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

ID PMID Title PublicationDate abstract
1425915 Molecular characterization of the V gamma 9 T cell receptor repertoire expressed in patien 1992 Nov We have characterized the variable (V)gamma 9 T cell receptor (TcR) repertoire expressed in synovial membrane (SMC) and peripheral blood mononuclear cells (PBMC) of five rheumatoid arthritis (RA) patients. The experimental approach was to sequence the junctional regions of polymerase chain reaction (PCR)-amplified V gamma 9 transcripts; gamma chain sequences were compared with those found in normal PBMC. For normal PBMC, a large proportion of V gamma 9 transcripts used the joining (J)gamma P gene segment whereas a few used J gamma 2. Despite this restriction in J gamma usage, there was extensive junctional region diversity with a unique sequence observed in each transcript examined. In contrast to normal PBMC, J gamma usage of V gamma 9 transcripts in PBMC of two patients was skewed towards J gamma 2. This deviation in J gamma usage was more pronounced in SMC since all patients expressed V gamma 9 transcripts in SMC which predominantly used J gamma 2, as opposed to J gamma P in normal PBMC. Further, approximately 60% of V gamma 9 transcripts in PBMC of each of three patients had identical junctional region sequences, although the specific sequences were unique in each patient. For two of these patients the dominant transcript found in the PBMC was detected in the corresponding SMC at about 10% and 40%, respectively. Overall, our findings indicate that V gamma 9-bearing T cells in RA peripheral blood are largely derived from clonal expansion whereas in the synovium there is expression of a population of these cells that are mainly polyclonal. This may reflect in vivo expansion in response to a V gamma 9/J gamma 2 region-specific antigen. The data presented in this report suggest that V gamma 9+ T cells may play a role in the development of RA.
8970050 Immunohistological characteristics of T cell infiltrates in different forms of childhood o 1996 Dec OBJECTIVE: To characterize synovial T cell infiltrate, in terms of CD4/CD8 ratio and level of activation of T cells, in juvenile rheumatoid arthritis (JRA) and juvenile spondyloarthropathy(JSpA), to correlate these findings with clinical outcomes of the different forms of disease, and to compare them with findings in adult RA synovium. METHODS: We studied synovial tissue specimens from 22 individuals with childhood onset of chronic arthritis (12 polyarticular JRA, 5 pauciarticular JRA, 5 JSpA) and 4 with adult RA. Specimens were selected from an initial bank from 40 patients on the basis of significant inflammation on hematoxylin and eosin and CD3 and CD68 monoclonal antibody staining (T cells and macrophages, respectively). Indirect immunohistochemistry was used with monoclonal antibodies to CD3, CD4, CD8, and interleukin 2 receptor alpha to determine CD4/CD8 ratios and the levels of activation within the T cell subsets. The distribution of gamma delta T cells was also studied. RESULTS: Two patterns of T cell infiltration were seen. The majority of patients had lymphocytic aggregates associated with diffuse infiltrates; a few tissue specimens had diffuse infiltrates without aggregates. The CD4/CD8 ratio was significantly lower in pauciarticular course JRA than polyarticular JRA (p < 0.01) and RA (p < 0.05). Similarly patients with JSpA had a significantly lower CD4/CD8 ratio than patients with polyarticular JRA (P < 0.05). The level of T cell activation (CD3+IL-2R+) was significantly higher in pauciarticular compared with both polyarticular JRA (P < 0.01) and RA (p < 0.05). In general, higher levels of activation of CD8 cells than CD4 cells were seen, particularly in the pauciarticular JRA and JSpA groups. gamma delta T cells were prominent in 2 patients. CONCLUSION: Demonstrated differences in T cell subset distribution between types of childhood chronic arthritis at a histopathological level may reflect different pathogenic mechanisms.
8345852 Gold-induced colitis: a case report and review of the literature. 1993 May A case of severe colitis requiring subtotal colectomy following administration of 35 mg Solganal b for intractable arthritis is described. Abdominal pain and watery diarrhea developed six weeks after the last dose of gold. Colonoscopy revealed mucosal edema and ulceration of the entire colon. Supportive measures failed and the patient required subtotal colectomy. Review of the literature revealed 29 cases, ranging in severity from limited ileal involvement to fulminant panenteritis. Most of the patients responded to intravenous fluids, steroids, and antibiotics, but four required surgery. The case described is notable for the delay in appearance of abdominal symptoms following the cessation of gold therapy. The mechanism of injury is unknown. Abdominal complaints in a patient who has received gold therapy, especially parenteral, merit strict attention, even if occurring several weeks after the final dose, and the diagnosis of gold colitis should be entertained.
8129790 Absence of lentiviral and human T cell leukemia viral sequences in patients with rheumatoi 1994 Mar OBJECTIVE: The etiology of rheumatoid arthritis (RA) is unknown, and the possibility that an infectious agent is involved has not been excluded. Lentiviruses can cause chronic arthritis in humans and in animals and have been suggested as candidate agents in RA. We therefore tested for the presence of lentiviruses and also for human T cell leukemia virus type I (HTLV-I)/HTLV-II in cells from patients with RA. METHODS: We used the polymerase chain reaction with degenerate primers designed to recognize highly conserved nucleotide sequences from 5 different pathogenic lentiviruses. This method allowed the detection of at least 1 infected cell/20,000 uninfected cells in control experiments. RESULTS: Testing of synovial cells and blood cells from patients with early RA and patients with established RA did not yield any specific viral product. CONCLUSION: Our results do not support the presence of lentiviruses or HTLV-like sequences in RA.
8234072 Advances in elbow arthroscopy. 1993 Sep Arthroscopy of the elbow is a very precise and demanding technique. Because of the proximity of neurovascular structures to the recommended portals, a thorough knowledge of regional and intraarticular anatomy is essential. The high degree of congruency of the articular surfaces and the relatively small capsular volume make sound arthroscopic skills a necessity. With proper precautions, the technique is safe and affords the opportunity to obtain valuable diagnostic information and to perform selected procedures without the morbidity of an arthrotomy.
8669234 The effect on joint fluid concentration of neuropeptide Y by intra-articular injection of 1996 Feb Twenty-two patients (29 joints) with temporomandibular joint (TMJ) arthritis of specific or unspecific nature were given one intra-articular glucocorticoid (GC) injection. The effect on subjective symptoms and clinical signs in the craniomandibular system and on joint aspirate concentration of neuropeptide Y-like immunoreactivity (NPY-LI) was evaluated at follow-up visits 2-3 or 4-6 weeks after treatment. In the patients with specific inflammatory joint disease the treatment resulted in an improvement of symptoms and clinical signs and in a reduction in the TMJ level of NPY-LI 2-3 weeks after treatment. In the patients with unspecific inflammatory joint disease there was also an improvement in the clinical variables and a reduction in the NPY-LI level after 2-3 weeks, but not on a statistically significant level. The results of this study show that intra-articular GC treatment causes a short-term decrease of the TMJ fluid level of NPY-LI in patients with specific inflammatory joint disease, while symptoms and signs improve.
8020457 Interpersonal stress, depression, and disease activity in rheumatoid arthritis and osteoar 1994 Mar The relationships among interpersonal stressors, depression, coping inefficiency, hormones (prolactin, cortisol, and estradiol), and disease activity were examined. The sample comprised 33 women with rheumatoid arthritis (RAs; age 37-78) and 37 women with osteoarthritis (OAs; age 47-91), who served as controls. In a regression analysis, interpersonal conflict events accounted for more than twice as much variance in depression in RAs than in OAs. In the RA patients, the immune-stimulating hormones prolactin and estradiol were significantly positively correlated with interpersonal conflicts, depression, coping inefficacy, and clinician ratings of disease activity, suggesting that RAs are more reactive to interpersonal stressors than are OAs, both psychologically and physiologically.
8971280 Review article: methotrexate in gastroenterology--dangerous villain or simply misunderstoo 1996 Dec Methotrexate has a place in the treatment of an increasing number of diseases. Its emerging role in the treatment of primary biliary cirrhosis and inflammatory bowel disease still requires further evaluation. Its toxicity profile is wide and is affected by a variety of factors. Hepatotoxicity from long-term use in patients with psoriasis and rheumatoid arthritis holds particular concern for the physician. Appropriate monitoring guidelines for hepatotoxicity can only be made after careful evaluation of available data and consideration of cost-to-benefit models.
7555295 [Long-term results of knee joint rehabilitation after fascia interposition]. 1992 The method, schedule and results of rehabilitation in patients with the chondral defects in knee joints treated by partial or total fascial grafting were presented. In the series of 114 patients followed up from 1 to 19 years after operation there were 56.1% good and fair results in the group with partial grafting and 26.6% in the group with total fascial grafting. An aggravation of rheumatoid process, coincidence of deformities in adjacent joints, weakening of muscles and ligaments in the knee and Hoffa pad grafting during the development of the method yielded 17.7% bad or unsatisfactory results.
1570496 A double-blind comparison of the gastroduodenal safety and efficacy of diclofenac and a fi 1992 This double-blind, parallel group study was conducted to evaluate the gastroduodenal safety and antiarthritic efficacy of a fixed combination of diclofenac sodium 50 mg and misoprostol 200 mcg, compared with a combination of diclofenac 50 mg and placebo. Three hundred and thirty-nine patients with rheumatoid arthritis and no significant gastric or duodenal mucosal damage were enrolled and received study medication (diclofenac/misoprostol, 164; diclofenac/placebo, 175) BID or TID for 12 weeks. Posttreatment gastroduodenal endoscopic examinations revealed ulcers in 11% of the diclofenac/placebo group, compared with only 4% of the diclofenac/misoprostol group (p = 0.034). Four-weekly assessments of arthritic condition revealed no clinically or statistically significant treatment differences. It was concluded that diclofenac/misoprostol caused significantly less gastroduodenal damage than diclofenac, but was as effective as diclofenac alone in the treatment of rheumatoid arthritis.
7578880 A subgroup of human VH3 germline genes that encode a high-avidity synovial rheumatoid fact 1995 We have previously derived and identified a highly avid monoclonal IgM rheumatoid factor (mRF), C6, from unstimulated rheumatoid synovial cells (RSC). At the time, the closet VH germline gene, VH26, demonstrated only 88% homology with C6. To identify the germline counterpart of C6, genomic DNA from the same rheumatoid arthritis (RA) patient from whom C6 was derived was used in the polymerase chain reaction (PCR). Four of the six closely related germline genes that we sequenced had exonic regions that were identical with the VH region of C6 cDNA. These six germline sequences differed in their intronic regions, suggesting that they were distinct, but closely related genomic sequences. To further evaluate the extent of these related genes we identified nine additional germline genes having VH-encoding exons that were 86-97% identical to the C6 cDNA sequence. Furthermore, we examined the polymorphic nature of the C6 VH gene using single strand conformation polymorphism (SSCP), and identified two peaks, confirming the existence of highly homologous genes. The sequence and polymorphism data suggest that: (1) the VH region of the high avidity mRF C6 was derived from an unmutated germline gene; (2) C6 was encoded by a VH gene belonging to a set of homologous genes within the larger VH3 family; and (3) in addition to somatic rearrangements of B-cell genes and antigen-driven somatic mutation, gene duplication and conversion events of germline genes could be important in generating diversity and polyclonality among high-affinity pathogenic autoantibodies.
8187449 D-penicillamine induced polymyositis causing complete heart block. 1994 Mar We describe a 63-year-old female patient with rheumatoid arthritis who developed complete heart block and features of polymyositis within a few weeks of starting treatment with D-penicillamine. We believe she is one of only three published patients in whom complete heart block accompanies penicillamine-induced polymyositis. The literature on penicillamine myositis is reviewed with special emphasis on cardiac problems. Patients taking D-penicillamine who develop features suggestive of polymyositis may develop insidious, but potentially life-threatening cardiac involvement and must be carefully monitored.
8961900 Shift toward T lymphocytes with a T helper 1 cytokine-secretion profile in the joints of p 1996 Dec OBJECTIVE: To investigate whether T cells in the inflamed joints of patients with rheumatoid arthritis (RA) preferentially produce the T helper 1 (Th1) cytokines, interferon-gamma (IFN gamma) and interleukin-2 (IL-2), or the Th2 cytokine, IL-4, when compared with corresponding peripheral blood-derived T cells. METHODS: Synovial fluid mononuclear cells (SFMC) and corresponding peripheral blood mononuclear cells (PBMC) from 10 patients with RA were analyzed, either directly or after in vitro stimulation, for the intracellular presence of Th1 and Th2 cytokines. The amount of secreted cytokine in the cell culture supernatants was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: IFN gamma-containing cells were detected in the unstimulated SFMC, but not in the PBMC, of 3 patients with RA. Cells positive for IL-2 or IL-4 were not detected in the unstimulated samples. Following stimulation, the mean percentage of cells containing Th1 cytokines was significantly increased in the SFMC compared with the PBMC; no differences were found in the mean percentage of IL-4-containing cells. A comparable shift toward Th1 cytokines was observed when the amount of secreted cytokine was determined by ELISA. CONCLUSION: A shift toward T cells with a Th1 cytokine profile was observed in the joints of patients with RA. Since an imbalance between Th1 and Th2 cells is thought to be of pathogenic significance, this finding might have implications for the development of new therapies for RA.
8450066 Modulation of monocyte activation in patients with rheumatoid arthritis by leukapheresis t 1993 Mar One of the hallmarks in rheumatoid arthritis (RA) is the intense activation of the monocyte-macrophage system. In the present investigation, the modulation of blood monocyte activation was studied with regard to the secretion of cytokines and inflammatory mediators, and to the expression of cytokine receptors. Patients with severe active RA underwent repeated leukapheresis procedures that removed all circulating monocytes. Highly enriched monocyte preparations from the first and third leukapheresis were studied. There were striking differences between the two monocyte populations. Cells obtained from the first leukapheresis constitutively released large amounts of prostaglandin E2 (PGE2), neopterin, interleukin 1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). In particular, IL-1 beta and neopterin production were further enhanced by stimulation with either interferon-gamma (IFN-gamma) or TNF-alpha without a synergistic effect. In contrast, cells derived from the third leukapheresis procedure showed a close to normal activation status with only low levels of cytokine and mediator production as well as a reduced response to cytokine stimulation. The number of the receptors for IFN-gamma and TNF-alpha was not changed between first and third leukapheresis. However, TNF-binding capacity was only detectable upon acid treatment of freshly isolated monocytes. A further upregulation was noted upon 24 h in vitro culture, suggesting occupation of membrane receptors and receptor down-regulation by endogenously produced TNF-alpha. Northern blot analysis of cytokine gene expression was in good correlation with the amount of mediators determined on the protein level. These data indicate that cells of the monocyte-macrophage system are already highly activated in the peripheral blood in RA patients with active disease. These cells can be efficiently removed by repeated leukapheresis and are replenished by monocytes that have, with respect to cytokine and mediator production, a considerably lower activation status.
8624621 Antineutrophil cytoplasmic antibodies in rheumatoid arthritis patients. 1996 Jan We determined the occurrence of antineutrophil cytoplasmic antibodies (ANCAs) and their specificities in 77 rheumatoid arthritis (RA) patients and compared them with 25 patients with psoriatic arthritis (Pso), 19 with drug-induced lupus erythematosus (DI-LE) and 11 with systemic lupus erythematosus (SLE). Thirty-two percent of RA patients had positive indirect immunofluorescence (IIF) stains (P or atypical ANCA). Twenty-nine per cent of patients with rheumatoid vasculitis (RAV), 48% with long-standing RA (LSRA) and 20% with early RA (Ely RA) had positive ANCAs compared with 4% of Pso patients, 47% of DI-LE patients and 45% of SLE patients. Western blotting (with polymorphonuclear cell extracts or alpha-granules) and alpha-granule enzyme-linked immunosorbent assay (ELISA) yielded variable results and proved unhelpful for characterizing the specificities of ANCAs. ELISAs based on commercial purified lactoferrin (LF), myeloperoxidase (MPO), human elastase (HLE) and cathepsin G (CG) showed that anti-HLE antibody was the most prevalent (14%) antibody in RA, followed by anti-MPO antibody and anti-LF antibody (10% each). Statistical analysis of antibody prevalence by clinical presentation showed that LSRA patients were more likely to have anti-HLE antibody and that DI-LE patients were more likely to have anti-CG antibody compared with the other patient groups. In lupus patients serial ELISA titration of ANCAs (LF and MPO) was found to be reliable for predicting the outcome. The overall incidence of ANCAs in RA patients was 33% by IIF.
1460939 [Serologic diagnosis of Lyme disease in patients with undifferentiated arthritis. Diagnost 1992 Dec 5 BACKGROUND: Arthritis is a frequent manifestation of Lyme disease. The diagnosis of this disease is especially supported by serological techniques which however have false positives or negatives. The aim of this study was to establish the frequency of serologies positive to Borrelia burgdorferi in patients with non-filiated arthritis and in other well defined rheumatic diseases. METHODS: A prospective study was performed to detect antibodies (AB) versus Borrelia burgdorferi in 43 patients with undifferentiated arthritis and in 100 patients with articular disease of precise diagnosis (rheumatoid arthritis, systemic lupus erythematosus, psoriasis arthropathy, and reactive arthritis/Reiter's syndrome). The technique was performed by indirect immunofluorescence and was repeated by enzymoimmunoassay in doubtful or positive results. Titers greater than 1/256 were considered as positive. RESULTS: Positive serology was found in two patients with undifferentiated arthritis and in one patient with Reiter's syndrome. None of the three patients referred the antecedent of erythema chronicum migrans. Positive serology was not observed in any of the patients with rheumatoid arthritis, systemic lupus erythematosus or psoriatic arthritis. CONCLUSIONS: A small proportion of patients with undifferentiated arthritis or Reiter's syndrome presented positive serology at low titers versus Borrelia burgdorferi with the interpretation of these results being difficult. The frequency of seropositivity in rheumatoid arthritis and systemic lupus erythematosus is very low.
8348268 Mast cells in the synovium and synovial fluid in osteoarthritis. 1993 Aug SF and synovium from normal individuals and patients with OA, RA and traumatic arthritis (TA) were studied for the presence of mast cells (MC). When compared with normals, patients with OA had large numbers of intact and degranulated MC in the synovium and SF of diseased joints. The numbers of MC are comparable with those in RA where they have been implicated in the pathogenesis of joint damage. These data raise the possibility that in OA too MC may participate in the pathological processes in articular and periarticular tissues.
7644186 [Diagnosis and differential diagnosis of psoriatic arthritis on basis of follow up of 215 1995 Apr 16 The interval between the appearance of the symptoms of psoriasis and/or arthritis and the setting up the diagnosis of the psoriatic arthritis was studied in 215 patients suffering from definite psoriatic arthritis. About 2.3 years were over until the setting-up of the diagnosis in these 30 patients whose psoriasis and arthritis began simultaneously. The interval to set up the diagnosis of psoriatic arthritis was 5.4 years in average if the psoriasis itself was the first sign and it was 8.6 years in case the arthritis preceded psoriasis. The symptoms promoting to set up the right diagnosis were in order to frequency as follows: appearance of psoriasis, sausage digits, distal interphalangeal involvements, nail changes and transformation the monoarthritis into asymmetrical oligoarticular or polyarticular form. The difficulty of the differential diagnosis was studied. 15 different previous false diagnoses were enumerated the rate of which was the highest (67.3%) in the group starting with arthritis. The authors call the attention to the importance of looking for psoriatic skin and nail changes in every nonclassified arthritic patient in the interest of an early diagnosis and right therapy in course of the follow-up.
7946242 Infection and arthritis. 1994 Aug Reactive arthritis is caused by an infection, and components of the triggering agent can be demonstrated at the site of inflammation. This fact has opened new views in studies regarding other rheumatic diseases, such as rheumatoid arthritis and ankylosing spondylitis. The possible role of infectious agents in their etiology and pathogenesis is being re-evaluated.
1565583 The medial gastrocnemius muscle flap in the treatment of wound complications following tot 1992 Apr There is greater potential for wound healing complication in rheumatoids, diabetics, and other patients with peripheral vascular disease. Local wound care in areas of avascularity and skin necrosis has poor results, especially if an ulcer is greater than 2 cm in diameter. Gastrocnemius muscle flap coverage of persistent wounds and areas of skin necrosis following total knee arthroplasty should be considered early in the course of such a complication.