Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3789778 | Nodular primary cutaneous amyloidosis. Isolation and characterization of amyloid fibrils. | 1986 Dec | A case of nodular cutaneous amyloidosis and Sjögren's syndrome occurred in a 63-year-old woman. Nodules had been seen for the past ten years and Sjögren's syndrome had accompanied amyloidosis for the last three years. The concomitant occurrence of nodular cutaneous amyloidosis and Sjögren's syndrome may not be by chance, since four of 12 cases of nodular cutaneous amyloidosis that have been reported to date in Japan were in patients with both amyloidosis and Sjögren's syndrome. The amyloid deposits in the tissue were stained with anti-lambda light-chain amyloid antibody. Amyloid fibrils were purified from the skin lesions in this patient and were characterized biochemically, immunologically, and ultrastructurally. The results indicated that the amyloid fibrils consisted of 29,000-, 20,000-, and 17,000- dalton peptides, the 29,000-dalton peptide of which was shown to react with the lambda light chain of immunoglobulin by immunoblot study. | |
| 2071616 | The outcome of decompressive laminectomy for degenerative lumbar stenosis. | 1991 Jul | The outcome of laminectomy for the relief of symptoms resulting from degenerative lumbar stenosis is not well established. Eighty-eight consecutive patients who had had a laminectomy for degenerative lumbar stenosis between 1983 and 1986 were studied. Eight of the patients had had a concomitant arthrodesis. The follow-up evaluation included a review of charts and standardized questionnaires that were completed by the patients. One year postoperatively, five patients (6 per cent) had had a second operation and five still had severe pain. By the time of the latest follow-up, in 1989, fifteen (17 per cent) of the original eighty-eight patients had had a repeat operation because of instability or stenosis; twenty-one (30 per cent) of the seventy patients who were evaluated by questionnaire in 1989 had severe pain. The factors found to be associated with a poor long-term outcome, defined as severe pain or the need for a repeat operation, or both, included co-existing illnesses (such as osteoarthrosis, cardiac disease, rheumatoid arthritis, or chronic pulmonary disease) (p = 0.004), the duration of follow-up (p = 0.01), and an initial laminectomy involving a single interspace (p = 0.04). We concluded that the long-term outcome of decompressive laminectomy is less favorable than has been previously reported, and that co-morbidity and a single-interspace laminectomy are risk factors for a poor outcome. | |
| 1996642 | Role of kallikrein-kinin system in pathogenesis of bacterial cell wall-induced inflammatio | 1991 Feb | The plasma kallikrein-kinin system is activated in Gram-negative sepsis and typhoid fever, two diseases in which bacterial products have been shown to initiate inflammation. Because a single intraperitoneal injection of bacterial cell wall peptidoglycan-polysaccharide polymers from group A steptococci (PG-APS) into a Lewis rat produces a syndrome of relapsing polyarthritis and anemia, we investigated changes in the role of the kallikrein-kinin system in this model of inflammation. Coagulation studies after injection of PG-APS revealed an immediate and persistent decrease in prekallikrein levels. High-molecular-weight kininogen levels decreased significantly during the acute phase and correlated with the severity of arthritis. Factor XI levels were decreased only during the acute phase. Antithrombin III levels remained unchanged, indicating that neither decreased hepatic synthesis nor disseminated intravascular coagulation caused the decreased plasma contact factors. Plasma T-kininogen (an acute phase protein) was significantly elevated during the chronic phase. PG-APS failed to activate the contact system in vitro. Thus the kallikrein-kinin system plays an important role in this experimental model of inflammation, suggesting that activation of this system may play a role in the pathogenesis of inflammatory bowel disease and rheumatoid arthritis in which bacterial products might be etiologically important. | |
| 2557044 | Regulation of human synovial fibroblast collagenase messenger RNA by interleukin-1. | 1989 Dec | Interleukin-1 (IL-1) may contribute to tissue destruction in rheumatoid arthritis, in part, by inducing messenger RNA (mRNA) that encodes interstitial collagenase. In human synovial fibroblasts in vitro, IL-1 induced collagenase mRNA accumulation 6 hours after being added to the cells. High levels of mRNA remained present for at least 48 hours after treatment. The rate of transcription of collagenase in isolated nuclei peaked after approximately 6 hours of treatment with IL-1 and declined thereafter, becoming nearly undetectable by 24 hours. The persistence of mRNA, in view of the transient peak of transcription, suggested that collagenase mRNA was stable in synovial fibroblasts. The half-life of collagenase mRNA after the synoviocytes were treated with actinomycin D was approximately 27 hours, both in the presence and in the absence of IL-1. It has been noted that induction of the expression of collagenase by phorbol esters requires fos protein synthesis and is mediated through a tetradecanoyl phorbol acetate response element in the 5'-flanking region of the gene. However, we found that cycloheximide, when added to synovial fibroblast cultures up to 6 hours after treatment with IL-1, inhibited the expression of collagenase mRNA. These results suggest that fos alone is unlikely to be sufficient for collagenase expression, and that additional factors, or alternative pathways, are involved in the induction of collagenase by IL-1. | |
| 3692575 | Modulation of phospholipase A2 activity in human synovial fluid by cations. | 1987 Dec | Cell-free, Ca2+-dependent phospholipase A2 activity (PLA2) was measured in human synovial fluid of patients with various kinds of arthritis using [1-14C] oleate-labelled autoclaved Escherichia coli as substrate. PLA2 activity at pH 7.0 and with 5 mM added Ca2+ was stimulated and then inhibited in a dose-dependent fashion by NaCl; maximal stimulation of 8.8 fold was found at 150 mM Na+. Similar effects were obtained with K+, Li+ and Ru+. In the absence of added Na+, PLA2 activity was maximal with 25 mM Ca2+ (145 nmols/hr/mg), but in the presence of 150 mM Na+, activity was maximal with 4 mM Ca2+ (415 nmols/hr/mg). PLA2 activity was optimal between pH 6.5-8.0 in presence of 150 mM Na+1 and 4 mM Ca2+. There was no significant difference between PLA2 activity in synovial fluids from rheumatoid and other types of arthritis. Neutral active, Ca2+-dependent PLA2 activity in acid extracts of human platelets, plasma, polymorphonuclear leukocytes and synovial fluid varied in response to added Na+. In presence of 150 mM added Na+ and 5 mM Ca2+, PLA2 activity in human synovial fluid was inhibited by all multivalent cations tested. In the absence of Na+, Cu2+ and Mg2+ stimulated PLA2 activity in a dose dependent fashion; whereas, Fe2+, Fe3+ and Al3+ were inhibitory. The extent of stimulation by Mg2+ was inversely related to the concentration of added Ca2+. | |
| 2327866 | [Rheumatoid purpura and acute post-infectious glomerulonephritis]. | 1990 Feb | The authors report the case of a 33 month-old child who presented some of the classical symptoms of the Henoch-Schoenlein purpura - arthritis, purpuric lesions of the lower extremities - associated with the full-blown picture of a post-infectious glomerulonephritis - low level of C3, proliferation of mesangial cells, exudation with large number of leukocytes, and C3 glomerular deposits. These findings and others previously described suggest that the Henoch-Schoenlein purpura is a syndrome and that some of its manifestations may occur in patients with post-infectious glomerulonephritis. | |
| 3710320 | Arthroscopy of the posterior subtalar joint: a preliminary report. | 1986 Apr | The technique of arthroscopy is, at the present time, available for the investigation of the subtalar joint. In this preliminary report, the relevant anatomy and technique are reviewed. Illustrative cases are presented to review some of its applications. It is the conclusion of the author that arthroscopy of the subtalar joint may be of value in the following situations: assessment of the articular cartilage in suspected cases of degenerative, rheumatoid, or infectious arthritis; evaluation of chronic pain syndrome in the hindfoot after injuries; and biopsy of the synovial lining, breakage of adhesions, joint lavage, and removal of loose bodies. | |
| 3285062 | Monoclonal gammopathies in patients with Sjögren's syndrome. | 1988 Feb | We studied 18 sera of Sjögren's syndrome (SS) with monoclonal gammopathy. Monoclonality was established by typical immunoelectrophoretic findings in all patients and confirmed by idiotypic (Id) studies in 12 patients. Four of the monoclonal gammopathies were of the IgG class, 8 were of the IgA class and 4 were of the IgM class, and 2 patients had 2 M proteins (IgMK/IgGK and IgAK/IgGK). The monoclonal rheumatoid factor (RF) was found in 6 patients (4 IgA and 2 IgM). A review of the literature revealed additional 19 monoclonal gammopathies (2 IgG, 9 IgA, 7 IgM and one Bence Jones protein) in Japanese SS patients. In non-Japanese SS patients, 27 monoclonal gammopathies (4 IgG, 2 IgA, 20 IgM and once Bence Jones protein) were reported. Both Japanese and non-Japanese patients showed a higher incidence of monoclonal gammopathies in primary than in secondary SS. The non-IgM class monoclonal gammopathies were predominant in Japanese SS patients, whereas monoclonal gammopathies were mostly confined to the IgM class in non-Japanese SS patients. These results indicate that monoclonal gammopathy is another significant complication of SS. | |
| 2584740 | The immunogenetic relationship between anti-Ro(SS-A)/La(SS-B) antibody positive Sjögren's | 1989 Dec | We have described previously the clinical features of a unique group of anti-Ro(SS-A) antibody positive Sjogren's patients who have cutaneous features of lupus erythematosus, most commonly subacute cutaneous lupus erythematosus, defined as the Sjogren's/lupus erythematosus overlap syndrome. Three of these patients are also mothers of infants with the neonatal lupus erythematosus syndrome, characterized by cutaneous lesions resembling subacute cutaneous lupus erythematosus or congenital heart block. Patients with Sjogren's/lupus erythematosus overlap syndrome, subacute cutaneous lupus erythematosus, and mothers of infants with the neonatal lupus syndrome characteristically have autoantibodies to Ro(SS-A), and in many cases, La(SS-B) antigens. The present study was designed to test the hypothesis that anti-Ro(SS-A)/La(SS-B) positive Sjogren's/lupus overlap patients and mothers of infants with neonatal lupus erythematosus syndrome are immunogenetically homogenous and closely related. We report a strong association with HLA-B8, DR3, DQw2, and DRw52 phenotypes and the HLA-B8, DR3, DQw2, DRw52 extended haplotype in both patient cohorts. Furthermore, we describe disease associations with HLA-DR3/DRw6 heterozygotes in both patient groups. These data demonstrate that anti-Ro(SS-A)/La(SS-B) positive Sjogren's/lupus overlap patients and neonatal lupus syndrome mothers are immunogenetically closely related to each other and appear to be more closely related to both primary Sjogren's syndrome and subacute lupus erythematosus, than to classical systemic lupus erythematosus. | |
| 3500906 | Low-grade lymphoma of immature T-cell phenotype in a case of lymphocytic interstitial pneu | 1987 Nov | A 19-year-old male patient presented with lymphocytic interstitial pneumonia and Sjögren's syndrome, confirmed by histopathology. He was treated with prednisone; 4 months later, cyclophosphamide was added. A lymph node taken at presentation revealed no histological signs of malignancy. Lymph nodes obtained 1 and 2 years later exhibited an effaced structure and a diffuse infiltration of small-sized lymphocytic cells compatible with a low-grade non-Hodgkin's lymphoma. The immunological phenotype of the lymphoma resembled that of immature T-cells present in the normal thymus cortex--positivity for CD1, CD2, CD4, CD7, CD38 and terminal deoxynucleotidyl transferase; faint positivity for CD5 and in the second specimen for CD3; negativity for CD6 and MHC class 1 antigen. The occurrence of such a peculiar lymphoma in Sjögren's syndrome has not been reported thus far. Small numbers of putative malignant cells were found on immunohistochemistry in a lymph node and a lung biopsy obtained at presentation. This is suggestive of one underlying pathogenetic event in the development of lymphocytic interstitial pneumonia, Sjögren's syndrome and non-Hodgkin's lymphoma. | |
| 3113785 | Transport defect of IgM into luminal space in selective IgA deficiency. | 1987 Sep | This study explored the pathogenesis of a transport defect of IgM into the lumen in a patient with selective IgA deficiency. In addition to the absence of IgM in the saliva, no IgM was localized on the luminal surface of colonic mucosa from the patient despite the presence of J chain-positive IgM cells. On tissue sections, IgM cells did not bind secretory component. The serum IgM also showed a negligible capacity to bind secretory component in vitro. Such abnormalities of IgM molecules as stated above seem to be clinicopathologically linked with IgA deficiency or its associated Sjögren's syndrome. | |
| 3106808 | Uniform detection of immunoglobulin-gene rearrangement in benign lymphoepithelial lesions. | 1987 Apr 30 | The term "benign lymphoepithelial lesion" is used to describe the salivary-gland lymphocytic infiltration and epithelial changes typically found in association with Sjögren's syndrome. We used Southern blot hybridization techniques to examine the immunoglobulin genes in salivary-gland tissue derived from eight patients with benign lymphoepithelial lesions. Three of these patients had intrasalivary non-Hodgkin's lymphoma complicating the lesions, whereas the lesions in the remaining five were all histologically benign. Ten samples from the eight patients all revealed rearrangement of both the heavy-chain and light-chain immunoglobulin genes. In one of the patients in whom non-Hodgkin's lymphoma involved both the salivary-gland lesion and an ipsilateral lymph node, the rearrangements of the heavy-chain and light-chain immunoglobulin genes detected at the two sites were identical. One other patient had two distinct benign lymphoepithelial lesions removed two years apart. The rearrangements of the heavy-chain as well as the kappa light-chain genes detected in these two lesions were entirely different. These data suggest that B-cell clonal expansion has an integral role in the pathophysiology of the benign lymphoepithelial lesion and may explain the increased incidence of lymphoma noted in association with this disorder. | |
| 1685512 | Specific HLA-DQA and HLA-DRB1 alleles confer susceptibility to Sjögren's syndrome and aut | 1991 | Primary Sjögren's syndrome (1. SS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the salivary glands and autoantibody production. In order to identify genetic factors that play a role in pathogenesis and predict extent of disease, we used Southern blot and polymerase chain reaction (PCR) methods to detect polymorphisms of the HLA-DRB1 (DR), HLA-DRB3 (DRw52), and HLA-DQA1 genes among 75 Caucasoid 1. SS patients and 150 Caucasoid controls living in the same geographic region of Southern California. We found significantly increased frequency of HLA-DR3 (P less than .001), HLA-DW52a (P less than .001), and HLA-DQA4 (P less than .05), in comparison to normal controls. Also, an increased frequency of heterozygosity for HLA-DQA1/DQA4 (P less than .05) was present among 1. SS patients. Autoantibodies to SS-A and to SS-B were significantly associated with DR3 (P less than .001), HLA-DQA4, (P less than .05), and DQA4/DQA1 heterozygotes (P less than .01). Among the 1. SS patients, clinical and laboratory features such as hypergammaglobulinemia, symmetric peripheral neuropathy, and hypothyroidism were significantly associated with HLA-DR3 (P less than .01) but not with HLA-DR2 (P greater than .10). In comparison, 1. SS patients with leukocytoclastic vasculitis were more frequently HLA-DR2 (P less than .05). These results using PCR methods confirm and extend prior studies that have used serologic methods. | |
| 1703233 | Sjögren's syndrome and primary biliary cirrhosis: presence of autoantibodies to purified | 1990 Nov | Sjögren's syndrome is well known for the presence of antibodies directed at specific nuclear antigens. However, the presence of antibodies reacting with a variety of other self antigens, including antimitochondrial antibodies, has often been reported although their significance is unknown. Moreover, patients with Sjögren's syndrome have been occasionally reported to be concordant with primary biliary cirrhosis. To address this issue we studied in a group of 96 patients with Sjögren's syndrome the presence of autoantibodies to the dihydrolipoamide acetyltransferases of both pyruvate dehydrogenase and branch chain ketoacid dehydrogenase and to alpha-ketoglutarate dehydrogenase; these latter enzymes are the mitochondrial target antigens of primary biliary cirrhosis. We report that 7 of the 96 patients reacted with the mitochondrial antigens that are prominent in primary biliary cirrhosis. Moreover, in those patients showing reactivity with mitochondrial antigens, the autoantibodies were directed at the same immunodominant epitopes that have been previously characterized in primary biliary cirrhosis. One of the 7 positive patients was known to have primary biliary cirrhosis. We hypothesize that the remaining 6 patients are at clinical risk for the development of primary biliary cirrhosis and/or that abnormalities would be found on liver biopsy. | |
| 1667508 | [Renal tubular acidosis in primary Sjogren's syndrome: study on the immunology and ultrast | 1991 Dec | The related antigens of EBV were examined by McAB against Epstein-Barr virus EAp 138. The related antibody of serous EBV VCA and EBNA of Sjogren's syndrome (SS) patients was examined by indirect immunofluorescence and immunoenzyme methods. EBV was found in the tubular epithelial cells by EM and the relationship between EBV and SS was studied. The results showed that (1) Around the nuclei and basement membrane of the proximal tubular epithelial cells there were positively reacting granules but not in the control group. (2) The related antibody of serous EBV VCA and EBNA showed positive reaction, and the highest titre was VCA-IgA 1:80, VCA-IgM 1:40, VCA-IgG 1:320 and EBNA-IgG 1:320 respectively. In addition, mature granules were found in the cytoplasm of the renal tubular epithelial cells. | |
| 2187976 | Quantification of plasma cells in labial salivary glands: increased expression of IgM in S | 1990 Mar | Plasma cells expressing IgG, IgA and IgM were quantified in labial salivary glands from patients with Sjögren's syndrome (SS) and compared with glands showing non-specific inflammatory changes and normal controls. In all glands the predominant isotype was IgA but in SS there was a significant increase in both the number and proportions of IgG and IgM positive cells (P less than 0.002). In particular, all SS cases contained greater than 10% IgM positive cells (mean = 26.8 +/- 15.5). The results suggest that accumulation of IgM positive plasma cells may be a specific finding in SS and support the concept that the glandular lesions may be a site of B-cell clonal expansion. Since most B-cell hyperproliferative states in SS, including lymphoma, are associated with synthesis of IgM simple quantification of plasma cells may have important diagnostic and prognostic significance. | |
| 2159609 | Epstein-Barr virus infection and immunologic dysfunction in patients with aqueous tear def | 1990 Mar | The authors tested their hypothesis that Epstein-Barr virus (EBV) infection is a risk factor for aqueous tear deficiency (ATD) by evaluating 38 ATD patients and 17 controls for serologic evidence of EBV infection. Aqueous tear deficiency was graded clinically as mild or severe. A linear trend toward elevated EBV capsid (P less than 0.05) and early antigen (P less than 0.001) titers was noted from control to severe ATD patients. Rubella and cytomegalovirus antibody titers were poorly correlated with EBV titers, suggesting that the elevated EBV antibodies in ATD patients were not due to nonspecific polyclonal B-cell activation. Epstein-Barr virus antigens were detected in two of six lacrimal gland biopsies from severe ATD patients with Sjögren's syndrome, but in none of the control glands. Aqueous tear deficiency patients were evaluated for immunologic dysfunction associated with EBV infection. Linear trends of elevated serum IgG (P less than 0.05), autoantibody and immune complex positivity (P less than 0.05), and reduced natural killer cell cytotoxicity (P less than 0.05) were found from controls to severe ATD patients. Furthermore, reduced T-helper lymphocyte counts (P less than 0.06) and an increased percentage of HLA-DR+ CD8 lymphocytes (P less than 0.05) were observed in severe ATD patients compared with the mild and control groups. A multivariate analysis of the data showed a significant correlation between severe ATD and elevated EBV early antigen titers, Sjögren's syndrome, and an increased percentage of HLA-DR+ CD8 lymphocytes. The authors' findings suggest that EBV infection may be a risk factor for development of ATD in a subset of ATD patients with greater disease severity, Sjögren's syndrome, and immunologic dysfunction. | |
| 1790636 | Effects of colony-stimulating factors on proliferation and activation of synovial cells. | 1991 Sep | Joint synovium of patients with rheumatoid arthritis plays an important role in initiation and progress of joint diseases. Proliferation and activation of synovial cells, including macrophages, are modulated by various cytokines and arachidoic acid metabolites. Two kinds of cytokines; granulocyte/macrophage colony-stimulating factors (GM-CSF), and monocyte/macrophage colony-stimulating factor (M-CSF) induce the proliferation or activation of monocyte/macrophages, and their progenitor cells or other stromal cells in bone marrow. We investigated the effects of GM-CSF and M-CSF on synovial cells. GM-CSF stimulated the proliferation of synovial cells and its effect was enhanced by the presence of indomethacin, like that of a potent stimulator of synovial cells, interleukin-1 beta (IL-1 beta). But GM-CSF did not induce the production of IL-1 beta. M-CSF neither stimulated the proliferation of synovial cells nor induced production of IL-1 beta by synovial cells. It was suggested that GM-CSF played some role in the proliferation of synovial cells of the joints. | |
| 1714231 | Antineutrophil cytoplasmic autoantibodies antigen specificity. | 1991 Aug | The results presented during the Third International ANCA Workshop, Washington, DC, 1990, allowed a better definition of the antigenic specificity of the antineutrophil cytoplasmic autoantibodies (ANCA). The large predominance of two major antigen specificities for proteinase 3 (PR3) and myeloperoxidase (MPO), in the group of vasculitic patients, was confirmed. PR3 and MPO are colocalized in the azurophilic granules of neutrophils and translocated to the cell surface during activation and thus are able to interact with ANCA after neutrophil preactivation. Furthermore, by comparison of amino acid and DNA sequences, the agreement was reached that PR3 was identical to AGP7, p29, and myeloblastin, described independently and involved in the control of growth and differentiation of leukemic cells. In addition to the two major ANCA antigens, a number of neutrophil cytoplasmic antigens recognized by ANCA have been previously identified (human leukocyte elastase [HLE], lactoferrin). It was established during the Third Workshop that these rare ANCA specificities, occurring in a limited number of patients, include a cationic antimicrobial protein (CAP57) and cathepsin G. However, the variety of ANCA antigen specificities contrasts with the fact that the vast majority of ANCA-positive sera are monospecific for a single ANCA antigen. Finally, the fine specificity of granulocyte-specific antinuclear antibodies (GS-ANA) occurring in rheumatoid arthritis and ulcerative colitis is still unknown, but clearly a substantial proportion of GS-ANA belongs to the ANCA family. | |
| 1882917 | Detection of antibodies against Borrelia burgdorferi in patients with uveitis. | 1991 Jul 15 | We determined the antibody response against Borrelia burgdorferi strains isolated from Japanese Ixodes ovatus and Ixodes persulcatus ticks by enzyme-linked immunosorbent assay and indirect immunofluorescence assay of serum specimens from 127 patients with uveitis. We examined samples of serum from Japanese patients with unclassified uveitis, iridocyclitis caused by herpes zoster virus, Behçet's disease, Vogt-Koyanagi-Harada syndrome, sarcoidosis, or other conditions (sympathetic ophthalmia, Posner-Schlossman syndrome and acute anterior uveitis with ankylosing spondylitis). Serum from healthy individuals and patients with Lyme disease served as negative and positive control samples, respectively. Significantly higher antibody titers were demonstrated in patients with uveitis than in control subjects. Of 29 patients with unclassified uveitis, nine (31) had significantly increased antibody titers against B. burgdorferi strain H014 by ELISA testing. Five patients also showed higher IgG and IgM responses than in three control subjects with Lyme disease. All positive controls showed joint problems characteristic of rheumatoid arthritis. One of three patients had uveitis. The patients were diagnosed as having Lyme disease on the basis of their history and serologic tests. A positive antibody response was recognized in several patients with Behçet's disease, Vogt-Koyanagi-Harada syndrome, sarcoidosis, and other conditions (acute anterior uveitis with ankylosing spondylitis), but not in control subjects. |