability in patients with early inflammatory polyarthritis (IP) can be charted or "tracked" over time. The disability score was also adjusted in an attempt to exclude the influence of current disease activity, with the aim of ascertaining that component of disability relating to other factors such as psychosocial factors and joint damage. METHODS: Four hundred thirty-three patients with early IP referred to the Norfolk Arthritis Register (NOAR) were followed annually using the Health Assessment Questionnaire (HAQ) for 5 years. HAQ scores at each year were divided into quartiles. The number of patients remaining in the same quartile from year to year was examined. The relationship between disease activity, assessed by swollen and tender joint counts, and HAQ was modelled, with the residual HAQ attributed to psychosocial factors and joint damage. RESULTS: From year to year, there was considerable within-individual variation in quartile, with only 48-65% of patients remaining in the same quartile. With increasing time, a greater proportion of patients remained in the same quartile. A statistically valid activity-adjusted HAQ score could not be computed. CONCLUSION: Disability in patients with early IP cannot be easily tracked over time. It is therefore not appropriate to construct longitudinal reference charts for disability in the early years, although it may be feasible for more established disease.
10337032 The levels of soluble granzyme A and B are elevated in plasma and synovial fluid of patien 1999 May Cytotoxic cells possess specialized granules which contain perforin and a group of serine proteinases termed granzymes. Granzyme-positive cells have been identified in synovial fluid and tissue of patients with RA, where they may play an important role as mediators of granule-mediated apoptosis, extracellular proteolysis, and cytokine induction. The aim here was to define further the involvement of cytotoxic cells in RA. Plasma and synovial fluid samples from the knee joint were obtained from 31 RA patients. The disease controls included 20 osteoarthritis (OA) patients and 10 reactive arthritis (ReA) patients. A recently developed capture ELISA was used to detect soluble granzymes A and B in all patients. Compared with OA and ReA disease controls, markedly increased levels of soluble granzymes A and B were detected in both plasma and synovial fluid of RA patients (P < 0.00001). When values for soluble granzymes A and B in plasma and synovial fluid were used simultaneously as independent variables, logistic regression analysis indicated that a diagnosis of RA could be predicted correctly in 84% of the RA patients and a diagnosis of non-RA in 90% of the controls. The markedly elevated levels of soluble granzymes A and B in plasma and synovial fluid of RA patients strongly suggest that cytotoxic cells are active participants in the pathogenesis of RA. Moreover, the results suggest that measurement of granzymes may assist the laboratory evaluation of patients with arthritis. Larger studies in patients with early disease may clarify the role of this test system in differential diagnosis.
9143255 Evidence that natural autoantibodies against the nerve growth factor (NGF) may be potentia 1997 May Nerve growth factor (NGF) was detected by enzyme-linked immunosorbent assay using the monoclonal anti-NGF antibody 27/21 in natural NGF autoantibodies (NGF NA) purified from sera of control human subjects as well as from sera of patients with rheumatoid arthritis, autoimmune thyroiditis and to a lesser degree in patients with systemic lupus erythematosus as well as in NGF NA from the synovial fluid of patients with spondylarthropathies. Our results suggest that NGF NA may be potential carriers of NGF in the circulation.
11409115 Long-term safety and efficacy of etanercept in patients with rheumatoid arthritis. 2001 Jun OBJECTIVE: Patients with rheumatoid arthritis (RA) treated with etanercept (Enbrel) in controlled studies of 3 to 6 months' duration had rapid and sustained improvement of their disease, with minimal safety issues. In this study, we examine safety and clinical benefit after longer term treatment with etanercept. METHODS: All adult patients with RA with a previously inadequate response to one or more disease modifying antirheumatic drugs, and who received at least one dose of etanercept as monotherapy in controlled or open label clinical trials were evaluated for safety and clinical benefit. Adverse event rates were compared as was evidence of continued benefit over time. RESULTS: Etanercept continued to be safe and well tolerated in 628 adult patients treated for a median of 25 mo (maximum 43 mo; 1109 patient-years). Nine percent of patients withdrew due to lack of efficacy and 7% due to adverse events. Most adverse events were mild, and no statistically significant increases in frequency of events were seen when patients received etanercept over longer periods of time. Clinical benefit was maintained with longterm therapy. A 100% improvement in individual disease activity measures was achieved by 17% to 28% of the patients. Fifty-five percent of patients who were taking corticosteroids (mean dose at baseline 6.6 mg/day) decreased or discontinued corticosteroid therapy while maintaining control of their arthritis symptoms. CONCLUSION: Etanercept continued to be safe and well tolerated, and its clinical benefit was sustained for a median of 25 mo and for as long as 43 mo in patients with RA.
9876392 Cartilage damaging activities of fibronectin fragments derived from cartilage and synovial 1998 Jul OBJECTIVE: To investigate whether fibronectin fragments (Fn-fs), shown to damage cultured cartilage, can be found in cartilage from patients with osteoarthritis (OA) or rheumatoid arthritis, or can be generated from fibronectin (Fn) within synovial fluids or from Fn in the matrix of cultured cartilage. To also determine whether cartilage or synovial fluid Fn-fs are active and, thus, could contribute to cartilage damage in vivo. METHODS: Fn-fs were immunochemically identified in cartilage extracts from patients with OA or rheumatoid arthritis or in bovine cartilage cultured with IL-1 alpha or in bovine synovial fluids treated with stromelysin-1 (MMP-3). The effect of removal of Fn-fs from OA synovial fluids was tested by passing fluids over an anti-Fn column and adding the resultant fluids to bovine cartilage cultures to measure proteoglycan (PG) degradation. Gelatin-Sepharose purified Fns from bovine plasma, synovial fluid or cartilage were digested with MMP-3 and the Fn-fs tested for degradation of PG in cultured cartilage. RESULTS: Extracts of cartilage from patients with rheumatoid arthritis or with OA contained a range of Fn-fs. Removal of Fn-fs from OA synovial fluids significantly reduced the resultant damage when the fluids were added to cultured cartilage. Addition of IL-1 alpha to cultured cartilage or of MMP-3 to synovial fluids enhanced generation of Fn-fs. Fn-fs, whether derived from bovine plasma or synovial fluid or cartilage Fns, damaged cartilage. CONCLUSIONS: These data demonstrate that although Fn-fs could be generated in vivo within synovial fluids and Fn-fs found in OA synovial fluid may contribute to cartilage damage in vivo, Fn-fs could also be generated within cartilage and amplify cartilage damage. Thus, Fn-fs may be both autocrine and paracrine regulators of cartilage metabolism.
10211875 Synovial fluid CD146 (MUC18), a marker for synovial membrane angiogenesis in rheumatoid ar 1999 Apr OBJECTIVE: CD146 (MUC18/MCAM/S-Endo) is a marker of tumor progression and metastasis formation in human melanoma. This molecule has also been identified in smooth muscle, endothelial cells, and activated T lymphocytes. We measured the synovial fluid levels of soluble CD146 in various human joint diseases, including rheumatoid arthritis (RA). In addition, we studied the distribution of CD146 in normal and RA synovial tissues. METHODS: CD146 was isolated from MEL-OH melanoma cells and characterized by Coomassie blue staining and Western blotting. Soluble CD146 was measured by competitive enzyme-linked immunosorbent assay in synovial fluids of 3 healthy individuals and 7 cadavers (controls), as wells as in patients with traumatic joint injury (n = 10), osteoarthritis (OA; n = 10), psoriatic arthritis (PsA; n = 10), other non-RA polyarthritis (NRAP; n = 10), and RA (n = 31). Immunohistochemistry was performed on 3 normal and 3 RA synovial tissues. Flow cytometric, reverse transcription-polymerase chain reaction, and Western blot analyses were performed on enzymatically separated RA synovial tissue cells. RESULTS: Compared with controls (mean +/- SD 10 +/- 2 ng/ml), significantly elevated synovial fluid levels of soluble CD146 were detected in patients with OA, PsA, and RA (17 +/- 7, 21 +/- 11, and 39 +/- 16 ng/ml, respectively; P < 0.02-0.001), but not in patients with traumatic joint injury or NRAP. Patients with early RA (<1 year after diagnosis) revealed the highest levels (51 +/- 15 ng/ml, n = 10; P < 0.001 versus controls). In RA, soluble CD146 correlated significantly with morning stiffness (P < 0.001), the number of tender joints (P < 0.02), and the number of swollen joints (P < 0.005), but not with the erythrocyte sedimentation rate (P = 0.07) or the C-reactive protein level (P = 0.57). CONCLUSION: Since CD146 is expressed almost exclusively by vascular endothelium, high levels of soluble CD146 found in RA synovial fluid, particularly in patients with early disease, could reflect increased activity of endothelial cells and angiogenesis.
9133970 Patients who develop inflammatory polyarthritis (IP) after immunization are clinically ind 1997 Mar Musculoskeletal symptoms may occur following various types of immunization, and it has also been suggested that, like infection, immunization may act as a trigger for rheumatoid arthritis (RA). A total of 48 of 898 (5.3%) patients with early inflammatory polyarthritis (IP) referred to the Norfolk Arthritis Register reported an immunization in the 6 weeks prior to symptom onset. There were no important clinical or demographic differences between the 48 immunized patients and 185 consecutive patients who did not report prior immunization. In addition, the frequencies of HLA-DRB1*01. *04 and the shared epitope in 33 of the immunized patients were similar to those in the 185 non-immunized patients and to those in 136 healthy controls. Further results from a case-control study suggest that the rate of immunization is higher amongst cases (5.5%) than age- and sex-matched controls (2.8%). In a small number of susceptible individuals, immunization may thus act as a trigger for RA.
11093600 CPH 82 (Reumacon) in refractory inflammatory arthritis. 2000 In this retrospective analysis of the DMARD CPH 82 in 44 Icelandic patients with severe refractory arthritis, clinical tolerance was good and serious side effects absent, although the majority were using the drug in combination with other DMARDS. Side effects leading to discontinuation were seen in 16% and the three year drug-survival was 51%.
10992514 Reverse transcriptase-PCR analysis of bacterial rRNA for detection and characterization of 2000 Oct Onset of rheumatoid arthritis (RA) is widely believed to be preceded by exposure to some environmental trigger such as bacterial infectious agents. The influence of bacteria on RA disease onset or pathology has to date been controversial, due to inconsistencies between groups in the report of bacterial species isolated from RA disease tissue. Using a modified technique of reverse transcriptase-PCR amplification, we have detected bacterial rRNA in the synovial tissue of late-stage RA and non-RA arthritis controls. This may be suggestive of the presence of live bacteria. Sequencing of cloned complementary rDNA (crDNA) products revealed a number of bacterial sequences in joint tissue from each patient, and from these analyses a comprehensive profile of the organisms present was compiled. This revealed a number of different organisms in each patient, some of which are common to both RA and non-RA controls and are probably opportunistic colonizers of previously diseased tissue and others which are unique species. These latter organisms may be candidates for a specific role in disease pathology and require further investigation to exclude them as causative agents in the complex bacterial millieu. In addition, many of the detected bacterial species have not been identified previously from synovial tissue or fluid from arthritis patients. These may not be easily cultivable, since they were not revealed in previous studies using conventional in vitro bacterial culture methods. In situ hybridization analyses have revealed the joint-associated bacterial rRNA to be both intra- and extracellular. The role of viable bacteria or their nucleic acids as triggers in disease onset or pathology in either RA or non-RA arthritis controls is unclear and requires further investigation.
10627692 The Kessel total shoulder arthroplasty. A 13- to 16-year retrospective followup. 1999 Aug Between 1982 and 1985, 23 Kessel total shoulder arthroplasties were performed on 22 patients with rheumatoid arthritis. A clinical and radiographic review of the 5-year experience was evaluated in 1988 and published in 1992. Ten years later a followup study was done. Of the 22 patients, 11 have died and two were seriously ill and could not participate. Of the remaining nine patients, one had revision surgery after 2 years, leaving eight patients with a mean age of 61 years for this followup study. Shoulder function was evaluated subjectively using the Simple Shoulder Test, and pain was evaluated using a visual analog scale. New radiographs were taken. In general, the patients had a low functional level, but they were able to sleep on the surgically treated side and to manage daily hygiene. Five patients were pain free, and the worst recorded pain during the day was 35 mm on the visual analog scale. Two patients had their scapular component cemented at primary surgery. The radiographs showed no radiolucent zones around these components. The six other scapular components had radiolucent zones of 1 to 3 mm. No radiolucent zones were detected around the humeral components.
9917675 Salvage procedures for complex soft tissue defects of the knee. 1998 Nov The management options for complex soft tissue defects about the knee are varied. Limb threatening conditions such as exposure of joint prosthesis or bone requires stable coverage to avoid amputation. A study was conducted to review the authors' management protocol and experience with complex defects about the knee. A retrospective analysis from 1986 to 1996 of 35 patients with complex defects about the knee was performed. Treatment options were based on the nature, size, location, and depth of the wound. A specific management protocol was applied for each patient. Treatments included local wound care, debridement and skin graft, fasciocutaneous flap, pedicled muscle flap, and free muscle transfer. Postoperatively, patients were evaluated using Knee Society objective and functional scores and other instruments to measure outcome. Successful salvage of the lower extremity was obtained in 34 (97%) patients. Salvage of the total knee prosthesis was obtained in 24 of 29 (83%) patients. Secondary plastic surgery procedures were necessary in eight (23%) patients. Secondary orthopaedic procedures were necessary in five (15%) patients. No patient required an amputation.