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

ID PMID Title PublicationDate abstract
8162007 [A comparative controlled trial of 2 administration modalities of tiopronin in rheumatoid 1993 May Thiopronin is a second line drug for rheumatoid arthritis with proven efficacy in controlled trials versus a placebo, D-penicillamine, or gold salts. This 4-month study was aimed mainly at comparing the efficacy and safety of two thiopronin regimens, i.e., 1 g/d for 2 weeks followed by 1.5 g/d (regimen A) versus 0.5 g/d for 1 month, 0.750 g/d during the second month, then 1 g/d (regimen B). Because earlier investigations have suggested a role for copper in the activity of D-penicillamine, a secondary goal of this study was to evaluate whether the clinical effects of thiopronin were related to changes in serum copper and ceruloplasmin levels. Among the 61 included patients, 32 received regimen A and 29 regimen B. The primary efficacy criterion was the physician's overall efficacy assessment. Efficacy was rated good or excellent in 65.5% of regimen A patients and 55.6% of regimen B patients. Eighteen of the 32 regimen A patients and 23 of the 29 regimen B patients experienced at least one adverse event (p = 0.055). Failure to tolerate the drug required withdrawal in 12 of the 32 regimen A patients (37.5%) versus 11 of the 29 regimen B patients (37.9%). Declines in serum copper and ceruloplasmin levels were not correlated with treatment efficacy or tolerance. These findings, together with previously reported data, suggest that treatment should be initiated in a dosage of 1 g/day and that thiopronin-related adverse events are not dose-dependent.
7606955 Feasibility of maximal cardiopulmonary exercise testing in patients with end-stage arthrit 1995 Jul STUDY OBJECTIVE: Although no studies exist, to our knowledge, that examine the feasibility and safety of stress testing in a consecutive series of patients with severe arthritis, musculoskeletal conditions are often listed as relative contraindications to graded exercise testing. The current study was designed to examine the feasibility of maximal exercise testing in patients with end-stage arthritis prior to total joint arthroplasty. DESIGN: An observational and descriptive study in a consecutive series of patients with severe arthritis. SETTING: This study was conducted in the outpatient clinics and cardiopulmonary exercise physiology laboratory of a rural teaching hospital. PARTICIPANTS: Sixty-one patients with severe osteoarthritis and rheumatoid arthritis were recruited from the orthopedic surgical service immediately before total joint arthroplasty of the hip, knee, or both. A reference group of 23 nonarthritic control patients were recruited from the general medical population of the same hospital and subjected to measures of arthritis severity. MEASUREMENTS AND RESULTS: The severity of arthritis was graded by assessment of variables reflective of subjective symptoms, lifestyle impact, joint deformity, and radiographic abnormality. Arthritic subjects underwent a single graded, maximal, symptom-limited, cardiopulmonary exercise test using an electronically braked ergometer and a metabolic cart. Subjects were first asked to pedal with their legs; those apparently incapable performed the same task using their arms. Ninety-five percent of subjects who presented for an exercise test were capable of symptom-limited exercise. Of 29 patients evaluated before hip replacement, 66% completed leg tests, 31% completed arm tests, and 3% were incapable of symptom-limited exercise. Of 30 patients evaluated before knee replacement, 57% completed leg tests and 37% completed arm tests, while 7% were incapable of symptom-limited exercise. Two patients were evaluated before hip and knee surgery; one completed a leg study and one completed an arm study. Among the 37 subjects completing leg tests, a mean percentage of age-predicted maximum heart rate (APMHR) of 92 +/- 11% and a mean respiratory exchange ratio (RER) of 1.15 +/- 0.13 were noted. Among the 21 completing arm tests, a mean percentage of APMHR of 87 +/- 11% and a mean RER of 1.10 +/- 0.10 were observed. High rates of achievement of physiologic values indicative of maximal exercise (80% or more of APMHR and RER > or = 1.0) were noted in individuals in both exercise groups. Similar findings were noted regardless of the patient's subjective symptomatic limitation to exercise and the presence or absence of documented or suspected coronary heart disease. CONCLUSIONS: Most patients with severe arthritis are capable of maximal, symptom-limited exercise using ergometry methods. Ergometry stress testing may be a viable, low-cost alternative to dipyramidole-thallium testing or cardiac catheterization in some patients with arthritis warranting objective assessment of known or suspected cardiac disease.
8326046 Psychosocial outcomes of children of unipolar depressed, bipolar, medically ill, and norma 1993 Jun The psychosocial functioning of children of unipolar depressed, bipolar, medically ill, and psychiatrically normal women was studied over a 2-year period. Ninety-six children aged 8-16 years were assessed at 6-month intervals on Child Behavior Checklist behavior problems, social competence, internalizing and externalizing behaviors, academic performance, and school behavior. The children of unipolar mothers showed significantly poorer functioning on all measures as compared with the other 3 groups of children, including bipolar offspring. A greater proportion of children in the unipolar group also had relatively chronic, clinically significant problems in psychosocial functioning. Children of bipolar women did not differ from children of psychiatrically normal women. Results are discussed in terms of the consequences of children's continuing exposure to maternal depression and attendant stressors, as well as the contribution of social and academic difficulties to a vicious cycle of maladjustment.
7654626 Do silicone breast implants cause autoimmune rheumatic diseases? 1995 Current estimates are that up to a million women in the U.S. have breast implants with the predominant type being the silicone gel implant. Concerns have been raised regarding the safety of silicone gel breast implants with focus upon whether escaped gel might cause inflammatory and immune responses that subsequently lead to autoimmune rheumatic diseases such as progressive systemic sclerosis (scleroderma), systemic lupus erythematosus (SLE), Sjögren's syndrome or rheumatoid arthritis. A spectrum of illnesses ranging from local symptoms to systemic disease is seen in some patients with silicone breast implants, however, it remains to be determined whether such illnesses in these patients are coincidentally associated or are secondary to the implants. Our understanding of the relationship between the presence of autoimmune rheumatic diseases and silicone breast implants is limited. The available data indicate that silicone elicits a minimal immunological response as compared to conventional antigens. The histological, immunological and epidemiological experimental data derived from patients with silicone implants, as well as those from animal studies, are reviewed. These data do not convincingly demonstrate that there is a cause and effect relationship between silicone breast implants and autoimmune diseases. Further investigations are needed to clarify the interaction of silicone with the cellular and humoral immune systems, as well as with host and environmental factors.
8082299 IL-1 alpha gene expression and protein production by fibroblasts from patients with system 1994 Sep We examined IL-1 alpha and IL-1 beta gene expression and protein production in human dermal fibroblasts from patients with systemic sclerosis (SSc) to investigate the abnormal function of SSc fibroblasts. Human dermal fibroblasts were biopsied from 13 patients with SSc, three patients with rheumatoid arthritis (RA) and five healthy normal controls (NC). Cells were cultured in serum-free media and total RNA was collected from second or third passage fibroblasts. In cultured SSc fibroblasts, IL-1 alpha and IL-1 beta mRNAs were constitutively expressed and intracellular pro-IL-1 alpha was present. These observations suggest that an autocrine effect of IL-1 alpha contributes to the fibrosis in SSc.
7973478 Intra-articular treatment of rheumatoid knee-joint effusion with triamcinolone hexacetonid 1994 Thirty-one patients with knee effusions associated with rheumatoid arthritis (RA) have been treated with two intraarticular (i.a.) injections of each 330 mg sodium morrhuate (SM) used for synoviorthesis versus a single injection of 20 mg triamcinolone hexacetonide (TA). During an observation period of one year, five articular parameters as well as patient's and doctor's global assessments were evaluated. TA showed an earlier onset and a longer duration of therapeutic effects with high statistical significance. The maximum improvement was significantly more pronounced with TA than with SM. Finally after one year improvement measured by a remission index was observed in 81% versus 33% resp. of all joints injected. Due to ineffectiveness of the primary treatment nine patients (60%) out of the SM group, but not patient out of the TA group had to be crossed over to the other treatment. SM usually caused a reactive effusion within hours after injection requiring arthrocentesis. In conclusion efficacy and tolerability are clearly better for TA than for SM.
8646434 Occurrence of pulmonary complications during methotrexate therapy in rheumatoid arthritis. 1996 May Treatment with methotrexate (MTX) in rheumatoid arthritis (RA) can lead to severe side-effects, especially pulmonary and haematological complications. The aim of this retrospective study was to evaluate, during a 6 yr period, the prevalence and severity of bronchopulmonary side-effects in RA patients treated with MTX. A cohort of 130 RA in-patients (106 women, 24 men) treated with MTX was studied for the occurrence of respiratory adverse events. Adverse bronchopulmonary side-effects were observed in 12 patients (two men, 10 women), with a mean disease duration of 15 yr. Only three patients had previously suffered from pulmonary disease. MTX treatment duration was between 1 month and 4.5 yr. The diagnosis was that of hypersensitivity pneumonitis (HSP) in four cases, non-HSP pneumonitis in five patients with one case of Pneumocystis carinii infection, and bronchitis in three cases. The initial respiratory symptoms were not discriminatory between the different conditions. Risk factors were not identified for the occurrence of HSP. HSP always occurred in the first 5 months of treatment. Two patients with HSP died, and another patient with opportunistic infection underwent tracheostomy. HSP represents a potentially lethal side-effect in RA patients treated with MTX. Improved education of patients and physicians should certainly lead to a reduction of both the prevalence and severity of pulmonary side-effects during MTX therapy in RA.
8424836 Degradation of human articular cartilage by neutrophils in synovial fluid. 1993 Jan OBJECTIVE: To determine whether surface-adherent immunoglobulins are capable of mediating synovial fluid (SF) neutrophil degradation of proteoglycan and collagen in intact, normal human articular cartilage, and to define the respective roles of neutrophil serine proteases and metalloproteases in degrading these cartilage constituents. METHODS: Pellet explants of normal human articular cartilage pretreated with bovine serum albumin (BSA) or IgG were incubated with polymorphonuclear cells suspended in SF (PMN-SF), or with supernatants derived from neutrophils stimulated with surface-associated IgG. Proteoglycan degradation was measured by assaying release of 35S-proteoglycan fragments from cartilage explants prelabeled with 35S-sulfate. Collagen degradation was measured by assaying hydroxyproline content in the PMN-SF preparations or neutrophil supernatants following their incubation with unlabeled explants. RESULTS: Significant release of both 35S fragments and hydroxyproline was noted following incubation of PMN-SF with IgG-treated pellets, compared with pellets treated with BSA. IgG preparations derived from pooled normal serum or rheumatoid arthritis SF were equally efficacious in mediating PMN degradation of cartilage collagens. Explant release of 35S fragments during incubation with PMN supernatant was completely inhibited when serine proteases were inactivated by diisopropyl fluorophosphate (DFP); however, release of 35S fragments was enhanced when metalloprotease activity was present in the supernatant. Release of hydroxyproline during incubation of explants with PMN supernatant was comparable in the presence of DFP or EDTA, but was markedly enhanced when both serine and metalloprotease activity were present in the supernatant. CONCLUSION: Neutrophils in SF are capable of degrading both proteoglycans and collagens in intact human articular cartilage. Degradation of these cartilage constituents is facilitated by immunoglobulins adherent to the cartilage surface and by the synergistic action of PMN serine and metalloproteases released during activation of neutrophils with surface-associated immunoglobulin.
8542209 Effectiveness of minimally supervised home aerobic training in patients with systemic rheu 1995 Nov The effectiveness of an exercise prescription and unsupervised home exercise programme was tested on 37 subjects with rheumatoid arthritis and 34 with systemic lupus erythematosus. Subjects were randomly assigned to control or stationary bicycling at home, using loaned bicycles. Exercise subjects (with bicycles) did better than controls, but not significantly, on all outcomed measures (exercise tolerance test, fatigue, depression and helplessness) at 3 months. Bicycles were reclaimed at 3 months and all subjects in both groups given instructions for home exercise. Exercise in the second 3 months was predicted primarily by baseline exercise habits and fatigue. It is concluded that although safe, unsupervised home exercise programmes may benefit few patients. Future research should address methods of stimulating and maintaining unsupervised exercise programmes in patients with systemic rheumatic disease.
8202673 [Reactivation of hepatitis B following withdrawal of chloroquine]. 1994 May 7 A severe flare-up of chronic hepatitis B infection with liver cell insufficiency has been observed in two patients after discontinuation of chloroquine administered either as malaria prophylaxis or as treatment of presumed rheumatoid arthritis. Chloroquine is known to inhibit the association of the major histocompatibility complex type II with hepatitis B virus antigens, thereby inhibiting T-cell mediated lysis of infected cells. Furthermore, it inhibits uptake of duck hepatitis B virus by duck liver cells. These in vitro studies and our clinical observations suggest that chloroquine inhibits the lysis of hepatitis B virus infected hepatocytes. Withdrawal of chloroquine in patients with chronic hepatitis B virus infection can lead to a rebound immune response manifesting as a reactivation of hepatitis B, similar to that observed after steroid withdrawal.
1378364 IgG antibodies from patients with primary Sjögren's syndrome and systemic lupus erythemat 1992 Jul Five synthetic peptides corresponding to the N-, the C- and a central domain in 60-kD SSA/Ro protein were prepared and tested with sera from 112 patients with systemic lupus erythematosus (SLE), 55 with primary Sjögren's syndrome (pSS) and 29 with rheumatoid arthritis. Among these five fragments, one representing residues 21-41, was recognized by antibodies in 57% of pSS patients. Interestingly, this peptide was recognized by only a few (less than or equal to 7%) of SLE sera, while 63% of pSS sera and 46% of SLE sera tested in parallel possessed antibodies reacting in ELISA with purified 60-kD SSA protein. The ELISA results were compared with the pattern of reactivity obtained in immunodiffusion and immunoblotting. The results indicate that the sensitivity of ELISA using peptide 21-41 and pSS sera was in the same range as immunoblotting and higher than immunodiffusion. Thus the peptide 21-41 proved useful for the detection of anti-SSA antibodies in the sera of patients with pSS. Furthermore, a positive ELISA using peptide 21-41 could be of potential use to discriminate pSS with systemic features from SLE. The fact that peptide 21-41 is recognized by antibodies in pSS but only by very few SLE sera implies that different mechanisms are involved in the anti-SSA immune response in these two autoimmune diseases.
8807026 Immunohistochemical analysis of an equine model of synovitis-induced arthritis. 1996 Jul OBJECTIVES: To use lipopolysaccharide (LPS) to create synovitis in the midcarpal joint of ponies, and to assess the morphologic, histochemical, and immunohistochemical effects of synovitis on articular cartilage of the third carpal bone. ANIMALS: 2- to 3-year-old ponies, 6 control (group 1) and 6 treated (group 2). PROCEDURE: Synovitis was induced in 1 midcarpal joint of group-2 ponies by intra-articular injections of LPS (0.02 micrograms/kg of body weight), morphine (0.1 mg/kg), and saline solution (group 2a) and a morphine and saline solution alone in the contralateral midcarpal joint (group 2b). Articular cartilage sections and attached synovial membrane from the third carpal bones were examined by immunohistochemical distribution of interleukin 1 beta, tumor necrosis factor (TNF)-alpha, TNF receptors (P55, P75) and 3-B-3(-) epitopes, and by localization of proteoglycans (metachromatic staining). Proteoglycan extracts were assessed by metachromatic staining or western blotting and immunohistochemical staining, using anti-3-B- antibodies. RESULTS: Enhanced immunoreactivity for the cytokines and receptors was found in inflamed synovial membrane and noncalcified cartilage (group 2a more than 2b). Metachromasia of the noncalcified cartilage was greater in group-1 than in group-2a and group-2b specimens. In group 2a, chondrocyte hypertrophy and enhanced immunoreactivity for 3-B-3(-) epitope in areas of increased cytokine immunoreactivity suggested possible phenotypic change of the chondrocytes in response to synovitis. Immunohistochemical analysis by western blotting of proteoglycan extracts indicated strong 3-B-3(-) epitope immunolocalization in group-2a, weaker staining in group-2b, and barely detectable stain in group-1 specimens, which correlated with in situ immunolocalization. CONCLUSIONS: Intra-articular administration of LPS may be used to induce a synovial environment conductive to increased immunoreactivity of interleukin 1 beta, TNF-alpha, and its receptors in equine synovial membrane and articular cartilage. These cytokines may be involved in the early phenotypic change of chondrocytes that is believed to occur in osteoarthritis and is characterized in this study by enhanced 3-B-3(-) epitope immunoreactivity and chondrocyte hypertrophy.
1321245 Decreased density of beta-adrenergic receptors on peripheral blood mononuclear cells in pa 1992 Feb There is growing evidence that the autonomic nervous system influences the immune response by activation and modulation of beta 2-adrenergic receptors (beta 2R) on immunocompetent cells. However, little is known about its pathogenetic role in autoimmune disease. Therefore, the number and the dissociation constants (beta 2R-KKD) of beta 2R on peripheral blood mononuclear cells (PBMNC) were determined in 21 patients with rheumatoid arthritis (RA) and 9 healthy age and sex matched controls [healthy donors (HD)] by a radioligand binding assay with [125I]iodocyanopindolol. The density of beta 2R (x +/- SEM = 2,120 +/- 103 binding sites/cell) and the beta 2R-KD (x +/- SEM = 6.8 +/- 0.8 pM) were significantly decreased in patients with RA compared to HD (number of beta 2R: 3,960 +/- 372, beta 2R-KD: 16.7 +/- 3.6, p less than 0.01). In RA, the number of beta 2R was significantly lower in patients with high systemic disease activity (n = 11, number of beta 2R: 1,850 +/- 134) than in patients with low inflammatory activity (n = 10, number of beta 2R: 2,418 +/- 95, p less than 0.004). In addition, there were significant negative correlations between the beta 2R density and an arbitrary systemic activity score (r = -0.74, p less than 0.001), the Ritchie index (r = 0.77, p less than 0.001), and various variables of disease activity (r = 0.59 to -0.78, p less than 0.005), respectively. Our data demonstrate the close interplay between the systemic inflammatory activity and the beta 2R characteristics in patients with RA. Our results provide further evidence that the immune response may be influenced by the sympathetic nervous system.
7775804 T-cell antigen receptors in rheumatoid arthritis. 1994 Rheumatoid arthritis (RA) is a systemic disease of unknown etiology characterized by chronic inflammation mainly in the joints. Several lines of evidence suggest that T cells are involved in the pathogenesis of the disease. RA is associated with certain HLA-DR alleles. Studies analyzing T-cell receptor transcripts in RA have found biased or preferential usage of certain V alpha and/or V beta gene segments by T cells infiltrating the synovial membrane or extravasating into the synovial fluid compared to peripheral blood. In certain patients few T-cell antigen receptor (TCR) clones dominated the infiltrating T cells, suggesting that T cells from the synovial membrane or the synovial fluid comprise oligoclonal populations of T cells. However, other studies have found a polyclonal population of T cells. In interpreting these results the phase of the disease (early vs. late RA), the source of T cells and the limitations of the methods used in these studies should be taken into consideration. However, it appears that synovial T cells comprise oligoclonal populations of T cells and that there is a bias towards particular TCR gene segments, although a specific TCR gene segment in RA has not emerged.
8832983 Significant changes in serum AST across hepatic histological biopsy grades: prospective an 1996 Mar OBJECTIVE: To describe the statistical association between serum AST and liver biopsy grade in patients with rheumatoid arthritis. METHODS: 94 patients from 3 prospectively followed cohorts underwent a total of 354 biopsies graded according to Roenigk. Blood samples for serum aminotransferase (AST) were obtained every 37.7 + or - 32.7 days (mean + or - SD) and 15.2 + or - 7.1 samples were obtained before each biopsy. For each prebiopsy interval, 4 AST functions were calculated: (1) mean, (2) maximum, (3) percentage abnormal, and (4) the presence or absence of at least one abnormality. Analysis of variance was performed to determine the effect of each of these variables on liver biopsy score. RESULTS: AST increased across biopsy grades: 26.5 IU + or - 10.7 IU (mean + or - SD) in Grade I biopsies, 28.4 + or - 10.9 in Grade II, and 35.4 + or - 21.1 in Grade IIIA (p = 0.0006, overall difference between classes). The percentage of abnormal prebiopsy AST values increased across biopsy grades: 8.7 + or - 13.9 (mean + or - SD) in Grade I biopsies, 12.3 + or - 17.5 in Grade II, and 18.6 + or - 27.1 in Grade IIIA samples [(p = 0.0014) overall difference between classes.] A mean prebiopsy AST in the abnormal range was more likely to be associated with a more abnormal liver biopsy grade (p = 0.01, Wilcoxon's rank sum test). AST values abnormal <49% of the time had a 97% specificity for a normal biopsy grade. CONCLUSION: Regular AST measurements are useful markers of hepatic histologic outcome, within the range of mostly normal histology reported here, in patients with RA receiving longterm weekly MTX.
8209545 [A comparative evaluation of the subfractional composition of the blood plasma by using la 1993 Jul Analysis presented by the authors confirms that laser correlative spectroscopy may be in principle a method for a study of plasma homeostasis on subfractional level in various orthopedic and traumatological diseases. The method allows to assess changes in the inner environment of the body with regard to diversity of structural and functional reorganization induced by various pathological processes.
8462039 Intravenous administration of gadolinium in the evaluation of rheumatoid arthritis of the 1993 Apr The authors sought to determine the utility of intravenously administered gadolinium chelates in magnetic resonance imaging (MRI) of patients with rheumatoid arthritis of the shoulder. One shoulder was examined for each of 12 patients--6 men and 6 women, ranging in age from 48 to 71 (average 63) years--with well-established disease. The patients had had the disease for 1 to 25 (average 13) years. Static MRI was performed before and after infusion of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) (0.1 mmol/kg body weight); T1-weighted or proton-density images (repetition time [TR] 600 to 1000 ms, echo time [TE] 15 to 30 ms) were obtained. Images obtained after enhancement were particularly useful in the differentiation of pannus from fluid and also allowed improved delineation of tears of the supraspinatus tendon. In addition, contrast-enhanced dynamic gradient-echo spoiled GRASS sequences (TR 50 ms, TE 11 ms, flip angle 70 degrees) were obtained for all patients; for these sequences the same slice was imaged repeatedly at 20-second intervals. The rate of increase of signal intensity in abnormal synovium varied from 0.64 to 5.83 (average 2.30, standard deviation [SD] 1.67) units/second; the enhancement factor ranged from 1.55 to 4.64 (average 2.63, SD 0.98). The authors conclude that for imaging the shoulder enhancement with Gd-DTPA allows improved distinction between synovial thickening and joint effusion and may improve assessment of the rotator cuff. The wide range in the rate of signal increase and total enhancement during dynamic imaging probably reflected heterogeneity in the study population.
8840221 Interleukin-10 (IL-10) secretion in systemic lupus erythematosus and rheumatoid arthritis: 1996 Jul Interleukin-10 (IL-10) is a major immunoregulatory cytokine and has a multitude of immunomodulatory effects in the immune system. In this study, we have examined the secretion and in vitro function of IL-10 in B cell hyperactivity in antibody production in two common autoimmune diseases, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). IL-10 was detectable in serum of all active SLE and serum and synovial fluid samples of all RA patients but in none of the normal controls. B cells and CD4+CD45RO+ "memory" T cells secreted highly enhanced levels of IL-10 in SLE and RA versus normals. Increased IgM and IgG production by B cells-CD4+CD45RO+ T cells in SLE and RA was IL-10 dependent, since neutralization of IL-10 cytokine by anti-IL-10 antibody drastically reduced Ig synthesis in these coculture experiments. B cell hyperactivity in autoantibody production in SLE and RA may be a function of IL-10-dependent CD4+CD45RO+ Th2 cell activation. Therefore, IL-10 may play an important role in highly disturbed immune system and B cell-T cell function in these immune disorders.
1417942 Peptidyl fluoromethyl ketones as inhibitors of cathepsin B. Implication for treatment of r 1992 Sep 25 Peptidyl fluoromethyl ketones (FMKs), with the amino acid sequence Phe-Ala held constant but with variable N-terminal groups, were synthesized and tested for inhibition of the cysteine proteinase cathepsin B. The FMKs were effective in inhibiting cathepsin B activity in vitro. The inhibition was time dependent and was not reversed by dialysis, suggesting covalent modification of the enzyme. Cathepsin B activity present in livers and kidneys of rats treated with FMKs was reduced by 22-91% 4 hr after a single oral dose of 25 mg/kg. The FMKs inhibited the severity of inflammation and the extent of cartilage and bone damage in adjuvant-induced arthritis. These effects were seen during the late-stage of the disease with no effect on onset or incidence of disease. This is consistent with inhibition of protease-mediated damage. These FMKs or derivatives may be of clinical value in the treatment of arthritis.
8833908 Genetic control of T cell receptor BJ gene expression in peripheral lymphocytes of normal 1996 Oct 1 The amino acids encoded at the junctions of T cell receptor (TCR) V and J genes directly interact with MHC bound peptides. However, the regulation of the human TCRBJ gene repertoire has been difficult to analyze, because of the potentially complex number of BJ gene rearrangements. To overcome this problem, we developed a PCR-ELISA method to study BJ gene expression, and compared peripheral T lymphocytes from 12 pairs of monozygotic twins, including 6 rheumatoid arthritis (RA) discordant pairs, and 5 normals. Analyses of the TCRBV5, 13 and 17 gene families, which have been reported to be increased in RA patients, showed: (a) the three TCRBV transcripts have common features of BJ gene usage; (b) TCR transcripts from each TCRBV family display a distinctive BJ gene profile, which is displayed better by CD4+ than CD8+ lymphocytes; (c) the BJ gene repertoires of monozygotic twins are more similar than those of unrelated individuals; and (d) the inflammation of RA does not induce specific changes in the genetically determined pattern of BJ expression. These results indicate that the frequency of expression particular TCRBV-TCRBJ recombinants in human lymphocytes is controlled genetically, and is maintained despite the presence of a chronic inflammatory disease.