Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3594962 | The SL/Ki system in connective tissue diseases: incidence and clinical associations. | 1987 Jan | In a clinical and serological study carried out on 516 subjects with different connective tissue diseases, anti-SL/Ki autoantibodies were found in 12% of patients with systemic lupus erythematosus, 14% of patients with mixed connective tissue disease, 18% of patients with different kinds of vasculitides, and 3% of patients with Sjögren's syndrome. In SLE patients, no significant clinical association was found with the SL/Ki system, but the incidence of the antibody was nearly three-fold higher in males than in females. Most sera contained other autoantibodies; a statistically significant serological association has been found between SL/Ki and PCNA antibodies (p less than 0.05). | |
| 2074922 | [Dermatopolymyositis, Gougerot-Sjögren's syndrome, Hashimoto's thyroiditis and glomerulop | 1990 | We present here a glomerulonephritis in a patient with dermatomyositis, Sjögren's syndrome and Hashimoto's thyroiditis. Glomerulonephritides are rarely described in dermatomyositis and Sjögren's syndrome. Glomerular histology is variable. Nephrotic syndrome and renal failure are not frequent. Moderate doses of corticosteroids produce a rapid improvement. | |
| 2789659 | Lymphocytic infiltrations of lip salivary glands in bone marrow recipients. A model for th | 1989 Aug | By use of a PAP staining technique, the immunohistopathology in repeated biopsies from the lip salivary glands (LSGs) from patients undergoing bone marrow transplantation (BMT) was studied. In the previously normal LSGs, focally arranged lymphocytes and adjacent epithelial DR-expression appeared within 12 weeks post BMT, reaching a maximum between 26 and 52 weeks post BMT. Two years post BMT, lymphocytic infiltrates and epithelial DR-expression were still present in half of the specimens but were not seen in the remaining ones. The immunohistopathological changes seen in LSGs post BMT were indistinguishable from what has been found in Sjögren's syndrome. The appearance, and in some patients the subsequent disappearance, of the lymphocytic infiltrates and the epithelial DR-expression, without correlation to clinical symptoms of chronic graft-versus-host disease or immunosuppressive treatment, emphasizes the dynamic nature of lymphocytic infiltration of LSGs in BMT patients. Whether this also pertains to naturally occurring Sjögren's syndrome remains to be elucidated. | |
| 3200833 | Molecular analysis of the 60-kDa human Ro ribonucleoprotein. | 1988 Dec | Ro, or Sjogren syndrome type A (SS-A), antigen is the most prevalent of the human systemic autoimmune specificities and exists as an inabundant ribonucleoprotein complex (RNP) composed of a 60,649-Da protein, as defined here by cDNA cloning, and the human Y RNAs. The recombinant 60-kDa Ro protein and human Y1 RNA were reconstituted in vitro, and the binding was enhanced by divalent cations. A region of the Ro amino acid sequence revealed a resemblance to the RNP consensus motif found in most RNA-binding proteins. In addition, Ro contained a potential "zinc-binding finger" motif that was distinct from the RNP consensus region and that may participate in the interaction with human Y RNAs or with other proteins. The recombinant Ro fusion protein also proved useful for the detection of autoantibodies in the sera of patients with autoimmune disorders. Possible functions of the Ro RNPs and their relationship to RNA polymerase III transcription are discussed. | |
| 3495841 | [Is the target of anti-cardiolipin antibodies the same in Gougerot-Sjögren syndrome and l | 1987 Mar | Forty-seven patients were diagnosed as having systemic lupus erythematosus (SLE) and 34 patients primary Sjögren's syndrome (SS); 30 controls were also studied. Anti cardiolipin (CL), anti double-stranded DNA (ds DNA) and anti single-stranded DNA (ss DNA) antibodies were determined by the enzyme-linked immunosorbent assay. Elevated anti-CL antibody levels were detected in 47.8 p. 100 (n = 46) of patients with SLE and in 85.3 p. 100 (n = 34) of patients with SS, but only once in controls. Elevated ss DNA were detected in 91.5 p. 100 (n = 47) of patients with SLE and in 18.3 p. 100 of patients with SS but never in controls. Elevated anti-ss DNA were detected in 93.3 p. 100 and 97.1 p. 100 respectively of patients with SLE and SS and in 3.3 p. 100 of controls. There was no correlation between anti-CL and thrombosis, circulating lupus anti coagulant or VDRL. The most striking association, however, was between anti-CL and anti ss-DNA antibodies in SLE. There was no correlation between anti-CL and anti ds-DNA antibodies in SLE patients. Anti CL antibodies were correlated both to ss-DNA and anti ds-DNA in SS patients. Absorption of positive anti-CL antibodies sera were done on DNA (ss-DNA and ds-DNA) affinity column chromatography: anti-CL antibodies were absorbed only by ss DNA in SLE and by both ss DNA and ds DNA in SS. | |
| 2359219 | [Urolithiasis due to renal tubular acidosis associated with Sjögren's syndrome]. | 1990 Mar | We encountered 4 patients with urolithiasis due to renal tubular acidosis (RTA) associated with Sjögren's syndrome. Laboratory results about RTA in 4 patients with Sjögrenhs syndrome were not significantly different from those in patients who suffered from urolithiasis due to RTA without Sjögren's syndrome. The incidence of urolitiasis in these cases was suspected to be higher than that in RTA patients without Sjögren's syndrome, because all 4 patients in this study had urolithiasis. When we examine patients with bilateral and multiple urolithiasis, particularly in middle-aged women, we should bear in mind that RTA and Sjögren's syndrome may exist in the background. | |
| 2332848 | Food induced ("allergic") arthritis: inflammatory synovitis in rabbits. | 1990 Mar | Progress in understanding rheumatoid (RA) and inflammatory arthritis has been limited in part because there has been no widely accepted animal model of naturally occurring human disease and because the clinical syndrome of RA may reflect the expression of multiple etiologies. We have considered that inflammatory joint disease may be induced and/or exacerbated by food related antigens. To facilitate our investigations, we studied inflammatory synovitis in rabbits induced by oral exposure to environmental antigens. In our preliminary experiments, we examined 9 Florida White, 30 New Zealand White, and 9 Old English rabbits. They were nourished with normal rabbit chow supplemented with either water or cow's milk beginning at age 7 to 26 weeks and observed for 81 to 204 days. Animals were then sacrificed. Histological sections of the knees were examined and graded in a blinded fashion for synovial cell hyperplasia, inflammation, and lymphoplasmocytic infiltration. In addition, serum levels of IgG antimilk, IgG antibovine serum albumin, IgG anticasein, and IgG-C3 complexes were quantified. We found no abnormalities among Florida White rabbits but observed histological synovitis in 53% of the milk fed New Zealand White (9/17), 40% of the water fed Old English (2/5), and all of the milk fed Old English rabbits (4/4) (p = 0.05, milk fed vs water fed animals). Milk fed animals had significantly (p less than 0.0005) greater levels of antibodies and complexes than water fed animals. Our data suggest that environmental antigens may be arthritogenic for some rabbit strains. These observations may provide an important model for the study of inflammatory joint disease analogous to oral, environmental antigen exposure in man. | |
| 2025304 | The American College of Rheumatology criteria for the classification and reporting of oste | 1991 May | Clinical criteria for the classification of patients with hip pain associated with osteoarthritis (OA) were developed through a multicenter study. Data from 201 patients who had experienced hip pain for most days of the prior month were analyzed. The comparison group of patients had other causes of hip pain, such as rheumatoid arthritis or spondylarthropathy. Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop different sets of criteria to serve different investigative purposes. Multivariate methods included the traditional "number of criteria present" format and "classification tree" techniques. Clinical criteria: A classification tree was developed, without radiographs, for clinical and laboratory criteria or for clinical criteria alone. A patient was classified as having hip OA if pain was present in combination with either 1) hip internal rotation greater than or equal to 15 degrees, pain present on internal rotation of the hip, morning stiffness of the hip for less than or equal to 60 minutes, and age greater than 50 years, or 2) hip internal rotation less than 15 degrees and an erythrocyte sedimentation rate (ESR) less than or equal to 45 mm/hour; if no ESR was obtained, hip flexion less than or equal to 115 degrees was substituted (sensitivity 86%; specificity 75%). Clinical plus radiographic criteria: The traditional format combined pain with at least 2 of the following 3 criteria: osteophytes (femoral or acetabular), joint space narrowing (superior, axial, and/or medial), and ESR less than 20 mm/hour (sensitivity 89%; specificity 91%). The radiographic presence of osteophytes best separated OA patients and controls by the classification tree method (sensitivity 89%; specificity 91%). The "number of criteria present" format yielded criteria and levels of sensitivity and specificity similar to those of the classification tree for the combined clinical and radiographic criteria set. For the clinical criteria set, the classification tree provided much greater specificity. The value of the radiographic presence of an osteophyte in separating patients with OA of the hip from those with hip pain of other causes is emphasized. | |
| 3259833 | Familial clustering of scleroderma spectrum disease. | 1988 Jun | This is the second case report of familial scleroderma (systemic sclerosis) in South Carolina. The family includes two cases of scleroderma meeting American Rheumatism Association criteria, one of systemic sclerosis sine scleroderma, and two other cases of undifferentiated connective tissue disease with features of scleroderma spectrum disorders; there are also two cases of Raynaud's phenomenon (one associated with rheumatoid arthritis), for a total of seven affected relatives. Evidence of scleroderma spectrum disorders was sought in six siblings of the two co-index cases and in 23 of the 35 offspring. Laboratory studies included antinuclear antibody determinations and typing for the following genetic markers: HLA (A, B, C, DR), complotypes, Gm and Km allotypes, and alpha-1 antitrypsin phenotypes. No common genetic markers restricted to affected members of this family were found, and no environmental exposures were detected that could explain this familial clustering of cases. This report should, however, add to the slowly accumulating information on the genetic characteristics of families at unusually high risk for scleroderma spectrum disorders. Positive antinuclear antibody tests at a titer of 1/40 or higher were present in 57 percent of the first-degree relatives of the affected cases. | |
| 2472445 | Preincubation of human synovial cells with IL-1 modulates prostaglandin E2 release in resp | 1989 Jul 15 | Kinins are vasoactive peptides whose potent inflammatory and bone resorbing properties suggest a role for these autacoids in the pathogenesis of inflammatory arthritis. We used cultured human synovial cells as a model to evaluate the effects of bradykinin on articular tissue. In resting synovial cells, bradykinin was a relatively ineffective stimulus for PGE2 production. However, after a period of preincubation with the cytokine, IL-1, which is itself a stimulus for PGE2 production, synovial cells exhibited a further striking time- and dose-dependent response to bradykinin. Maximal release of PGE2 was observed in response to 10(-7) to 10(-6) M bradykinin after first pretreating the cells for 24 h with 5 to 10 U/ml of IL-1. rIL-1 alpha and IL-1 beta, as well as rTNF-alpha, induced a similar response to bradykinin in synovial cells, whereas recombinant IL-2 did not. The bradykinin analog, lysylbradykinin, was equipotent in inducing PGE2 release from IL-1 pretreated synovial cells, whereas des(Arg9) bradykinin, substance P, and neurokinins A and B were ineffective in this regard in both IL-1-pretreated and in resting cells. Synovial cells derived from patients with rheumatoid arthritis and osteoarthritis responded similarly to bradykinin. The synergistic response in PGE2 production induced by IL-1 and bradykinin was significantly inhibited by pretreatment with 1 microM indomethacin or dexamethasone (96 and 94% inhibition, respectively). In addition, the response was abrogated by pretreatment with 10 micrograms/ml of cycloheximide or actinomycin D (81 and 97% inhibition, respectively). These data provide the first description of synergism of IL-1 with a noncytokine peptide in human synovial cells. The ability of IL-1 to increase the responsiveness of synovial tissues to bradykinin may play an important role in potentiating inflammatory responses within the joint. | |
| 1810520 | Pharmacology, pharmacokinetics, and therapeutic use of meclofenamate sodium. | 1991 | Meclofenamic acid is a nonsteroidal anti-inflammatory drug (NSAID) approved for use in arthritis (osteo and rheumatoid), analgesia (mild to moderate pain), dysmenorrhea, and heavy menstrual blood loss (menorrhagia). At least three different biochemical effects have been defined for meclofenamic acid. It is a potent inhibitor of the enzyme cyclooxygenase, thereby inhibiting the production of prostaglandins. It also inhibits the release of 5-HETE and LTB4 from human neutrophils stimulated with calcium ionophore and antagonizes the response of tissues to certain prostaglandins. These mechanisms may explain in part the pharmacological profile and clinical effectiveness of this compound. The rapid onset of activity of meclofenamic acid and its duration of action may be the result of its pharmacokinetic profile. Sodium meclofenamate is completely bioavailable from capsules relative to an oral suspension dosage form. Maximum meclofenamic acid plasma concentrations are achieved in 0.5-2 h following doses of capsules. Meclofenamic acid is extensively metabolized. One of the metabolites, metabolite 1, is approximately 20% as active as the parent compound in inhibiting cyclooxygenase activity in vitro. This metabolite accumulates in plasma during repeated dosing. It is possible that this metabolite may contribute to at least some of the activity observed following administration of sodium meclofenamate. | |
| 2173501 | Abnormal vitamin D3 metabolism in patients with primary Sjögren's syndrome. | 1990 Sep | Recent studies have suggested that vitamin D3 may have an immunoregulatory role in vitro. The vitamin D3 metabolism in 35 patients with primary Sjögren's syndrome was investigated by measuring blood concentrations of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) and 25-hydroxyvitamin D3 (25-OHD3), as well as phenotypes and blood concentrations of Gc globulin, the main vitamin D3 binding protein in the blood. 25-OHD3 concentrations were diminished, but those of 1 alpha,25-(OH)2D3 were normal. There was no significant difference between the distribution of Gc phenotypes in the patients with primary Sjögren's syndrome and normal controls. Likewise, blood concentrations of Gc globulin corresponded to normal values. Among patients with increased concentrations of IgM rheumatoid factor there was a significant negative correlation between the serum titres of IgM rheumatoid factor and 25-OHD3 concentrations. | |
| 3070730 | Co-existent anti-La antibodies and rheumatoid factors bear distinct idiotypic markers. | 1988 | This study describes the distribution of isotypes and idiotypes of two autoantibody populations, anti-La and rheumatoid factor, which co-exist in both the sera and saliva of patients with primary Sjögren's syndrome. The two autoantibodies are distinguished not only by their antigenic specificity but also by the nature of their idiotypic markers. IgA anti-La antibodies bearing restricted idiotypes are specifically enriched in saliva compared to serum suggesting their local synthesis. In contrast, rheumatoid factors bear cross-reactive idiotypes and may arise as a direct consequence of the secondary immune response. | |
| 3082300 | Urinary monoclonal free light chains in primary Sjögren's syndrome: an aid to the diagnos | 1986 Mar | Three patients, two with typical primary Sjögren's syndrome (SS) and the third with several features of SS, including abnormal sialography and reduced tear secretion, developed B cell non-Hodgkin's lymphoma (NHL) of parotid or lung, or both. Isoelectric focusing of concentrated urine specimens in agarose, followed by immunofixation, demonstrated the presence in each patient's urine of monoclonal free light chains of the same class as that shown on the tumour cells. In one patient the level of urinary free light chains was monitored and found to correlate with disease activity. Similar techniques showed no monoclonal light chains in the urine from a further 26 cases of SS with no clinical evidence of lymphoma. The detection of monoclonal urinary free light chains may provide an early diagnostic clue to the development of lymphoma in patients with SS and be a means of tumour monitoring. | |
| 3102255 | Molecular analysis of the murine lupus-associated anti-self response: involvement of a lar | 1987 Jan | The mRNA encoding heavy and light chains of a hybridoma-derived monoclonal IgM, kappa anti-immunoglobulin (rheumatoid factor) and an IgG3, kappa anti-histone autoantibody from systemic lupus erythematosus and arthritis-prone MRL/Mp-lpr/lpr mice have been molecularly cloned, and the nucleotide sequences corresponding to their variable regions have been determined. To investigate whether autoantibodies with specificities frequently observed in lupus disease might share common structural components, the sequences obtained in this study have been compared with those of a monoclonal MRL/Mp-lpr/lpr IgM, kappa anti-DNA autoantibody previously analyzed in our laboratory (J. Exp. Med. 1985. 161: 805). The 3 immunoglobulins employed different heavy chain variable region (VH) genes belonging to the large J588 VH gene family, kappa light chain variable region (V kappa) genes from 3 different V kappa groups, and different diversity and joining segments. Our findings suggest that murine lupus-associated autoantibodies of different specificities do not have genetic components in common to signal their self-reactive nature and are encoded by a large number of immunoglobulin gene elements. | |
| 2082018 | HLA-B27 and rheumatic diseases of childhood. | 1990 Nov | In childhood, the histocompatibility antigen HLA-B27 is associated with juvenile ankylosing spondylitis, Reiter's syndrome, and the sacroiliitis of juvenile psoriatic arthritis, and inflammatory bowel diseases. The low frequency of signs or symptoms of spine or sacroiliac joint disease at onset differentiate these disorders from their adult counterparts and make early diagnosis difficult. The presence of enthesitis and the absence of rheumatoid factor and antinuclear antibody suggests the diagnosis of one of the seronegative spondyloarthropathies. The mechanisms by which HLA-B27 positivity confers susceptibility to disease are uncertain. To date, no genetically determined differences in the HLA-B27 molecule, or in the T cell receptor which recognizes antigen in the context of HLA-B27, have been consistently shown to be associated with the presence of disease. There is no explanation for the onset of disease in childhood in some individuals. | |
| 2648375 | Lyme disease. The hidden pandemic. | 1989 Apr | Physicians will recognize Lyme disease faster if they maintain a high index of suspicion in a young patient with arthritis accompanied by negative rheumatoid factor and antinuclear antibody in combination with cardiac conduction problems or lymphocytic meningitis. The Lyme spirochete (Borrelia burgdorferi) has notable sensitivity to tetracycline, penicillin, and erythromycin; therefore, proper and complete treatment of the disease, once it is identified, can be easily achieved. Finkel observed that Lyme disease manifests itself as a "great imitator," as do many disorders caused by a spirochete. The total impact of Lyme disease on public health will be known only when the disease is fully recognized, consistently reported, and adequately managed. | |
| 2117658 | Variation of MHC class I and II antigen expression in relation to lymphocytic infiltrates | 1990 Jun | The occurrence of MHC antigens on epithelial cells in lip salivary glands obtained from patients with various connective tissue diseases and from bone marrow recipients was studied. The amount of infiltrating lymphocytes correlated to an increase in MHC class I and II antigen expression, but not to diagnosis or glandular function. Interferon-gamma + infiltrating cells were scanty. The role of interferon-gamma as the main inducer of MHC antigens and the notion "aberrant" HLA-DR thought to perpetuate chronic autoimmune disease are questioned. | |
| 2519015 | Immunopathogenesis of Sjogren's syndrome: "facts and fancy". | 1989 | Sjogren's syndrome (Ss) is an ideal model to study the pathogenesis of both autoimmunity and malignancy. It occurs as an organ specific autoimmune disease, alone or in association with almost every other autoimmune disorder, as a systemic disorder, and finally it can evolve to B-cell-lymphoid malignancy. The most consistent finding in the syndrome, the B-cell-hyperreactivity, follows the same steps of evolution. It starts as polyclonal, but not random, since the autoantibody profile correlates with the disease subgroups and the systemic manifestations and it seems to be controlled by the MHC gene composition. Further, in the systemic form of the disease it presents as a poly-oligo-mono-clonal process and ends up to monoclonal (IgMk) B-lymphoid malignancy. Studies on the T-immunoregulatory subsets and function can not explain this B-cell hyperreactivity. The initial trigger is unknown. Estrogens, known as immunoenhancers possibly promote the B-cell hyperreactivity and certain genes controlling HLA class-II MHC molecules may represent susceptibility factors for the development of the disease. The discovery of lymphokines and particularly the B-cell growth and differentiation factors as well as the rapid development of the retro-virology field may give answers pertinent to the pathogenesis of Ss and to B-cell lymphoid malignancy. | |
| 2390852 | Monoarthritis of the ankle in diabetes mellitus without neuropathy: a report of three case | 1990 Jun | Diabetes mellitus is associated with several non articular rheumatic conditions and is a cause of Charcot's arthropathy. We report three cases of long-standing insulin-dependent diabetics who developed an inflammatory monoarthritis of the ankle. There was no evidence of a peripheral neuropathy or sepsis. They were all seronegative for rheumatoid factor. In two the synovitis persisted; in the third there was a gradual resolution. This type of inflammatory synovitis has not been previously described in diabetes. It developed after a mean duration of diabetes of 34.3 years (range 18-52 years). We suggest that it may be associated with microvascular changes in diabetes, possibly involving hypoxic reperfusion. |