Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2784733 | A common anti-cardiolipin antibody idiotype in autoimmune disease: identification using a | 1989 Feb | We have recently produced a series of human monoclonal antibodies reacting with cardiolipin. One of these, H3, a polyspecific IgM/k derived from a normal individual, was used to raise mouse monoclonal antibody to its idiotype. Two anti-idiotypic antibodies, S2.9 (IgG2b) and S2.10 (IgM) were selected for their specific reaction with H3.S2.9 did not react with five other human monoclonal antibodies of IgM/k class despite the fact that these shared some antigen-binding characteristics with H3.S2.9 was able to block the binding of H3 to all of its cross-reactive antigens including cardiolipin, while S2.10 was not. S2.9 was equally efficient in blocking the binding of H3 to three of its cross-reactive antigens, cardiolipin, diphtheria and tetanus toxoids; greater than 90% inhibition could be achieved at an equimolar ratio of H3 to S2.9. The anti-idiotype S2.9 was used to demonstrate the presence of the H3 idiotype in serum. This idiotype was found in amounts greater than that seen in 42 normal individuals, in 30 of 36 patients with systemic lupus erythematosus (SLE), eight of 20 patients with rheumatoid arthritis (RA), 8 of 20 patients with Felty's syndrome as well as 10 of 23 patients with syphilis. Not one of nine patients with drug-induced lupus syndrome had abnormal levels. In patients with SLE and Felty's syndrome there was a good correlation between the amount of anti-cardiolipin antibodies and the amount of H3 idiotype (rs = 0.70 and 0.69 respectively). No such correlation was found in syphilitics or in patients with RA. In patients with SLE the H3 idiotype was present on IgM and IgG anti-cardiolipin antibodies. In 15 of 16 SLE sera with high levels of cardiolipin antibody, S2.9 blocked binding of serum antibodies to cardiolipin by 13-72%, with a mean value of 49%. One patient had a high level of anti-cardiolipin antibody which could not be blocked by S2.9. These results indicate that a mouse monoclonal antibody which reacts with an idiotope in the antigen-binding region of a naturally-occurring phospholipid antibody also defines a common idiotype of anti-cardiolipin antibodies in patients with autoimmune disease. | |
| 1700795 | Potent toxicity of 2-chlorodeoxyadenosine toward human monocytes in vitro and in vivo. A n | 1990 Nov | Lymphoid cells were thought to be uniquely susceptible to excess 2'-deoxyadenosine (dAdo), when exposed to inhibitors of adenosine deaminase (ADA). However, we now find that human monocytes are as sensitive as lymphocytes to dAdo or to the ADA-resistant congener 2-chloro-2'-deoxyadenosine (CldAdo). Monocytes exposed in vitro to CldAdo, or to dAdo plus deoxycoformycin rapidly developed DNA strand breaks. Both the DNA damage and the toxicity of CldAdo or dAdo toward monocytes were blocked by deoxycytidine, but not by inhibitors of poly(ADP-ribose) polymerase. A partial decrease in RNA synthesis and a gradual decline of cellular NAD were early biochemical events associated with monocyte DNA damage. Low CldAdo concentrations (5-20 nM) inhibited monocyte phagocytosis and reduced the release of interleukin 6. Higher CldAdo concentrations led to a dose- and time-dependent loss of monocyte viability. Circulating monocytes disappeared within 1 wk in patients with cutaneous T cell lymphoma or with rheumatoid arthritis during continuous CldAdo infusion. The marked sensitivity of human monocyte function and survival to CldAdo in vitro, together with the monocyte depletion in patients receiving CldAdo chemotherapy, suggests that CldAdo or other dAdo analogues offer a novel therapeutic strategy for chronic inflammatory and autoimmune diseases characterized by inappropriate monocyte deployment or function. | |
| 2268750 | Osteomalacia and osteoporosis in femoral neck fracture. | 1990 Nov | Iliac crest bone histomorphometry, plasma and urine biochemistry and clinical history were examined in 78 unselected patients (68 women, 10 men) at the time of femoral fracture. Histological abnormalities occurred in 56 of the 78 biopsies. The commonest of these was a low bone volume of less than 15% which, irrespective of other abnormal histological features, was present in 37 of the biopsies. On the basis of the histomorphometry, patients could be classified into four main groups. Normal histomorphometry (bone volume greater than 15%, osteoid surfaces less than 24%, mineralising surface greater than 60%) was present in 22 patients, 23 had osteoporosis as the only abnormality (bone volume less than 15%, osteoid surface less than 24%, mineralising surface greater than 60%), nine had osteomalacia (osteoid surfaces greater than 24%, mineralising surface less than 60%, osteoid width greater than 13 microns) and 13 had decreased mineralising surfaces. Of the remainder, five had increased osteoid surface and six had insufficient osteoid to assess mineralising surface. Plasma and urine biochemistry in the four groups showed that, compared to age-matched controls, all groups had reduced plasma albumin. In comparison to the group with normal histomorphometry, patients with osteoporosis had a higher plasma calcium (P less than 0.01), tubular reabsorption of calcium (P less than 0.05) and plasma vitamin D binding protein (P less than 0.01); patients with osteomalacia had a higher plasma creatinine (P less than 0.02) and parathyroid hormone (P less than 0.02) and lower plasma 24,25-dihydroxyvitamin D (P less than 0.02), urinary calcium/creatinine ratio (P less than 0.02) and tubular reabsorption of phosphate (P less than 0.02). The biochemistry in patients with decreased mineralising surface was no different from patients with a normal biopsy. The prevalence of both osteoporosis and osteomalacia increased with age and, in subjects over the age of 90, osteoporosis occurred in 71% of patients and osteomalacia occurred in 29% of patients. The osteomalacic group were significantly older than the other three groups (P less than 0.05). The histomorphometry did not relate to the site of fracture (subcapital or intertrochanteric). A history of stroke, gastrectomy, rheumatoid arthritis, steroid treatment, thyroid disease, alcohol abuse and anti-convulsant therapy was present in patients with femoral fracture but did not relate to any particular histomorphometric classification. | |
| 2253682 | Characterization of B cell growth in systemic lupus erythematosus. Effects of recombinant | 1990 Nov | B cells from systemic lupus erythematosus (SLE) patients have been shown to be hyperactive as measured by proliferation and immunoglobulin production. We find that B cells from 6 of 13 SLE patients, in the absence of prior activation, respond two to three times better to recombinant 12-kDa B cell growth factor (BCGF) than do normal or rheumatoid arthritis B cells (p less than 0.005). B cells from normally responsive SLE patients require an anti-mu antibody activation step to generate similar proliferative signal in response to r12-kDa-BCGF. There are no clinical or serological parameters that distinguish these hyperresponsive SLE patients from the normally responsive SLE patients. The combination of r12-kDa-BCGF and interleukin 4 (IL4) gives an enhanced response with both normal and SLE B cells. Transforming growth factor type beta (TGF-beta) suppresses the response to r12-kDa-BCGF in a dose-dependent fashion using B cells from both healthy donors and SLE patients. We conclude that peripheral blood B cells are in an activated state (as detected by response to 12-kDa-BCGF) in approximately 50% of SLE patients. These B cells respond normally to regulation by IL4 and TGF-beta. A therapeutic approach aimed at reducing the B cell hyperactivity in SLE would involve suppressing the effects of 12-kDa-BCGF and IL4 while at the same time enhancing the effects of TGF-beta. | |
| 2575220 | Sequence and chromosomal assignment of a novel cDNA identified by immunoscreening of a thy | 1989 Sep | An immunoglobulin G (IgG) preparation of the serum from a patient with active Graves' disease was used to isolate cDNA clones from a lambda gt11 cDNA library of human thyroid follicular carcinoma tissue by immunoscreening. One of these clones, hML-7, is further characterized herein by sequencing, Northern analysis, and chromosomal mapping. The clone reacted with IgG preparations from the sera of 14 of 19 patients with active Graves' disease but not with IgG preparations from 11 normal individuals, three patients with toxic thyroid adenoma, and three with rheumatoid arthritis. The hML-7 cDNA hybridized to a 3.6 kilobase (kb) mRNA transcript in poly(A+) RNA preparations from human thyroid tissue and continuously cultured rat thyroid cells; expression of this transcript in rat FRTL-5 thyroid cells was positively regulated by TSH. The 3.6 kb transcript was less abundant in rat liver (BRL3A) cells or differentiated rat (L6) myoblasts than in cultured rat thyroid cells and was not detectable in mouse L-M fibroblasts, human IM-9 lymphocytes, Chinese hamster ovary cells, or human cervical carcinoma cells. The cDNA from hML-7 was sequenced and compared with the sequence of cross-hybridizing cDNA clones isolated from human Graves' thyroid and rat FRTL-5 thyroid cell lambda gt11 expression libraries. A 1.05 kb open reading frame, which is highly conserved between human and rat, was defined. The predicted amino acid sequence of 348 residues exhibited a strong homology with the mitochondrial ADP/ATP carrier protein (adenine nucleotide translocase; ADP/ATP translocator) and with two other members of the same mitochondrial protein family, the phosphate carrier and the hydrogen ion uncoupling protein. The gene represented by the hML-7 cDNA has been assigned to human chromosome 10. | |
| 3121194 | Effect of aurothioglucose on glutathione and glutathione-metabolizing and related enzymes | 1987 | The antirheumatic drug aurothioglucose is an inhibitor of the selenoenzyme GSH peroxidase. During chrysotherapy, the decreased levels of erythrocyte GSH and serum sulfhydryls of rheumatoid arthritis patients are normalized concomitant with clinical efficacy. This investigation examined the in vivo and in vitro effect of gold(I) as aurothioglucose on enzymes related to the GSH redox cycle or metabolism. The enzymes measured were GSH peroxidase, GSSG reductase, gamma-glutamyl transpeptidase, gamma-glutamylcysteine synthetase, GSH S-transferase, GSH thiotransferase, glucose-6-phosphate dehydrogenase, superoxide dismutase and catalase. Rats were injected with 30 mumol aurothioglucose/kg body wt. daily for 7 days by intramuscular injection. GSH levels in aurothioglucose-treated rats were 68% higher in erythrocytes (P less than 0.005) and 45% higher in kidney (P less than 0.001) than in control rats. Treatment with aurothioglucose did not elevate plasma or liver GSH. The enzyme activities that were changed by aurothioglucose treatment were GSH peroxidase in kidney (41% decreased, P = 0.005) and liver (13% decreased, P less than 0.05), gamma-glutamyl transpeptidase in kidney (15% decreased, P less than 0.05), and catalase in kidney (58% decreased, P less than 0.001). Kidney glucose-6-phosphate dehydrogenase activity was increased 50% (P less than 0.005) and GSH S-transferase was increased 72% (P less than 0.001). In vitro the only liver enzymes inhibited more than 50% by concentrations of less than 50 microM aurothioglucose were GSH peroxidase (50% inhibited by 25 microM aurothioglucose) and GSH thiotransferase (50% inhibited by 5 microM aurothioglucose). Studies of in vitro enzyme inhibition by aurothioglucose could not be used to predict decreased enzyme activities in vivo. Although decreased activities of two major enzymes that utilize GSH, GSH peroxidase and gamma-glutamyl transpeptidase, coincided with elevated GSH in kidneys of aurothioglucose-treated rats, a direct cause and effect relationship remains speculative. | |
| 2700902 | Idiotypes and autoimmunity. | 1989 | The reports discussed above have increased our knowledge of idiotypes, mainly with respect to additional CRI on autoantibodies and to a relatively new aspect of 'pathogenic idiotypes'. It is obvious that much remains to be discovered about the normal role of idiotypes and how they might be involved in the pathogenesis of autoimmune disorders. The relationship of the idiotypic network to tolerance is a matter of speculation; tolerance implies the ability to distinguish between 'foreign' and self-antigens and it is important to remember that antibody V regions are also self-antigens. Several mechanisms have been proposed to explain immunological tolerance. Originally, it was envisaged that the repertoires of both T and B lymphocytes were in some way purged of potentially self-reactive clones. However, it is now evident that self-reactive lymphocytes do exist but are normally held under control. Finally, it may be that certain self-antigens are simply never exposed to immune surveillance. It seems that the control of self-reactive lymphocytes is central to the question of tolerance. In the absence of autoimmune disease, autoantibodies can be produced, for example, after many infectious diseases or vaccinations. However, this type of perturbation of the immune system is associated with the short-term production of low titres of low-affinity antibodies, generally of the IgM isotype, which are thought to represent germline gene products. Homeostasis is soon re-established, possibly by regulatory T cells interacting with autoreactive B cells through their idiotypic receptors.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 3048806 | Differential isotype recognition of two centromere associated polypeptides by immunoblotti | 1988 Jun | On investigating the immunoblotting profile of 65 systemic sclerosis patients, a 140 kD polypeptide was recognised by sera from 16, when immunoblotted against a nuclear-enriched K562 cell sonicate. All 16 sera contained anticentromere antibodies (ACA) detected by immunofluorescence (IF) and 15 of 16 also recognized a 19 kD polypeptide on immunoblotting. Two ACA positive sera failed to recognize the 140 kD polypeptide but one of these recognized the 19 kD polypeptide. The 140 kD polypeptide identified a group with more limited skin involvement (P less than 0.05) and all 16 had Raynaud's phenomenon. The sera from three of 100 systemic lupus erythematosus (SLE) patients also recognized both polypeptides. On investigating the isotype specificity, the 140 kD polypeptide was strongly detected by an IgM autoantibody and the 19 kD polypeptide by an IgG autoantibody. | |
| 3282919 | Autoantibodies to the core proteins of hnRNPs. | 1988 Apr 11 | A novel autoantibody reacting the the core polypeptides of hnRNP particles has been detected in the serum of a patient with systemic lupus erythematosus (SLE) and Sjögren's syndrome manifestations. Immunoblot analysis, using either rat liver or HeLa nuclear extracts as the antigen source, demonstrated that the autoantibody interacts with a specific subgroup of the core polypeptides of hnRNP particles, namely A2, B1 and B2, but not with A1, C1 and C2. | |
| 3550074 | Syndrome of temporal arteritis with perivascular infiltration by malignant cells in a pati | 1986 Dec | A patient with follicular small cleaved cell lymphoma presented with Sjögren's syndrome and symptoms of polymyalgia rheumatica and temporal arteritis. Biopsy of the temporal artery showed an extensive perivascular infiltrate by malignant cells without evidence of giant cells. | |
| 1686576 | [Relationship between HLA D region gene and primary Sjögren's syndrome]. | 1991 Oct | Primary Sjögren's syndrome is characterized by lymphocytic infiltration of the salivary and lacrimal glands and by autoantibody production. In order to identify the genetic factors that play a role in the pathogenesis and to predict the progress of the disease we used the restriction fragment length polymorphism and polymerase chain reaction method to detect the polymorphism of HLA-DRB1, DRB3, DQA and DQB genes among 75 Caucasoid primary SS patients, and compared the results with normal controls living in the same area. We found (1) significant increased frequency of HLA-DR3 (54%) and DRw8 (13%) (P less than 0.001); (2) increased frequency of the HLA-DRB3 allele DRw52a and of the HLA-DQA allele DQA 4 (P less than 005); (3) increased frequency of heterozygosity for DQA 1/DQA 4 (P less than 005); (4) autoantibody SSA and SSB associated with DR3 (P less than 002 and P less than 0001 respectively). | |
| 2473859 | Autoimmune response to the Ro/SSA particle is directed to the human antigen. | 1989 Jun | Autoantibodies to defined cellular antigens in systemic lupus erythematosus (SLE) are usually directed to conserved epitopes on ubiquitous macromolecules including histone, Sm + nRNP (URNP particles), DNA, and La(SSB). We report here that the autoimmune response to the Ro(SSA) RNA protein particle is directed to epitopes on the human antigen which are not conserved in evolution. Ro(SSA) from bovine, rat, and mouse Ro(SSA) particles cross-react with human autoantibodies less effectively than does human Ro(SSA), and antigenically active Ro(SSA) is not detectable in chicken thymus extracts with the assays employed. These data suggest a special role for the Ro(SSA) antigen in the initiation and/or perpetuation of the anti-Ro(SSA) response in autoimmune disease. | |
| 1664736 | BG-104 enhances the decreased plasma superoxide scavenging activity in patients with Behç | 1991 | BG-104, a compound of Chinese herbs, has been reported to exert superoxide scavenging activity (SSA) in cell free systems. This report addresses in vivo effects of BG-104 in various disorders. The plasma SSA and laboratory parameters were determined in patients Behçet's disease (BD), Sjögren's syndrome (SjS) or hematological malignancy (M), and the effects of BG-104 treatment on these parameters were studied and compared with those of another antioxidant, vitamin E (alpha-tocopherol). The plasma SSA was significantly lower both in patients with BD and M, and in patients with SjS without antioxidant treatment as compared to that in healthy controls, and it showed an inverse correlation with disease activities. The treatment with BG-104 and/or vitamin E significantly enhanced the plasma SSA in all disorders studied. Both the erythrocyte sedimentation rates, the absolute number of neutrophils, as well as C-reactive protein levels were significantly lower in patients treated with BG-104 and/or vitamin E than those without these drugs. These results indicate that the BG-104 has an anti-inflammatory effect through enhancing plasma SSA in patients with BD, SjS or M. | |
| 2554513 | Small cell lung cancer in a patient with neutropenia due to Felty's syndrome. | 1989 Nov | A patient with severe neutropenia due to Felty's syndrome had limited stage small cell lung cancer, resulting in a therapeutic dilemma. Because he had a cellular bone marrow and no history of recurrent infection, we decided to administer full doses of cytotoxic chemotherapy with curative intent. A durable remission was achieved without complication, despite persistent severe peripheral neutropenia. It may be possible to administer aggressive chemotherapeutic regimens to selected patients with Felty's syndrome when there is the potential for cure of malignant disease. | |
| 2464497 | At least three distinct B cell epitopes reside in the C-terminal half of La protein, as de | 1988 Dec | The La antigen is a nuclear protein that is one of the major target antigens of autoantibodies found in the sera of patients with primary Sjögren's syndrome. The formation of such autoantibodies is therefore likely to reflect the basic immunopathogenesis of this disorder. A recombinant DNA strategy has been used to examine the La protein for sequences that encode autoimmunizing B cell epitopes. We have isolated and characterized a 1.2-kb-long cDNA from a human liver cDNA library encoding a region of the La protein; this region contains 296 amino acids, including the C terminus. A sub-library of recombinant DNA in the expression vector pEX was made from portions of the La cDNA. Individual fusion proteins were tested by immunoblotting and enzyme-linked immunosorbent assay for their ability to react with anti-La autoantibodies contained in sera from patients with Sjögren's syndrome. In this way, we have identified at least three distinct epitopes in the C-terminal half of the La protein. Every anti-La serum tested contained antibodies against all three of the antigenic regions identified. Furthermore, most of the sera display similar ratios between the titers of antibodies with the three kinds of specificity. Our data suggest that the production of anti-La autoantibodies may be antigen driven. | |
| 3496360 | Lupus/Sjögren's autoantibody specificities in sera with paraproteins. | 1987 Jul | Antinuclear antibody and anti-RNA-protein autoantibodies were determined in 143 sera containing paraproteins and 39 control sera. Antinuclear antibodies were commonly present in the paraprotein sera by indirect immunofluorescence. 19 of 143 sera (13%) had elevated anti-Ro/SSA activity in a solid phase Ro/SSA binding assay, and 5 (3.5%) had Ro/SSA precipitating autoantibody. Eighteen sera had La/SSB binding autoantibodies (12%) but only one had an anti-La/SSB precipitin. Anti-nRNP(Sm) was not detected in any of these sera. The solid phase anti-RNA protein assays were repeated using anti-lambda and anti-kappa conjugates. Both lambda and kappa light chain autoantibodies were found in all positive sera consistent with polyclonal anti-Ro/SSA and anti-La/SSB responses. Paraprotein sera containing Ro/SSA precipitins were analyzed by isoelectric focusing followed by exposure to 125I-labeled Ro/SSA and autoradiography. All sera with anti-Ro/SSA binding paraproteins also contained polyclonal anti-Ro/SSA. Our data are consistent with the hypothesis that anti-Ro/SSA paraproteins are common and arise from a previously present polyclonal anti-Ro/SSA response. | |
| 3490935 | Interleukin 2 defect in the peripheral blood and the lung in patients with Sjögren's synd | 1986 Sep | We studied interleukin 2 (IL-2) production both in the peripheral blood and the lung in patients with Sjögren's syndrome (SS). IL-2 production of the peripheral blood mononuclear cells (PBMC) was significantly impaired in patients with SS (P less than 0.001). The patients with extraglandular disease and with associated connective tissue disease were more defective in IL-2 production. The defect could not be attributable to culture conditions. Both OKT4+ and OKT8+ T cells were deficient in producing IL-2. However, impaired IL-2 production could be partly restored by either (1) adding PMA to the PHA-stimulated culture, or (2) supplementing indomethacin (IM) from the initiation of the culture, or (3) depletion of adherent cells from PBMC. Furthermore, SS T cells were more sensitive to PGE1 than normal controls. In contrast, the response of PBMC to IL-2 was not disturbed in SS. IL-1 production of SS PBMC was not defective although there seemed to be suppressive factor(s) produced by SS adherent cells. In addition, IL-2 production of SS pulmonary lymphocytes was also decreased, suggesting that IL-2 producing cells might not be sequestrated in the lung. These data suggest that qualitative T cell defects and suppressor macrophages might be responsible for defective IL-2 production in SS and that IL-2 deficiency may contribute to the disordered immunoregulation in SS. | |
| 3940247 | Primary biliary cirrhosis, Sjogren's syndrome, and transverse myelitis. | 1986 Jan | A 35-yr-old woman with coexistent primary biliary cirrhosis and Sjogren's syndrome developed recurrent transverse myelitis. The histopathologic appearance was that of an angiitis associated with necrotizing myelopathy involving the cervical and thoracic spinal cord. | |
| 1701273 | Detection of a human intracisternal A-type retroviral particle antigenically related to HI | 1990 Nov 23 | Sjögren's syndrome is an autoimmune disease that is characterized by dryness of the mouth and eyes. The loss of salivary and lacrimal gland function is accompanied by lymphocytic infiltration. Because similar symptoms and glandular pathology are observed in certain persons infected with human immunodeficiency virus (HIV), a search was initiated for a possible retroviral etiology in this syndrome. A human intracisternal A-type retroviral particle that is antigenically related to HIV was detected in lymphoblastoid cells exposed to homogenates of salivary tissue from patients with Sjögren's syndrome. Comparison of this retroviral particle to HIV indicates that they are distinguishable by several ultrastructural, physical, and enzymatic criteria. | |
| 2597211 | Differences in the fine specificity of anti-Ro (SS-A) in relation to the presence of other | 1989 Dec | In sera from patients with systemic lupus erythematosus or Sjögren's syndrome, we determined the fraction of antibody that remained reactive with human Ro (SS-A) after absorption with bovine spleen extract, and the reactivity with the 60-kd and 54-kd red blood cell Ro (SS-A) bands by Western blot. Of the 3 groups of sera studied, those containing anti-Ro (SS-A) alone had the highest degree of reactivity with human Ro (SS-A) after absorption with bovine spleen extract, followed, in descending order, by sera containing anti-Ro (SS-A) and anti-La (SS-B), and sera containing anti-Ro (SS-A) and anti-nuclear RNP. The groups of sera could be distinguished on this basis. Sera with anti-Ro (SS-A) and anti-nuclear RNP could also be distinguished from the other 2 types of sera by their uniform and preferential reactivity with the 60-kd red blood cell Ro (SS-A), by Western blot analysis. These findings indicate that there are both qualitative and quantitative differences, associated with the presence of other autoantibodies, in the fine specificity of anti-Ro (SS-A) sera. |