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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antiphospholipid antibodies (APAb) are often found in systemic lupus erythematosus (LE) (secondary antiphospholipid syndrome), leading to arterial or venous thrombosis. In primary antiphospholipid syndrome other LE-associated symptoms are not detectable. We present the clinical course and therapy of three patients with this rarely reported disease, discussing immunopathology and therapy. Three young patients (28, 29 and 31 years) were seen at the university eye clinic, presenting severe occlusive vasculitis with vitreal haemorrhages and/or thrombosis. The first patient did not respond to any therapy (various immunosuppressives, plasma-pheresis, laser coagulation) and ended up with defective light perception in both eyes. The second patient also had light perception as final outcome in spite of acetylsalicylic acid, steroids and immunosuppression. The third patient established complete reperfusion on an arteriovenous occlusion after haemodilution and acetylsalicylic acid. Antibodies directed against phospholipids interfere with the blood clotting system in many ways (activation and aggregation of thrombocytes, endothelial function, coagulation cascade). The optimal therapy of this severe disease is unclear, suggesting that acetylsalicylic acid seems to be important, while the effect of immunosuppression or steroids is uncertain.
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PMID:[Retinal vasculitis and antiphospholipid antibodies]. 784 30

Evidence has accumulated suggesting the existence in humans of polarized T helper (Th) cell subsets, coded as Th1 and Th2, with defined cytokine secretion profiles. Immune responses to intracellular bacteria and viruses result in the preferential development of the Th1 cell subset. Th1 cells express cytolytic activity against antigen-presenting cells and provide helper function for IgM, IgG and IgA synthesis only at low T/B cell ratios. In contrast, Th2 cells develop in response to allergens or helminth antigens, provide help for all immunoglobulin classes, including IgE, and lack cytolytic potential. The cytokine milieu in the microenvironment plays a fundamental role in determining the functional phenotype of the subsequent antigen-specific Th1 or Th2 responses. In recent years it has become clear that Th1 and Th2 cells play different roles not only in protection against exogenous offending agents, but also immunopathology. Th2 cells are involved in immunopathology induced by helminths and are responsible for the initiation and maintenance of allergic disorders. Th1 cells seem to be involved in contact dermatitis, acute allograft rejection and organ-specific autoimmunity, such as thyroid autoimmune disorders, diabetes mellitus or multiple sclerosis, whereas less polarized patterns of Th cells are detectable in target organs of patients with rheumatoid arthritis. Sjogren's syndrome or systemic lupus erythematosus.
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PMID:Human Th1 and Th2 cells: functional properties, regulation of development and role in autoimmunity. 785 16

The prevalence of serum anti-DNA antibodies was evaluated by ELISA using oxidatively damaged DNA as antigen in 21 patients with systemic lupus erythematosus (SLE), in 9 spouses and in 15 first-degree relatives. These were compared with 12 healthy controls. There was no significant difference in the levels of serum antibodies detected between the group of spouses and normal controls with all results within the normal range of the assay. Binding of serum antibodies to the oxidatively damaged DNA was detectable in 12 (80%) of the relatives studied, and the range of values obtained overlapped significantly with the SLE patient group. The relevance of these antibodies to the immunopathology of SLE is unclear since they appear to be present in the absence of any clinical symptoms. However, they may be useful predictively as a marker for those individuals who are more likely to develop SLE.
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PMID:Binding of anti-DNA antibodies to oxidatively damaged DNA in spouses and relatives of patients with systemic lupus erythematosus. 800 28

Anti-DNA antibodies have been successfully induced in normal, nonautoimmune mice by immunization with complexes formed with a DNA-binding peptide, Fus1, and native, B form, mammalian DNA. Fus1 is a 27-amino acid peptide from the internal domain of a ubiquitin fusion protein from Trypanosoma cruzi. The structure of this peptide is homologous to the consensus amino acid sequence for a DNA-binding, "zinc finger" motif, and the peptide binds to DNA. A panel of six anti-DNA antibody-producing hybridomas, two IgM and four IgG2a, have been generated from a single BALB/c mouse immunized with Fus1-DNA. The V region structures for both H and L chains of the induced anti-DNA antibodies are highly homologous if not identical to the V region structures of spontaneous anti-DNA antibodies from autoimmune (NZB x NZW)F1 mice. The DNA specificities of the anti-DNA antibodies were also similar to those of autoimmune anti-DNA antibodies. Three of the four induced IgG antibodies bound equally well to native and denatured DNA. These results demonstrate that antibody specific for nDNA can be induced with immunogenic complexes of native DNA. They also demonstrate that monoclonal representatives of the induced anti-DNA antibodies have serologic and structural characteristics similar if not identical to those of spontaneous anti-DNA antibodies from autoimmune mice. The experimental system described here should provide insight not only about the structural basis for autoimmunity to DNA but also the function of anti-DNA antibody in the immunopathology of SLE.
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PMID:Structural similarity of antibody variable regions from immune and autoimmune anti-DNA antibodies. 849 96

Systemic lupus erythematosus (SLE) is an autoimmune disease occasionally involving the conjunctiva, sclera or cornea. The immunopathology of the active epibulbar lesions has not been studied in detail. Conjunctival biopsies from 11 SLE patients with active epibulbar lesions and from 12 age-matched individuals undergoing cataract surgery were analysed by light microscopy, immunofluorescence and immunoperoxidase techniques. SLE patients presented with scleritis (3 cases), peripheral ulcerative keratitis (5 cases) or progressive cicatrising conjunctivitis (5 cases). Histologically, SLE specimens showed moderate subepithelial and perivascular mononuclear cell infiltration or granuloma formation in the substantia propria, and squamous metaplasia; thrombosis was not seen. Immunoreactant deposition was present at the epithelial basement membrane in 4 of 5 cases with cicatrising conjunctivitis. Vascular immunodeposits wer detected in 4 cases. The epithelium showed increased T helper cells (CD4+), granulocytes and natural killer cells (CD67+), dendritic cells (CD1+), and an increase in HLA-DR expression compared with normal tissue. In the substantia propria, B cells (CD22+), macrophages (CD14+), dendritic cells, activated T cells (CD25+, CD3+), the T helper (CD4+)/T suppressor (CD8+) ratio and HLA-DR expression were all increased. These observations suggest that the rare epibulbar manifestations in SLE result from immune-complex-mediated reactions.
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PMID:Histology and immunopathology of systemic lupus erythematosus affecting the conjunctiva. 894 91

The author highlights some of the clinical, biological and serological signs associated with systemic lupus erythematosus and use them as keys to enter into the most recent advances in the immunopathology of the disease, in particular the mechanisms underlying the production of pathogenic autoantibodies.
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PMID:Systemic lupus: from the bedside to the laboratory bench. 935 Feb 96

Interleukin-1 (IL-1) is thought to play an important role in the immunopathology of systemic lupus erythematosus (SLE). IL-1 receptor antagonist (IL-1ra) exhibits a dose-responsive inhibition of IL-1 effects, and Fcr receptors play a key role in IL-1ra production. To clarify the relationship between IL-1, IL-1 receptor antagonist (IL-1ra) production, and Fcr receptors in SLE, fifteen untreated lupus patients (9 females and 6 males) were evaluated. IL-1 and IL-1ra production from both monocytes and neutrophils was determined by both a murine thymocyte proliferation assay and ELISA. The expression of Fcr receptors on both monocytes and polymorphonuclear cells was measured by flow cytometry. There was no significant difference between IL-1 beta and IL-1ra production from ex vivo monocytes between lupus patients and normals. However, serum IL-1ra was significantly higher in lupus patients than in normals. The expression of FcrRII (CD32) on monocytes was lower in lupus patients than in normals. There was no correlation between the expression of FcrRII and the serum immune complexes; the production of IL-1ra and the expression of CD32, serum immune complex levels, and serum IgG. Both serum IL-ra and the production of IL-1ra had no correlation to SLEDAI, C3, C4, C1q, or ESR. These observations suggest that although IL-1 and IL-1ra may not play a major role in the initiation of pathogenesis of lupus, the low FcrRII expression in lupus may reflect low immune complex clearance and contribute to disease pathogenesis.
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PMID:Interleukin-1 and interleukin-1 receptor antagonist in systemic lupus erythematosus. 939 6

In both mice and humans, functionally distinct helper T (Th)-cell subsets, known as Th1 and Th2 cells, are characterized by the patterns of cytokines they produce. These two polarized forms of the specific cellular immune response provide a useful model for explaining not only the different types of protection, but also the pathogenic mechanisms of several immunopathological disorders. The development of polarized Th1 or Th2 responses depends on either environmental factors, including dose of antigen, nature of immunogen and cytokines (IL-12 and interferons or IL-4) at the time of antigen presentation, or other undefined factors in the individual genetic background, mainly at level of the so-called "natural immunity". Th1-dominated responses are potentially effective in eradicating infectious agents, including those hidden within the host cells. When the Th1 response is poorly effective or exhaustively prolonged, it may result in host damage. In contrast, Th2 responses are apparently insufficient to protect against the majority of infectious agents, but can provide some protection against parasites. Th2 cells are able to make unpleasant the life of parasites in the host and tend to limit potentially harmful Th1-mediated responses. Thus, Th2 cells may be regarded as a part of down regulatory (or suppressor) mechanism for exaggerated and/ or inappropriate Th1 responses. The Th1/Th2 paradigm applied to the study of chronic inflammatory disorders or autoimmune diseases allowed to understand that a number of diseases are mediated by Th1 cells, the two clearest examples being multiple sclerosis and thyroid autoimmunity. In other disorders, Th1/Th2 polarization is less prominent, or rather Th2 responses tend to predominate, such as in systemic lupus erythematosus, progressive systemic sclerosis or allergic diseases. It is of note that in experimental models in animals, a number of diseases can be prevented by switching immune responses from Th1 to Th2 or from Th2 to Th1. Moreover, the Th1/Th2 concept suggests that modulation of the relative contribution of Th1- or Th2-type cytokines makes possible to regulate the balance between protection and immunopathology, as well as the development and/or the severity of some immunologic disorders.
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PMID:The concept of type-1 and type-2 helper T cells and their cytokines in humans. 950 98

Hormonal factors linked to age, gender, and reproductive status are undoubtedly involved in regulating the onset of numerous autoimmune diseases. For example, systemic lupus erythematosus (SLE), a disease characterized by immune complex-mediated pathology linked to excess Th2 cytokine production (e.g., IL-10) primarily affects women in the reproductive years. Rheumatoid arthritis (RA), a disease characterized primarily by cell-mediated joint immunopathology linked to deficient Th2 cytokine production, is also more common in women, but, in contrast to SLE, the highest incidence is at menopause. Pregnancy-associated changes in these diseases, however, provide the most compelling evidence that hormonal factors play a major role in modulating the expression of these diseases. SLE often flares during pregnancy, whereas RA commonly remits during pregnancy and flares or initially develops in the postpartum period. These observations appear to be explained by the accumulating data indicating that during pregnancy cell-mediated immune function and Th1 cytokine production (e.g., IL-12, interferon-gamma) are suppressed, and humoral immunity and Th2 cytokine production (e.g., IL-4, IL-10) are enhanced. These patterns reverse in the postpartum period. In other words, antithetical Th1/Th2 cytokine profiles appear to characterize pregnancy and the postpartum period. Strong evidence now indicates that changes in the production of cortisol, progesterone, and estrogen play a major role in modulating Th1/Th2 cytokine balance.
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PMID:Hormones, pregnancy, and autoimmune diseases. 962 35

L7 is one of the ribosomal proteins frequently targeted by autoantibodies in rheumatic autoimmune diseases. A computer search revealed a region within the immunodominant epitope of L7 (peptide II) that is highly homologous to amino acid sequence 264-286 of the RNA polymerase major sigma factor of the eubacterium Chlamydia trachomatis. Anti-L7 autoantibodies affinity purified from the immunodominant epitope were able to recognize this sequence as they reacted with purified recombinant sigma factor. Immunofluorescence labeling experiments on C. trachomatis lysates revealed a punctate staining pattern of numerous spots when incubated with the affinity-purified anti-peptide II autoantibodies. Binding of autoantibodies to peptide II was inhibited by the homologous sigma peptide. This is the first demonstration of epitope mimicry between a human and a chlamydial protein on the level of B cells. Antibody screening revealed a significant correlation between the presence of anti-L7 autoantibodies and C. trachomatis infection in patients with systemic lupus erythematosus and mixed connective tissue disease. Our results suggest that molecular mimicry is involved in the initiation of anti-L7 autoantibody response and may represent a first glance into the immunopathology of Chlamydia with respect to systemic rheumatic diseases.
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PMID:Correlation between chlamydial infection and autoimmune response: molecular mimicry between RNA polymerase major sigma subunit from Chlamydia trachomatis and human L7. 984 29


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