Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 6191591 | Basophil histamine release induced by leukocyte nuclei in patients with rheumatoid arthrit | 1983 May | Leukocyte suspensions containing basophils were obtained from 23 patients with rheumatoid arthritis (RA). When these cells were incubated with leukocyte nuclei from normal persons, histamine release was seen in 11 of the 15 patients with active disease, but not in the quiescent group or in normal individuals. The dose-response curve for histamine release was similar to that obtained by specific antigen in type I allergy. By removal from and refixation to the cells of surface Ig, the release of histamine was respectively, abolished and restored, just as in similar experiments in hay fever patients. The dependence of pH for removal was also identical with that found in type I allergy. Antinuclear antibodies of the IgE class (IgE ANA) mainly directed against the granulocyte nuclei were often found in serum and on the cell surface of the RA patients, but not in normal individuals. A correlation was found between these titres in serum and on the cell surface. No correlation was found between ANA in serum and on the cell surface, on the one hand and disease activity and histamine release on the other. In a group of 12 patients with another joint disease, osteoarthrosis, only two patients showed histamine release, and in contrast to the other patients they showed swelling of more than two joints. The present investigation supports our hypothesis of an involvement of an autoimmune type I reaction directed against nuclear components in the RA disease. | |
| 2579703 | A comparison of normal and pathological synovial fluid. | 1985 Feb | Synovial fluid from 16 normal subjects was compared with that from 149 patients with a variety of rheumatic disorders. Normal fluid had fewer cells and a lower content of beta-glucuronidase than osteoarthritic samples. Particles, including occasional birefringent crystals, were seen in normal fluids as well as pathological samples. Alizarin red staining particles (presumed to contain apatite) were seen in all diagnostic groups; their numbers showed some correlation with radiological calcification in and around the joints and with a hypertrophic subchondral bone response. Lactate levels were highest in septic arthritis. No assay showed disease specificity. | |
| 790946 | Acute gastric mucosal injury during continuous or interrupted aspirin ingestion in humans. | 1976 Nov | The effect of continuous versus interrupted high-dose aspirin (ASA) for 14 days was evaluated in a randomized double-blind study in 8 rheumatoid arthritis patients. Acute gastric mucosal injury was measured by serial gastroscopy and gastric biopsy. Significant gross mucosal damage was seen in all patients following 3 days of ASA (P less than 0.01) and persisted without significant change in severity to the end of the study. Histologic gastritis in areas free of hemorrhages and erosions was not increased significantly by ASA. In spite of gross mucosal injury, symptoms occurred infrequently. Serum pepsinogen I, but not serum gastrin, increased significantly following 3 days of ASA, and the elevation persisted to the end of the study. The extent of mucosal injury at 14 days was not significantly different in those receiving ASA continuously from those on an interrupted schedule. Thus, gastric mucosal adaptation to ASA in man was not demonstrated. | |
| 6236544 | Enumeration of T cell subsets with monoclonal antibodies in minor salivary glands of patie | 1984 Aug | Labial salivary glands of 51 patients with rheumatoid arthritis and those of 25 control patients were examined by the ANAE (acid alpha-naphthyl acetate esterase) technique to determine the percentages of B- and T-lymphocytes and mononuclear phagocytes (MPS cells). Using monoclonal antibodies (OKT3 for all T cells, OKT4 for helper/inducer T cells, OKT6 for thymocytes, and OKT8 for suppressor/cytotoxic T cells) T cell subsets were enumerated. B-lymphocytes predominated in both series of salivary glands, and the percentages of B and T cells were equal in both series. The absolute cell counts in the salivary glands of rheumatics were significantly higher (P less than 0.001) than in those of healthy controls. The number of OKT4+ cells was increased in rheumatics, leading to an elevated OKT4+/OKT8+ ratio when compared with that in controls (P less than 0.01). The results suggest that the basic phenomenon behind the B cell hyperactivity noticed in rheumatics might be due to increased activity of T helper cells rather than reduced number of T suppressor cells, which were shown to remain almost unaffected in the salivary glands of patients with rheumatoid arthritis. | |
| 618915 | Humoral and cellular sensitivity to collagen in type II collagen-induced arthritis in rats | 1978 Jan | We have recently described a new animal model of arthritis induced by intradermal injection of a distinct type of collagen found in cartilage (type II collagen). Since immunologic sensitivity to collagen could play a role in the pathogenesis of this type II collagen-induced arthritis in rats, the ability of purified types of native collagens to induce cellular and humoral responses was quantified by antigeninduced tritiated thymidine incorporation into lymphocytes by collagen and passive hemagglutination, respectively. Rats injected intradermally with native heterologous or homologous type II collagens in adjuvant developed type-specific cellular as well as humoral reactivity. Types I and III collagens were less immunogenic than was type II. The latter collagen induced brisk cellular and humoral responses that were equivalent whether complete Freund's adjuvant or incomplete Freund's adjuvant were employed. Both responses could be induced by native type II collagens modified by limited pepsin digestion, indicating that they are not attributable to determinants in the telopeptide regions of the molecule. Thus, these studies demonstrate the unique immunogenic as well as arthritogenic properties of the type II collagen molecule and indicate that both result from a helical conformation of its structurally distinct alpha-chains. Further, they suggest that type II collagen may, by humoral or cellular mechanisms, provoke or perpetuate inflammation in other arthritic diseases. | |
| 6183736 | Circular dichroism of immune complexes, IgG and Fab gamma with unique antigenic determinan | 1982 Sep | IgG-IgG and IgG-IgM complexes were isolated from one rheumatoid arthritis (RA) serum by affinity chromatography to immobilized F(ag')2 gamma of specific antibodies against unique determinants in the complexes. Both IgG nd IgM, when isolated from these complexes, contained the unique determinants. The circular dichroism (CD) spectrum of IgG differed from that of normal IgG at neutral pH. At pH 3 both IgG and IgM displayed normal CD spectra, and only one third of the molecules now had affinity for the immobilized ligand. The molecules with affinity at pH 3 exhibited an abnormal CD spectrum at pH 3, and a normal CD spectrum was obtained only of those components that lacked affinity. One-third of the Fab gamma isolated from the IgG and IgG complexes with the unique determinants contained the unique determinants that were lacking in the rest of the same principal the Fc gamma fragments. The CD of the two Fab gamma preparations showed the same principal differences as the CD of the molecules with and without affinity to the ligand at acidic pH. | |
| 7011611 | Antibody response to streptococcal cell wall antigens associated with experimental arthrit | 1980 Dec | The antibody response to group A streptococcal cell wall components was measured in rats during the development of chronic, remittent experimental arthritis. The arthritis was induced by a single intraperitoneal injection of an aqueous suspension of group A streptococcal cell wall fragments and antibodies were measured by a radioactive antigen-binding assay. Antibodies in serum against both peptidoglycan and A polysaccharide reached maximum levels at 1 or 2 weeks and declined to preimmunization levels by day 63. The kinetics and magnitude of the antibody responses were similar in neonatally thymectomized and non-thymectomized rats. A relationship between chronic joint lesions and anti-peptidoglycan concentration in serum was indicated, since all rats which produced high levels of antibody developed severe chronic arthritis. However, 46% of the rats which produced very low levels of antibody also developed moderate to severe arthritis. There was no correlation between anti-A polysaccharide antibodies and joint disease, although the concentration of this antibody was 10- to 100-fold greater than the anti-peptidoglycan. We conclude that antibody can be a component in the pathogenesis of this experimental model of arthritis, but its role requires further elucidation. | |
| 6355184 | Impaired T cell capping and receptor regeneration in active systemic lupus erythematosus. | 1983 Nov | It is currently unclear whether the T cell dysfunctions observed during active systemic lupus erythematosus (SLE) reflect a disorder intrinsic to the T cell or defects that result from interaction with anti-T cell autoantibody. To determine whether a disorder intrinsic to the T cell exists in SLE, the T cell capping mechanism was selected as a model of cellular function. The normal T cell capping mechanism is a rapid, energy-dependent and coordinated sequence of membrane events that consists of microaggregation, capping, endocytosis, and regeneration of the surface molecule. The monoclonal antibodies OKT3, OKT4, and OKT8, directed against the T cell-specific membrane glycoproteins T-3, T-4, T-8, served as specific probes of the glycoproteins' mobility within the membrane and membrane glycoprotein regeneration. When compared with greater than 91% T cell capping in normal and control subjects with active Sjögren's syndrome, active rheumatoid arthritis and active tuberculosis, only 49-60% of T cells from active SLE patients completed the capping sequence (SLE vs. healthy controls; T-3, P less than 0.002; T-4, P less than 0.004; T-8, P less than 0.002). Colchicine (10(-5) M), which inhibits microtuble polymerization and augments the rate of normal T cell capping, failed to restore the abnormal capping. However, as judged by the elapsed time intervals to half-maximal capping, the capping kinetics of the T cells able to initiate capping were not significantly different from controls. Fluorescence microscopy demonstrated an abnormal staining pattern characterized by microaggregation of ligand-glycoprotein complexes on resting T cells, coarse aggregation of ligand-glycoprotein complexes over the surfaces of cells that failed to cap, and cleaved or disrupted caps. After clearance of determinants by capping, greater than 94% of T cells from healthy controls regenerated T-3, -4, and -8 within 24 h. In contrast, only 20-40% of capped T cells from active SLE patients reexpressed new determinants. With improving disease activity, the proportion of cells capping and regenerating T-3, -4, and -8 increased, but remained significantly below control levels. In conclusion, this study has identified a disorder of T cell surface glycoprotein mobility and regeneration affecting the majority (60-80%) of both the T-3+, T-4+, (inducer/helper), and T-3+, T-8+ (suppressor) subsets during active SLE. Although the impaired capping and reexpression improve with disease remission, a residual defect persists. The data support the concept of a disorder intrinsic to the T cell in SLE. | |
| 378481 | Antibody penetration into living cells. I. Intranuclear immunoglobulin in peripheral blood | 1979 Mar | We have shown recently (Alarcón-Segovia, RuÃz-Argüelles & Fishbein, 1978) that an IgG anti-RNP antibody obtained from a patient with mixed connective tissue disease (MCTD) can penetrate viable mononuclear cells (MNC) from normal donors via their Fc receptors. Live MNC from twelve MCTD patients incubated with goat anti-Ig antibody had intranuclear antibody with a speckled pattern in a mean of 5.5% of all MNC and 57.3% of all Fc receptor-bearing MNC. We found intranuclear immunoglobulins in all twelve patients with MCTD which were present only in cells with Fc receptors. Only three out of twenty-one patients with systemic lupus erythematosus (SLE) were found to have intranuclear antibody in a mean of 17.2% of their Fc receptor-bearing cells. Further experiments with MNC from SLE patients revealed a partial blocking of penetration of antibody via Fc receptors. MNC from ten scleroderma, ten rheumatoid arthritis patients and eleven normal controls did not have intranuclear immunoglobulin. In vivo penetration of autoantibodies into Fc receptor-bearing cells in MCTD, and probably in SLE as well, may represent an important pathogenetic mechanism. | |
| 6334745 | Clinical relevance of PM-1 antibody and physiochemical characterization of PM-1 antigen. | 1984 Oct | Using an improved immunodiffusion test with partially purified antigen, PM-1 antibody was identified in the serum of 18 patients. In 67% this system was associated with a polymyositis-scleroderma overlap, it occurred less frequently in polymyositis, dermatomyositis and scleroderma, and was not detected in other rheumatic diseases. The predominant clinical features of PM-1 positive patients were muscle weakness, sclerodactyly, Raynaud's phenomenon and pulmonary disease; widespread sclerodermatous features with infrequent. Characterization of the PM-1 antigen showed it to be a heat sensitive, trypsin sensitive acidic protein associated with the cell nucleus and possibly with nucleoli. | |
| 1171399 | Progressive multifocal leukoencephalopathy: a complication of immunosuppressive treatment. | 1975 Jul | Progressive multifocal leukoencephalopathy developed in a patient with rheumatoid arthritis after treatment with an immunosuppressive agent (chlorambucil). We fell that this case lends further support to the concept that an altered immunologic state is important in the appearance of this infection, which is probably viral in origin. | |
| 6376799 | A systematic survey of HLA-A,B,C and D antigens and drug toxicity in rheumatoid arthritis. | 1984 Jun | One hundred sixty-two consecutive patients with rheumatoid arthritis (RA) were studied for possible association between HLA antigens, particularly DR antigens, and disease characteristics and adverse reactions to gold or D-penicillamine treatment. The frequency of HLA-DR4 was significantly increased: 62% in RA compared to 23% in controls. An association of HLA-DR4 with a positive family history for RA was also found. HLA-DR4 was not associated with subcutaneous nodules or keratoconjunctivitis, presence of rheumatoid factor, or ANA positivity. No increased prevalence of HLA-DR3 was found in patients who developed drug related toxicity (e.g., proteinuria for gold or D-penicillamine). Of the 27 patients in whom proteinuria developed, only 5 were DR3 positive. A significant association with D-penicillamine induced proteinuria and HLA-B8 gene was found. Our results obtained in a systematic survey do not confirm previous reports of a significant association between HLA-DR3 and drug toxicity, but confirm the association between HLA-DR4 and the development of RA and HLA-B8 and D-penicillamine induced proteinuria. | |
| 125343 | Antibodies to nucleic acids in human and murine lupus. | 1975 Jun | Antibodies to nucleic acid are present in the sera of patients with systemic lupus erythematosus and in the sera of NZB/NZW F1 mice, an animal model for human systemic lupus erythematosus. Sera can be fractionated by sucrose-density gradient ultra-centrifugation and individual fractions assayed for binding of radioactive DNA, RNA or DNA: RNA hydridsive DNA, RNA or DNA: RNA hybrids. Immunoglobulin determinations can also be performed on these fractions. Antinucleic acid antibody activity can be recovered both in the 19S IgM and 7S IgG fractions. Individual variations from patient to patient suggest that more detailed analysis of immunoglobulin classes may provide insights into the pathogenesis of lupus. | |
| 3892636 | Peripheral blood mononuclear cells stimulate prostacyclin levels of human synovial fibrobl | 1985 | Fibroblast-like synovial cells, isolated from intact joints of non-arthritic human donors and from explants of rheumatoid and non-rheumatoid synovial tissue, released prostacyclin (PGI2) when incubated in conditioned medium from human peripheral blood mononuclear cells (MCCM). The effect of MCCM on the rate of PGI2 synthesis (measured by radioimmunoassay as the stable product, 6-keto-PGF1 alpha) was clearly established within 2 h and appeared to require RNA and protein synthesis as judged by inhibition with actinomycin D and cycloheximide, respectively. Low concentrations of dexamethasone suppressed the increase in PGI2 levels. Prostaglandin E2 (PGE2) levels were also raised by the MCCM and reduced by dexamethasone. All-trans retinoic acid did not stimulate the levels of either prostanoid. These findings offer an explanation for some of the inflammatory events occurring in rheumatoid lesions. | |
| 1191354 | Effect of topical administration of antiinflammatory drugs to rats with adjuvant arthritis | 1975 Sep | Oral or intramuscular administration of antiinflammatory agents produces numerous undesirable side effects. This work explores the hypothesis that topical administration of such agents directly to the site of inflammation would have beneficial antiinflammatory effects. Topical administration of steroidal and nonsteroidal antiinflammatory drugs to rats with adjuvant arthritis was as effective as oral or intramuscular administration. Peak blood levels of radioactivity following administration of equal doses of hydrocortisone-3H were considerably lower after topical administration than after oral administration. | |
| 197499 | Bone-to-bone, joint-to-bone and joint-to-joint ratios in normal and diseased skeletal stat | 1977 Jul | Bone-to-bone, iliosacral joint-to-os sacrum and joint-to-joint ratios were computed using the region-of-interest technique 2 to 3 hrs. after injection of 99mTc Sn-methylene-diphosphonate or 99mTc Sn-pyrophosphate in 139 patients with skeletal diseases (bone tumours, degenerative changes of the spine and joints, inflammatory changes of joints) as well as in 123 patients with normal skeletal states. In the latter group, iliosacral joint-to-os sacrum ratios decreased with increasing age of the patients. In patients with osseous metastases of the spine ratios of 0.80 to 4.0 occurred ( reference area second vertebra below or above the affected vertebra). In degenerative changes of the spine values of 0.80 to 1.69 were computed. These results show, that 74% of the spine metastases could not be differentiated from benign changes of the spine by determining their relative amounts of bone uptake. In bone tumours of the extremities and in rheumatoid or gouty arthritis of the small joints (hands and feet) the highest ratios, i.e. contrasts, occurred referring to a contralateral reference area. Osteoarthritic and inflammatory alterations of the big joints could not be differentiated because of percentual distribution of the increased joint-to-joint ratios turned out to be nearly identical. | |
| 266304 | [Compensatory skeletal growth modifications]. | 1977 Jan | Impaired growth at one end of a long bone may be compensated by increased growth at the intact end. In experiments, such a compensatory growth was less frequently observed in the cartilaginous structures of the skull than in the sutures. Achondroplasia is an example of compensatory growth in the neurocranium, the disturbed growth of the base of the skull being compensated by an increase of the calvarium according to the space required by the contents of the cranial cavity. In the face, compensatory changes may be observed in conjunction with increased adenoids, as a result of impaired growth of the mandible in case of juvenile rheumatic arthritis or in conjunction with condylar fractures in young age. The processes of growth during orthodontic treatment constitute the border-area between compensatory and adaptive growth. | |
| 415139 | Reduced Fc-receptor bearing cells in peripheral bloods of patients with systemic lupus ery | 1977 Winter | Previous reports described that human red cells sensitized with one of Rh antisera (Ripley) make rosette formations (Fc-rosette with some lymphocytes. These Fc-rosettes were well inhibited by aggregated human IgG as well as hypocomplementemic systemic lupus erythematosus (SLE) sera and rheumatoid synovial fluids. In the present study, Fc-receptor bearing lymphocytes were considerably reduced in peripheral bloods of SLE (16.0 +/- 7.6%) and rheumatoid synovial fluids (15.6 +/- 5.3%). On the other hand, EAC-rosette formation rates of peripheral bloods of SLE (32.0 +/- 13.2%) and rheumatoid synovial fluids (30.3 +/- 11.2%) did not significantly differ from normal peripheral bloods (28.3 +/- 2.9%). E-rosette forming lymphocytes were reduced in peripheral bloods of SLE (48.7 +/- 15.7%) and in rheumatoid synovial fluids (49.0 +/- 14.6%) whereas 61.7 +/- 8.6% in normal peripheral bloods. Reduced Fc-rosette formation rates correlated well with the Fc-rosette inhibitory rates. In addition, eluates from the lymphocytes in rheumatoid synovial fluids also inhibited Fc-rosette formation. These results suggested that immune complexes present in peripheral bloods of SLE and rheumatoid synovial fluids are bound to the Fc-receptors on the lymphocytes, block the additional binding of the sensitized red cells, and result in the reduction of Fc-rosette formation. | |
| 1059274 | [Immunological study in carcinogenesis. Distribution of tissue incompatibility antigens (s | 1975 | By means of a micromethod of lymphocytotoxic test the content of eleven HL-A antigens (1, 2, 3, 5, 7, 8, 9, 10, 11, 12 and 13) was studied in 200 healthy human subjects, 100 patients with rheumatoid polyarthritis and 82 patients with bone tumors. The latter included 50 patients with benign tumors (osteoblastoclastomas, chondroblastomas, chondromas, non-osteogenic fibromas) and 32 patients with malignant tumors (chondro- and osteosarcomas, Ewing sarcoma, malignant osteoblastoclastomas). It was found that in patients with different bone tumors antigen HL-7 was encountered reliably more frequently than in control groups, in patients with malignant tumor also antigen HL-A10 was more often detected. The most frequently observed haplotyes in oncological patients were HL-A3/7 and HL-A2/7. In patients with rheumatoid polyarthritis antigen HL-A3 was found more rarely and antigen HL-A10 more frequently than in healthy subjects. The most frequent haplotypes in this group were as follows: HL-A2/7, HL-A2/8 and HL-A11/12. The possible mechanisms of the relationship between HL-A antigens and the development of pathology are discussed. Some considerations are offered concerning the possibility to utilize HL-A typing for an accessory differential diagnosis. | |
| 1097258 | A new method for the evaluation of analgesic activity using adjuvant-induced arthritis in | 1975 Apr | A bioassay was developed for the assessment of analgesic activity by using pain resulting from a reproducible pathological condition. The vocalization displayed by rats with adjuvant-induced polyarthritis was defined as an expression of pain, and a decrease of this response was established as specifically demonstrating analgesic activity. This method was capable of detecting the analgesic activity of morphine-like and narcotic antagonist-type analgesics, as well as the activity of the antipyretic analgesics. The relative potencies of known analgesic agents determined with this technique closely approximated the potencies of these analgesics in man. The instrumentation for recording and measuring the vocal response of arthritic rats is described. |