Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3260430 | [The Ha(La) antibody as a serologic marker of systemic lupus erythematosus]. | 1988 Mar | Ha(La)-antibodies are detected by counterimmunoelectrophoresis (CIE) in sera of systemic lupus erythematosus (SLE) patients, but not in sera of patients with progressive systemic scleroderma (PSS) (n = 38), rheumatoid arthritis (n = 91), ankylosing spondylitis (n = 97), and other rheumatic diseases (n = 452). This antibody specificity was found in 27 out of 103 SLE patients (26%). However, 50% of SLE patients with Sjögren's syndrome (n = 12) showed the Ha(La)-antibody, suggesting a strong association in this clinical subgroup. Thus the Ha(La)-antibody can serve as a serological marker and helpful diagnostic tool for SLE. Additionally, the Ha(La)-antibody reacts with specific puffs in polytene chromosome preparations of Drosophila melanogaster. Therefore, this heterologous antigen system is suitable for the identification of Ha(La) sera. | |
| 1717605 | A human renal cancer line as a new antigen source for the detection of antibodies to cytop | 1991 Sep 20 | Autoantibodies directed against cytoplasmic antigens of neutrophils (ANCA), especially proteinase 3 (C-ANCA), have proved to be a useful clinical tool to support the diagnosis or to monitor disease activity in Wegener's granulomatosis (WG). Till now, human neutrophil granulocytes have represented the major antigen source used to detect antibodies in WG by the immunofluorescence technique (IFT). We have tested serum samples of 164 patients with different connective tissue diseases (50 suffering from clinically active WG) performing IFT on a human renal cancer line (SK-RC11) and have found antibodies against the nuclear and cytoplasmic antigens in 39 patients. C-ANCA+ sera displayed a characteristic diffuse cytoplasmic staining pattern. Antibody titers measured with human granulocytes were comparable to titers obtained using culture cells. Antibody binding could be inhibited by preabsorption with an extract of human granulocytes or purified proteinase 3. A protein of 29 kDa MW could be isolated by affinity purification using a SK-RC11 extract and a high-titer C-ANCA+ serum and antigenic identity was further confirmed by IFT using a monoclonal antibody to proteinase 3. Treatment of tumor cells with cytokines (interferon, tumor necrosis factor) led to a time dependent translocation of the antigen into the nucleus and back to the cytoplasm. The antigen was also expressed on the surface of live cells colocalized with MHC II. In addition, 21 WG patients had antibodies to cytoplasmic organelles identified by laser scanning microscopy as secretory vesicles of the Golgi complex, and five had antibodies to nuclear antigens. This is, to the best of our knowledge, the first report of proteinase 3 in human non-leukemic cells. Our data demonstrate, that the repertoire of antigens recognized by antibodies in WG sera is not limited to human neutrophils and monocytes and indicates a possible functional role of the antigenic proteins. | |
| 1672123 | Restriction fragment length polymorphism of two HLA-B-associated transcripts genes in five | 1991 Jan | The restriction fragment length polymorphism of the two human HLA-B-associated transcripts (BATs) genes, BAT1 and BAT2, identifying polymorphic bands of 12, 8, 2.5, and 1.1 kb, and at 3.3, 2.7, 2.3, and 0.9 kb, respectively, was investigated in patients with primary biliary cirrhosis (PBC), systemic lupus erythematosus (SLE), pauciarticular juvenile rheumatoid arthritis (P-JRA), rheumatoid arthritis (RA), and primary Sjögren's syndrome (pSS), and in healthy Danes. The BAT2/RsaI 2.7-kb band fragment was more frequent in PBC, pSS, and SLE than in controls, but the p values did not reach significance when corrected for multiple comparisons. For pSS and SLE, the associations may be secondary to primary associations with HLA-B8 because the BAT2/RsaI 2.3-kb band, which is allelic to the BAT2/RsaI 2.7-kb band, is strongly negatively associated with HLA-B8 and HLA-DR3. The only significance obtained shows that the HLA-B8 frequency is increased in BAT2/RsaI 2.7-kb positive pSS patients as compared to the corresponding controls indicating that the HLA-B8 association may be strongest. No missing or extra DNA fragments were observed in the disease groups when compared with controls indicating that gross deletions or duplications of the BAT1 and BAT2 genes in the patients are unlikely. In conclusions, it cannot be excluded that the BAT2/RsaI 2.7-kb band may contribute to the susceptibility to PBC, pSS, and SLE. | |
| 1765975 | Clinical course of patients with anti-RNP antibodies. A prospective study of 32 patients. | 1991 Oct | Thirty-two patients with high and low anti-RNP antibody titers were followed prospectively during a mean observation of 65 months. The following 4 titer patterns were observed: persistently high, low increasing to high, high decreasing to low and persistently low titers. At first admission, 17 of the 23 patients with high anti-RNP titers did not fulfill the criteria of defined connective tissue diseases (CTD). The clinical courses were characterized by the appearance of new organ manifestations and at the end of the study 17/23 fulfilled the criteria for mixed CTD (MCTD). A development towards systemic lupus erythematosus (SLE) was seen in one, concomitant with decreasing anti-RNP titer. None developed symptoms compatible with progressive systemic sclerosis. The 9 patients with a low anti-RNP titer were characterized by a stable clinical course, including 4 with SLE, 2 with Raynaud's phenomenon, and one each with Sjögren's syndrome, discoid lupus erythematosus and rheumatoid arthritis + Sjögren's syndrome. The most frequently occurring clinical manifestations among the patients with MCTD were Raynaud's phenomenon, puffy hands, arthritis, myalgias, and sicca symptoms. Myositis and impaired pulmonary function were also seen, but glomerulonephritis was not. The symptoms were fluctuating and the manifestations clinically different from other well defined CTD. The morbidity was moderate and the mortality low. High anti-RNP titer observed at any time seems associated with a clinical syndrome phenotypically different from other CTD favoring the notion of MCTD being a distinctive clinical syndrome. | |
| 2148638 | Synovial cells responding to a 65-kDa mycobacterial heat shock protein have a high proport | 1990 Nov | We have analysed the ability of T cells from synovial fluid mononuclear cells (SFMC) and from peripheral blood mononuclear cells (PBMC) of inflammatory arthritic diseases to proliferate in response to mycobacterial antigens (65-kDa heat shock protein [hsp] of BCG, whole BCG) and to rat collagen type II. The SFMC demonstrated a significantly greater ability to respond to 65-kDa hsp of BCG, and to whole BCG, compared with PBMC from the same patients. With collagen type II, only a small proportion of the patients showed a proliferative response, although with this antigen also SFMC responded better than PBMC. There was no difference between SFMC and PBMC in the response to control antigen (tetanus toxoid), phytohaemagglutinin (PHA), or interleukin 2 (IL-2). A high proportion of cells in SFMC-derived short-term T-cell lines were of TcR gamma delta type, often exceeding the number of TcR gamma beta type. There was a significantly higher proportion of TcR gamma delta cells in the SFMC lines compared with the PBMC lines, and a large part of the TcR gamma delta cells in the SFMC cultures was CD8+. The SFMC lines had a high proportion of delta-TCS-1+ cells (V delta 1) among their TcR gamma delta cells, always exceeding the percentages of Ti gamma A+(V gamma 9) and BB3+ (V delta 2). In the PBMC lines, the distribution of TcR gamma delta subtypes was markedly different, with a Ti gamma A+/BB3+ population in the majority. These data argue for a different subpopulation distribution of TcR gamma delta cells in synovial fluid compared with peripheral blood of patients with inflammatory arthritic diseases. | |
| 1711323 | Sera from patients with autoimmune disease recognize conformational determinants on the 60 | 1991 Jun | Anti-Ro antibodies are found in a large proportion of patients with systemic lupus erythematosus and primary Sjögren's syndrome. These antibodies also characterize neonatal lupus, subacute cutaneous lupus erythematosus, and vasculitis associated with Sjögren's syndrome and rheumatoid arthritis. Anti-Ro-positive sera may contain either or both of 2 sets of antibodies, recognizing either a 60-kd or a 52-kd polypeptide component of the Ro particle. We found in this study that the immune response to the 60-kd Ro antigen is heterogeneous. Some sera specifically recognize the native Ro antigen but fail to bind the corresponding denatured polypeptides. In addition, after immunodepletion using the denatured 60-kd Ro polypeptide, all anti-Ro-positive sera tested still contained high titers of antibodies recognizing conformational determinants on the Ro antigen. The frequent immunodominance of anti-Ro antibodies targeted to conformational determinants suggests that native autoantigens may directly drive the autoimmune response. | |
| 2682546 | [Vasculitis associated with connectivitis]. | 1989 Mar | A great number of vasculitis in childhood is associated with Rheumatic disease. Vascular lesions involve small vessels of various organs. These are described in systemic lupus erythematosus, juvenile rheumatoid arthritis, dermatomyositis, scleroderma, mixed connective tissue disease, Behçet syndrome, Sjögren syndrome. | |
| 3296151 | Essential fatty acid and prostaglandin metabolism in Sjögren's syndrome, systemic scleros | 1986 | Evidence from biochemical studies and from experimental animals indicates that abnormalities of essential fatty acid (EFA) and eicosanoid metabolism could lead to salivary and lacrimal gland atrophy and to immunological and cardio-vascular defects. Measurements of EFA levels in erythrocytes from patients with primary Sjögren's syndrome have shown that abnormalities are indeed present. Controlled clinical trials of supplementation with gamma-linolenic acid (GLA) as evening primrose oil (Efamol) in both primary Sjögren's syndrome and systemic sclerosis have given positive results. There are strong arguments to indicate that sophisticated manipulation of EFA metabolism may have a role to play, not only in Sjögren's syndrome but also in other rheumatological disorders. | |
| 2459983 | Rheumatoid nodule and subcutaneous granuloma annulare. A comparative histologic study. | 1988 Feb | We performed histologic and selected histochemical and immunohistochemical studies on rheumatoid nodules (RN) from 12 patients and lesions of subcutaneous granuloma annulare (SGA) from nine patients. The mean age for patients with RN was 56 years, while that for SGA patients was 19 years. In contrast to those with RN, none of the patients with SGA had arthritis. RN tended to show homogeneous, eosinophilic necrobiosis, giant cells within palisaded foci, and significant stromal fibrosis; while lesions of SGA showed pale, edematous necrobiosis, an absence of giant cells, and lesser degrees of fibrosis. The single most helpful histochemical method was alcian blue, which stained necrobiotic foci in all cases of SGA but in only one case of RN. Epithelioid cells in both disorders stained positively for muramidase. IgM was found in vessel walls in two cases of RN. While the mechanisms of these disorders are not entirely clear, it appears that RN can usually be reliably distinguished from SGA on histologic grounds alone. | |
| 3065568 | [Tectonic keratoplasty in perforated corneal ulcer in Sjögren's syndrome (report of 10 ey | 1988 Dec | The authors report on eight patients with perforated corneal ulcers (six unilateral, two bilateral) and Sjögren's syndrome associated with rheumatoid arthritis. Five patients were evaluated serologically at the time of perforation. Circulating immune complex-like material, positive latex and Waaler-Rose tests, C-reactive protein and pathologic complements C3 and C4 were found in all patients. One patient with features clinically similar to those seen in the patients with Sjögren's syndrome had an iridocyclitis associated with HLA-B 27, with circulating immune complexes but negative latex and Waaler-Rose tests. Penetrating keratoplasty was performed in three eyes, eccentric keratoplasty in one, a penetrating mini-keratoplasty in four, and a tectonic sclerokeratoplasty in three. The keratoplasties had to be repeated in one case after ten years because of endothelial decompensation, in another case three months postoperatively because of a bacterial corneal ulcer, and in a third for optical reasons. After follow-up periods of between 12 and 1 1/4 years it was established that even though the interventions were sometimes extensive, the prognosis was good provided rheumatologic check-ups were thorough. | |
| 2051592 | [Anesthetic management of a patient with Sjögren's syndrome associated with an allergic r | 1991 Apr | We described the anesthetic management of a 24-year-old woman with Sjögren's syndrome, complicated by systemic lupus erythematosus, rheumatoid arthritis and renal tubular acidosis. She not only had hepatorenal dysfunction associated with this condition, but also had allergic reactions to various antiphlogistics and sedatives. In selecting anesthesia for the present case, care was taken to choose anesthesia that would cause no aggravation of the injured hepatorenal function. Application of nitrous oxide and isoflurane for the induction and maintenance of anesthesia enabled us to a control the patient without special problems. Artificial nose and belladonna were also used for the treatment of dryness of the respiratory and digestive systems and other mucosae. With regard to the patient's allergic predisposition, simple medications were used with sufficient care. | |
| 2208788 | In vitro production of B cell growth factor and B cell differentiation factor by periphera | 1990 Oct | The activation of B lymphocytes and formation of immune complexes have been suggested to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). To investigate the mechanisms of activation of B lymphocytes, we studied the production of B cell growth factor (BCGF) and B cell differentiation factor (BCDF) in patients with IPF and those with interstitial pneumonia associated with collagen vascular diseases (IP-CVD), in comparison with healthy controls. Culture supernatants of peripheral blood mononuclear cells from patients with IPF induced more IgM and IgA production by B lymphocytes than those from healthy controls, indicating a higher production of BCDF in the patients. Culture supernatants of T lymphocytes obtained from bronchoalveolar lavage fluids (BALF) of patients with IPF induced higher proliferation of B lymphocytes than those from healthy controls, indicating a higher production of BCGF. An increase in production of BCGF and BCDF was not observed in patients with IP-CVD. In the light of these results, it was suggested that there may be an imbalance in T lymphocyte subsets that release lymphokines like BCGF and BCDF in patients with IPF, and that the subsets may differ between blood and BALF. It remains to be elucidated whether the activation of B lymphocytes depending on T lymphocytes determines the development of disease in IPF. | |
| 3718551 | Sjögren's syndrome. Proposed criteria for classification. | 1986 May | The term "Sjögren's syndrome" (SS) is frequently used to describe the occurrence of keratoconjunctivis sicca and xerostomia in association with an autoimmune disorder. However, well-defined criteria for the classification of SS have not been established, and this diagnosis is being applied to a wide spectrum of conditions, ranging from clear "autoimmune" disease in some patients, to sicca complaints without evidence of a systemic immune process in elderly patients. Here, we review the clinical and laboratory features of patients referred for evaluation of sicca symptoms. In particular, we emphasize the need for care in choosing the site for minor salivary gland biopsy, and we describe the histologic features that aid in the evaluation of these biopsy specimens. In an attempt to identify a population of patients whose conditions might have a common etiopathogenesis and, thus, a common treatment program, we propose the following criteria for a diagnosis of SS: 1) objective evidence of keratoconjunctivis sicca, as documented by rose bengal or fluorescein dye staining; 2) objective evidence of diminished salivary gland flow; 3) minor salivary gland biopsy, obtained through normal mucosa, with the specimen containing at least 4 evaluable salivary gland lobules, and having an average of at least 2 foci/4 mm2; 4) evidence of a systemic autoimmune process, as manifested by the presence of autoantibodies, such as rheumatoid factor and/or antinuclear antibody. The diagnosis of "definite SS" would be made when all 4 criteria are met; the diagnosis of "possible SS" would be made when 3 criteria are present. Specific exclusions for this diagnosis are preexisting lymphoma, graft-versus-host disease, sarcoidosis, and acquired immunodeficiency disease.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 3084278 | Immunoglobulin deposits in labial mucosal epithelium of patients suspected of Sjögren's s | 1986 Feb | Lower lip biopsies from twenty-three consecutive patients under evaluation for Sjögren's syndrome, and from six normal controls, were investigated for deposits of immunoglobulins, fibrinogen and C3, using a direct immunofluorescence technique. Deposits of both IgG and IgA were demonstrated in the mucosal epithelium in three of six patients with primary Sjögren's syndrome. Similar IgG deposits were found in two of three patients with xerostomia and in one of three patients with Sjögren's syndrome secondary to rheumatoid arthritis. Immunoglobulins were located in close relation to cell surfaces in the basal and suprabasal layers of the epithelium. Double labelling experiments indicated a partial topographic concordance between the immunoglobulin deposits and OKT6 positive Langerhans cells in the epithelium. No deposits of immunoglobulins, fibrinogen or C3 were found in the remaining eleven patients and six normal controls. We conclude that deposits of IgG and IgA in the labial mucosal epithelium seem to be a characteristic finding in patients with primary Sjögren's syndrome as well as in patients with xerostomia. The diagnostic value of this new observation needs to be clarified in future studies. | |
| 1684923 | New aspects in the treatment of immunomediated diseases. | 1991 Nov | The following constitutes a summary of lectures delivered during the session "New aspects in the treatment of immunomediated diseases" which was held during the 25th Annual Scientific Meeting of the European Society for Clinical Investigation in Pisa, Italy on 6th April 1991. The aim of this session was to present and discuss some of the novel therapeutic modalities currently being employed either in experimental models or in phase I clinical studies. | |
| 2055025 | Sjogren's syndrome and keratoconjunctivitis sicca. | 1991 May | Keratoconjunctivitis sicca patients diagnosed on the basis of a history, dry-eye symptoms, and definite clinical signs of keratoconjunctivitis sicca, with the associated symptoms of dry mouth and/or arthritis, had measurements of tear osmolarity, Schirmer tear test without anesthetic, stimulated parotid salivary flow, and serum analysis for the presence of autoantibodies associated with Sjogren's Syndrome. In contrast to previous studies, a lower incidence of SS-A or SS-B (1-3%), ANA (41-47%), DNA (11-16%), and RF (9-12%) serum antibodies was detected. Salivary-stimulated parotid flow was abnormally decreased in 59% of the patients. Sjogren's syndrome, as indicated by the presence of serum antibodies, appears to have a lower incidence in keratoconjunctivitis sicca than considered previously. | |
| 1685490 | Strong primary selection for the Dw4 subtype of DR4 accounts for the HLA-DQw7 association | 1991 Sep | Felty's syndrome (FS) is a rare complication of rheumatoid arthritis (RA) previously shown to be strongly associated with HLA-DR4 and less significantly with HLA-DQw7. To map more precisely the HLA locus responsible for susceptibility to FS, we have examined HLA-DR4 and DQ beta-chain polymorphisms in FS patients and controls using restriction fragment length polymorphism analysis and polymerase chain reaction amplification in conjunction with oligonucleotide probing. The increased frequency of DR4 in FS (93% vs. 32% controls) was due almost entirely to enrichment for the Dw4 subtype (88% vs. 20% controls) with a secondary increase of the Dw14 subtype. Dw10 and Dw13 subtypes of DR4 were absent from the patient group. Increase in DQw7 frequency among DR4 FS patients could be accounted for by linkage disequilibrium between Dw4 and DQw7 alleles. Whereas susceptibility to RA is strongly associated with a conserved HLA-DR beta epitope associated with several DRB1 alleles, it is primarily the Dw4 allele which is associated with progression to Felty's syndrome. The finding that amino acid sequence variation at the DR4B1 locus rather than DQB1 is associated with development of FS will have important implications for the development of novel immunotherapies which are major histocompatibility complex allele-dependent. | |
| 3473624 | Respiratory involvement in patients with Sjögren's syndrome: is it a problem? | 1986 | We examined the pulmonary involvement in 40 patients with primary Sjögren's syndrome (1 degree SS), and 26 patients with secondary SS (2 degrees SS) and compared them with 100 healthy matched controls, 40 patients with rheumatoid arthritis (RA) without evidence of SS and 30 patients with scleroderma. The respiratory evaluation included questionnaire, physical examination, chest roentgenogram and pulmonary function studies (spirometry, flow/volume curve, total lung capacity and diffusion: DLCO). The most common symptom in 1 degree SS was dyspnea (25%). Xerotrachea was present only in 1 degree SS (12.5%) while pleurisy only in 2 degrees SS and RA (7.7% and 2.5% respectively). The most common functional defect in 1 degree SS was interstitial lung disease (30%) and in 2 degrees SS and RA airways obstruction (46% and 32.5% respectively). Finally, small airways disease was frequent in all patient groups, as well as the control group. Comparison between patients with glandular and extraglandular SS revealed that xerotrachea was a manifestation of glandular and diffuse interstitial lung disease of extraglandular SS. Finally, comparison of patient groups and controls revealed statistical significant differences in: FVC and DLCO between extraglandular 1 degree SS/controls, FEV1/FVC ratio between 2 degrees SS/controls and the same between RA/controls, FVC, TLC, DLCO between scleroderma/controls, DLCO between scleroderma/SS and separately between scleroderma/1 degree SS and scleroderma/extraglandular 1 degree SS (which were the subgroups of SS with lowest DLCO). Diffusion impairment correlated with the presence of cryoglobulins and low complement levels, suggesting immune complex deposition as a mechanism of the interstitial lung disease.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 3296145 | Diagnostic significance of immunohistological skin examination in patients with primary Sj | 1986 | Clinically unaffected skin from 57/84 (68%) patients with primary Sjögren's syndrome (primary SS) was found to contain intraepidermal in vivo deposits of IgG, using a direct immunofluorescence technique. Similar IgG deposits were found in only 4/26 (14%) patients with secondary SS, in 3/28 (11%) patients with rheumatoid arthritis without SS (RA), in 2/13 (15%) patients with systemic lupus erythematosus without SS (SLE), in 10/41 (24%) patients with other well-defined connective tissue disease (CTD) and in 2/65 (3%) of normal controls (p less than 0.001 for all groups compared to primary SS). Intraepidermal IgG deposits were found in 5/12 (42%) patients with incipient primary SS and in 6/15 (40%) patients with ill-defined CTD (NS). None of the patients with primary SS had immunoglobulin deposits in the dermo-epidermal junction zone, while this was observed in 12% of the patients with RA and in 20% of the patients with SLE. We conclude that the presence of intraepidermal IgG deposits is valuable in the differential diagnosis between primary SS and RA or SLE, even if RA and SLE are complicated with SS. Examination for intraepidermal IgG deposits should supplement the lupus band test. | |
| 1664987 | Reactivation of Epstein-Barr virus in Sjögren's syndrome. | 1991 | Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by severe dryness of the eyes and mouth, resulting from lymphocytic infiltration of the lacrimal and salivary glands. SS may exist as a primary condition (primary SS, 1.SS) or as a secondary condition (2.SS) in association with rheumatoid arthritis, systemic lupus erythematosus, or progressive systemic sclerosis. In some 1.SS patients, there may be involvement of the extraglandular organs, including skin, kidney, liver, lung and nervous system. Furthermore, these patients may develop a lymphoproliferative syndrome that includes lymphadenopathy and increased risk of lymphoma. In the pathogenesis of SS, a role for Epstein-Barr virus (EBV) has been suggested because: (a) EBV is present in salivary gland epithelial cells of normal individuals and exaggerated immune responses against EBV could play a role in the destruction of salivary glands in SS; (b) SS salivary gland biopsies contain increased levels of EBV DNA in comparison to normal salivary glands, indicating viral reactivation and inability of lymphoid infiltrates to control EBV replication in SS patients; and (c) salivary gland epithelial cells in SS patients express high levels of HLA-DR antigens and may present EBV-associated antigens to immune T cells in SS patients. Therefore, SS may represent a situation in which genetically predisposed individuals (i.e., HLA-DR3-DQA4-DQB2) have a persistent but ineffectual T cell immune response against EBV at its site of latency. Among 14 non-Hodgkin's lymphomas that developed in SS patients, EBV DNA was detected in increased amounts in the tumor tissue of one patient. Characterization of this tumor DNA revealed: (a) polyclonal immunoglobulin gene rearrangements; (b) EBV DNA with an unusual restriction fragment length polymorphism pattern involving the Bam M fragment; and (c) EBV terminal repeat sequences suggestive of viral replication, similar to those reported in EBV lymphomas occurring in other immunocompromised individuals. Early recognition of this clinical problem may allow beneficial use of antiviral agents. |