bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presence of cutaneous interferon-a producing cells in patients with systemic lupus erythematosus
Authors: Blomberg S , Eloranta M L , Cederblad B , Nordlind K , Alm G L , Rönnblom L 
Published: November 2003

Systemic lupus erythematosus (SLE) patients have increased levels of interferon-alfa (IFN-a) in the circulation but a reduced number of functionally intact natural IFN-a producing cells (IPC) in peripheral blood. In search for tissue localisation of activated IPC, we investigated skin biopsies from SLE patients for the occurrence of such cells. Eleven SLE patients with inflammatory skin lesions and six healthy controls were biopsied. An immunohistochemical technique (IH) and in situ hybridisation (ISH) were used to detect intracellular IFN-a protein and IFN-a mRNA, respectively. In all 11 biopsies from SLE lesions, a high number of IPC were detected by IH. In the nonlesional SLE biopsies we could also demonstrate IPC in 10=11 patients. In 6=11 SLE patients, IFN- a mRNA containing cells could be detected in the specimens. A low number of IPC were detected in 1=6 healthy controls by IH, but no ISH positive cells were seen. Our results demonstrate that SLE patients have active IPC in both dermal lesions and in noninflammatory skin. A recruitment of IPC from blood to peripheral tissues may explain the low number of circulating natural IPC in SLE patients. Because the type I IFN system is involved in the SLE disease process, these results are of interest for the understanding of the pathogenesis in SLE.
Systemic lupus erythematosus in Aborigines and Caucasians in central Australia: a comparative study
Authors: Segasothy M , Phillips P A 
Published: November 2003

The objective of this study was to determine whether there are differences in the prevalence, clinical and laboratory manifestations, and morbidity and mortality of systemic lupus erythematosus (SLE) between Aborigines and Caucasians in Central Australia. The medical records of all patients diagnosed with SLE upto December 1999 were reviewed retrospectively. Prevalence of SLE was 1:1360 for Aborigines and 1:5170 for Caucasians. The prevalences of malar rash, discoid rash, photosensitivity, oral ulcers, pleuritis, anticardiolipin antibodies and lupus anticoagulant were higher in Caucasians than in Aborigines. The prevalences of anti-Sm antibody and anti-RNP antibody were higher in Aborigines than in Caucasians. These differences did not attain statistical significance. There was a low prevalence of renal disease in Aborigines and Caucasians. Mortality was low in Aborigines and nil in Caucasians. Although there is a high prevalence of SLE in Aborigines in Central Australia, renal involvement and mortality are low.
The effects of a human IgM monoclonal anticardiolipin antibody on pregnancy in a transgenic mouse model
Authors: Mason A N , Mageed R A , Mackworth-Young C G 
Published: November 2003

The clinical features of antiphospholipid (or Hughes') syndrome (APS) are most commonly seen in individuals who have raised levels of IgG anticardiolipin antibodies. Most murine models of the syndrome have involved the administration of such antibodies to normal mice. However, APS can occur in the presence of raised levels of serum IgM anticardiolipin antibodies alone. The present study was designed to see if an IgM monoclonal antibody can induce changes in mice similar to those seen in human APS. This antibody, BH1, has previously been derived from a patient with primary APS. In its ligand-binding and idiotypic characteristics it is representative of antiphospholipid antibodies (aPL) found in the serum of patients with APS. In order to minimise the immune response to human IgM, we used transgenic mice (F15) which express, and are predicted to be tolerant of, human immunoglobulin m chains. The features of APS may develop more readily in individuals who have an existing autoimmune disorder, such as systemic lupus erythematosus (SLE). We therefore crossed these transgenic mice with New Zealand Black (NZB, SLE-prone) mice, and used the progeny (F15 × NZB/F1) in our experiments. Twenty-four F15 × NZB/F1 mice were given BH1, or a control IgM antibody, (A5566) immediately preceding and then three times during pregnancy There was a reduction in the mean number of foetuses in animals given BH1 compared with those given A5566 (8.6 vs 11.0; P 0.05), and a similar reduction in mean total foetal weight per pregnancy (9.05 vs 12.73 g; P 0.05). Two mice showed a marked reduction in platelet count. No evidence of thrombosis was detected macroscopically or histologically. Our results show a lower incidence of APS-type features compared to previous studies in which mice have been administered aPL. This may be because BH1 is an IgM antibody. Nevertheless, the data support the concept that IgM aPL of particular ligand-binding specificities may have a direct pathogenetic role in certain cases of human APS.
Morphologic capillary changes and manifestations of connective tissue diseases in patients with primary biliary cirrhosis
Authors: Fonollosa V , Simeón C P , Castells L , Garcia F , Castro A , Solans R , Lima J , Vargas V , Guardia J , Vilardell M 
Published: November 2003

The objective of this study was to investigate the presence of nailfold capillary abnormalities and extrahepatic signs of connective tissue disease in patients with primary biliary cirrhosis (PBC), as compared to patients with other chronic liver diseases. We evaluated 22 patients with PBC and 15 patients with other chronic liver diseases as a control group. Nailfold capillaroscopy was performed by two observers blinded to clinical findings using a Wild M3 stereomicroscope with an Intralux 5000 Volpi cold light lamp. We detected nailfold capillary abnormalities in 20 out of 22 (91%) PBC patients. Twelve of these 20 patients (54%) showed capillary alterations characteristic of systemic sclerosis. In the control group only two out of 15 patients (13%) presented alterations and in both cases they were a nonspecific type. The presence of nailfold capillary abnormalities was significantly greater in PBC patients than in the control group (P < 0.001). Eleven out of the 22 PBC patients (50%) had extrahepatic signs of connective tissue disease and most of them were related to systemic sclerosis; patients with other chronic liver diseases did not present rheumatic manifestations (P < 0.001). In PBC patients there was a significant association between systemic sclerosis capillary pattern and rheumatic manifestations (P < 0.03). The high prevalence of nailfold capillary abnormalities characteristic of systemic sclerosis in patients with PBC and the correlation with sclerodermal manifestations suggests that this capillaroscopic finding could be a useful indicator to investigate rheumatic manifestations in these patients.
Dual binding capabilities of anti-double-stranded DNA antibodies and anti-ribosomal phosphoprotein (P) antibodies
Authors: Takeda I , Rayno K , Movafagh F B , Wolfson-Reichlin M , Reichlin M 
Published: November 2003

The aimof this study is to identify distinctive properties of pathogenic anti-double stranded DNA antibodies and anti-ribosomal P antibodies. The binding activity of anti-dsDNA and anti-ribosomal P antibodies to their cognate antigens in 0.15 M and 1.5 M NaCl solutions on ELISA was examined. All anti-dsDNA and anti-ribosomal P antibodies exhibited a loss of their binding activity from37.5 to 100% and from2.3 to 97.4% in high ionic strength buffers, respectively. In contrast, anti-U1RNP antibodies and anti-Ro/SSA antibodies lost from0 to 32.7% and from0 to 40.1% of their binding activity, respectively. Anti-dsDNA and anti-ribosomal P antibodies from patients with nephropathy showed significantly higher binding activity in high ionic strength buffers than those frompatients without nephropathy. Study of paired sera fromlupus nephritis patients revealed that anti-dsDNA and anti-ribosomal P antibodies frompatients during disease flare show stronger binding activity in high ionic strength buffer than those during remission. Most anti-dsDNA and anti-ribosomal P antibodies bind their antigens by ionic interactions that are sensitive to high salt. Such dual binding capability of anti-dsDNA and anti-ribosomal P antibodies may underlie their multiple cross reactivities to various epitopes and help elucidate the pathogenic potential of autoantibody subsets.
Fas expression on peripheral blood lymphocytes in systemic lupus erythematosus (SLE): relation to lymphocyte activation and disease activity
Authors: Bijl M , Horst G , Limburg P C , Kallenberg C GM 
Published: November 2003

Levels of apoptotic lymphocytes have been found to be increased in SLE and persistence of apoptotic cells has been associated with autoantibody production. Increased lymphocyte Fas (CD95) expression due to lymphocyte activation may account for increased susceptibility to Fasmediated apoptosis in SLE. Flowcytometry was performed to evaluate membrane expression of Fas in combination with the activation markers CD25, HLA-DR and CD38 on, respectively, CD4+, CD8+ and CD19+ lymphocytes of SLE patients with inactive (n = 20) and with active disease (n = 13). SLEDAI-scores were calculated. Healthy volunteers (n = 14) served as controls. Percentages of CD4+ T-cells expressing CD25 and CD19+ B-cells expressing CD38 were increased in patients with active disease compared to controls (P = 0.03, P = 0.04, respectively). In contrast to CD4+ and CD8+ cells, percentages of CD19+ cells expressing Fas were increased in SLE patients with active disease (P = 0.0002 vs controls). In these patients percentages of cells double positive for both CD38 and Fas were increased compared to patients with inactive disease (P = 0.006) and controls (P = 0.0007). Percentages of CD19+ cells expressing Fas correlated with SLEDAI-scores. In SLE patients, percentages of Fas-expressing B-lymphocytes are increased, are related to the state of lymphocyte activation, and correlate to disease activity. Increased Fas expression results in a higher susceptibility for Fas-mediated apoptosis, which might contribute to the increased levels of apoptoticlymphocytes in SLE patients.
Anticardiolipin antibodies are not associated with rheumatic heart disease
Authors: Ilarraza H , Márquez M F , Alcocer A , Bañales J L , Nava A H , Reyes P A 
Published: November 2003

The aim of this study was to examine the prevalence of anticardiolipin antibodies in rheumatic valve heart disease. Serum samples of 31 consecutive patients with rheumaticheart disease and documented valve involvement, as well assix patients with acute rheumatic fever were tested for IgGanticardiolipin antibodies by a validated ELISA. No anticardiolipin antibodies were found when a cut-off point set at mean 5 s.d. was applied. We can conclude that anticardiolipin antibodies are notpresent in rheumatic heart disease patients and, as suggested by several observations, these antibodies do not appear to have a pathogenic role in this particular disease.
Suppression of renal disease and mortality in the female NZBNZW F1 mouse model of systemic lupus erythematosus (SLE) by chenodeoxycholic acid
Authors: Suwannaroj S , Lagoo A , McMurray R W 
Published: November 2003

The objective of this study was to examine the effects of ursodeoxycholic (UDCA) and chenodeoxycholic acid (CDCA) on autoimmune disease in the NZBNZW F1(B =W) mouse model of systemic lupus erythematosus (SLE).The development of murine lupus was assessed in female B/W mice given UDCA or CDCA. At 6 week intervals mice were examined for weight change, albuminuria, anti-DNA antibody and total IgG levels. Morbidity and mortality were assessed daily. UDCA-and CDCA-treated mice were examined at 24 weeks of age for serum cytokines, lymphocyte phenotype, and in vitro cytokine production after immunization with DNP-KLH. Liver and kidneys were examined histopathologically.The administration of UDCA and CDCA was tolerated without side effects. Weight gain in UDCA-or CDCA-treated and control mice was identical through 24 weeks of age. CDCA, but not UDCA, suppressed the development of renal disease. CDCA-treated B/W mice also had improved survival compared to UDCA-treated or control B/W mice. There were no significant effects of CDCA on anti-DNA antibodies, serum total IgG, or other immunologic parameters. CDCA-treated mice had lower serum IFN-g concentrations compared to control and UDCA-treated mice.The bile acid, CDCA, significantly inhibited the development of renal disease and modestly prolonged lifespan in the female B/W mouse model of SLE. Suppression of glomerulonephritis was associated with lower serum IFNg concentrations. Further investigation is needed to verify potential mechanisms of action, but these findings suggest that bile acids may alter the development or progression of autoimmunity.
Polymorphisms of the human prolactin gene—implications for production of lymphocyte prolactin and systemic lupus erythematosus
Authors: Stevens A , Ray D W , Worthington J , Davis J RE 
Published: November 2003

Hyperprolactinaemia is associated with systemic lupus erythematosus (SLE) but the mechanism is unknown. Prolactin is expressed not only by pituitary lactotrophic cells but also by T-lymphocytes under the control of an alternative upstream promoter region. T-lymphocytes from SLE patients have been shown to secrete more prolactin than controls, thus implying a possible underlying difference in regulation. This may be due to genetic polymorphism that can be determined by scanning for mutations and using a variety of methods to determine their function. A polymorphism may also be used in disease association studies as it may be in linkage disequilibrium with a disease gene on the same haplotype. Single nucleotide polymorphisms (SNPs) have been found across the prolactin gene region including the extrapituitary and the pituitary promoter regions. These SNPs have been examined for genetic association with SLE and potential effects upon the function of the gene. One SNP in the lymphocyte specific upstream promoter affects prolactin transcription and disease association studies in a cohort of SLE cases demonstrated an increased frequency of the PRL-1149 G allele compared to control subjects. This indicates a possible mechanism for the association of prolactin with SLE. Although prolactin is likely to be one of several predisposing factors in the pathogenesis and progression of SLE, this suggests that manipulation of lymphocyte prolactin production (rather than pituitary production) might be a useful therapeutic approach.
Effects of prolactin on signal transduction and gene expression: possible relevance for systemic lupus erythematosus
Authors: Hooghe R , Dogusan Z , Martens N , Velkeniers B , Hooghe-Peters E L 
Published: November 2003

Receptors for prolactin (PRL-R) are expressed in normal leukocytes from rat and man. PRL signals through PRL-R associated Janus tyrosine kinase (Jak)-2 and signal transducers and activators of transcription (Stat). In addition, in human leukocytes PRL also activates the p38 MAP kinase pathway. PRL, at physiological concentrations, stimulates the expression of the interferon regulatory factor (IRF)-1 gene in rat spleen and bone marrow cells. In man, genes induced by PRL include several members of the `suppressors of cytokine signaling' (SOCS) family and inducible nitric oxide synthase (iNOS; in mononuclear cells and in granulocytes) and IRF-1 (in granulocytes). Thus, in normal leukocytes, PRL induces the expression of several genes relevant to innate and acquired immune responses. Sex hormones, such as estrogen and PRL, have been implicated in the pathogenesis of murine and human SLE. Also defective signaling in leukocytes is a feature of the disease. What the origin is of aberrant signaling processes in SLE lymphocytes and how they relate to tolerance breakdown and immunopathology is still unknown. It is not unlikely that PRL is a player at some level. The exact contribution of PRL to immune responses in normal subjects and in SLE patients is not known. Further work should also indicate whether PRL might contribute to the onset or progression of the disease and assess the possible benefits of manipulating PRL concentrations in patients.
Anti-dsDNA antibody avidity determination by a simple reliable ELISA method for SLE diagnosis and monitoring
Authors: Villalta D , Romelli P B , Savina C , Bizzaro N , Tozzoli R , Tonutti E , Ghirardello A , Doria A 
Published: November 2003

High avidity anti-dsDNA antibodies are more specific for SLE diagnosis, and more closely associated with renal involvement than intermediate or low-affinity anti-dsDNA antibodies. ELISA methods are largely used to detect anti-dsDNA, but their high sensitivity is inversely related to specificity because they also detect low avidity antibodies.We developed an ELISA assay based on the law of mass action and the competitive binding of dsDNA in solution and coated to microwells with anti-dsDNA antibodies. A simplified Scatchard plot analysis system was used to measure anti-dsDNA antibody avidity which was expressed as apparent affinity constant (Kaa), and quantified in liters per unit (l=U). We prospectively studied 101 consecutive SLE patients, who were followed for 3 years; three serum samples were sequentially collected from each patient during follow-up for determination of IgG anti-dsDNA antibody concentration, and anti-dsDNA avidity. SLE disease activity was estimated using the European Consensus Lupus Activity Measure (ECLAM) index. Sera from 100 healthy subjects and 133 patients with other connective tissue diseases or infectious diseases were also assayed as controls. The mean Kaa in SLE patients was 65.2±47.3 l=U, with no variations over time. Anti-dsDNA-positive SLE patients had higher Kaa values (79.1±46.8) than anti-dsDNA negative patients (27.2±20.1; P < 0.001). No correlation emerged between anti-dsDNA avidity and the ECLAM activity index score. Avidity was significantly higher in patients with renal involvement vs patients without this complication (78.2±50 vs 59.9±45.6 l=U; P = 0.0013). This simple ELISA method could be very useful in the diagnostic phase to differentiate high avidity anti-dsDNA autoantibodiesthat are characteristicallyfound in SLE patients from low avidity antibodies that can also be found in other inflammatory diseases. Moreover, our data confirm the predictive value of high avidity anti-dsDNA antibodies for the development of lupus nephritis.
Anti-β2-glycoprotein I autoantibodies require an antigen density threshold, consistent with divalent binding
Authors: Reddel S W , Wang Y X , Krilis S A 
Published: November 2003

Autoantibodies binding β2-glycoprotein I (B2GPI) are an important finding in the antiphospholipid syndrome. While antibodies from mice or rabbits immunized with B2GPI readily bind B2GPI coated on a polystyrene microwell plate, anti-B2GPI autoantibodies only do so when using a modified microwell plate with a negatively charged surface. This study demonstrates that, for the detection of anti-B2GPI autoantibodies in an ELISA using modified plates, an antigen coating concentration threshold exists, such that minimal or no binding occurs below a certain coating concentrationof antigen, even though antigen is easily demonstrable on the plate. This is consistent with the hypothesis that autoantibodies require divalent binding to B2GPI for detection, as sufficient antigen density for two protein molecules to be sufficiently close to enable divalent binding would only be expected to occur at higher coating concentrations. Several mutant forms of B2GPI developed for epitope determination experiments are shown to have decreased binding to microtitre plates compared to wild-type. If wild-type and mutants are assayed for antibody binding near the threshold a significant diminution in binding to mutants occurs that is the result of inadequate binding to the plate, but could be misinterpreted as the result of interruption of an epitope by the mutation.
4-Aminoquinoline antimalarials enhance UV-B induced c–jun transcriptional activation
Authors: Nguyen T Q , Capra J D , Sontheimer R D 
Published: November 2003

Previous work has documented that the earliest observable response in mammalian cells following ultraviolet (UV) irradiation is the activation of plasma membrane-associated Src tyrosine kinases. These molecules then trigger a signalling cascade that results in activation of the transcription factor AP-1 which subsequently transactivates the early immediate genes including c–jun. This pathway has been postulated to play a protective role against UV damage. As aminoquinoline antimalarials such as chloroquine are known to downregulate several photoinduced cutaneous disorders including LE-specific skin disease, we asked whether chloroquine might be capable of modulating this early limb of the UV light response. A431 cells (a human epidermal keratinocyte cell line) that had been transfected with a c–jun luciferase reporter gene construct were then treated with physiologically relevant concentrations of chloroquine followed by exposure to 0—125 J/m2 of UV-B from a bank of unfiltered FS20 lamps. Chloroquine pretreatment resulted in a dose–dependent increase in luciferase activity in permanently transfected A431 cells (luciferase activity was increased by 45% at 2.5 × 10-5 M chloroquine and 125 J/m2 of UV-B). Hydroxychloroquine pretreatment also resulted in an increase in luciferase activity. Primaquine, an 8-aminoquinoline, did not influence the UV-B induced c- jun activity. Furthermore, chloroquine did not have a similar impact on HSP-70 gene activity during heat shock. These studies suggest that the beneficial effect of the 4-aminoquinoline antimalarials in various photodermatoses including cutaneous LE might result in part from the capacity of these drugs to enhance the protective early limb of the UV response.
Survival analysis of 306 European Spanish patients with systemic lupus erythematosus
Authors: Blanco F J , Gómez-Reino J J , de la Mata J , Corrales A , Rodríguez-Valverde V , Rosas J C , de la Camara A Gómez , Pascual E 
Published: November 2003

Objective: To describe survival of lupus in South European Spanish patients. Patients and Methods: Observational study of all SLE Spanish patients seen at three University Hospitals between 1975 and 1993. The charts of all patients were retrospectively reviewed. Sixtyfour clinic and laboratory variables were extracted from charts. Univariate analysis, multivariate Cox proportional hazard regression analysis, actuarial life tables and multiple logistic regression analysis were used to calculate survival probability and identify variables associated with survival. Results: Three hundred and six (275 female and 31 male) patients were identified. Their mean age at diagnosis was 31.9 years (range 4 to 85). The mean duration of followup was 79 (1—126) months. Thirty-one patients died. The most common cause of death was infection (29%). Five, 10 and 15 years' survival rate was 90%–0.0158, 85%–0.0262 and 80%–0.0413, respectively. Log-rank analysis showed that male sex, proteinuria and nephropathy at diagnosis were associated with poor survival. By univariate and multivariate analysis male gender, nephropathy and CNS involvement were associated with worse survival. Conclusion: In SLE patients from Spain, rate of survival is similar to other Caucasian patients, and better than other ethnic groups of Spanish ancestry. Other factors rather than genetic factors could explain our findings.