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At least 199 records · Page 11Linked to original sources
PubMed1992

Expression of inactive stage anti-dsDNA idiotypes on anti-ssDNA antibodies in a lupus patient during active stage of lupus cerebritis.

The possibility that idiotypes (Ids) defined on anti-double stranded DNA (dsDNA) antibodies during active and inactive stages of lupus (1/84 Id and 4/90 Id, respectively) were expressed on anti-DNA antibodies during a subsequent active period (9/90) of the disease was investigated in a lupus patient with lupus cerebritis. Using rabbit (R)-anti-Ids specific to 1/84 Id and 4/90 Id in inhibition assays, the 4/90 Id was shown to be expressed on the framework regions of anti-single stranded DNA (ssDNA) but poorly on co-existing anti-dsDNA antibodies of active (9/90) stage. The 1/84 Id was poorly expressed on both types of 9/90 anti-DNA antibodies. While the 9/90 anti-ssDNA significantly bound to immobilized ssDNA and several single-stranded polynucleotides, only ssDNA inhibited the binding of the anti-ssDNA to ssDNA, suggesting its monospecificity toward ssDNA. Western blot analysis following isoelectric focusing showed that a spectrotype pattern of 4/90 Id-positive 9/90 anti-ssDNA IgG was similar to that of the 4/90 anti-dsDNA, suggesting that they are of related clonal origin. The present study suggests the idiotypic heterogeneity of anti-DNA antibodies and the shift of antigen specificity within an idiotypically related anti-DNA population during exacerbation of the disease.

Animals↗
PubMed1997

Thyroid antibodies and their relation to antithrombin antibodies, anticardiolipin antibodies and lupus anticoagulant in women with recurrent spontaneous abortions (antithyroid, anticardiolipin and antithrombin autoantibodies and lupus anticoagulant in habitual aborters).

OBJECTIVE: This study was undertaken to evaluate the incidence of thyroid autoantibodies in women with a history of recurrent spontaneous abortions (RSA) and to investigate their relationship to non-organ specific autoantibodies. STUDY DESIGN: 28 euthyroid non-pregnant habitual aborters were analysed for thyreoglobulin (TG), thyroid peroxidase antibodies (TPO), and autoantibodies to thromboplastin, cardiolipin and lupus anticoagulant. 28 multigravidae without previous abortions or endocrine dysfunctions served as controls. RESULTS: 11 of 28 women with recurrent spontaneous miscarriage (39%), but only 2 of 28 controls (7%) (Chi square test: p < 0.01) demonstrated positive titres of TG, TPO, or both antibodies, 12 patients were positive for antithrombin antibodies and 3 for anticardiolipin. Only one women was lupus anticoagulant positive. No significant correlation between thyroid antibody positivity and positivity for antiphospholipids (Fisher's exact test: p = 0.441), anticardiolipin (p = 0.664) or lupus coagulant (p = 0.607) was found. CONCLUSIONS: The incidence of thyroid antibodies in euthyroid women with recurrent pregnancy loss appears to be significantly increased compared with controls of reproductive age without previous abortions. No correlation between the presence of thyroid autoantibodies and non-organ specific autoantibodies could be established.

Abortion, Habitual↗
PubMed2002

Comparison of the responsiveness of lupus disease activity measures to changes in systemic lupus erythematosus activity relevant to patients and physicians.

Both the revised Systemic Lupus Activity Measure (SLAM-R) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) are valid and reliable measures of disease activity in systemic lupus erythematosus (SLE). However, more study of their responsiveness is needed. The purpose of this study was to compare the responsiveness of SLAM-R and SLEDAI to disease activity changes relevant to physicians and patients. Patients were evaluated monthly for up to 12 months. At each visit, the physician completed SLAM-R and SLEDAI. Patients and physicians assessed whether relevant improvement or worsening of disease activity had occurred since the previous visit. Based on repeated measurements, effect size (ES), standardized response mean (SRM), and control-standardized response mean (CSRM) were calculated for each response category, with bootstrap-based 95% confidence intervals (CIs). Seventy-six patients contributed 471 score changes. For physicians' responses, the CSRMs for SLAM-R and SLEDAI were -0.47 versus -0.42 for improvement, 0.04 versus 0.003 for no change, and 0.65 versus 0.66 for deterioration. For patients, the CSRMs for SLAM-R and SLEDAI were -0.31 versus -0.18 for improvement, -0.08 versus 0.06 for no change, and 0.48 versus 0.05 for deterioration. Only for SLAM-R did the 95% CIs exclude zero when improvement or deterioration were detected. Similar results were found for ES and SRM. Both SLAM-R and SLEDAI are responsive to changes in SLE disease activity important to physicians. Only SLAM-R is responsive to changes important to patients. These differences may result from the inclusion of subjective SLE manifestations in SLAM-R.

Adult↗
PubMed2003

Defective activity of ERK-1 and ERK-2 mitogen-activated protein kinases in peripheral blood T lymphocytes from patients with systemic lupus erythematosus: potential role of altered coupling of Ras guanine nucleotide exchange factor hSos to adapter protein Grb2 in lupus T cells.

The integrity of the Ras/Raf/mitogen-activated protein kinase (MAPK) cascade is critical for maintenance of T cell tolerance, a process that fails in patients with systemic lupus erythematosus (SLE). In this study we have examined the activity of mitogen-activated protein kinases ERK-1 and ERK-2 in resting and TCR-activated peripheral blood T lymphocytes from patients with SLE. We also examined the binding of Ras guanine nucleotide exchange factor, human Son of Sevenless (hSos), to cytosolic adapter protein growth factor receptor-bound protein 2. T cells from lupus patients showed diminished catalytic activity and TCR-driven dual phosphorylation of ERK-1 and ERK-2 upon stimulation through the TCR/CD3 receptor, a defect that may be related to altered translocation of hSos to the Ras/Raf membrane complex and diminished nuclear translocation of trans-acting factor AP-1. Defective MAPK activity triggered by TCR/ CD3 activation may alter the coordination of signals needed for normal interleukin-2 production and maintenance of tolerance in lupus T cells.

Adaptor Proteins, Signal Transducing↗
PubMed2001

A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus.

In systemic lupus erythematosus, antibodies against double-stranded DNA are a major contributor to renal disease. We have previously demonstrated that the pentapeptide Asp/Glu-Trp-Asp/Glu-Tyr-Ser/Gly is a molecular mimic of double-stranded DNA. This sequence is also present in the extracellular domain of murine and human NMDA (N-methyl-D-aspartate) receptor subunits NR2a and NR2b. Here we show that the NR2 receptor is recognized by both murine and human anti-DNA antibodies. Moreover, anti-DNA antibodies with this cross-reactivity mediate apoptotic death of neurons in vivo and in vitro. Finally, we show that the cerebrospinal fluid of a patient with systemic lupus erythematosus contains these antibodies and also mediates neuronal death via an apoptotic pathway. These observations indicate that lupus antibodies cross-react with DNA and NMDA receptors, gain access to cerebrospinal fluid and may mediate non-thrombotic and non-vasculitic abnormalities of the central nervous system.

Animals↗
PubMed2003

Lupus lymphadenitis simulating Kikuchi's lymphadenitis in patients with systemic lupus erythematosus: a clinicopathological analysis of six cases and review of the literature.

Kikuchi's disease (KD) or Kikuchi's lymphadenitis (KL) is a self-limiting disease mostly affecting the cervical lymph nodes of young individuals. Whether the reported cases of KL associated with systemic lupus erythematosus (SLE) were genuine KL or lupus lymphadenitis (LL) simulating KL in SLE patients is not clear. We analyzed six cases of KD-like lymphadenitis occurring in SLE patients and 12 reported cases to clarify the relationship between KL and SLE. We found that not all cases occurred simultaneously with SLE. Eight cases occurred either before or after SLE. These cases might have true KL independent of SLE with the exception of two cases that occurred after SLE, but the patients still had lupus activity. The 10 cases that coexisted with SLE most likely had LL rather than KL. This was supported by the immunohistochemical finding of sparse cytotoxic T cells in those lymph nodes in contrast to abundant cytotoxic T cells usually seen in a typical KL. We conclude that KL is not related to SLE, and KD-like lymphadenitis coexisting with SLE should be regarded as LL. Pathologists should be aware of the possibility that LL can mimic KL in patients with SLE, especially necrotizing-type KL.

Adolescent↗
PubMed1992

A controlled trial of plasmapheresis therapy in severe lupus nephritis. The Lupus Nephritis Collaborative Study Group.

BACKGROUND: The prognosis of patients with systemic lupus erythematosus who have glomerulonephritis is poor, despite treatment with immunosuppressive therapy. Plasmapheresis therapy has been used, but there have been few controlled clinical observations of its efficacy. METHODS: We carried out a randomized, controlled trial comparing a standard-therapy regimen of prednisone and cyclophosphamide (standard therapy) with a regimen of standard therapy plus plasmapheresis in 86 patients with severe lupus nephritis in 14 medical centers. The patients underwent plasmapheresis three times weekly for four weeks. Drug therapy was standardized, with strict adherence to nine detailed medical-management protocols. RESULTS: Forty-six patients received standard therapy, and 40 patients received standard therapy plus plasmapheresis. The mean follow-up was 136 weeks. Six patients (13 percent) in the standard-therapy group and eight patients (20 percent) in the plasmapheresis group died. Renal failure developed in 8 patients (17 percent) in the standard-therapy group, as compared with 10 (25 percent) in the plasmapheresis group. Thirty patients (35 percent) reached stopping points--14 (30 percent) in the standard-therapy group and 16 (40 percent) in the plasmapheresis group. A similar number of patients in each group had a decrease in both the serum creatinine concentration and urinary protein excretion to approximately normal values. Patients treated with plasmapheresis had a significantly more rapid reduction of serum concentrations of antibodies against double-stranded DNA and cryoglobulins. CONCLUSIONS: Treatment with plasmapheresis plus a standard regimen of prednisone and cyclophosphamide therapy does not improve the clinical outcome in patients with systemic lupus erythematosus and severe nephritis, as compared with the standard regimen alone.

Adult↗
PubMed2001

CD4(+) T cells from lupus-prone mice are hyperresponsive to T cell receptor engagement with low and high affinity peptide antigens: a model to explain spontaneous T cell activation in lupus.

Polyclonal CD4(+) T cell activation is characteristic of spontaneous lupus. As a potential explanation for this phenotype, we hypothesized that T cells from lupus-prone mice are intrinsically hyperresponsive to stimulation with antigen, particularly to those peptide ligands having a low affinity for the T cell receptor (TCR). To test this hypothesis, we backcrossed the alpha and beta chain genes of the AND TCR specific for amino acids 88-104 of pigeon cytochrome C (PCC) to the Fas-intact MRL/Mp(+)(Fas-lpr) and to the H-2(k)-matched control backgrounds B10.BR and CBA/CaJ (MRL.AND, B10.AND, and CBA.AND, respectively), and assessed naive CD4(+) TCR transgenic T cell activation in vitro after its encounter with cognate antigen and lower affinity altered peptide ligands (APLs). MRL.AND T cells, compared with control B10.AND and CBA.AND cells, proliferated more when stimulated with agonist antigen. More strikingly, MRL.AND T cells proliferated significantly more and produced more interleukin 2 when stimulated with the APLs of PCC 88-104, having lower affinity for the transgenic TCR. These results imply that one of the forces driving polyclonal activation of alpha/beta T cells in lupus is an intrinsically heightened response to peptide antigen, particularly those with low affinity for the TCR, independent of the nature of the antigen-presenting cell and degree of costimulation.

Amino Acid Sequence↗
PubMed1976

Lupus erythematosus cell preparation-antinuclear factor incongruity. A review of diagnostic tests for systemic lupus erythematosus.

The cases of 20 patients, each of whom has a positive lupus erythematosus cell preparation and a negative antinuclear factor test, are presented. The concept of a false-positive lupus erythematosus preparation is suggested. Five common mechanisms causing a false-negative antinuclear factor test are discussed and evaluated. Clinical material from the 20 patients is described and pitfalls in diagnosing systemic lupus erythematosus are reviewed.

Antibodies, Antinuclear↗
PubMed2005

The CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index): an outcome instrument for cutaneous lupus erythematosus.

We developed and validated a measurement instrument (CLASI-Cutaneous Lupus Erythematosus Disease Area and Severity Index) for lupus erythematosus that could be used in clinical trials. The instrument has separate scores for damage and activity. A group of seven American Dermato-Rheumatologists and the "American College of Rheumatology Response Criteria Committee on SLE (systemic lupus erythematosus)" assessed content validity. After a preliminary session, we conducted standardized interviews with the raters and made slight changes to the instrument. The final instrument was evaluated by five dermatologists and six residents who scored nine patients to estimate inter- and intra-rater reliability in two sessions. Consultation with experts has established content validity of the instrument. Reliability studies demonstrated an intra-class correlation coefficient (ICC) for inter-rater reliability of 0.86 for the activity score (95% confidence interval (CI) = 0.73-0.99) and of 0.92 for the damage score (95% CI = 0.85-1.00). The Spearman's rho (Sp) for intra-rater reliability for the activity score was 0.96 (95% CI = 0.89 to 1.00) and for the damage score Sp was 0.99 (95% CI = 0.97-1.00). Clinical responsiveness needs to be evaluated in a prospective clinical trial, which is ongoing.

Humans↗
PubMed1984

The lupus inhibitor in thromboembolic disease and intrauterine death in the absence of systemic lupus.

This study describes the use of a modified dilute thromboplastin assay for demonstration of the lupus coagulation inhibitor in plasma. A one-stage clotting inhibition assay is used in which the ability of the test plasma to prolong the clotting time of normal plasma is measured. The method is easy to perform and suitable for routine use. Clinical and laboratory data from five patients with the inhibitor but without systemic lupus erythematosus are presented. Thromboembolic manifestations were observed in three patients and obstetric complications possibly due to placenta thrombosis in two. One patient showed a bleeding tendency, associated with prothrombin deficiency. A number of pathological coagulation analyses and other laboratory data may be due to affinity of the lupus inhibitor for negatively charged phospholipids in vitro.

Abortion, Spontaneous↗
PubMed1992

Immunofluorescence microscopy of healthy skin from patients with systemic lupus erythematosus: more than just the lupus band.

Many papers have been published on the lupus band in systemic lupus erythematosus (SLE), but little information exists on the possible diagnostic value of the lupus band and other microscopic immunofluorescence phenomena found in clinically normal skin of patients with SLE. In a study of 297 subjects (66 patients with SLE, 81 patients with other forms of LE, and 150 patients with other systemic connective tissue disorders) it was found that: (a) granular deposits of IgA, IgG, and IgM in the basal membrane zone and in the deeper blood vessels were more common in patients with SLE than in the other two groups; (b) depending on the clinical differential diagnosis, IgA and IgG deposits at the epidermal basal membrane can be specific for SLE; (c) using logistic regression analysis sets of variables can be selected with a high potential to discriminate between SLE and the other groups; and (d) immunofluorescence variables do not duplicate the information for the diagnosis of SLE given by the American Rheumatism Association (ARA) criteria or other laboratory methods. From these results, it is concluded that immunofluorescence microscopy of clinically normal skin is a valuable diagnostic method which should be reconsidered as a potential criterion for the diagnosis of SLE in the next evaluation of the ARA criteria.

Adolescent↗
PubMed1967

Immunopathologic studies of systemic lupus erythematosus (SLE). I. Tissue-bound immunoglobulins in relation to serum antinuclear immunoglobulins in systemic lupus and in chronic liver disease with LE cell factor.

We studied the composition of tissue-bound immunoglobulins and of antinuclear factors by immunofluorescent techniques in five patients with systemic lupus and two with chronic liver disease associated with positive LE cell tests. Renal glomeruli in all seven demonstrated deposits of bound gammaG-globulin and complement, although the presence of gammaA- and gammaM-immunoglobulins was variable. Blood vessel walls contained primarily gammaG-globulin and complement in the systemic lupus patients, but such deposits were absent from vessels in the two with chronic liver disease. We observed antinuclear factors, demonstrated by immunofluorescence, in all three immunoglobulin classes. In six of the seven patients, evidence was obtained of a correspondence between the classes of bound immunoglobulins in glomeruli and vessels and the serum titers of antinuclear immunoglobulins. These observations are consistent with the concept that immunoglobulin deposits in tissues may be derived at least in part from antinuclear factors. Neither bound immunoglobulins nor complement was observed in liver parenchyma of the two patients with chronic liver disease or in two patients with systemic lupus and liver pathology. It thus seems doubtful that serum antibodies play a primary role in the pathogenesis of forms of chronic liver disease associated with positive LE cell tests.

Adult↗
PubMed1996

Occasional series: lupus around the world systemic lupus erythematosus research in the Asia-Pacific region: a co-ordinated and co-operative approach.

Research on SLE in the Asia-Pacific region is presently conducted separately in various centres. A co-ordinated and co-operative approach is advocated for a long-term, prospective study on lupus patients in this region. A pilot study involving Beijing, Shanghai and Singapore has been initiated with the intention of expanding it to a larger study, involving up to 1000 newly diagnosed lupus patients who will be followed up for 10 years. The study design and term definitions are patterned after that of the Euro-Lupus project so as to allow for meaningful comparisons. The protocol was discussed, pretested and revised before arriving at the final version to be used. The principal co-ordinators met and discussed with all pioneer participating rheumatologists to ensure common understanding of definitions and standardisation of laboratory procedures. Preliminary results are expected to be presented in about six months' time together with an invitation for more rheumatologists to participate in the project.

China↗
PubMed2006

Hepatocyte growth factor prevents lupus nephritis in a murine lupus model of chronic graft-versus-host disease.

Chronic graft-versus-host disease (GVHD) induced in (C57BL/6 x DBA/2) F1 (BDF1) mice by the injection of DBA/2 mouse spleen cells represents histopathological changes associated with systemic lupus erythematosus (SLE), primary biliary cirrhosis (PBC) and Sjogren's syndrome (SS), as indicated by glomerulonephritis, lymphocyte infiltration into the periportal area of the liver and salivary glands. We determined the therapeutic effect of hepatocyte growth factor (HGF) gene transfection on lupus using this chronic GVHD model. Chronic GVHD mice were injected in the gluteal muscle with either HVJ liposomes containing 8 microg of the human HGF expression vector (HGF-HVJ liposomes) or mock vector (untreated control). Gene transfer was repeated at 2-week intervals during 12 weeks. HGF gene transfection effectively prevented the proteinuria and histopathological changes associated with glomerulonephritis. While liver and salivary gland sections from untreated GVHD mice showed prominent PBC- and SS-like changes, HGF gene transfection reduced these histopathological changes. HGF gene transfection greatly reduced the number of splenic B cells, host B cell major histocompatibility complex class II expression, and serum levels of IgG and anti-DNA antibodies. IL-4 mRNA expression in the spleen, liver, and kidneys was significantly decreased by HGF gene transfection. CD28 expression on DBA/2 CD4+ T cells was decreased by the addition of recombinant HGF in vitro. Furthermore, IL-4 production by DBA/2 CD4+ T cells stimulated by irradiated BDF1 dendritic cells was significantly inhibited by the addition of recombinant HGF in vitro. These results suggest that HGF gene transfection inhibited T helper 2 immune responses and reduced lupus nephritis, autoimmune sialoadenitis, and cholangitis in chronic GVHD mice. HGF may represent a novel strategy for the treatment of SLE, SS and PBC.

Animals↗
PubMed1999

The composition of the lupus band test (LBT) on the sun-protected non-lesional (SPNL) skin in patients with cutaneous lupus erythematosus (CLE).

The objective of this study was to analyse the different immunoreactants at the dermo-epidermal junction (DEJ) of patients with cutaneous lupus erythematosus (CLE). Sun-protected non lesional (SPNL) skin biopsies from 65 patients with specific cutaneous manifestations of LE and from 18 patients with other dermatologic diseases were tested using the direct immunofluorescence (DIF) technique. Nineteen out of 65 patients with CLE were affected by systemic LE (SLE). We used the conventional chi-squared test to analyse statistical differences between CLE-SLE and CLE-non-SLE groups in the immunological composition of lupus band test (LBT). C3 was the most common component while IgM were the most frequent immunoglobulins (Igs) of LBT in LE patients. No immunoreactants could be demonstrated at the DEJ in patients with other dermatologic diseases. No statistical differences could be found between CLE-SLE and CLE-non-SLE groups as regards the detection of the different immunoreactants at the DEJ. A positive LBT (even for the presence of only one immunoreactant at the DEJ) performed on SPNL skin represents a useful and specific criterion to distinguish patients with lupus erythematosus (LE) from those without LE. We also believe in a prognostic value of a positive LBT on SPNL skin when the deposition of at least two immunoreactants is demonstrated, and especially if the deposits are composed of IgG.

Antibodies, Antinuclear↗
PubMed2002

Propylthiouracil-induced lupus-like syndrome developing in a Graves' patient with a sibling with systemic lupus erythematosus.

A 13-year-old girl with Graves' disease, whose younger sister had systemic lupus erythematosus, developed polyarthralgia, fever, neutropenia, hypergammaglobulinemia, and microscopic hematuria after treatment with propylthiouracil (PTU) for 2 years. Myeloperoxidase-anti-neutrophil cytoplasmic antibodies were strongly positive. Anti-single- and anti-double-stranded DNA antibodies were positive, whereas LE cells and anti-Sm antibodies were negative. PTU was discontinued and all symptoms subsided gradually. Two years later, the microscopic hematuria had disappeared completely. Both patients had the identical HLA-DR alleles (HLA-DR9). These present two cases in siblings suggest that both sisters had lupus diathesis, and that the elder sister developed a PTU-induced lupus-like syndrome.

Adolescent↗
PubMed2005

Lupus vasculopathy combined with renal infarction: unusual manifestation of lupus nephritis.

A 30-year-old woman with a 10-year history of systemic lupus erythematosus was admitted to our hospital because of the onset of hypertension and renal dysfunction. Renal arteriogram revealed multiple renal infarctions, and cut-off or tapering-stenosis in the interlobular arteries. Renal biopsy showed concentric intimal thickening with narrowed lumen in some arterioles and deposition of IgG/IgM/complement 3 in the wall of arteriole without any active lesions or immune complex deposition in glomeruli. The present case indicates that this type of renal vascular lesion in lupus nephritis, lupus vasculopathy, may cause renal infarction and the loss of renal function without active glomerular lesions.

Adult↗