Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3487760 | The salivary gland component of Sjögren's syndrome: an evaluation of diagnostic methods. | 1986 Jul | The diagnostic value of sialography, scintigraphy, sialometry, and labial salivary gland biopsy--as indicators of salivary gland dysfunction in Sjögren's syndrome (SS)--was evaluated in 41 patients suspected of having SS. In about 70% of the cases, each of the four examinations showed changes that could indicate a salivary gland component of SS. However, the disease specificity of sialographic and scintigraphic examinations was low. Although the specificity of the labial salivary gland biopsy examination is considered high, our study revealed some cases in which a focus score of 1 to 3 was not accompanied by abnormal changes in either sialometry, sialography, or scintigraphy. At a focus score of more than 3, a fair amount of agreement on the results of the various diagnostic procedures was found. Because labial salivary gland examination shows only minor salivary glands and sialography and scintigraphy include only major salivary glands, variance between different diagnostic procedures is expected. This indicates a potential diagnostic role for sialographic and scintigraphic examination when the labial salivary gland biopsy is insufficient. | |
| 2036821 | Alveolitis correlates with clinical pulmonary involvement in primary Sjögren's syndrome. | 1991 Jun | Bronchoalveolar lavage (BAL) was performed in 23 patients with primary Sjögren's syndrome (1Ss) and ten healthy controls to evaluate alveolitis and correlate it with pulmonary and systemic manifestations. Patients with 1Ss had higher BAL total cell count (9.2 +/- 6.7 millions/ml vs 6.1 +/- 2.9 millions/ml) and higher percentage of lymphocytes 23.3 +/- 15.6 percent vs 6.5 +/- 2.9 percent, p less than 0.001) than controls. Twelve patients (group A) constituted the "high alveolitis" group (lymphocytes greater than 15.2 percent) and ten (group B) constituted the "low alveolitis" group (lymphocytes less than 15.2 percent). Group A had more frequent cough (6/12 vs 2/10, p = 0.07), dyspnea (4/12 vs 1/10), and roentgenologic evidence of interstitial lung disease (5/12 vs 0/10, p less than 0.05). They also had lower total lung capacity (85.6 +/- 14.2 percent pred vs 105.8 +/- 23.3 percent pred, p less than 0.05) and Dco (87.7 +/- 20.6 percent pred vs 103.6 +/- 21.0 percent pred). All patients with +3 or +4 grading or lymphocytic infiltrates in lip biopsy specimen belonged in group A (5/12). Finally, T-helper/T-suppressor ratio was lower in group A than in group B. The intensity of alveolitis was not correlated with clinical or serologic manifestations of systemic disease. | |
| 1982291 | ICAM-1 and LFA-1 expressions in the lesional skin of annular erythema associated with Sjö | 1990 Dec | ICAM-1 and LFA-1 expression was studied in the lesional skin of ten cases of annular erythema associated with Sjögren syndrome. Most of the infiltrating mononuclear cells around blood vessels expressed LFA-1 in addition to its strong expression on vascular endothelial cells and focal expression on the epidermal basal cell layer in 3 cases. ICAM-1 expression on vascular endothelial cells was similar to LFA-1, although relatively focal and weak expression was observed on mononuclear cells. ICAM-1 expression on keratinocytes was focal and limited to the basal cell layer in annular erythema. These findings suggest that strong expression of ICAM-1 on endothelial cells but not keratinocytes and LFA-1 on mononuclear cells might play some role in the induction of skin lesions in annular erythema associated with Sjögren syndrome. | |
| 1700940 | Immunologic and viral factors in Sjögren's syndrome. | 1990 Jul | Sjögren's syndrome is a multifactorial disease in which genetic and possibly viral factors play major roles. The recent development of an SS-like disease in patients infected with HIV-1 suggests a possible retrovirus. | |
| 2805454 | Androgen control of autoimmune expression in lacrimal glands of MRL/Mp-lpr/lpr mice. | 1989 Dec | The purpose of the present study was to determine, by utilizing an animal model of Sjögren's syndrome, whether androgen therapy might ameliorate autoimmune sequelae in the lacrimal gland. Age-matched female MRL/Mp-lpr/lpr mice were administered subcutaneous implants of placebo- or testosterone-containing pellets after the onset of disease. Lacrimal glands and, for comparison, submandibular glands were collected from sacrificed mice immediately prior to androgen administration and following 17 and 34 days of maintained hormone exposure. Tissues were processed for light microscopy and examined with a computer-assisted image analysis system. Results demonstrated that testosterone exposure dramatically reduced lymphocyte infiltration in lacrimal tissue: following 34 days of treatment, the percentage infiltrate had undergone a 12-fold decrease. This hormone action, which was time dependent, involved significant abrogations in both infiltrate size and number. Testosterone administration also induced a significant 2- to 3-fold rise in lacrimal gland weight and acinar area and a 2-fold reduction in acinar density/field, compared to values in placebo-treated controls. In addition, androgen administration significantly decreased the magnitude of lymphocyte infiltration in submandibular glands. Overall, our findings demonstrate that androgen therapy may reverse autoimmune sequelae in lacrimal, as well as submandibular, glands in a mouse model of Sjögren's syndrome. | |
| 2788854 | Oral candidiasis in Sjögren's syndrome: prevalence, clinical correlations, and treatment. | 1989 Sep | Red, nonulcerated, uncomfortable oral mucosal lesions that are often thought to be caused by chronic xerostomia develop in some patients with Sjögren's syndrome (SS). However, we find that these lesions (1) clinically resemble chronic atrophic candidiasis (CAC), (2) usually yield Candida species from their surface, and (3) can be eliminated by topical antifungal drugs in spite of continuing xerostomia. In 246 patients who had primary or secondary SS, we correlated the presence or absence of atrophic oral mucosal lesions with the patient's salivary function and other clinical features. The 91 patients (37%) who had these lesions were older, had a greater frequency of primary SS and of oral symptoms, had had oral symptoms for a longer period, had more salivary gland inflammation, and had lower stimulated parotid flow rates than the 155 patients without CAC (p less than 0.05). However, unstimulated whole salivary flow rates and denture status were not significantly different. Topical antifungal treatment, begun on 47 patients, eliminated lesions in some. The methods of treating CAC are discussed. Candida-associated oral mucosal lesions do not develop in all patients with SS, but in susceptible patients, SS leads to a reversible form of CAC that is not associated with dentures. | |
| 3246135 | Effect of vitamin A treatment on immune reactivity and lipid peroxidation in patients with | 1988 Dec | Patients with Sjögren's syndrome were treated with vitamin A (100,000 U) daily during a two-week period. The vitamin treatment significantly elevated their ADCC and NK activity. The lymphocyte blast transformation, however was not noticeably changed. After the treatment, the retinyl-ester and retinol level of the plasma significantly increased as did the plasma level of vitamin E. The level of TBA reactive substances (malondialdehyde) in the plasma increased, whilst the glutathione peroxidase and catalase activity of erythrocytes decreased. The activity of the plasma glutathione peroxidase increased, but not significantly. | |
| 3689002 | Clinical studies of renal disease in Sjögren's syndrome. | 1987 Oct | When 17 patients with Sjögren's syndrome, without apparent clinical manifestations of renal disease, were examined renal function studies frequently indicated abnormalities in their renal phosphate handling. The percentage tubular reabsorption of phosphate (%TRP) was decreased in six (35.3%), and maximal tubular reabsorption rate for phosphate (TmPO4/GFR) was low in eight (47.1%). In contrast, indices of renal calcium handling and serum parathyroid hormone levels were normal, suggesting that the abnormalities of phosphate metabolism were due not to extrinsic, but rather to intrinsic disease processes occurring in the kidney in Sjögren's syndrome. When the patients were divided into two groups according to the presence or absence of a renal tubular acidification defect (RTAD), patients with RTAD were younger (p less than 0.005), had longer disease duration (p less than 0.01), lower creatinine clearance (p less than 0.05), and higher incidence of low %TRP (p less than 0.05). Thus the patients with lower creatinine clearance generally had disease of longer duration at diagnosis and tended also to have defects in concentrating and acidifying the urine. | |
| 3365028 | Evidence that Chlamydia trachomatis causes seronegative arthritis in women. | 1988 Apr | Chlamydia trachomatis elementary bodies (EBs) were found in synovial membranes or synovial fluid cell deposits from five of 15 women with seronegative mono- or oligoarthritis by means of a fluorescein conjugated anti-chlamydial monoclonal antibody (Micro Trak; Syva). Genital tract specimens were taken from only five of the patients, one of whom had intra-articular EBs, but none was chlamydia positive. Six of 10 patients tested were HLA-B27 positive, and chlamydial IgG antibody, measured by microimmunofluorescence, was present at a titre of 1/greater than or equal to 64 in the sera of five of the 15 patients, three of the five having EBs in their joints. In contrast, chlamydial EBs were not detected in the joints of a control group of 10 other women, most of whom had rheumatoid arthritis. None of them was HLA-B27 positive, and only one had a chlamydial antibody titre of 1/greater than or equal to 64. Neither Mycoplasma hominis nor ureaplasmas were isolated from the synovial fluids of seven patients and five controls who were tested. Antibody to M genitalium, however, was detected in five of the 10 patients but in none of the controls. This evidence apart, there was no other suggest that mycoplasmas or ureaplasmas might be responsible for arthritis which could not be attributed to chlamydiae. | |
| 3102726 | Rioprostil prevents gastric bleeding induced by nonsteroidal antiinflammatory drugs in dog | 1986 Oct | Gastrointestinal irritation is the most significant side effect in patients chronically taking nonsteroidal antiinflammatory drugs (NSAID) for treatment of arthritic conditions. Rioprostil, a primary alcohol prostaglandin E1 analog, prevents gastric bleeding induced by several NSAID in a rat model of arthritis that is similar in many aspects to human rheumatoid arthritis. Daily oral dosing of rioprostil (50 micrograms/kg BID for 15 days) did not influence the course of the adjuvant disease in rats or alter the antiinflammatory or analgesic effect of the NSAID. In a 13 week efficacy study in dogs, rioprostil (40-60 micrograms/kg, PO) completely prevented gastric hemorrhagic lesions induced by daily administration of aspirin. | |
| 2747074 | [Clinical aspects of sarcoidosis with autoantibodies]. | 1989 Feb | Among 64 sarcoidosis cases, 6 cases with autoantibodies or autoimmune disorders are described. All 6 cases were females over 40 years old, and made up 24% of the original 25 patients over 40 years old. Rheumatoid factor was observed in 2 cases, anti-DNA antibody in 4 cases and anti-microsomal antibody in 2 cases. Four cases of sarcoidosis were associated with ITP or Hashimoto's disease or rheumatoid arthritis. The presence of these autoantibodies or autoimmune diseases seemed to correlate with continued disease activity of sarcoidosis. The analysis of the clinical features of sarcoidosis with coexistent autoimmune diseases may clarify immunologic processes involved in the pathogenesis of both disorders and also provide clues to understanding the relatively poor clinical outcome of longstanding sarcoidosis. | |
| 2449699 | [The testing of long-term antirheumatics in animals]. | 1987 Oct | There is no group proof of long acting antirheumatics (LAA) in laboratory animal models, and it is not to be expected without an identical rheumatoid arthritis model in animals and with regard to the heterogeneity of LAA. However, LAA are to be detected according to D-penicillamine-like, levamisol-like etc. actions, which can be disclosed in the adjuvant arthritis as well as in the B. pertussis-vaccine pleuritis in rats the latter model best by including parameters of inflammatory exudate cells. Modification of the models or of model parameters (BCG-sensibilization, PPD reaction, vasoreactivity, RNA content of exudate cells, SH groups, copper zinc) are hardly advantageous, contrarily to dosage. Other models, among them paw edemas, do not permit sufficient testing of LAA, even not the methyl-albumin mice paw edema. There is no problem of pharmacologically separating LAA actions from nonsteroidal or steroidal antiphlogistics actions. | |
| 3566822 | Immunity to cartilage proteoglycans in BALB/c mice with progressive polyarthritis and anky | 1987 Mar | Intraperitoneal injection of human fetal cartilage proteoglycan (depleted of chondroitin sulfate) in Freund's complete or incomplete adjuvant induces a chronic erosive polyarthritis and spondylitis in all female BALB/c mice. This occurrence is strain-specific but not haplotype-specific, and it is sex-related. The development of the arthritis is associated with the natural presence of cellular immunity to the immunizing antigen and to chondroitinase ABC-treated mouse cartilage proteoglycan. In addition, relatively more antibody to the immunizing proteoglycan is elicited in arthritic mice, and antibodies are produced that cross-react with native mouse proteoglycan. This combination of immune responses is not observed in mice that do not develop arthritis. Associated with the arthritis is the development of cytotoxicity to mouse chondrocytes and, in some animals, of rheumatoid factor, immune deposits in joint tissues and kidneys, and the production of autoantibodies to mouse type II collagen. These observations might be related to our earlier demonstration that immunity to human cartilage proteoglycan is observed in some patients with ankylosing spondylitis. | |
| 2457937 | Immunogenic and antigenic epitopes of immunoglobulins. XXIII. Idiotypy and molecular speci | 1988 Aug | The expression of idiotypic and variable region-associated isotypic determinants on a panel of human monoclonal rheumatoid factors (RF) was studied by means of murine hybridoma antibodies produced to two IgM-RF paraproteins. Fourteen RF paraproteins from patients with cryoglobulinaemia and one (RF-AN) from an Epstein-Barr virus (EBV)-established B-cell line from a patient with rheumatoid arthritis (RA) were studied. Nine RF paraproteins expressed a VkIIIb light chain sub-subgroup-associated cross-reactive idiotype and seven of these nine also expressed a heavy chain-associated cross-reactive idiotype. The reactivity of the monoclonal RF with human IgG subclass paraproteins revealed four patterns of molecular specificities: (1) RF reactive with an epitope common to all IgG subclasses; (2) RF reactive with an epitope expressed on IgG1, 2, 4 and G3m(s,t) which has histidine at 435, but not G3m(b) or G3m(g) which have arginine at 435; (3) RF reactive with an epitope expressed on IgG1, 2, and 4, but not IgG3 irrespective of allotypic markers; (4) RF reactive with epitopes expressed on some, but not all paraproteins within the subclasses. Four of five RF paraproteins that expressed both the heavy and light chain-associated idiotopes showed a similar pattern of reactivity with IgG subclass proteins. | |
| 3349688 | Colloidal chromic phosphate 32P synovectomy in antigen-induced arthritis in the rabbit. | 1988 Apr | Radioisotopes have been employed in the therapy of chronic arthritis, in particular, rheumatoid arthritis for many years. A variety of isotopes have been popularized, and in the last ten years a colloidal solution of radioactive chromic phosphate 32P has been in use apparently with equivalent efficacy to others such as 169erbium, 90yttrium, and 165dysprosium. No controlled studies on this modality have been reported and few animal studies were found. The efficacy of therapeutic doses of 32P as a medical synovectomy and its effect on rabbit joints with antigen-induced arthritis were observed in 62 arthritic knee joints in 31 adult rabbits treated on one side with 0.1 microCi of 32P, the opposite serving as control. The animals were observed over a period of 11 months and examined by histologic and biochemical means. The synovium showed no evidence of radiation necrosis in treated joints. Cartilage of treated and control joints showed similar changes consistent with chronic arthritis, persistent synovitis, progressive chondrocyte degeneration, and decreased matrix metachromasia. The radiosynovectomy had neither removed synovium nor protected the cartilage. Its efficacy in humans is therefore questionable. | |
| 1750798 | Major histocompatibility complex class II genes and systemic sclerosis. | 1991 Nov | 1. In no ethnic group is the overall association between systemic sclerosis and the MHC strong enough for direct clinical use. MHC associations do support the classification of the disease into limited cutaneous systemic sclerosis and diffuse cutaneous systemic sclerosis. 2. Indications are that associations between specific subsets of patients with systemic sclerosis and genetic markers will assume greater importance both diagnostically and prognostically. The group with lung fibrosis look prime candidates, for example. 3. Genetic markers are useful means of relating chemically induced systemic sclerosis like disorders with the classical disease. Vinyl chloride disease provides an example. 4. Evidence is emerging of strong associations between certain genetic markers and autoantibody production; a similar story has emerged in systemic lupus erythematosus. We believe that, eventually, genetic tests will be used to influence treatment in at least a subset of patients with systemic sclerosis but that a dramatic breakthrough will not be made until we know how the genetics of the disease relate to the primary biochemical disease characteristic--that is, the overproduction of collagen. In this respect it has been suggested that the 5' flanking DNA of dermal collagen genes is particularly susceptible to the action of Scl-70 (topoisomerase I). A problem is how to tie this and the other observations discussed above together. The association of autoantibodies with topoisomerase I provides a tentative link between the MHC and collagen gene expression. Although the role and reason for anti-Scl-70 in systemic sclerosis is unknown, humoral autoimmunity, at least in systemic lupus erythematosus, seems to be strongly dependent on specific HLA genes. With an understanding of the function of MHC products at the molecular level, HLA and disease associations can now be analysed on a mechanistic level. For insulin dependent diabetes mellitus it has been shown that the MHC determined susceptibility to the disease is conferred by neutral residues (Val, Ser, Ala), at position 57 of the DQ beta chain, while Asp at this position correlates with resistance. A similar phenomenon has been described in rheumatoid arthritis. Although DR4 in general is associated with rheumatoid arthritis, it is heterogeneous, but a subtype of DR4 which is characterised by positively charged residues at positions 70 and 71 of the beta chains is not found in patients with rheumatoid arthritis (Wordsworth B P et al, unpublished data). A similar approach applied to the study of systemic sclerosis is likely to be similarly rewarding. The precise subtyping of the class II genes and the characterisation of their associated haplotypes is therefore required for a complete understanding of the contribution of the MHC to the disease. Additional genes linked to the MHC must not be overlooked, and are relevant to associations of haplotypes with the disease. Of particular interest are the recent reports of a new class of proteins, which are determined by genes in the MHC and which are considered to play a part in the assembly of the antigen peptide/MHC molecule complex. | |
| 2805451 | Genetic control of inflammatory arthritis in congenic lpr mice. | 1989 Dec | To determine the genetic requirements for the development of inflammatory arthritis in MRL-lpr/lpr mice, clinical, serologic, and pathologic features of lpr/lpr and +/+ mice of MRL, B6, C3H, and AKR strains were studied. Arthritis was evaluated by histopathologic examination of the knee joint, while sera were tested for the presence of rheumatoid factor (RF) and anti-DNA activity by ELISA. Of the strains tested to age 7 months, only the MRL-lpr/lpr mice developed histologic evidence of arthritis. All lpr mice, however, produced both IgM RF and IgG RF, although amounts varied among strains. These results indicate that the lpr gene as well as another gene(s) in the MRL background are necessary for the development of inflammatory arthritis and that this lesion may be independent of RF production. | |
| 2429978 | Monoclonal antibodies defining a minor and a private idiotope on human rheumatoid factors. | 1986 Sep | Two mouse monoclonal antibodies (mAb A216-5 and L 49-3) with antiidiotypic activity against two human monoclonal IgM rheumatoid factors (IgM RFs) were defined. Each of these monoclonal antibodies (two mouse IgG 1K) reacted with an idiotope located on the heavy chain of the immunizing monoclonal IgM RF and was able to inhibit RF fixation to the antigen. These monoclonal antibodies did not react with other monoclonal IgM RFs from patients with macroglobulinemias or cryoglobulinemias and, therefore, did not recognize the known cross-reactive idiotopes of human monoclonal RFs. The presence of both 216-5 and 49-3 idiotopes on polyclonal IgM RFs from unrelated patients was undetectable by the inhibition assays. However, using a four-stage solid-phase radioimmunoassay, the 216-5 idiotope (minor), but not the 49-3 idiotope (private), was frequently present at a low concentration on polyclonal IgM RFs from patients suffering from rheumatoid arthritis, primary Sjögren syndromes, various infectious diseases, systemic vasculitis, and sarcoidosis and during aging. Interestingly, the 216-5 idiotope was undetectable among polyclonal IgM RFs of 12 normal adults. The main conclusions of these data are the following. The definition of minor and private idiotopes of human RFs requires the use of assays able to detect low amounts of antibodies among polyclonal Ig. The anti-IgG B cells which are sometimes clonally expanded during Waldenström diseases and cryoglobulinemias can also be activated during nonneoplastic diseases, among the other RF-secreting B cells.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 2585409 | An assessment of the Arthritis Impact Measurement Scales in 3 ethnic groups. | 1989 Aug | The Arthritis Impact Measure Scales (AIMS) have established validity and reliability in general adult populations with medically diagnosed rheumatoid arthritis. Our analysis extends this work to a community based sample of elderly individuals with self reported joint systems in 3 ethnic groups: Hispanics (N = 100), whites of Eastern European origin (N = 112) and blacks (N = 105). With the exception of the Social Activity and ADL scales, acceptable reliability and validity of the AIMs scales are found for all 3 groups. The assumption of factor invariance across ethnic groups is also supported. | |
| 3175694 | Avascular bone necrosis in an untreated case of chronic myelogenous leukemia. | 1988 | Hip pain due to aseptic necrosis of the femoral head was the first clinical manifestation of chronic myelogenous leukemia in a 9-year-old white female. An erroneous diagnosis of rheumatoid arthritis was first entertained. Physical examination showed splenomegaly, complete blood count revealed leucocytosis of 359,000. The initial radiograph of the involved hip was negative. Biopsy revealed aseptic necrosis of the femoral head. Chronic myelogenous leukemia (CML) was diagnosed on the basis of the peripheral blood smear and bone marrow biopsy. Two months later, radiograph, radionuclide bone scan, and magnetic resonance imaging (MR) of the involved hip were positive for aseptic necrosis of the femoral head. |