Browse

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

ID PMID Title PublicationDate abstract
8062447 CD23 hyperexpression in rheumatoid arthritis: evidence for a B cell hyperresponsiveness to 1994 Sep We have studied the causes of membrane CD23 (mCD23) hyperexpression in rheumatoid arthritis (RA). Modifying a previously developed in vitro system, we cultured RA and control peripheral blood (PB) mononuclear cells for 18 hr with medium, anti-CD3 monoclonal antibody (mAb), recombinant (r) IL-4, or phorbol myristate acetate (PMA). After T cell depletion by rosetting, mCD23 was assessed by indirect immunofluorescence. RA PB B cells expressed mCD23 in a percentage significantly higher than controls unstimulated (16.7% vs. 6.6%) and after culture with anti-CD3-stimulated T cells (53% vs. 37.2%) or IL-4 (47% vs. 30%), but not after PMA (37.5% vs. 31%). We did not see differences in the percentages of resting B cells between RA and controls. Our results show an intrinsic RA PB B cell hyperesponsiveness to different T cell signals that might be mediated by in vivo priming through surface immunoglobulin.
7919874 [3D-ultrasound of soft tissues and joints]. 1994 Jun Sonography has become a reliable diagnostic method in musculo-skeletal diseases. It allows a simple and noninvasive examination of joints and soft tissues. Especially in rheumatic diseases meaningful findings can be obtained. In the present study first results of three-dimensional (3D) sonography of the musculo-skeletal system are reported. The method was first validated by examining healthy test persons and criteria for regular findings were defined. In the second part of the study an unselected group of patients with inflammatory and noninflammatory joint and soft tissue diseases were examined and the obtained results were compared with the findings of the conventional real-time sonography. Comparison of the 2D and 3D procedure showed a superiority of the 3D method with regard to the assessment of large (hip), middle-sized (elbow) and small joints (finger, toe). Additional information about the synovial space, the surface of the cartilage, and the thickness of the synovial membrane was provided by 3D sonography. Volumetry of joint effusions and Baker cysts was easier to perform and more reliable than with the conventional method. Soft tissue alterations could be delineated reliably, depending on their size. Our results demonstrate that 3D sonography can improve the diagnostics of musculo-skeletal diseases. In the future, 3D sonography should play an important part in the diagnosis of joint and soft tissue diseases.
8207604 [Serum antibodies to type II collagen and immune complex in cases of Menière's disease]. 1994 May In a previous study, endolymphatic hydrops was induced in 36% of guinea pigs immunized with type II collagen and a dominant negative SP was recorded from these hydropic animals. These results suggested that the immune response to type II collagen may have a role in the etiopathology of some cases of Menière's disease. In this study, we evaluated the levels of serum antibody to type II collagen and three other immune indexes in patients with Menière's disease, especially those who showed negative SP dominance on electrocochleography. Twenty-nine Menière's cases, 22 normal volunteers serving as controls, 28 RA cases, and 9 patients complaining of vertigo were examined to detect serum immune indexes. Menière's patients exhibited high values of serum anti-type II collagen antibody as compared to control subjects. Furthermore, total IgG, C3, anti-type II collagen antibody and circulating immune complex were increased with the highest levels being in the RA group, followed by Menière's disease and then the control group. These results probably reflect the extent of immune reaction development. The immune response may be generalized in RA cases and/or local in Menière's disease. Our study results suggest the development of certain immune status abnormalities in our cases, which lends support to the idea of an immunologic disorder playing a role in the etiology of some cases of Menière's disease.
1460075 The boutonniere deformity. 1992 Nov Understanding the pathophysiology of the boutonniere deformity requires a complete understanding of the anatomy of the dorsal tendon apparatus. This unique tendon mechanism often becomes unbalanced, requiring correction of its components. Splinting is the cornerstone of treatment for the boutonniere deformity. In the acute stage, splinting ensures that the continuity of the central tendon to its insertion into the middle phalanx is maintained, and in the chronic stage, its function is to correct the flexion contracture of the PIP joint and stretch the retinacular ligaments. Splinting is also important postoperatively because it permits healing of the central tendon and lateral bands in their correct anatomic positions. Without proper splinting, the patient with the boutonniere deformity could not be successfully treated. Frequently, surgery is necessary, and the choice of procedure depends on the stage of the condition and the extent of the defect in the extensor tendon mechanism. The procedure also depends on the success of the splinting program and stretching of the tight retinacular structures. If passive joint mobility can be restored and if tendon imbalance and retinacular tightness persist, rebalancing is necessary. This rebalancing can be accomplished by a tenotomy of the terminal extensor tendon, a lysis or release of the retinacular structures, or release of the insertion of the extensor tendon at the base of the proximal phalanx. Reconstituting the defect in the central tendon over the PIP joint is accomplished by using a variety of procedures, including mobilization and advancement of the more proximal portion of the central tendon, shifting the lateral bands, or a tendon graft.
7605867 Assessment of collagen type II induced arthritis in mice by whole blood chemiluminescence. 1994 Lucigenin-enhanced chemiluminescence can be measured in 100 microliters samples of whole, unseparated mouse blood. A procedure for doing so is here described in detail, using a standard clinical luminometer. The assay measures the TPA-induced oxidative burst from granulocytes and macrophages, which is believed to depend on the overall level of inflammation in the body. It is here applied to mice suffering from type II collagen-induced arthritis, and its relation to overt disease symptoms (the arthritis score) is characterised during the course of the disease. A correlation between the assay and the arthritis score is found at the height of the disease (r = 0.42, p = .039), but not at early or very late time points, although there is a strong hint that the results of an early assay may predict the subsequent disease course. The assay provides a rapid, convenient, quantitative and economical method of assessing disease activity, which can be carried out repeatedly on the same individual. It should be applicable in other mouse models of chronic inflammatory disease. It may find application for rapid screening of novel anti-rheumatic drugs and treatments.
1310453 Variable gene usage of T cell receptor gamma- and delta-chain transcripts expressed in syn 1992 Feb The synovial tissue and fluid of patients with rheumatoid arthritis (RA) contain activated T cells that probably have a central role in the disease process which leads to joint destruction. A subset of T cells, gamma delta T cells detected at the site of inflammation, may be important in the pathogenesis of the disease. This study investigated variable (V) gene usage of gamma delta T cell receptors (TcRs) expressed in synovia and peripheral blood of patients with RA by using the polymerase chain reaction (PCR) to amplify TcR gamma- and delta-chain transcripts. Most patients showed no restriction in V gamma gene usage since synovial mononuclear cells (SMC) expressed TcR gamma-chain transcripts which used the same set of V gamma genes as peripheral blood mononuclear cells (PBMC). In contrast, the majority of patients expressed a restricted SMC V delta-chain repertoire biased towards V delta 1, but V delta 2 mRNA transcripts were also detected, albeit at low levels in some patients. The TcR delta-chain repertoires of PBMC from healthy control subjects were also characterized. There was variation in the TcR delta-chain repertoires of PBMC from patients when compared with controls, particularly with respect to expression of V delta 4. V delta 4 mRNA transcripts were expressed in PBMC of only two of seven RA patients in contrast with eight of the nine controls (P = 0.03). These findings are compatible with reports that gamma delta T cells in the rheumatoid synovium are reactive to Mycobacterium tuberculosis and that response to M. tuberculosis is restricted to V gamma 9/V delta 2-bearing T cells, if a superantigen is involved in the pathogenesis of RA.
1484656 Autoimmune diseases in pregnancy. 1992 Dec Autoimmune diseases are a significant problem in women of reproductive age. This article reviews some of the more common autoimmune disorders and discusses their diagnosis and management during pregnancy. The effects of the autoimmune disorder on pregnancy and the effects of pregnancy on the course of the autoimmune disorder are also discussed with an emphasis on the implications for clinical management.
8053954 Genetic typing of patients with inflammatory arthritis at presentation can be used to pred 1994 Aug OBJECTIVE: To test the hypothesis that genetic characterization of patients at the time they present with inflammatory arthritis can predict subsequent destructive disease. METHODS: We evaluated 177 patients with early arthritis. Patients were serologically tested for rheumatoid factor (RF) and were DNA oligotyped for the presence of conserved base sequences in the third hypervariable region (HVR3) of the DRB1 gene, previously shown to be associated with severe rheumatoid arthritis (RA). Homozygosity in the patient's genotype was confirmed using restriction fragment length polymorphism analysis. The main outcome measure was radiologic erosions at 1 year. RESULTS: At presentation, 120 patients fulfilled the American College of Rheumatology 1987 criteria for RA, 64% of whom possessed the conserved base sequences, compared with 45% of 347 healthy controls (P < 0.001) and with 56% of 57 patients with other inflammatory arthritis (P not significant). Within the RA population, the frequency of Dw4/Dw14 compound heterozygotes was disproportionately increased. The presence of either HVR3 or RF had a relative risk of 13.49 for erosions, with a sensitivity of 95% (specificity 39%); the presence of both HVR3 and RF had a relative risk of 8.13, with a specificity of 88% (sensitivity 53%). All but 1 patient with the Dw4/Dw14 genotype developed erosions within 1 year. CONCLUSION: Knowledge of a patient's HLA-DR type and RF status allows clinically useful prediction of erosive disease; patients possessing Dw4/Dw14 represent a particularly high-risk subgroup.
8237312 Prognosis of total hip replacement in Sweden. Follow-up of 92,675 operations performed 197 1993 Oct A prospective, national multi-center study of all reoperations after total hip replacement (THR) was started by the Swedish Orthopedic Association in 1979. The material comprises all THR performed in Sweden, presently more than 10,000 yearly or 130 THR per 100,000 inhabitants; uncemented implants have been used in less than 2 percent. The main reasons for revision have been aseptic loosening 79 percent, infection 10 percent, technical error 6 percent, and dislocation 2 percent. The cumulative rate of revision for deep infection has dropped from 0.9 percent to < 0.5 percent for implants inserted 1979 and 1983, respectively. With the Charnley prosthesis as the gold, standard the performance of other prostheses was analyzed. Improved cementation techniques and anti-infection measures have continuously reduced the revision risk. The register demonstrates that the average orthopedic surgeon cannot match the results achieved by experts. However, the vast majority of THR, worldwide, are not performed by experts. Quality-assurance in this sector of orthopedics demands a continuous analysis of the outcome of these operations.
1418628 Specific DNA amplification utilizing the polymerase chain reaction and random oligonucleot 1992 Nov The polymerase chain reaction (PCR) allows rapid amplification of DNA of known sequence. In many situations, part of a genetic sequence is known, but adjacent sequences of interest are unknown. This is common in investigations of antigen receptor genes from B and T lymphocytes, which are composed of a constant region of known sequence and a variable region, for which the sequence may not be known. Herein is described a method to amplify DNA when sequence information is available for only one primer. This procedure utilizes a primer of known sequence in conjunction with a mixture of short random primers. Application of this method to the amplification of T-cell antigen receptor cDNA is described.
1467486 [The production and characteristics of an interleukin-6-dependent hybridoma]. 1992 Jul The interleukin-6-(IL-6)-alpha dependent B-cell heterohybridomas were obtained by the fusion of X65.Ag8.653 cells with spleen cells from August rats immunized with lipopolysaccharide E. coli. One of these hybridomas (D6C8) was found to be most dependent on IL-6 for its surviving and growth. Human recombinant IL-1 beta and tumor necrosis factor-alpha could not induce the in vitro growth of this cell line. Presence of elevated level of IL-6 was demonstrated in the sera of patients with rheumatoid arthritis. A specific and sensitive detection of the IL-6 activity in test samples makes it possible to study the presence and role of IL-6 in various immunological disorders.
8194257 Extensor mechanism reconstruction with an allograft after total knee arthroplasty. 1994 Jun The authors report on a series of 15 knees in which an extensor mechanism allograft was used to treat a rupture of the patellar tendon associated with a total knee arthroplasty. Nine of the knees have greater than two-year follow-up evaluation (average, 4.1 years; range, 2.3-7 years). Postoperatively, the average flexion was 106 degrees. All but three patients achieved full passive extension. Six of the nine knees had no extensor lag. The average post-operative clinical score for the follow-up group was 78 points. Graft complications include one early graft rupture, one early quadriceps junction failure, and one patellar component loosening. One graft fractured after revision of a metal-backed patella.
8300409 T-cell receptor V-gene usage in synovial fluid lymphocytes of patients with chronic arthri 1993 Aug In this study we analyzed the usage frequencies of the TCR V-gene segments by alpha beta+ T cells present in synovial fluid of 17 patients with chronic arthritis, including rheumatoid arthritis. The results of this study, obtained from semiquantitative PCR analyses, showed that in all patients most of the TCR V alpha- and V beta-gene segments could be detected both in fresh PBMCs and in fresh SFMCs. The relative frequencies of use of these V-region genes were variable between the different patients. Although there was some skewing of increased usage frequencies of particular TCR V alpha and V beta genes among SFMC-derived TCRs when compared with PBMCs, we could not correlate such increased TCR V-gene usage with the inflammation in the joints as a disease-specific marker.
1294304 Oral sugar clearance and root caries prevalence in rheumatic patients with dry mouth sympt 1992 The relationship between root caries, oral sugar clearance, salivary flow rate, and salivary counts of mutans streptococci, lactobacilli and candida has been studied in a group of 22 rheumatic patients (age range 40-72 years). The study group comprised all subjects volunteering for a clinical trial on relief of dry mouth symptoms. The median salivary flow was 0.09 ml/min at rest and 0.9 ml/min during chewing stimulation. The median sugar clearance time was about 5 min in the sublingual area and 16 min in the lower buccal vestibule. For subjects with 0-2 root caries lesions the clearance time at both sites was shorter than for subjects with 3 or more lesions (p < 0.05). A long oral clearance time was significantly correlated with age, root caries (DS and DFS), low resting salivary flow, and high salivary counts of mutans streptococci. It is concluded that root caries in rheumatic patients with low salivary flow is significantly related to oral sugar clearance time.
8203950 Humoral immune response against minor collagens type IX and XI in patients with cartilage 1994 Apr OBJECTIVES: The humoral immune response against a broad spectrum of cartilage antigens (cellular and matrix antigens) was studied in a group of patients who showed resorption and/or rejection of transplanted cartilage in nasal surgery. METHODS: Sera were obtained from patients with successful and unsuccessful cartilage grafting in the nose, from age and sex-matched healthy donors and from patients with rheumatoid arthritis. Antibodies to cartilage components were analysed by the following methods: (1) indirect immunofluorescence on cartilage sections, (2) ELISA using cultured human chondrocytes, isolated chondrocyte membranes and purified collagens type I, II, III, VI, IX and XI, and (3) immunoblotting with purified collagens and chondrocyte cell membranes. RESULTS: In the cartilage grafting group showing resorption problems, levels of anti-collagen antibodies were significantly higher against native collagen types IX (p < 0.002) and XI (p < 0.002) compared with the non-resorption group and the normal donors. Both transplantation groups revealed elevated reactivities against isolated chondrocytes in the ELISA. In contrast, no reactivity was detectable against collagens type II, III, and VI and chondrocyte cell membranes by both ELISA and immunoblotting. CONCLUSIONS: These data demonstrate for the first time the existence of a humoral immune response, primarily directed against the so called 'minor cartilage collagens', in patients showing cartilage resorption. Autoreactivities to collagen which are typical of inflammatory rheumatic diseases may also play an important role in the repeated failure of cartilage grafting.
7863387 [The significance of HLA DR6 and DR8 among patients with rheumatoid arthritis]. 1994 Dec Among 380 patients with rheumatoid arthritis (RA), there were 63 cases who had HLA DR4 without any other counterpart DR type (Group DR4.*), 30 with DR6 but without DR4 (Group DR6.DR4-), 37 with both DR6 and DR4 (Group DR6.DR4+), 34 with DR8 but without DR4 (Group DR8.DR4-), and 15 with both DR8 and DR4 (Group DR8.DR4+). 53, 29, 32, 32, or 13 female RA patients respectively from Groups DR4.*, DR6.DR4-, DR6.DR4+, DR8.DR4-, or DR8.DR4+ were investigated for the severity of their disease. 40 joints in 18 patients, 2 in 1, 19 in 8, 13 in 6, or 10 in 4 respectively from Groups DR4.*, DR6.DR4-, DR6.DR4+, DR8.DR4-, or DR8.DR4+ had had the previous history of total joint replacement operations for the diseased hips (THR) or knees (TKR). The number of cases (p < 0.01) or that of joints (p < 0.001) was significantly less among Group DR6.DR4- patients than the corresponding figure among Group DR4.* patients. Significantly smaller (p < 0.02) number of cases with DR6 (Groups DR6.DR4- and DR6.DR4+ combined) had experienced THR's and/or TKR's than those in Group DR4.*. Group DR8.DR4- patients had undergone THR/TKR operations in smaller number of the joints (p < 0.05) in comparison to Group DR4.* patients, though the difference was not significant when the numbers of operated cases were compared between the Groups. The age at RA onset among Groups DR4.*, DR6.DR4-, DR6.DR4+, DR8.DR4-, or DR8.DR4+ was 38.5 +/- 14.2 (mean +/- SD) years, 46.6 +/- 12.2, 41.7 +/- 11.7, 44.9 +/- 13.1, or 40.8 +/- 10.2 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
7503950 Expression and function of CD5 and CD28 in patients with rheumatoid arthritis. 1993 Sep To assess the role of CD5 and CD28 in the pathogenesis of the decreased cellular immune function in patients with rheumatoid arthritis (RA) we analysed the expression and function of these T-cell surface molecules. The expression of CD5 as well as of CD28 in synovial and peripheral blood T cells was similar to that of control T cells. Monoclonal antibodies (mAb) directed at CD28 and CD5 were able to provide an accessory signal to anti-CD3 activated T cells both from the synovial fluid and from the peripheral blood. However, the proliferation induced by anti-CD3 mAb in conjunction with anti-CD5 or anti-CD28 mAb was always higher in peripheral blood (PB) T cells compared to the paired synovial fluid T cells. After simultaneous ligation of CD5 and CD28, proliferation was induced in the PB T cells. However, when compared to control PB T cells, this proliferation was significantly lower in the RA patients. Purified normal memory (CD45RO+) T cells proliferated less strongly than naive (CD45RA+) T cells, but no difference was observed between rheumatoid and normal memory T-cell proliferative responses. However, enriched PB CD45RA+ T cells from rheumatoid patients proliferated less vigorously to CD5 and CD28 ligation when compared to normal enriched CD45RA+ T cells. Synovial fluid (SF) T cells, which are mainly of the memory cell type, did not proliferate after simultaneous ligation of CD5 and CD28. This refractory state of synovial T cells could not be explained by a difference in the surface expression of CD5 or CD28. Our data suggest that the cellular immune dysfunction in the PB from rheumatoid patients may be due to a decreased responsiveness of the naive T-cell subset to accessory signals provided by CD5 and CD28. In addition, SF T cells appear hyporesponsive to stimulating signals provided through CD5 and CD28.
8546529 Determination of interstitial collagenase (MMP-1) in patients with rheumatoid arthritis. 1995 Dec OBJECTIVES: To investigate whether interstitial collagenase (MMP-1) concentration in synovial fluid can be useful as a marker for disease activity in rheumatoid arthritis (RA), to determine the main route by which collagenase degrades the matrix of articular cartilage, and to investigate if an imbalance between metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMP) is responsible for the activity of MMPs in RA. METHODS: Collagenase concentrations were measured in synovial fluid and paired serum samples using a specific sandwich enzyme linked immunosorbent assay. Collagenase activities were also assayed in synovial fluid samples. Synovial tissues obtained from the same patient were examined by immunohistochemical staining and the numbers of cells expressing collagenase were counted. RESULTS: Collagenase concentrations in synovial fluid did not correlate with C reactive protein and collagenase levels in serum, but did correlate positively with the degree of synovial inflammation, and increased with increasing numbers of cells identified as expressing collagenase in synovial tissue. Collagenase activities did not correlate with TIMP-1 concentrations, but did correlate strongly with the ratios of collagenase concentration to TIMP-1 (r = 0.73). CONCLUSION: The collagenase concentration in synovial fluid cannot be used as a marker for systemic disease activity, but can be used as a marker for the degree of synovial inflammation in the joint from which the sample is aspirated. In advanced RA, most of the collagenase is probably produced in synovial lining cells and released into synovial fluid, where it degrades the matrix of articular cartilage. An imbalance between MMP and TIMP may be of importance in the degradation of extracellular matrix of articular cartilage in RA.
8368021 [Clinical use of magnification radiography in rheumatologic differential diagnosis]. 1993 May Rheumatologic joint disorders were examined with high-definition microfocal magnification radiography. The magnification technique was compared to conventional radiographs (mammographic film-screen combinations). The microfocal x-ray unit had a spot size of 20-130 microns. Fourty patients with early arthritis (history of less than 18 months) were examined; x5 magnification was used. Digital luminescence radiography was employed to minimize radiation dose. Digital image processing included simulation of conventional technique and edge enhancement. Magnification radiographs and conventional technique were evaluated. In 20/40 patients articular lesions were detected. Magnification radiography gave additional information in 14/20 patients: in 5/14 patients lesions were seen only with magnification radiography (erosions n = 3, loss of the cortical white line n = 2), in 9/14 patients the extent of the lesions could be evaluated better. Hence, magnification radiography proved a valuable mean in early diagnosing and evaluating rheumatic disease.
7712926 [The abnormalities of the cellular immunity in rheumatoid synovium]. 1994 Sep With the technique of immunohistochemical (ABC) method monoclonal antibodies were used to identify the lymphocyte subsets, macrophage and the expression of class II MHC (HLA-DR, HLA-DQ) antigens in the synovium cells from 18 RA patients and 8 patients with osteoarthritis as control. The results showed that the main cellular abnormality at the sublayer of the synovium was the appearance of lymphoid follicles which mainly consisted of the infiltration of T lymphocytes (77.8%).50.6% of them were CD4+, which mainly consisted by of CD45RO+ cells in the rheumatoid synovium on the consecutive sections. The increased ratio of CD4/CD8 in RA patients was significantly higher when compared with that in the controls (2.11 +/- 0.93 vs 0.63 +/- 0.13, P < 0.001). In advanced RA with fibrosis of joints, the ratio tended to decrease and was accompanied with reduction of infiltrated lymphocytes. Compared with T cells CD20+ B lymphocyte not only had a lower percentage (25.2%), but also showed a characteristic picture of locating in the centre of the follicles. The fact that most of the CD4+ T cells was helper memorized lymphocytes with CD4 phenotype of positive TAC(+) (interleukin-2 receptor) and that up to 54.2% was anti-HLA-DR and 54.1% anti-HLA-DQ monoclonal antibodies indicated that these T lymphocytes were activated in vivo. Cells with anti-CD68+ were seen all over the RA synovium. Class II HLA and CD68 molecule were also expressed on the endothelium cells of the small vessels. It is suggested that the activated lymphocytes, macrophages and endothelium cells and their abnormal distribution may indicate the abnormalities of the cellular immunity in rheumatoid synovium.