Browse

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

ID PMID Title PublicationDate abstract
7597380 Glycosylation of IgG during potentially arthritogenic lentiviral infections. 1995 Agalactosyl IgG [Gal(0)] was first discovered in patients with rheumatoid arthritis (RA). However, the proportion of this glycoform is also raised in tuberculosis and leprosy. This has helped reinforce the suggestion that RA may be triggered by a mycobacterium-like slow bacterial infection. On the other hand, arthritis can occur in mycobacterial diseases, so raised Gal(0) could be associated with a tendency to arthritis, rather than with a particular type of infection. Therefore, we wished to find out whether the percentage of Gal(0) [%Gal(0)] is increased in sheep and goats following infection with maedi visna virus or caprine arthritis encephalitis virus (CAEV), both of which can lead to inflammatory synovitis. We found that the normal level of Gal(0) in these species is much lower than in humans. Goats infected with CAEV or Mycobacterium paratuberculosis (used as a control mycobacterial infection) had a significant increase in %Gal(0), though it was still below the level seen in normal humans. Studies by Western blot confirmed the presence of terminal N-acetylglucosamine on heavy chains, and percentages of Gal(0) comparable to those seen in human RA could be generated by exposing goat IgG to streptococcal beta-galactosidase. The rise in %Gal(0) was greatest in members of infected herds that were just starting to manifest arthritis, and tended to be lower in those in which severe carpitis had developed at the time of bleeding, implying the possibility that raise %Gal(0) may be an early or predisposing event for the development of arthritis.(ABSTRACT TRUNCATED AT 250 WORDS)
8617986 Suppression of antigen-induced arthritis in rabbits by ex vivo gene therapy. 1996 May 1 Gene therapy offers a novel approach to treating human joint diseases such as rheumatoid arthritis. In the present study, we have used the retrovirus, MFG-IRAP, to transfer the human IL-1 receptor antagonist protein (IRAP) gene to rabbits' knees and have assessed its impact on inflammatory and chondrodestructive aspects of the acute phase of antigen-induced arthritis in these joints. Surprisingly, intra-articular expression of IRAP was three- to fivefold higher in arthritic knees than in nonarthritic knees, accumulating to levels of over 20 ng/knee in the highest expressing joints. This level of expression produced a marked chondroprotective effect but a milder anti-inflammatory one. Both the increased cartilage matrix catabolism and the inhibition of matrix synthesis that occur in antigen-induced arthritis were abrogated in the presence of the IRAP gene; the latter effect was particularly strong. Of the indices of inflammation that were examined, only leukocyte influx into the joint space was inhibited, and this effect declined with time. Concentrations of rabbit IL-1 were reduced by the IRAP gene, suggesting inhibition of an autocrine induction loop. These data demonstrate that the course of arthritic disease in the rabbit knee can be altered by genetic manipulation, thus encouraging the further development of gene treatments for human joint diseases.
8444627 Exercise maintenance of persons with arthritis after participation in a class experience. 1993 Spring This study investigated factors related to an initial exercise experience to explain exercise maintenance in 120 adults with rheumatoid arthritis or osteoarthritis. Integral secondary analysis was used to incorporate data from a prospective, controlled trial of exercise (Minor et al.: Arthritis Rheum 32:1396, 1989) with data collected at 18 months follow-up. The dependent variable was self-directed exercise (min/wk) reported at 3, 9, and 18 or more months after exercise class participation. Predictor variables included physical, psychosocial, disease, and programmatic factors. The all possible regressions search procedure resulted in three explanatory models (p = .0001). At 3 months the model (R2 = .45) included initial aerobic capacity, depression, and anxiety; and changes in depression and social activity. The 9-month model (R2 = .35) consisted of initial anxiety and physical activity, change in depression, support of friends for exercise, and exercise behavior at prior assessment. At 18 or more months (R2 = .42), model variables were initial aerobic capacity, change in pain, and exercise behavior at the two prior assessments. Neither disease nor program factors appeared as significant. This limited study indicates that factors associated with exercise behavior in this sample are similar to those in the general population; explanatory factors change over time, and changes ascribed to a trial behavior may influence subsequent decision making.
1601639 Immunomodulation of proteoglycan-induced progressive polyarthritis by leflunomide. 1992 Mar Proteoglycan-induced arthritis is a mouse model displaying many similarities to human rheumatoid arthritis and ankylosing spondylitis which has been documented by clinical and histopathological studies. The development of the disease in genetically susceptible BALB/c mice is dependent upon the expression of both cell-mediated and humoral immunity to host mouse cartilage proteoglycan. Since both development and regression of acute inflammatory processes in joints correlate directly with the serum antibody level to mouse cartilage proteoglycan, it is believed that these autoreactive antibodies may play a key role in the pathological mechanism of proteoglycan-induced arthritis. The treatment of arthritic animals with an immunomodulating agent (leflunomide) suppressed acute inflammatory events, protected animals from new inflammatory episodes or acute exacerbations in chronically inflamed joints and blocked pathological processes in arthritic joints, which otherwise led to progressive deformities, ankylosis and the loss of articular cartilage. We conclude that the suppressive effect of leflunomide (HWA 486) in proteoglycan-induced arthritis primarily is due to the suppression of autoantibody formation and that the drug may be a potential agent in human therapy as well. Further, we feel that this novel model of murine polyarthritis will extend further the pharmacological repertoire necessary to discover innovative antirheumatic drugs.
8921928 Spondylarthropathy with distal joint involvement. 1996 To study whether the presence of distal joint involvement in spondylarthropathy corresponds to a particular set of the disease, one hundred and twenty six patients with spondylarthropathy were included in a retrospective study. Two groups of patients were defined according to the presence or the absence of distal joint involvement and their clinical, radiological, and biological features were compared. The patients with distal joint involvement had a later onset of spondylarthropathy and showed higher levels of biological markers of inflammation in their peripheral blood. However, no great difference appeared between the two groups of patients. Spondylarthropathy with distal joint involvement cannot be separated from spondylarthropathy without distal joint involvement and appears to be the same disease.
8397717 Anti-collagen autoantibodies are found in women with silicone breast implants. 1993 Jun There have been several anecdotal reports that silicone breast implants are associated with an increased incidence of autoimmune disease. Based upon these data as well as the theoretical potential of silicon and silicone immune interactions, we hypothesized that an immune response to a silicone breast implant would include host reactivity against components of the microenvironment within the implant milieu. To test this hypothesis, we obtained detailed histories and performed examinations of 57 consecutive, self-referred patients concerned about their breast implants. Eleven of these women were excluded for various reasons including previous exposure to bovine collagen. The remaining 46 women, as well as 45 normal women of approximately the same age and living in the same geographic region, were tested using a sensitive ELISA for the presence of autoantibodies to human native type I collagen, denatured type I collagen, native type II collagen and denatured type II collagen. Known positive and negative sera were included in all assays and the ELISA was performed and interpreted blindly. Positive sera were defined as an ELISA value of three standard deviations above the mean of the normal controls. Using these stringent criteria, there was a statistically significant incidence of antibodies to collagen in women with silicone breast implants. In fact, 35% of women with silicone breast implants had such antibodies; this is higher than we have observed in any other autoimmune disease and is similar to that of chronic erosive rheumatoid arthritis. We believe that silicone breast implants, in genetically susceptible hosts, may pose a significant risk for immunopathology.
1578463 Ultrasonography in the study of prevalence and clinical evolution of popliteal cysts in ch 1992 Mar The prevalence and clinical evolution of popliteal cysts in children with knee arthritis is not well known. Using ultrasonography, we studied 44 children with clinically detectable knee effusions secondary to juvenile rheumatoid arthritis (n = 35), spondyloarthritis (n = 3) and psoriatic (n = 2), septic (n = 2) and lupus (n = 2) associated arthritis. Popliteal cysts, defined as anechoic or hypoechoic masses measuring at least 1 cm in 2 of 3 dimensions, were identified in 27 children (61%). Of the 30 children with bilateral arthritis, 11 (37%) had bilateral cysts. The size of the cysts ranged from 1 to 40 cm3 (median 3.0 cm3). There was a significant correlation between the presence of a cyst and popliteal pain and the size of the suprapatellar effusion (p less than 0.001) but not the child's age or underlying diagnosis (p greater than 0.05). A cohort of 25/27 children with cysts were followed prospectively with serial sonograms for 18-24 months. The resolution of the cyst followed that of the suprapatellar effusion in those children whose arthritis improved or resolved. Two children (8%) had rupture of the popliteal cysts. Popliteal cysts are readily documented in children with knee effusions using ultrasonography, and their presence and evolution correlates with the size of the suprapatellar effusion.
8832993 Arthritis associated with HIV infection in Zimbabwe. 1996 Mar OBJECTIVE: To document the clinical and immunogenetic features of arthritis associated with heterosexually acquired human immunodeficiency virus (HIV) infection. METHODS: All patients were assessed by a rheumatologist and standard laboratory tests were performed. RESULTS: There were 3 common clinical presentations. (1) Oligo/polyarticular arthritis (22 men, 4 women). HIV infection had not previously been diagnosed in 24 of these patients but persistent generalized lymphadenopathy (85%) and weight loss (42%) were present. Joints commonly involved were ankles (65%) and knees (54%), often with associated enthesitis (31%) and dactylitis (23%). Followup data in 18 patients showed that arthritis resolved completely in 9 patients (one subsequently recurred), improved by >50% in 5 patients, was unremitting in 3 patients, and recurred frequently in one patient. None of 7 patients tested were HLA-B27 or B7 positive. (2) Reiter's syndrome (RS) (21 men, 3 women; incomplete RS 18 patients,complete RS 6 patients). Lymphadenopathy was present in 19 patients (79%) and 4 patients were previously known to have HIV infection. Involvement of knees (80%) and ankles (58%) was common, as were enthesitis (29%) and dactylitis (13%). Followup data in 21 patients showed that 14 resolved (5 with recurrences), 2 improved by >50%, and 5 had continued arthritis. HLA-B27 was not found in 13 patients tested but a cross reacting antigen was found in 6 patients. (3) Symmetrical polyarthritis (4 men, 4 women). Symmetrical arthritis of the wrists (8 patients) and peripheral interphalangeal (PIP) and metacarpophalangeal (MCP) joints (7), as well as lymphadenopathy (5), nodules (4), rheumatoid factor (3), and erosive radiographic changes (one patient) were seen. (4) Miscellaneous. Other types of arthritis included 3 patients with psoriasis and arthritis and one patient each with Behcet's disease, Salmonella septic arthritis, and secondary syphilis. CONCLUSION: Arthritis associated with HIV in this population is most commonly characterized by oligoarticular, asymmetrical, large joint arthritis, with or without features of Reiter's syndrome, and is not associated with HLA-B27.
7788155 Assessing clinical competence: recognition of case descriptions of rheumatic diseases by g 1995 Apr The objective of this study was to detect strengths and weaknesses in the diagnosis of rheumatic diseases by general practitioners in order to set up post-graduate training accordingly and to assess whether open-ended questions give results comparable with multiple choice-type questions. Fifty-one general practitioners were given eight written cases: rheumatoid arthritis (RA), ankylosing spondylitis (AS), reactive arthritis, psoriatic arthritis (PsA), systemic lupus erythematosus (SLE), gout, polymyalgia rheumatica and pseudogout. Only signs and symptoms were provided. All cases were derived from real patients with a definite diagnosis. Each case was presented in both types of question formats. The cases were also presented to 23 rheumatologists. We found that in the open-ended question format 57.1% of the general practitioners gave the correct answers. Cases of RA, AS, gout and PsA were correctly diagnosed by > 70% of the general practitioners. Cases of polymyalgia rheumatica and reactive arthritis were correctly diagnosed by 55 and 39% of the general practitioners, respectively. The cases of pseudogout and SLE were correctly diagnosed by less than 11% of the general practitioners. Fifty-two per cent of the general practitioners gave the correct answers to the multiple choice-type questions. There was no statistical difference in the correct answers between the open-ended questions and the multiple choice-type questions. We concluded that assuming generalization of the results, training of general practitioners should include polymyalgia rheumatica, reactive arthritis, SLE and pseudogout.
8531352 [Sjögren's syndrome as a lymphoaggressive disorder; bcl-2 expression in lymphocytes infil 1995 Oct Sjögren's syndrome (SS) is a unique disease which develops a high incidence of lymphoproliferative disorder such as monoclonal gammopathy or malignant lymphoma. In order to elucidate the mechanism of the progression from polyclonal to monoclonal lymphoproliferation in SS patient, we analyzed the monoclonal nature and the expression of bcl-2 protein in the salivary glands. Formalin-fixed, paraffin-embedded salivary gland (labial salivary glands, 45; parotid glands, 6; submaxillary glands, 1) tissues or lung tissues (interstitial pneumonia in 2 patients with SS) were serially sectioned and evaluated using the standard avidin-biotin-peroxidase (ABC) technique. Murine monoclonal primary antibodies obtained from Dakopatts to B-cells (L26; CD20) and T-cell markers (UCHL1; CD45RO) and bcl-2 protein were employed. The bcl-2-positive areas were stained with T and B cell markers in serially sectioned specimens. Lymphocytes forming the LEL were mostly composed of CD20-positive B-cells and these cells expressed bcl-2 protein. In the lip biopsy specimens, 36 of 45 patients showed small areas of bcl-2 expression in periductal lymphocytes. The expression of bcl-2 protein in the cells plays a crucial role in the cells escaping apoptotic cell death, living long and resulting in autoantibody production, and obtaining the increased risk of monoclonal proliferation of the cells. These findings provide further evidence for understanding the mechanism of monoclonal transformation from polyclonal lymphoproliferation in autoimmune reaction.
8050187 Sjögren's syndrome: autoimmune epithelitis. 1994 Aug Sjögren's syndrome (SS), the ideal model to study autoimmunity and lymphoid malignancy, is a common chronic disease which in the last 30 years has been studied extensively on clinical and pathophysiological grounds. Clinical studies regarding kidney disease in SS patients have shown that the predominate lesion is interstitial nephritis which produces tubular dysfunction. Studies on lung involvement have previously indicated that one-fourth of SS patients suffer from subclinical, interstitial lung disease. Reevaluation, however, of the pulmonary disease, using functional, radiologic (including CT-scan), and histopathologic studies, revealed that the lesion starts peribronchially. Finally, evaluation of liver disease in SS patients revealed that this consists of a pericholangeal round-cell infiltrate resembling the early lesion of primary biliary cirrhosis. These clinical studies suggest that the majority of extraglandular manifestations of SS are due to the attraction of lymphocytes by different epithelial tissues. Studies of the epithelial cells of minor salivary glands from SS patients have shown that these inappropriately and selectively express HLA class II molecules and the protooncogene c-myc. Evaluation of cytokines in the minor salivary glands from these patients, by in situ hybridization, revealed that the mRNA of the proinflammatory cytokines IL-1 and IL-6 also comes from the epithelial cells. Finally, proviral DNA is incorporated in the DNA of epithelial cells. On the basis of these clinical and basic observations, we suggest that the major suffering cell in SS patients is the epithelium and thus we propose this descriptive term "autoimmune epithelitis" instead of "Sjögren's syndrome.
1294741 Absence of HLA-B8 and HLA-DR3 in Japanese patients with Sjögren's syndrome positive for a 1992 Dec Forty Japanese anti-SSA(Ro) positive patients with Sjögren's syndrome were typed for HLA-A, B, C, DR and DQ antigens. No patient had either HLA-B8 or HLA-DR3 which has been reportedly associated with the immune response to SSA(Ro) antigens in white and black patients. Our patients had higher frequencies of HLA-DRw8 and HLA-DRw52 than the control population.
1372936 Topology of innervation of labial salivary glands by protein gene product 9.5 and synaptop 1992 Jan Glandular secretion and integrity, local blood flow, salivary secretion, pain perception and neurogenic inflammation can all be controlled by the nervous system. Therefore, the pattern of innervation of labial salivary glands (LSG) was studied in 10 patients with Sjögren's syndrome using neuronal markers: protein gene product 9.5 (PGP 9.5), a cytoplasmic, noncytoskeletal epitope and synaptophysin, a glycoprotein present in presynaptic vesicles. PGP 9.5 immunoreactive nerve fibers were found surrounding the acini, salivary ducts and blood vessels. The rich innervation of LSG was even more evident in immunofluorescence stained sections analyzed using confocal laser scanning imaging. Synaptophysin immunoreactive nerve endings and preterminal varicosities also demarcated the LSG acini. Furthermore, in the small foci, PGP 9.5 and synaptophysin immunoreactive nerve fibers were found amid inflammatory mononuclear cells and in extensive inflammatory areas nerve fibers were found in the peripheral parts of such infiltrates. This suggests a possible neurogenic influence on the local cellular inflammation. When LSG patient samples were compared to unaffected glands from 7 controls, acinar atrophy was found in the areas devoid of a local delivery system of neurogenic trophic stimuli, suggesting this as a possible cause of glandular degeneration. It may become necessary to incorporate this neglected, but existing system into our current view on the local but possibly centrally controlled or influenced pathogenetic mechanisms of Sjögren's syndrome.
8622278 [Two cases of primary Sjögren's syndrome with pulmonary involvement histopathological stu 1996 Feb We report two cases of primary Sjögren's syndrome with pulmonary involvement, in which open lung biopsies were done. The patient in the first case was a 58-year-old woman and the patient in the second case was a 54-year-old woman. Both patients were admitted to our hospital because of dry coughing and exertional dyspnea. Chest X-ray films and CT scans showed interstitial shadows in both cases and multiple bullae in the first case. Pulmonary-function tests showed decreased diffusing capacity, and examination of bronchoalveolar lavage fluid revealed increased percentages of lymphocytes. Open-lung biopsy specimens showed thickening of the alveolar septa and interstitial mononuclear cell infiltration, composed predominantly of lymphocytes, with lymphoid follicles in both cases, and peribronchiolar mononuclear cell infiltration in the first case. Therefore, the histopathological diagnosis was cellular interstitial pneumonia with lymphoid follicles. Both patients were treated with oral corticosteroids. Symptoms were relieved and laboratory findings improved.
9036579 [The use of plasmapheresis in treating Sjögren's disease (syndrome)]. 1996 The efficacy of treatment of stomatological manifestations and visceral diseases in patients with Sjogren's disease (syndrome) by therapeutic complexes including plasmapheresis is assessed. Plasmapheresis was administered to 7 inpatients in an intermittent mode with exfusion of up to 1 liter of plasma per session. A course consisted of one to three sessions, the total duration of treatment was three to four weeks. The efficacy of plasmapheresis in a complex of therapeutic measures was assessed from the time course of the clinical picture, results of studies of the function of salivary glands, and parameters of metabolic processes and immunity. Plasmapheresis helped attain long remissions and improved the general status of the patients, this being paralleled by a positive time course of local symptoms of the disease and the principal homeostasis parameters.
7495347 Transforming growth factor beta 2 in labial salivary glands in Sjögren's syndrome. 1995 Sep OBJECTIVE: To compare the distribution and the amount of transforming growth factor beta (TGF beta) in labial salivary glands (LSG) in patients with Sjögren's syndrome (SS) and healthy controls. METHODS: LSG from SS patients (n = 10) and healthy controls (n = 6) were labelled with peroxidase-antiperoxidase staining for TGF beta 2, which was quantitated in image analysis using Video Interactive Display System software. RESULTS: In all LSGs in SS and healthy controls, TGF beta 2 was found in endothelial cells of the capillaries and in the capsular and stromal fibroblasts. In LSGs in SS, TGF beta 2 was also found in some lymphocytes in the inflammatory cell foci and in fibroblasts in fibrotic areas. The TGF beta 2 staining index (microns 2/mm2 tissue) was greater in SS than in control LSGs (3670 (SEM 430) v 2061 (176); p < 0.01), with no difference between the primary and secondary forms of SS (p > 0.05). CONCLUSION: The localisation and the level of expression of TGF beta 2 indicate its involvement in local tissue fibrosis, and may reflect attempts at immunosuppression.
7702063 Membranoproliferative glomerulonephritis with primary Sjögren's syndrome. 1995 Apr Glomerular involvement in primary Sjögren's syndrome is rare and only five cases of membranoproliferative glomerulonephritis have been reported. We present a case of a 31-year-old white woman with primary Sjögren's syndrome who developed nephrotic syndrome. Evaluation showed no evidence of an associated connective tissue disease. Kidney biopsy was consistent with type I membranoproliferative glomerulonephritis. The patient's nephrotic syndrome resolved spontaneously, a course that has not been reported previously in this setting.
7712925 [Labial salivary gland biopsy in the diagnosis of Sjogren's syndrome]. 1994 Sep Labial salivary gland biopsy (LSG-B) along with Schirmer test and kerato-conjunctival staining with fluorescein dye was performed in 196 patients with suspected Sjogren's syndrome (SS). Of the 196 patients, 117 were found to have 2 or more lymphocytic focus scores (LFS/4mm2) on their LSG-B specimens. 92 of them having keratoconjunctivitis sicca (KCS) as well met the diagnostic criteria of SS. Among the cases (25) without KCS, 16 with another CTD were diagnosed as secondary SS. 9 cases were classified as probable primary SS in this study because they had clinical manifestations of SS. Of the 11 cases with KCS only, 6 with another CTD were diagnosed as secondary SS; 5 befitted primary SS for abnormal findings on sialography. We also found that lymphocytic infiltration in LSG-B was much more severe in primary SS than in secondary SS; this could be attributed to the use of immunotherapy for the accompanying CTD in secondary SS. There was good association in our study between the severity of lymphocytic infiltration and systemic involvement.
8336308 Pleuropulmonary abnormalities in primary Sjögren's syndrome. 1993 May Sixteen patients with primary Sjögren's syndrome (1 degree SS) who complained of dyspnea were investigated with high resolution computerized tomography of the thorax, bronchoalveolar lavage, and transbronchial biopsy. Six patients had evidence of interstitial fibrosis, 5 had a peribronchiolar lymphocytic infiltration and 3 had pleural thickening. We conclude that significant pulmonary disease is not uncommon in patients with 1 degree SS.
1496160 The immunogenetics of Sjögren's syndrome. 1992 Aug The fact that patients with SS, either primary or associated with another connective tissue disease, show a striking tendency toward familial aggregation of SS, other autoimmune disease and autoantibodies suggest a role for genetic factors in the pathogenesis of this disease. What these factors are is as yet not known; however, it is clear that autoantibodies found in high frequency in SS, specifically anti-Ro and anti-La, are associated with HLA class II alleles, found at the HLA-DQA1 and DQB1 loci, which have in common the presence of specific amino acid residues that are found in the second hypervariable region of the first (outermost) domain. Additional roles for T-lymphocyte receptor and immunoglobulin genes are also suggested. Family studies, however, indicate the presence of an additional autosomal dominant gene(s), not linked to HLA or immunoglobulin heavy or light chain genes, in predisposition to SS. Identification of this additional genetic factor(s) should provide important clues in the pathogenesis of SS.