Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3260693 | [Immunopathology of the salivary glands of the lips in Sjögren's syndrome]. | 1988 | The cellular composition of the salivary gland infiltrates in primary Sjogren's syndrome and the presence of lymphokines were evaluated using the Avidin-Biotin-Peroxidase technique in 10 biopsies from Sjogren's syndrome patients. The predominant cell was the T-helper/inducer lymphocyte. T-helper/T-suppressor ratio ranged from 1/1 to 10/1. Only few M were observed while NK cells were rare. More than 50% (50-100%) of the infiltrating cells were HLA-DR positive while epithelial cells were positive from 40-90% in all but 2 cases in which the positivity was 10%. The infiltrating cells were also positive for Leu-10 antigen (40-95%) in contrast to the epithelial cells. Both infiltrating and epithelial cells were reacting with anti IL-2 MoAb in high percentages (50-100%), while none of the infiltrating cells expressed IL-2 receptor. Finally, 40-100% of the infiltrating cells were IFN-gamma positive. The above data indicate that a salivary gland lesion in Sjogren's syndrome is the result of an immune process in which T-lymphocytes predominate producing lymphokines while the epithelial cells by expressing class II MHC molecules, play an important role in the general picture. | |
| 1720280 | Congenital heart block: successful prophylactic treatment with intravenous gamma globulin | 1991 Nov | In mothers with anti-Ro-positive antibodies whose previous pregnancies have ended in deliveries of infants with congenital heart block, prophylactic therapeutic strategies are used to try to diminish the production and passage into fetal circulation of autoantibodies. Intravenous gamma globulin was given at 14 and 18 weeks' gestation and prednisone was given from 14 weeks' gestation to a woman with Sjögren's syndrome. The pregnancy ended with delivery of an infant without congenital heart block. | |
| 3118826 | T lymphocyte activation state in the minor salivary glands of patients with Sjögren's syn | 1987 Sep | Local lymphoplasmacytoid infiltration of the diseased exocrine glands is a cardinal sign of Sjögren's syndrome (SS). The state of T lymphocyte activation present in these local infiltrations was studied by three different techniques: determination of interleukin 2 (IL2) receptor (Tac) on cell surface membrane; autoradiography combined with immunoperoxidase staining of T cell epitopes; and electron microscopic analysis of the lymphoblast subclasses. Although 64 (SEM 4)% of the local inflammatory cells expressed Ia antigen, only 4 (SEM 1)% of them displayed the T cell activation antigen Tac. Autoradiography-immunoperoxidase double labelling showed that less than 1% of all T cells in situ were [3H]thymidine incorporating blasts. This finding suggests that although T lymphocyte is the dominant cell in situ, only a few of these cells have passed the G0/G1 interphase, and even fewer have been pushed to the S phase of the cell cycle by IL2. Transmission electron microscopy showed that few T blasts were present, even though there were many plasma cells. This result further confirms the impression that only a minor T cell subpopulation in situ is blast transformed despite the fact that many of the local T lymphocytes in the diseased salivary glands in SS are Ia positive. | |
| 2551310 | Autostimulatory factor produced by B-cell lines from patients with Sjögren's syndrome. | 1989 Aug | Sjögren's syndrome (SS) is an autoimmune disease with a predisposition to transform into a B-cell lymphoma. Stable B-cell lines were established (without exogenous stimulation other than fetal bovine serum) from the peripheral blood of three SS patients. These cell lines secreted immunoglobulin (either IgG, IgM or both) and expressed cytoplasmic immunoglobulin. They were positive for the B-cell markers Leu 12 and Leu 16, and also for HLA-DR and the transferrin receptor. The cells lacked CD3 and the IL-2 receptor. Supernatants from these cell lines had autostimulatory activity. When 24-h culture supernatants were added to freshly cultured peripheral blood mononuclear cells, the proliferation index was 2-3 times higher as compared to cells cultured with HB101 medium alone. This autostimulatory activity can be attributed to a B-cell growth factor since these supernatants were also able (1) to support the growth of BD9 cells and (2) to augment the proliferation of PB B cells preactivated with S. aureus Cowan strain I. Furthermore, the supernatants did not contain IL-1, IL-2, or gamma-interferon. Thus, B cells that grow spontaneously from the peripheral blood of SS patients spontaneously produce a B-cell growth factor. This factor could contribute importantly to the autoantibody production, tissue lymphoid infiltration and B-cell lymphoma seen in this disease. | |
| 3494556 | Analysis of serum and synovial fluid IgA in Reiter's syndrome and reactive arthritis. | 1987 May | The presumed antecedent infection which precedes Reiter's syndrome and reactive arthritis is frequently across a mucosal surface, and IgA immune responses may play a role in this process. Twelve of 29 patients with these conditions demonstrated elevation in serum IgA levels, and serum IgA levels in the postdysentery group (mean 3.21 g/liter +/- 1.27) were higher (P less than 0.01) than those in the posturethritis group (mean 2.40 g/liter +/- 0.80). In 10 of the 12 patients, IgA was the only immunoglobulin increased. There was no evidence of activation of complement in serum or synovial fluid. Using a complement-dependent assay, we were unable to demonstrate circulating IgA immune complexes. Sucrose density gradient ultracentrifugation analysis was used to assess IgA immune complexes in a non-complement-dependent manner. IgA of 11s was in fact demonstrated by this technique but appeared to be polymeric IgA on the basis of specific binding of secretory component and resistance to acid dissociation. IgA rheumatoid factor was not present. Synovial fluid revealed levels of polymeric IgA higher (mean 56.7% +/- 12.9) than did serum (23.7% +/- 13.9, P less than 0.001) despite higher levels of total IgA in serum than in synovial fluid (synovial fluid:serum ratio of IgA, mean 0.53 +/- 0.11). Although elevation in serum IgA in postdysenteric arthropathies suggests mucosal acquisition of antigen, the study does not implicate IgA circulating immune complexes in the pathogenesis of these diseases. | |
| 2533935 | Age related alteration in levels of keratan sulfate in sera of orthopaedic patients. | 1989 Dec | Using the monoclonal antibody to the keratan sulfate(KS), we modified the assay system for detecting of serum KS levels (Thonar, et al. Arthritis Rheum. 28:1367-1376, 1985). This method is based on the enzyme-linked immunosorbent assay (ELISA). The dogfish KS was most effective and sensitive, in this system. KS levels were measured in 45 patients with no complaints of arthralgia, no history of arthritis and no remarkable change in the laboratory data, including erythrocyte sedimentation rates, rheumatoid factor, uric acid and C-reactive protein. Age related changes were apparent in serum levels of KS. Age related catabolism in normal articular cartilage and serum KS levels will aid to estimate the turnover of articular proteoglycan. | |
| 2949358 | Isolated lesions of the manubriosternal joint in patients with inflammatory back pain and | 1986 | The prevalence of radiological lesions of the manubriosternal joint was assessed in 151 patients with chronic inflammatory back pain and in 31 controls with non-inflammatory back pain. Nineteen out of these 151 patients and none of the controls showed unequivocal lesions of the manubriosternal joint without accompanying radiological lesions of the sacroiliac joints or the lumbar spine. Thoracic pain and stiffness were present in 7 out of the 19 patients and in 3 out of the 31 controls (P less than 0.05); peripheral enthesopathy was present in 10 out of the 19 patients and in 4 out of the 31 controls (P less than 0.01); none of the patients or controls had rheumatoid factor, subcutaneous nodules, or peripheral arthritis. The suggestion of a "manubriosternal joint syndrome" is warranted by these findings. | |
| 2178224 | Interleukin-1 stimulates and all-trans-retinoic acid inhibits collagenase gene expression | 1990 Jul | Collagenase production by synovial fibroblast-like cells (synoviocytes) plays a major role in cartilage and bone destruction in rheumatoid arthritis. Interleukin-1 (IL-1) increases collagenase secretion by elevating the steady state levels of collagenase mRNA in cultured rheumatoid synoviocytes, while all-trans-retinoic acid (RA) has the opposite effect. We have studied the regulation of collagenase gene transcription by IL-1 and RA in synoviocytes by transient transfection of plasmid constructs containing deletion mutants of the 5'-flanking region of the collagenase gene or the isolated phorbol ester-responsive element ligated to a chloramphenicol acetyltransferase reporter gene. We show that the phorbol ester-responsive element of the collagenase gene mediates both positive and negative regulatory effects, respectively, of IL-1 and RA on transcription. In addition, we show that IL-1 and 12-O-tetradecanoyl-phorbol-13-acetate transiently induce c-jun and c-fos expression and that retinoic acid inhibits IL-1 and 12-O-tetradecanoyl-phorbol-13-acetate induction of c-fos, but not c-jun. These results suggest that RA inhibits collagenase transcription at least in part through inhibition of c-fos. | |
| 3317807 | Criteria for the classification of osteoarthritis of the knee and hip. | 1987 | The Osteoarthritis (OA) Criteria Subcommittee of the American Rheumatism Association set out to develop (a) a classification of OA that includes recognised subsets; and (b) subsets of OA identified by a combination of clinical and laboratory features. For the purposes of classification, OA should be specified if of unknown origin (idiopathic, primary) or if related to a known medical condition or event (secondary). Clinical criteria for classification of idiopathic OA of the knee were developed through a multicentre study group involving 130 patients with OA and 107 comparison patients. Comparison diagnoses included rheumatoid arthritis (RA) and other painful conditions of the knee exclusive of referred or para-articular pain. Variables from the history, physical examination, laboratory test results and radiographs were used to develop sets of criteria that serve different investigative purposes: clinical examination (sensitivity 89%; specificity 88%); clinical examination and laboratory tests (sensitivity 88%; specificity 93%); clinical examination, laboratory tests and radiographs (sensitivity 94%; specificity 88%). In contrast to prior classification criteria, the proposed criteria utilise decision trees or algorithms. Clinical criteria for classification of idiopathic OA of the hip are under development. Comparison groups are comprised of patients with other rheumatic diseases (e.g. RA), periarticular pain (e.g. trochanteric bursitis) and referred pain (e.g low back pain). From a method of opinion sampling, OA of the hip may be suggested by a combination of clinical criteria including the following: age greater than 40 years, weight-bearing pain, pain relieved by sitting, antalgic gait, decreased painful range of motion, a normal erythrocyte sedimentation rate (ESR) and a negative rheumatoid factor test. | |
| 2962745 | Characterization of a T-cell subset prevalent in immunoregulatory disorders in humans. | 1988 Feb | T cells from individuals with certain autoimmune diseases (rheumatoid arthritis, graft-versus-host disease, acquired immunodeficiency syndrome) express high levels of a cell surface sialoglycoprotein with a molecular weight of 140 kDa (gp140). Although a low frequency of gp 140+ T cells was detected in the blood of normal individuals, upon stimulation with autologous EBV-transformed B cells (AMLR), the frequency of expression of gp140 was increased threefold. To further characterize gp 140+ T cells, rosetting techniques with ox erythrocytes coated with monoclonal anti-gp 140 antibody were used to isolate T-cell subsets for phenotypic, cell cycle, and functional analysis. The majority of gp140+ T cells expressed cytotoxic/suppressor (CD8+) phenotype in both normal and AMLR-activated states. Unstimulated gp140+ T cells had significantly greater nucleic acid content, as measured by acridine orange and flow cytometry, than gp140- T cells. Surprisingly, the gp140+ T-cell subset had a less proliferative response in vitro to pokeweed or phytohemaglutinin mitogens. These results suggest that gp140+ T cells in normal individuals and in patients with autoimmune diseases may have been activated previously in vivo and that they are relatively resistant to reactivation in vitro. | |
| 2403399 | Structural characterization of the second major cross-reactive idiotype group of human rhe | 1990 Sep | Rheumatoid factors (RF) are the most common type of functional antibodies among naturally occurring human monoclonal IgM proteins. A large subset of these autoantibodies use structurally homologous light chains of the kappa III subgroup, which bear the 6B6.6 cross-reactive idiotype (CRI). Although antibody binding activity requires both heavy and light chains, information about the heavy chains used by these autoantibodies is limited. To investigate these proteins, the murine monoclonal antibodies, 5-14 and 6-10, were generated by immunization with the heavy chains of the 6B6.6 CRI-positive RF, COR and LEW. These antiidiotypic antibodies reacted with 8 of 11 autoantibodies that coexpressed the 6B6.6 CRI. All 8 RF had heavy chains from the VH4 gene family, as assessed by reactivity with a VH4-specific primary sequence-dependent antibody. The same RF were also identified by the previously described murine monoclonal antiidiotype, LC1. Further experiments revealed that the LC1 antibody delineates a subfamily of VH4 heavy chains that is preferentially used in kappa III-6B6.6 CRI-positive IgM-RF. The cumulative data suggest that 13-22% of RF express both the kappa III-6B6.6 and VH4-LC1 CRI. These findings document that RF autoantibody activity requires specific VL-VH pairing, and that a subset of idiotypically related VH4 heavy chains is commonly expressed in disease-associated monoclonal IgM-RF. | |
| 1918992 | The rheumatoid factor reactivity of a human IgG monoclonal autoantibody is encoded by a va | 1991 Oct 15 | To determine the genetic and molecular basis for rheumatoid factor (RF) autoantibody reactivity in patients with destructive, erosive arthritis, we established a human lymphoblastoid cell line (hRF-1) from a patient with polyarthritis that produced an IgG RF mAb, mAb hRF-1. Studies of isolated H and L chains showed that the specificity of RF reactivity is conferred by mAb hRF-1 L chains. The L chain gene was cloned from a cDNA library prepared from hRF-1 cells. The nucleotide sequence was similar to known V kappa II L chains except for a two nucleotide change corresponding to a change of two amino acids in an invariable region of FR3. A germ-line gene with one of the nucleotide changes was identified by polymerase chain reaction in multiple cell lines, including K562 that does not rearrange Ig genes, but the other nucleotide change appeared to be due to mutation. Either or both of these amino acid changes may contribute to the RF reactivity, because an antibody with the same V kappa II L chain except for these two amino acid changes in FR3 did not have RF reactivity. The RF reactivity of isolated L chains from mAb hRF-1 was confirmed by transfecting COS cells with an expression vector encoding the hRF-1 kappa-chain and showing that the secreted k-chains had RF reactivity. Expression of this variant V kappa II L chain gene may form the basis for RF autoantibody reactivity in some patients. | |
| 2970668 | Abnormal helper-inducer/suppressor-inducer T-cell subset distribution and T-cell activatio | 1988 Aug | We have previously shown that rheumatoid synovial T cells are virtually all helper-inducer (CD4+4B4+UCHL1+) rather than suppressor-inducer (CD4+2H4+) cells. CD8 cells were also largely 4B4+. In addition, the majority of T cells were HLA-DR+. To investigate whether these findings were specific for rheumatoid disease, we studied the prevalence of these markers in a variety of chronic inflammatory arthropathies such as ankylosing spondylitis, Reiter's syndrome, and psoriatic arthritis. Again, almost 90% of the T cells were 4B4+UCHL1+ and only 11% were 2H4+; 50% expressed the HLA DR antigen. Thus this phenotypic distribution represents a final common pathway of chronic synovitis and may help to explain the immunopathology of the lesion. | |
| 2954204 | [Acne-pustulosis-hyperostosis-osteitis syndrome. Results of a national survey. 85 cases]. | 1987 Mar | The authors report the data collected by a national investigation organized by the French Society of Rheumatology, concerning the osteo-articular manifestations of severe acne, palmo-plantar pustulosis and primary thoracic and peripheral hyperostosis. This investigation collected 85 case-reports including 13 severe acne, 44 PPP and 28 hyperostosis without the dermatitis mentioned above. From this investigation, it appears that dermatological and osseous pictures described under various denominations, present common characteristics and transition forms justifying their common study under the acronym SAPHO (Syndrome Acne-Pustulosis-Hyperostosis-Osteitis). The bony involvement, especially anterior thoracic, but also vertebral and even peripheral seems to be the common denominator between these diseases. It realizes a true rheumatoid inflammatory osteitis, osseous counterpart of synovial and cartilagenous affections in inflammatory rheumatoid diseases. This group has rather loose connections with common psoriasis and slightly more definite relationships with primary ankylosing spondylarthritis. These clinical and immunogenetic connections occur also through bony involvement. | |
| 3689461 | Quantitation of retroviral gp70 antigen, autoantibodies, and immune complexes in extravasc | 1987 Nov | MRL-lpr/lpr (MRL/l) mice spontaneously develop a disease that is characterized by glomerulonephritis, diffuse vasculitis, and arthritis associated with high levels of autoantibodies that include IgG rheumatoid factor (RF). To define the immunopathogenic mechanisms that lead to the development of extravascular lesions such as arthritis, we implanted a tissue cage subcutaneously in arthritic MRL/l mice and compared components of the tissue cage fluid, which resembles the extravascular fluid, with those of sera. When compared with those of sera, tissue cage fluids from arthritic MRL/l mice had similar levels of RF and one-third the amount of C1q immune complexes. In contrast, anti-DNA activities in tissue cage fluids corresponded to only 10% of the serum activities and, most strikingly, nephritogenic retroviral gp70-anti-gp70 immune complexes were almost undetectable in tissue cage fluids. This was also the case for another strain of autoimmune mice, (New Zealand black X New Zealand white)F1 mice, although they did not produce RF. The absence of gp70 immune complexes in tissue cage fluids could be due to markedly limited diffusion of gp70 antigen in these fluids. These results strongly suggest that serum proteins, including autoantigen and autoantibodies, appear in extravascular fluid in a selective manner, depending on their size and charge. Their specific properties in sera or extravascular fluid could partly account for the different manifestations of vascular and extravascular lesions observed in autoimmune mice. | |
| 2332849 | Food induced ("allergic") arthritis: clinical and serologic studies. | 1990 Mar | These studies sought to confirm our recent report of a patient with rheumatoid-like arthritis (RA) with clinical and immunologic milk sensitivity, to assess the prevalence of food related rheumatic symptoms, and to identify clinical and serological features of these patients. Thirty percent of our patients with RA alleged food related ("allergic") arthritis. Sixteen patients have now completed 19 double blind, controlled food challenge studies: 3 demonstrated subjective and objective rheumatic symptoms after double blind, encapsulated food challenges. The 3 were virtually asymptomatic when receiving elemental nutrition or not taking the offending foods. One was our milk sensitive patient who had increased IgG4 anti-alpha-lactalbumin, IgG-milk complexes, and delayed skin and cellular reactivity to milk; one developed inflammatory synovitis after shrimp ingestion and had increased IgG antishrimp; and another was a cardiac care unit (CCU) nurse who experienced rheumatic symptoms after exposure to nitrates. All were seronegative with palindromic symptoms and nonerosive disease. IgG, G4, A, M, and E antifood, Ig-food immune complexes, and in vitro cellular reactivity to foods were not otherwise distinctively abnormal in these or other patients with rheumatic diseases. Thus most patients alleging food induced rheumatic symptoms did not show these on blinded challenge, but some did. Probably not more than 5% of rheumatic disease patients have immunologic sensitivity to food(s). Such patients have been identified only by controlled challenge studies. These observations suggest a role for food allergy in at least some patients with rheumatic disease. | |
| 2222539 | Intravenous pulse cyclophosphamide therapy in myositis and Sjögren's syndrome. | 1990 Oct | We describe a patient with primary Sjögren's syndrome who developed myositis. The results of muscle pathologic analysis before and after treatment with monthly pulses of cyclophosphamide (intravenously), are presented. | |
| 2491051 | [The CREST syndrome associated with the sicca syndrome]. | 1989 Oct | A case of CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal hypomotility, sclerodactyly, and telangiectasia) that initially showed Raynaud's phenomenon, sclerodactyly and polyarthralgias, 3 years later completing the process, associated to sicca syndrome, is presented. The esophageal affectation showed a loss of peristalsis of the inferior 2/3, as well as hypotonia of the gastroesophageal sphincter. We comment the prognostic relationship between CREST syndrome and the centromeric region antibodies. | |
| 2802799 | Effect of low dietary lipid on the development of Sjögren's syndrome and haematological a | 1989 Sep | A diet low in fat was found to retard the development of autoimmune disease in (NZB x NZW)F1 mice, whereas diets high in fat content were associated with more severe disease. The ability of a reduced lipid intake to ameliorate the progression of autoimmune disease was indicated by preserved lacrimal gland secretion (measured by a modified Schirmer test), decreased infiltration of inflammatory cells into the exocrine tissue, and decreased severity of immunohaemolytic anaemia as indicated by near-normal packed cell volume and reticulocyte values. These results suggest that nutritional intervention may be of some help in reducing the severity of pathological abnormalities associated with human systemic lupus erythematosus and Sjögren's syndrome. | |
| 1722441 | T cells bearing gamma/delta T cell receptor and their expression of activation antigen in | 1991 Nov | T cells bearing gamma/delta T cell receptor (gamma/delta + T cells) and their expression of activation antigen (HLA-DR) or the marker of natural killer (NK) cells (CD56), were examined in the peripheral blood lymphocytes (PBL) from twenty-two patients with Sjögren's syndrome (SS) by three-color flowcytometry to elucidate possible pathological roles of the T cell subset in SS. The frequency of gamma/delta + T cells in PBL was not elevated in SS patients, while that of gamma/delta - T cells, which are T cells bearing the alpha/beta T cell receptor (alpha/beta + T cells), was significantly low in the patients, as compared with 22 healthy controls. We found that the proportions of activated cells (HLA-DR+) in both the gamma/delta + and alpha/beta+T cell subsets were significantly higher in the patients than in the controls. The proportions of HLA-DR+ cells in cells in both patients and controls. Furthermore, the frequency of activated cells in both T cell subsets correlated with the duration of disease in SS patients. However, no difference was found in the percentages of total CD56+ cells, CD56+CD3- cells (true NK cells), CD56+CD3+T cells, CD56+gamma/delta+T cells, or CD56-gamma/delta+T cells between the patients and controls. The above results indicate that immunologic activation in SS patients is progressive and involves both alpha/beta+ and gamma/delta+ T cell subsets. |