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ID PMID Title PublicationDate abstract
7759769 Effects of ethinylestradiol on the course of spontaneous autoimmune disease in NZB/W and N 1995 Feb Sex hormones affect (auto)immune responses in various ways. Investigations of the effects of estrogens have produced contradictory results. We studied the effects of gender, gonadectomy and of (supra)physiological doses of (the orally active) ethinylestradiol (EE) in two spontaneous autoimmune disease models: the NZB/NZW F1 and NOD mice. In both models we confirmed the female preponderance and the aggravating effects of gonadectomy in males but not in females. The accelerated mortality found in NZB/W mice treated with supraphysiological doses of EE was not associated with increased proteinuria, increased IgG-type anti-DNA levels or increased mononuclear cell infiltrations in the submandibular gland. In contrast, we found a severe reduction in body weight and in the weights of various organs (indications of toxicity), and a decrease rather than an increase in proteinuria and in mononuclear cell infiltrations (indications for autoimmunity). Physiological doses of EE did not significantly affect disease symptoms. In the NOD model a near-physiological, non-toxic dose of EE did not cause consistent changes on immunological disease symptoms either. Therefore, we conclude that the sexual dichotomy in spontaneous autoimmune models is due to protective effects of androgens and that the mortality by estrogens is due to toxic effects rather than accelerated autoimmunity.
8711537 [A case of Sjögren's syndrome with an eyelid tumor, a so-termed pseudolymphoma of the iac 1996 Feb The female subject, 64 years old, subjectively noticed a mild dryness of the eyes and bilateral, submandibular swelling in 1988. The clinical symptom was mild, and such autoantibody and hyper-gammaglobulinemia as often observed in Sjögren's syndrome were not recognized. However, by judging from the results of gum test (9 mL/10 min), salivary gland scan (Grade 2) and the labial biopsy, we diagnosed the case as Sjögren's syndrome. We then administered prednisolone at 40 mg at the onset of treatment and gradually decreasing the dosage over 3.5 years, and the symptoms improved. As an eyelid tumor in the left eye was noticed in 1991 and began to enlarge, the subject was hospitalized in June of 1992. The biopsy of the tumor (2.0 x 1.7 cm) showed marked polyclonal lymphoproliferation with lymphoid follicles which was determined by immunohistological staining. The case was a patient with a lymphoproliferative lesion from a lacrimal gland which is equal to a so-termed pseudolymphoma. Since there are some reports concerning the transition from pseudolymphoma to malignant lymphoma, this patient should be followed carefully.
7677303 Hepatitis C: a multifaceted disease. Review of extrahepatic manifestations. 1995 Oct 15 PURPOSE: To review the available data on the association between hepatitis C virus (HCV) infection and conditions reportedly related to infection with the virus and to assess the clinical implications of these associations. DATA SOURCES: Pertinent articles were identified using the Paperchase database, which simultaneously searches the MEDLINE (1966 to present), Health (1975 to present), AIDSLINE (1980 to present), and Cancerlit databases. STUDY SELECTION: All studies for a given association were reviewed, but special attention was paid to randomized controlled trials where applicable. RESULTS: According to the available data, HCV infection appears to be strongly associated with essential mixed cryoglobulinemia, membranoproliferative glomerulonephritis, and porphyria cutanea tarda. Evidence strongly suggests that HCV has a direct pathogenetic role in some patients with the first two conditions. The association with Mooren corneal ulcers and autoimmune thyroiditis is suggested, but more data are needed to confirm it. The data for the association between HCV infection and the Sjögren syndrome, lichen planus, and idiopathic pulmonary fibrosis remain weak. Although interferon therapy has been effective in patients with both essential mixed cryoglobulinemia and membranoproliferative glomerulonephritis, a high relapse rate has been noted in the latter condition. CONCLUSIONS: Patients with essential mixed cryoglobulinemia, membranoproliferative glomerulonephritis, and porphyria cutanea tarda should be tested for HCV infection. Conversely, signs and symptoms of these conditions should be sought in patients with chronic HCV infection. Interferon therapy is currently recommended only for patients with symptomatic essential mixed cryoglobulinemia.
8531377 [Lymphoproliferative disorders in patients with Sjögren's syndrome--Vg gene rearrangement 1995 Oct Sjögren's syndrome (SS) is a unique disease which develops a high incidence of lymphoproliferative disorders (LPD) such as monoclonal gammopathy or malignant lymphoma. In order to elucidate the mechanism responsible for the emergence of monoclonal B cell proliferation at the site of a chronic autoimmune reaction, the rheumatoid factor (RF) related germline gene Vg and expression of the bcl-2 gene in the lymphoepithelial lesion (LEL) were studied. Predominant usage of the Vg or Vg-like genes was found in the peripheral blood leukocytes in SS patients and abundant expression of bcl-2 protein in the lymphocytes in and around the LEL were observed. These results suggest that RF clones were activated resulting into monoclonal proliferation and overexpression of bcl-2 protein play a role allowing the cell to escape a apoptotic cell death resulting into the increased risk of monoclonal proliferation in SS patients.
1494582 [Primary pulmonary nodular amyloidosis and multiple emphysematous bullae in Sjögren syndr 1992 Dec The authors report on a very rare case of an isolated primary nodular pulmonary amyloidosis with multiple emphysematous bullae in Sjögren's syndrome. The circular foci present in both lungs in disseminated form were immunohistochemically speaking amyloid deposits of the AL-lambda type. There were no pointers to other organ manifestations or monoclonal immunoglobulins in the serum and/or urine.
1410901 [Inflammatory neuropathies]. 1992 May Inflammatory neuropathy is the term used for all neuropathies associated with an inflammatory infiltrate of the nerves and/or nerve roots. Broadly speaking, there are two types of inflammatory neuropathies: those caused by an identified infectious agent, and those of uncertain origin for which an autoimmune process is usually blamed. Among the neuropathies of infective origin, leprosy is the most important owing to its frequency and to the physiopathological and therapeutic problems it still poses to clinicians and researchers, since the form and severity of nerve lesions depend on cellular immunity to the bacillus' antigen rather than on the bacillus itself. Retroviral infections, caused by the virus of AIDS more than by the virus of tropical spastic paraplegia, are responsible for numerous neuropathies the mechanisms of which are discussed here. The principal inflammatory neuropathies of uncertain origin are polyradiculitis and its different forms, and the heterogeneous group of neuropathies associated with Sjögren's syndrome.
8862680 Clinical significance of antinuclear antibodies in systemic rheumatic diseases. 1996 Aug Autoantibodies directed to intracellular antigens can be detected in many systemic rheumatic diseases. In this review, we discuss the clinical significance of antinuclear antibodies (ANA) associated with systemic lupus erythematosus (SLE), Slögren's syndrome, scleroderma and polymyositis/dermatomyositis, the immunogenetic factors associated with these four autoimmune diseases, and the possible role of autoantibodies in the etiopathogenesis of autoimmune disease. The antibodies associated with systemic rheumatic diseases serve as important tools in the initial diagnosis, and they are also useful in the evaluation of prognosis. However, for correct conclusions, the autoantibody findings should be carefully considered and interpreted in clinical context.
8907071 Molecular biology of autoantigens in rheumatic diseases. 1996 Feb The advent of molecular biologic techniques has provided new approaches that are of great utility to the study of autoimmune-mediated responses. In the past few years, there has been a remarkable accumulation of knowledge concerning the molecular identity and function of autoantigens, and further consolidation for the use of autoantibodies as diagnostic markers in clinical rheumatology. The understanding of basis methodologies in molecular biology applied to the study of autoantigens, in particular, techniques for cloning and analyzing genes that are important in rheumatic diseases, is valuable for both basic scientists and clinicians interested in diagnostic and prognostic markers of various connective tissue diseases.
8729419 [Still disease in adults revealed by a digestive manifestation]. 1995 Dec Adult Still's disease is characterized by typical spiking fever, oligopolyarthritis, neutrophilic leukocytosis and involvement of various organs. We report a case which illustrated typical digestive features of Still's disease as dysphagia, peritonitis and manifests the hitherto unreported complication of gastric ulcerations. Treatment with prednisone was started in order to control arthritis, resulting in improvement of both gastric ulcerations (partially resistant to omeprazole treatment) and arthralgia. After seven years of follow-up, the patient remains clinically and biochemically stable with steroid and methotrexate treatment.
8835243 Increased soluble CD23 molecules in serum/saliva and correlation with the stage of sialoec 1995 Nov OBJECTIVE: We examined the soluble CD23 (sCD23) molecules in sera and saliva from patients with Sjögren's syndrome. METHODS: The determination of sCD23 and other soluble molecules were made by the enzyme-linked immunosorbent assay. RESULTS: The amounts of sCD23 in the sera/saliva were significantly increased in the patients compared to the controls and the levels were significantly correlated with sialoectasis. CONCLUSION: The findings suggest that increased sCD23 molecules in saliva from patients with Sjögren's syndrome may reflect active sialoectasis.
8531364 [T cell receptor repertoire of infiltrating T cells in the interstitial nephritis of patie 1995 Oct We examined the T cell receptor (TCR) repertoire of infiltrating T cells in the kidney, labial salivary glands (LSGs) and peripheral blood lymphocytes (PBLs) in Sjögren's syndrome (SS) patients with interstitial nephritis. The TCR V beta gene repertoire in kidney was more restricted compared with that in LSGs and PBLs. The TCR V beta 2 gene was predominantly expressed in six of seven kidneys (86%). Junctional sequence of TCR V beta 2 gene shows that some of these cells expanded clonally. The identical TCR clones in the kidneys were not detected in LSGs and the amino acid (Arg96) in the CDR3 region of V beta 2 gene was conserved specifically in kidneys. These findings suggest that T cells infiltrating in the kidneys from SS patients with interstitial nephritis identify different autoantigens from LSGs rather than superantigen.
7788146 Cytokine mRNA expression in the labial salivary gland tissues from patients with primary S 1995 Apr The pattern of cytokine mRNA expression in frozen minor salivary gland tissues from patients with primary Sjögren's syndrome (pSS) (n = 12) and controls (n = 8) using an in situ hybridization technique and oligonucleotide probes of interleukin-1 beta (IL-1 beta), tumour necrosis factor alpha and beta (TNF-alpha and TNF-beta), interleukin-6 (IL-6), interleukin-2 (IL-2) and its receptor (IL-2R), interleukin-4 (IL-4), interleukin-10 (IL-10), interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta) was examined. In addition to in situ hybridization, immunohistochemistry was used to identify the subset of cells expressing IL-2 and IL-4 mRNA. Mononuclear cells involved in the minor salivary gland lesions of pSS patients were found to express mRNA for pro-inflammatory cytokines such as TNF-alpha and IL-1 beta, and cytokines involved in the regulation of B- and T-cell function (IL-2 and IL-6). In contrast, only three biopsies from patients with pSS express mRNA of inhibitory cytokines such as IFN-gamma and TGF-beta. Furthermore mRNA for IL-6 and IL-1 beta was also detected in the glandular epithelial cells suggesting that these cells may play a role in the pathogenesis of autoimmune lesion in Sjögren's syndrome. IL-10 mRNA was not detected while IL-4 mRNA was primarily detected in naïve T-lymphocytes of patients with a mild and early lesion. These results suggest that local production of cytokines by both mononuclear and epithelial cells may be involved in the immune-mediated destruction of exocrine glands in patients with pSS.
8033568 Three different types of dry eye syndrome. 1994 May We analyzed patients with dry eye syndrome with regard to autoimmune conditions. A total of 116 patients with dry eye syndrome were divided into three groups: simple dry eye (SDE), i.e., dry eye with no circulating autoantibodies; autoimmune positive dry eye (ADE), dry eye with circulating autoantibodies; and Sjogren's syndrome (SS), dry eye associated with Sjogren's syndrome. Schirmer test showed values of 3.0 +/- 2.2 mm in SDE, 3.1 +/- 2.0 mm in ADE, and 2.4 +/- 2.3 mm in SS reflecting the inadequacy of this test in differentiating among the groups. However, Schirmer test with nasal stimulation showed values of 19.1 +/- 12.4 mm in SDE and 16.4 +/- 10.9 mm in ADE, which were significantly higher than the 7.0 +/- 6.6 mm found in SS (p < 0.01). Moreover, ocular surface alterations evaluated by vital staining and brush cytology were significantly milder in SDE and ADE than in SS. SDE and ADE have less ocular surface abnormalities with good reflex tearing, whereas SS has less reflex tearing and more squamous metaplasia.
8255460 Antineuronal antibodies in patients with neurologic complications of primary Sjögren's sy 1993 Dec Neurologic complications of both the central and peripheral nervous systems occur frequently in patients with primary Sjögren's syndrome (primary SS), but the underlying cause of these complications is unknown. We studied the presence of antineuronal antibodies in relation to neurologic complications in a consecutive series of 45 patients with primary SS. Twenty-five patients had neurologic complications: 12 patients with polyneuropathy, three with psychiatric disorders, four with carpal tunnel syndrome, seven with migraine, seven with myalgia, and four with other complications (transverse myelitis, stroke, Bell's palsy, and pyramidal signs). Ten patients had more than one neurologic complication. Eleven patients had major and 14 had minor complications according to criteria used for rating neurologic complications in patients with systemic lupus erythematosus. Antineuronal antibodies were present in six of 11 (55%) patients with major neurologic complications and in four of 34 (11%) of patients without major neurologic complications (p = 0.001). This difference could be attributed mainly to the group of patients with polyneuropathy. Three of the 10 sera of patients with positive antineuronal antibodies had antibodies reacting with a 38-kd neuronal protein on immunoblotting, identical to the anti-Hu antibody reactivity in paraneoplastic neurologic disease associated with small-cell lung cancer.
8457223 Linkage studies of HLA and primary Sjögren's syndrome in multicase families. 1993 Apr OBJECTIVE: To define the role of HLA-DR phenotype in the expression of primary Sjögren's syndrome (SS). METHODS: A family study of Caucasian probands with definite primary SS was conducted. Relatives with features of primary SS were classified according to the Fox criteria. Several types of linkage analysis between primary SS and HLA haplotype (HLA-A, B, and DR) were performed. RESULTS: A trend toward haplotype sharing between affected siblings was evident for definite/probable primary SS when analyzed by the Green and Woodrow method. This reached statistical significance when data from other published family studies were included. LOD scores and analyses using the Penrose method showed little evidence of linkage. CONCLUSION: In view of the strong association with HLA-DR3, these results suggest that the HLA-DR3 allele is an important susceptibility factor for expression of primary SS in Caucasians. The apparent haplotype sharing may be a consequence of this association. The potential influence of other genetic factors (major histocompatibility complex [MHC] and non-MHC) is discussed.
8274726 Detection of anti-SSB antibodies in patients with rheumatic diseases. 1993 Mar Anti-SSB antibodies were measured by ELISA in patients with various kinds of connective tissue diseases using SSB antigen purified from fresh rabbit thymus. The SSB antigen reacted with anti-SSB standard serum, and the positive rates in SS, SLE, RA, PBS and MCTD were 55.1%, 48.3%, 32.8%, 30.8% and 26.3%, respectively. The titers of anti-SSB antibodies were higher in SS and SLE patients than in other connective tissue disease patients. However, 10% of normal individuals were found to have anti-SSB antibodies with low titers. The anti-SSB antibodies detected were mainly of IgG isotype. Preliminary analysis of clinical data showed no relationship between anti-SSB and systemic involvement in SS.
8856621 The prevalence and meaning of fatigue in rheumatic disease. 1996 Aug OBJECTIVE: To determine the prevalence of fatigue in rheumatic disease; to characterize the strength of associations between demographic and clinical features and fatigue; to identify predictors of fatigue, and to determine the consequence of clinically significant fatigue. METHODS: 1488 consecutive patients with rheumatic disease were assessed with the Clinical Health Assessment Questionnaire, a health status instrument with scales for fatigue, pain, global severity, sleep disturbance, gastrointestinal problems, anxiety, depression, health status, health satisfaction, and work ability. All patients underwent rheumatic disease examinations and laboratory testing. RESULTS: Fatigue measured by visual analog scale (VAS) was present in 88-98% of patients, but clinically important levels of fatigue (> or = 2.0 on VAS) were present in more than 41% of patients with rheumatoid arthritis (RA) or osteoarthritis (OA) and 76% of those with fibromyalgia (FM). Fatigue was related to almost all demographic and clinical variables, but in multivariate analyses the strongest independent predictors of fatigue were pain, sleep disturbance, depression, tender point count and Health Assessment Questionnaire (HAQ) disability. About 90% of the R2 of the model (all patients = 0.51, RA = 0.49, OA = 0.45, FM = 0.41) was explained by pain, sleep disturbance, and depression. In RA assessed by erythrocyte sedimentation rate, joint count and grip strength, no association of the inflammatory process with fatigue could be found in the multivariate analyses. In measuring health status, fatigue was strongly associated with work dysfunction and general measures of health (VAS of global severity, health status, and health satisfaction). CONCLUSION: Fatigue is common across all rheumatic diseases, associates with all measures of distress, and is a predictor of work dysfunction and overall health status. The correlates of fatigue are generally similar across RA, OA and FM. Fatigue assessment adds much to understanding and management of patients and diseases.
7932408 Synergistic inhibition of T cell proliferation by gold sodium thiomalate and auranofin. 1994 Jun OBJECTIVE: Gold compounds have been employed as therapeutic agents for rheumatoid arthritis (RA) for many years, but the molecular mechanism of their action is unknown. Our studies were undertaken to compare the immunosuppressive activities of parenteral gold (gold sodium thiomalate; GSTM) and orally active gold (auranofin; AF). METHODS: The effects of GSTM and AF on in vitro models of human T cell activation were examined. RESULTS: GSTM and AF were found to exert a synergistic inhibitory effect on human T lymphocyte proliferation in vitro. The concentrations of GSTM and AF that synergistically inhibit T cell proliferation were easily attainable in the serum or synovium of patients treated with these agents. The synergistic inhibitory effect of GSTM and AF was not apparent when interleukin 2 (IL-2)R expression or IL-2 production was examined. The inhibitory effects of GSTM and AF could not be explained by a synergistic effect on proximal signal pathways. CONCLUSION: Our results demonstrate that GSTM and AF exert distinct effects on T cell responsiveness and together synergistically inhibit mitogen induced T cell proliferation. These results suggest the possibility that the combination of GSTM and AF may exert a heightened therapeutic effect in RA compared to the action of either agent alone.
8981926 The human immunoglobulin V(H) gene repertoire is genetically controlled and unaltered by c 1996 Dec 15 The factors controlling immunoglobulin (Ig) gene repertoire formation are poorly understood. Studies on monozygotic twins have helped discern the contributions of genetic versus environmental factors on expressed traits. In the present experiments, we applied a novel anchored PCR-ELISA system to compare the heavy chain V gene (V(H)) subgroup repertoires of mu and gamma expressing B lymphocytes from ten pairs of adult monozygotic twins, including eight pairs who are concordant or discordant for rheumatoid arthritis. The results disclosed that the relative expression of each Ig V(H) gene subgroup is not precisely proportional to its relative genomic size. The monozygotic twins had more similar IgM V(H) gene repertoires than did unrelated subjects. Moreover, monozygotic twins who are discordant for RA also use highly similar IgM V(H) gene-subgroup repertoires. Finally, the V(H) gene repertoire remained stable over time. Collectively, these data reveal that genetic factors predominantly control V(H) gene repertoire formation.
8578314 Acute-phase proteins in osteoarthritis. 1995 Oct The joint destruction of osteoarthritis (OA) comprises loss of articular cartilage resulting from an imbalance of enzyme-catalized cartilage breakdown and regeneration. OA is thought to derive from defective chondrocyte metabolism and thus to inherently lack the large-scale systemic response that is the hallmark of rheumatoid arthritis (RA). Because of the apparent absence of systemic inflammation in OA, acute-phase response proteins have not been as extensively studied in OA as they have been in RA. The diagnosis of OA almost always involves radiographic assessment of joint damage, which is useful only after the disease process has been underway for several months. Radiographic evaluation cannot give a good assessment of current disease activity and is a relatively insensitive indicator of prognosis. Cartilage breakdown products can potentially serve as direct surrogate markers of OA disease activity, but have not been extensively used because of their limited sensitivity and the technical difficulties associated with their measurement. Markers of disease activity in RA are indirect and are derived from the acute-phase response, a cycle of temporal changes in cellular and metabolic function. The early part of the acute-phase response involves the local action and production of cytokines such as interleukin-1 (IL-1), tumor necrosis factor (TNF-alpha) and IL-6. In the late acute-phase response, these cytokines can effect many systemic changes, including increased production of acute-phase proteins (APP). Three valuable surrogate markers of disease activity in RA are provided by the acute-phase response: the time-honored erythrocyte sedimentation rate (ESR) and the newer APPs C-reactive protein (CRP) and serum amyloid A (SAA). As in RA, the joint destruction of OA involves IL-1, TNF-alpha, and IL-6; however, OA can be viewed as an indolent stimulus of the later (systemic) acute-phase response. Recent studies of the acute-phase response in OA suggest that the concentrations of CRP and SAA are elevated in OA, but to a lesser extent than in RA. In the future, long-term monitoring of CRP concentrations in the blood may permit the earlier detection and more effective treatment of OA.