Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2712611 | A study of headaches and migraine in Sjögren's syndrome and other rheumatic disorders. | 1989 Apr | Migraine occurs with increased frequency in patients with systemic lupus erythematosus and in subjects suffering from Raynaud's phenomenon without any underlying connective tissue disorders. A possible link between migraine and Raynaud's phenomenon has been suggested. Two rheumatic conditions where Raynaud's phenomenon occurs very commonly are scleroderma and primary Sjögren's syndrome. It is possible that migraine is also common in these disorders but has been unrecognised. Therefore, the prevalence of migraine was assessed by a questionnaire in 191 subjects suffering from various connective tissue disorders and control subjects. Migraine was diagnosed in 16/35 (46%) patients with primary Sjögren's syndrome, 31/97 (32%) patients with scleroderma, 4/33 (12%) patients with rheumatoid arthritis/Sjögren's syndrome compared with 3/26 (11%) control subjects. A family history of headaches was more common in the patient groups than controls. There was a significant association between occurrence of Raynaud's phenomenon and migraine. Small vessel pathology may underlie both migraine and Raynaud's phenomenon in these connective tissue disorders--as has been suggested in systemic lupus erythematosus. The findings stress the need to ask specifically about complaints of headaches/migraines in patients with scleroderma and primary Sjögren's syndrome for the appropriate total management of these patients. | |
| 1851828 | Detection of Epstein-Barr virus antigens and DNA in major and minor salivary glands using | 1991 Apr | This study has investigated the presence of Epstein-Barr virus (EBV) in parotid (n = 12), submandibular (n = 15), and minor salivary glands (n = 25) using immunohistochemical methods for detection of EBV-encoded antigens and the polymerase chain reaction (PCR) for detection of viral DNA. Major salivary glands were from patients without connective tissue disease. Labial glands were from patients with primary Sjogren's syndrome (n = 10), rheumatoid arthritis (n = 8), or from normal individuals (n = 7). None of the glands exhibited specific reactivity for lytic (EA-D, EA-R, VCA) or latent (EBNA-2, LMP) viral antigens. Antibodies to EA-D, when used at 20-50 times their optimal concentration, gave lumenal staining of ducts and acini of all the specimens tested (n = 14), irrespective of the presence (n = 8) or absence (n = 6) of EBV-DNA by PCR. Ductal immunoreactivity for the EBV/C3d (CR2, CD21) receptor was found in 40 per cent of specimens. PCR detected EBV-DNA in 64 per cent submandibular, 46 per cent parotid, and 80 per cent of minor glands. There were no significant differences in the detection of EBV-DNA between specimen/patient groups. Only type A EBV was detected by strain typing PCR. These results indicate that EBV (type A), undetected immunocytochemically, is commonly present at low copy numbers within salivary glands irrespective of a clinical diagnosis of Sjogren's syndrome. | |
| 3689460 | Subclinical lung inflammation in primary Sjögren's syndrome. Relationship between broncho | 1987 Nov | To directly evaluate whether a subclinical alveolar inflammation is associated with primary Sjögren's syndrome (SS), we evaluated the distribution of cells obtained by bronchoalveolar lavage (BAL) from the lower respiratory tract in 29 patients who had primary SS, but who were free of clinical pulmonary symptoms and had normal findings on chest roentgenograms. There was no difference in total cell counts of specimens from patients versus those of controls. An abnormal differential cell count was noted in 16 patients (55%). Two patterns of alveolitis were observed: a pure lymphocyte alveolitis (greater than 18% lymphocytes, present in 11 patients) and a neutrophil alveolitis (greater than 4% neutrophils, present in 5 patients). There was associated lymphocytosis in 4 of the patients with neutrophil alveolitis. All patients had normal results on pulmonary function tests. Patients with abnormal BAL findings showed clinical and biologic indexes of more severe disease than did those with normal BAL results, as demonstrated by greater extraglandular extension of the disease, higher mean values of serum gamma globulins and serum beta2-microglobulin, and higher prevalence of rheumatoid factor and of antinuclear antibody. Thus, our data demonstrate that BAL permitted the detection of subclinical inflammatory alveolitis in 55% of our patients with primary SS. A long-term followup is required to determine whether these patients will develop obvious pulmonary involvement. | |
| 2827246 | Potential role of Epstein-Barr virus in Sjögren's syndrome. | 1987 Aug | Sjögren's syndrome is an autoimmune disease characterized by lymphocytic infiltration and destruction of salivary and lacrimal glands. This condition may occur as a primary condition or may be associated with other autoimmune disorders such as rheumatoid arthritis or systemic lupus. Because the environmental factors that initiate SS are unknown, we have investigated the potential role of EBV, CMV, and other viruses. We observed that epithelial cells in salivary gland biopsies of patients with SS contained antigens reactive with monoclonal antibodies against EBV-associated antigens. These antigens were not found in other tissues of patients with SS and were not detectable in salivary gland biopsies from normal persons and patients with other autoimmune diseases lacking SS. The molecular weight of the antigens present in the SS salivary gland extracts was similar to that expressed in cells containing reactivated EBV. Also, the content of EBV DNA in the saliva of patients with SS was significantly greater than in age-, sex-matched controls or persons with other autoimmune disorders. These studies provide one of the first examples where a specific viral agent may be implicated in perpetuating a chronic autoimmune disease. These results also may provide insight into other autoimmune diseases where the target organ is less accessible to biopsy. | |
| 1680190 | Soluble interleukin 2 receptor levels in serum and its relationship to T cell abnormality | 1991 Jun | Systemic lupus erythematosus (SLE) is associated with alterations in immune regulation that results in T cell activation and release of the soluble interleukin 2 receptors (sIL-2R) in serum. SLE, a disease with varied clinical manifestations also has regulatory T cell subset abnormalities in blood. Levels of sIL-2R in serum of patients with active SLE were higher than in those with other common rheumatic diseases. Patients with active SLE and an increased percentage of CD4+ CDw29+ helper inducer (memory) and decreased percentage of CD4+ CD45R+ suppressor inducer (virgin) T cell subsets in blood demonstrated elevated levels of sIL-2R in serum. When compared with clinical manifestations of the disease, the sIL-2R levels in the sera of the patients with active SLE and thrombocytopenia were higher (mean 1710 units/ml) than those in active SLE with nephrotic syndrome (mean 1230 units/ml) or in active SLE with central nervous system disease (mean 1157 units/ml). However, patients with active SLE with humoral immunodeficiency (hypogammaglobulinemia) had highly elevated levels of sIL-2R in serum as compared to other patients with active SLE. The highly elevated levels of sIL-2R in serum may indicate that in vivo T cell activation plays an important role in this disease. | |
| 3102595 | Comparison of T cell receptor gene rearrangements in patients with large granular T cell l | 1987 Mar 15 | Felty's syndrome (FS) refers to the occurrence of rheumatoid arthritis, splenomegaly, and neutropenia. A subset of these patients has recently been described with a chronic T cell leukemia of large granular lymphocytes (LGCL). To examine the spectrum of lymphocyte abnormalities in FS and LGCL, we examined phenotypic and genotypic properties of lymphocytes from eight FS patients. In two of these FS patients, we observed an elevated proportion of T cells with an unusual phenotype (CD3+/Leu-7+/Leu-8-/CR3+) (46 +/- 5% of mononuclear cells). The FS lymphocytes had large granular morphology on Wright-Giemsa stain and were active in antibody-dependent cellular cytotoxic activity. This phenotype, morphology, and activity was similar to LGCL patients except that the latter T cells additionally expressed the Fc-IgG receptor recognized by monoclonal antibody Leu-11 (CD 15). In the remaining six FS patients, the proportion of CD3+/Leu-7+/CR 3+ T cells was only 10 +/- 8%, which was not significantly different from age-matched normal subjects (6.6 +/- 2.2%). To determine the clonality of T lymphocytes in FS and LGCL, we examined DNA for rearrangements of the T cell antigen receptor beta-chain (Ti beta) and gamma-chain (Ti gamma) genes by using Southern blotting techniques. We found a clonal rearrangement of the Ti beta 1 and Ti gamma genes in both LGCL patients. In contrast, no clonal rearrangements of Ti beta or Ti gamma genes were detected in lymphocytes from the FS patients. These results indicate that FS patients are heterogeneous in their phenotype and that one subset exhibits polyclonal expansion of an unusual lymphocyte subset. | |
| 3764727 | [Pulse therapy in the complex treatment of severe forms of Sjögren's syndrome and disease | 1986 | Ten patients with Sjögren's disease and 5 patients with systemic lupus erythematosus combined with Sjögren's syndrome received therapy with high doses of 6-methylprednisolone (pulse-therapy) and cyclophosphamide. Improvement of the stomatological signs of the disease was noted in all the patients: salivation increased, the parotid glands considerably decreased in size, parotiditis recurrences were absent or seldom, and the number of the functioning salivary glands of the lower lip increased. The above therapy showed a positive effect on ophthalmological symptoms of the disease in 5 patients. Combination therapy (6-MP and CP) was effective for the management of such systemic symptoms of SD and SS as arthritis, lymphadenopathy, hepatosplenomegaly, exudative polyserositis, polyneuritis, ulcerative-necrotic vasculitis, cerebrovasculitis, cryoglobulinemic purpura and glomerulonephritis. A significant decrease in the levels of immunoglobulins especially IgA, A-nDNA, cryoglobulins, titers of rheumatoid factors, circulating immune complexes and an increase in the complement were noted in response to therapy. | |
| 3675012 | Sjögren's syndrome and fibrosing alveolitis complicated by pulmonary lymphoma. | 1987 Sep | The case of a middle aged woman who presented with fibrosing alveolitis, in her mid-forties, followed by a sicca syndrome and who subsequently developed a pulmonary lymphoma (B cell) while receiving azathioprine therapy is recorded. Of interest was the absence of polyclonal B cell activation, e.g., production of rheumatoid factor, hypergammaglobulinaemia, high titre antinuclear antibodies or antibodies to extractable nuclear antigens (ENA) during most of her illness. Persistently raised IgM levels and low IgA levels were demonstrated. The relevance of azathioprine to development of the lymphoma is discussed. | |
| 2078046 | Epidermal cell surface-associated IgG in patients with primary Sjögren's syndrome: in vit | 1990 | In vivo deposits of IgG have previously been demonstrated in the epidermal intercellular area of clinically unaffected skin from 68% of patients with primary Sjögren's syndrome (primary SS). This study compared circulating IgG from patients with primary SS with that from secondary SS in their ability to bind normal human epidermal cells in vitro. We observed a granular pattern of IgG binding to the normal epidermal cell surfaces with 9 of 18 sera from patients with primary SS (50%), 3 of 19 sera from patients with SS secondary to rheumatoid arthritis (16%) (p = 0.025), and none of 24 normal control sera (p less than 0.001). In a subsequent analysis of polyethylene glycol separated sera from two normal controls and two primary SS patients, the epidermal IgG binding capacity was found only in the precipitates of the patients. These findings support our previous hypothesis that the in vivo intraepithelial IgG deposits in primary SS patients are due, at least in part, to cell surface-bound immune complexes. | |
| 2979816 | Autoantibody production in Sjögren's syndrome: a hypothesis regarding defects in somatic | 1988 Jan | Patients with primary Sjögren's syndrome (SS) have rheumatoid factor (anti-IgG Fc antibody, RF) in their sera that contains a crossreactive idiotype (CRI) defined by monoclonal antibody 17-109. This CRI is shared by SS patients and certain patients with Waldenstrom's macroglobulinemia. This CRI was not found in increased frequency in RF from rheumatoid arthritis patients lacking SS. The structural basis for this CRI is the highly conserved kappa chain of the Vk IIIb sub-subgroup. In SS patients, the CRI is present on both IgA RF and IgM RF, accounting for 5-20% of the total RF. Recent studies have shown that a germ line encoded kappa variable region gene (Humkv 325, cloned from a placental DNA library) has DNA sequence that encodes the variable region amino acid sequences of CRI positive kappa chains. Using MoAb 17-109, we have been able to determine the tissue distribution of CRI+ B-cells. We found an increased frequency in the salivary gland biopsies of SS patients and also in their intestinal mucosal tissues (i.e. Peyer's patch). In comparison, we also detected an increased frequency of CRI+ B-cells in the Peyer's patch regions of normals. Taken together, these results suggest that CRI+ B-cells may play an important role in normal mucosal immunity and these CRI+ B-cells have migrated to the salivary gland in SS patients as part of the inflammatory process directed at autoantigens or exogenous antigen(s) located at a mucosal surface.(ABSTRACT TRUNCATED AT 400 WORDS) | |
| 1833873 | Primed and naive helper T cells in labial glands from patients with Sjogren's syndrome. | 1991 | This study has investigated the presence and distribution of B cells, T cells and T-cell subsets within labial glands of patients with primary Sjogren's syndrome (n = 9) and secondary Sjogren's syndrome associated with rheumatoid arthritis (n = 8) using a sequential double immunoperoxidase technique and true colour image analysis. The composition of the inflammatory infiltrates was similar in glands from both patient groups. B cells were normally present within large foci with few detected in diffuse infiltrates such that the ratio of T:B cells in foci (2.4:1) was significantly lower than in diffuse infiltrates (7.3:1; P less than 0.001). In all infiltrates helper T cells (CD8-, CD3+) predominated over suppressor/cytotoxic cells (CD8+, CD3+; 2.7:1). Analysis of primed (CD45RA-, CD45RO+) and naive (CD45RA+, CD45RO-) CD8- T cells showed that the ratio of the primed to naive subset was significantly higher in focal (4.2:1) compared to diffuse (1.5:1; P less than 0.001) areas of lymphoid infiltration. These results indicate that the focal lymphocytic infiltrates characteristic of Sjogren's syndrome contain B cells associated with a T-cell population consisting predominantly of primed CD8- helper T cells. This latter population may be responsible for upregulating glandular B-cell activity in Sjogren's syndrome. | |
| 3748683 | Utility of rheumatoid factor in the diagnosis of juvenile rheumatoid arthritis. | 1986 Sep | Rheumatoid factor is commonly used by clinicians to assess children with possible juvenile rheumatoid arthritis. To assess its usefulness, we reviewed the case histories of patients in whom latex agglutinating rheumatoid factor was determined during 1981 to 1982 at our institution. A total of 437 charts were available for review. There were 11 patients with positive tests for rheumatoid factor, of whom five had juvenile rheumatoid arthritis, all polyarticular. A total of 426 children had negative results, of whom 100 had juvenile rheumatoid arthritis. This yields a sensitivity of 4.8% and a specificity of 98%. We then estimated the prevalence of juvenile rheumatoid arthritis in three clinical settings: a primary practitioner's office, a tertiary children's hospital walk-in clinic, and a pediatric rheumatology center. The predictive values and marginal benefits for rheumatoid factor were then calculated in those settings using Bayes' theorem. In the two general outpatient settings, the primary practitioner's office and tertiary walk-in clinic, the positive predictive values were 0.7% and 0.5%, respectively; marginal benefits were 0.4% and 0.3%, respectively. Rheumatoid factor testing appeared to be of some benefit in the pediatric rheumatology center with a positive predictive value of 72.5% and marginal benefit of 22.5%. In no case was rheumatoid factor testing helpful in establishing a diagnosis of juvenile rheumatoid arthritis or in ruling it out. Testing for rheumatoid factor is a poor screening procedure for juvenile rheumatoid arthritis in the general situations in which it is more likely to be requested and of supportive diagnostic value only in the highly restricted population of older children with polyarticular arthritis. | |
| 20144111 | Inheritance of rheumatoid arthritis. | 1987 | The inheritance of rheumatoid arthritis was investigated in three areas in Sweden where nearly the total population over the age of seven (22, 707 persons) was examined for the prevalence of rheumatoid arthritis (ARA-criteria). No significantly higher frequencies of rheumatoid arthritis were found among relatives of rheumatoid arthritics than among matched relatives of matched controls. The results are disappointing and throw no new light on possible inheritance of rheumatoid arthritis. | |
| 2830658 | Reactivation of Epstein-Barr virus in Sjögren's syndrome. | 1987 Oct | Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration and destruction of salivary and lacrimal glands. This condition may be limited to glandular tissues or may be associated with other autoimmune disorders such as rheumatoid arthritis or systemic lupus erythematosus. Since the environmental factors that initiate SS are unknown, we have investigated the potential role of Epstein-Barr virus (EBV), cytomegalovirus (CMV) and other viruses. We observed that epithelial cells in salivary gland biopsies of SS patients contained antigens reactive with monoclonal antibodies against EBV-associated antigens. These antigens were not found in other tissues of SS patients and were absent in salivary gland biopsies from normals and patients with other autoimmune diseases lacking SS. Also, the content of EBV DNA in the saliva of SS patients was significantly greater than in age- and sex-matched controls or individuals with other autoimmune disorders. These studies provide one of the first examples where a specific viral agent may be implicated in perpetuating a chronic autoimmune disease. However, great caution must be used before an etiologic role can be attributed to an ubiquitous agent such as EBV. | |
| 2930601 | Expression of the major rheumatoid factor cross-reactive idiotype in juvenile rheumatoid a | 1989 Mar | The major rheumatoid factor cross-reactive idiotype (RF-CRI), defined by prototypic monoclonal IgM rheumatoid factors, is expressed in high frequency by pokeweed mitogen-derived plasma cells from patients with rheumatoid arthritis who express RF in their sera. Unlike adults with rheumatoid arthritis, most patients with juvenile rheumatoid arthritis are seronegative for RF, as detected by classic IgG binding assays. We report that approximately 50% of seronegative patients with juvenile rheumatoid arthritis express the RF-CRI in high frequency among their pokeweed mitogen-derived plasma cells, and that approximately 33% of patients express the RF-CRI in high titer in their sera. The possible mechanisms for expression of an idiotypic marker of RF without expression of IgG binding activity by classic assays are discussed. | |
| 3711614 | A unique presentation of juvenile rheumatoid arthritis: proximal interphalangeal joint syn | 1986 May | Juvenile rheumatoid arthritis seldom involves the small joints of the hand. We are reporting three patients with proximal interphalangeal joint synovitis as the initial manifestation of juvenile rheumatoid arthritis. This form of presentation of the disease should be recognized so that treatment will not be unduly delayed especially for the ophthalmologic manifestations of juvenile rheumatoid arthritis. | |
| 20144090 | Prevalence of rheumatoid arthritis in densely and thinly populated areas in sweden. | 1987 | The prevalence of rheumatoid arthritis in 1,287 persons living in densely populated areas and 1, 287 persons living in thinly populated areas, matched as to sex, age, occupation and geographical area, was compared. The patient material was obtained in an epidemiological survey of rheumatoid arthritis (ARA definition) performed in Sweden in 1961. 1.6% of the inhabitants in densely populated areas and 2.5% in thinly populated areas had rheumatoid arthritis (classical, definite, probable, possible). The differences were indicative but not significant. Classical plus definite rheumatoid arthritis, however, showed exactly the same prevalences in the two populations (0.5%). Probable plus possible rheumatoid arthritis was indicatively more prevalent in the thinly populated areas (2.0%) than in the densely populated (1.1%). | |
| 2495873 | Anti-SSB/La antibodies in Sjögren's syndrome and related autoimmune diseases. Results of | 1989 Jan | A quantitative immunoassay using a highly purified antigen from HeLa cells has allowed us to detect antibodies to SSB/La in 11/20 patients with primary Sjögren's syndrome (SS), 15/33 with SLE, and 11/35 with progressive systemic sclerosis (PSS). However, positive results were found in only 2/12 patients with idiopathic Raynaud's disease and 2/20 with rheumatoid arthritis, including 4 with secondary SS. Anti-SSB/La were associated with extraglandular manifestations in primary SS, and with a diffuse sclerodermic pattern in PSS. In SS, SLE and PSS, a positive anti-SSB/La test was strongly associated with nodal or spleen enlargement and with an increased level of gamma-globulins. A direct association was also found with positive tests for rheumatoid factors, anti-SSA/Ro and anti-Scl 70. An inverse relationship was however found with anti-nRNP +/- Sm and anticentromere antibodies. Our data suggest that anti-SSB/La antibodies can be regarded as a marker of B-lymphocyte activation in patients with either primary SS, SLE or PSS. | |
| 3021847 | Detection of Epstein-Barr virus-associated antigens and DNA in salivary gland biopsies fro | 1986 Nov 15 | Sjogren's syndrome (SS) is an autoimmune disorder characterized by lymphocytic infiltration of salivary and lacrimal glands. To determine whether Epstein-Barr virus (EBV) might play a role in the pathogenesis of this disorder, we used monoclonal antibodies and DNA probes to detect evidence of viral gene products and genomes in these patients' tissue biopsies and saliva. Cytoplasmic staining of epithelial cells (i.e., ductal and/or acinar cells) with monoclonal antibody against the EBV-encoded early antigen (EA-D) was noted in 8/14 salivary gland biopsies from SS patients. This antibody did not react with normal salivary glands or salivary gland tumors, nor with other tissues from SS patients. The reactive antigen in SS biopsies had a m.w. of 52,000 on the basis of immunoblotting experiments, similar to the EA-D antigen found in lymphoblastoid cells lytically infected with EBV. EBV DNA was detected in parotid biopsies from two SS patients in amounts ranging from 0.1 to 3 pg per 20 micrograms of cellular DNA. Southern blotting was used to demonstrate the reactivity with Bam V, Eco D, and Bam M probes. Parotid saliva samples from 8/20 SS patients contained EBV DNA detectable by slot blot hybridization. EBV DNA was not detected in saliva of age-matched controls, rheumatoid arthritis patients lacking sicca symptoms, or patients with benign parotid tumors. The presence of EBV in salivary gland and saliva samples was associated with clinically more severe SS, as manifested by extraglandular symptoms such as vasculitis, occurrence of "pseudolymphoma", and marked abnormalities in immunoglobulin levels. These results demonstrate an elevated content of EBV in salivary glands of SS patients, and suggest that this virus may play a role in pathogenesis. | |
| 3252114 | [Rubella antibody levels in patients with rheumatoid arthritis]. | 1988 | Rubella virus as an etiological agent in Rheumatoid arthritis has been investigated. Synovial fluid obtained from 28 cases and the sera from 70 cases (43 girls, 27 boys) has been screened for hemagglutination inhibition antibodies. As a control group, 36 cases (20 normal, 16 children with non-rheumatoid arthritis) were incluated in the study. There was no difference in the antibody titers of the two groups. Therefore, we could not establish a direct relation of Rubella virus with rheumatoid arthritis. |