Characterization of anti-endothelial cell antibodies in systemic lupus erythematosus (SLE).

IgG anti-endothelial antibodies (AEA), as measured by ELISA or immunoblotting technique could be detected in serum samples of 56 out of 64 patients with SLE (88%) and mainly occurred in monomeric form. AEA were not cell specific, because the binding reactivity was absorbed partially by both fibroblasts and peripheral blood mononuclear cells. No correlation was found between the presence of AEA and anti-nuclear antibodies. Immunoblotting revealed reactivity of AEA against endothelial antigens ranging in size from 15 to 200 kD. AEA titres were significantly higher in patients with joint or skin abnormalities, compared with patients without these abnormalities. A significant correlation was found between nephritis in SLE and the presence of AEA reactivity against endothelial membrane antigens of 38, 41 and 150 kD. These data show that the pattern of AEA reactivity in serum of SLE patients is heterogeneous, and suggest that AEA against a limited number of antigens may be involved in the pathogenesis of nephritis in SLE.     

核因子kappa B与体外循环相关性的研究进展

核因子kappa B(NF—κB)是许多促炎因子高表达所必需的转录因子。近年来，随着分子生物学技术的发展，NF—κB对免疫、应激和炎症反应以及淋巴细胞分化和生长的调控作用成为研究的热点。作者就NF—κB在缺血-再灌注及体外循环损伤机制中的作用作一综述，并简要介绍阻断NF-κB激活干预治疗的研究进展。     

Three clinical reports of Kikuchi's lymphadenitis combined with systemic lupus erythematosus

Summary The authors describe three cases of systemic lupus erythematosus (SLE) associated with Kikuchi's histiocitic necrotizing lymphadenitis (HNL). Two patients presented a cytomegalovirus infection concomitantly with Kikuchi's lymphadenitis; in one of them the onsets of SLE and HNL were simultaneous. In the third case an inguinal HNL was concomitant with vaginitis of unknown aetiology.     

Serum glomerular binding activity is highly correlated with renal disease in MRL/lpr mice.

The pathogenesis of lupus nephritis is felt to be mediated by anti-DNA antibodies. However, the anti-DNA response and renal disease do not entirely correspond. We recently developed a new assay which detects immune elements based on their ability to bind glomeruli as an alternative approach to understanding the pathogenesis of this disorder. The glomerular binding activity (GBA) defined by this assay consists of immune elements containing IgG which interact specifically with renal tissue, the binding of which is DNase-inhibitable, but which do not bind to DNA directly. In the current study we assessed the relationship between GBA and renal disease in MRL/lpr mice (both untreated and cyclophosphamide-treated) and compared it with the anti-DNA assay. Both assays were highly correlated with renal disease in untreated mice in terms of proteinuria. In cyclophosphamide-treated mice, however, only a weak correlation between the anti-DNA assay and proteinuria was apparent. GBA, in contrast, was more strongly correlated with proteinuria in treated mice. This correlation improved substantially when the DNase-sensitive component of the GBA was used. GBA appeared related to, but not covariant with, the anti-DNA response. These results demonstrate that GBA is a better correlate of murine lupus nephritis than the anti-DNA assay, and suggest that the immune elements detected by this assay, the DNase-sensitive component in particular, may be pathogenically important.     

Antibody Mediated Complete Congenital Heart Block in the Fetus

Complete congenital heart block (CCHB) affects 1:20,000–25,000 live births and is usually an atrioventricular block; 30–50% of fetuses with CCHB will have a structural anomaly, though recently attention has focused on the etiological influence of autoimmune disease, such as systemic lupus erythematosus. The diagnosis is established by detailed two-dimensional ultrasound scanning of the heart to exclude anomaly coupled with M-mode echocardiography and Doppler blood velocity patterns in the major vessels to detect the uncoupling of atrial and ventricular rhythms. Risk factors for an affected child are discussed. A previously affected child, high titers of anti-Ro antibodies, the presence of anti-Ro (SS-A) and anti-La (SS-B), and maternal HLA DR3 confer high risk. Antibody mediated CCHB is irreversible. Plasmapheresis and immunosuppression have been attempted in affected mothers, with limited success, to reduce the likelihood of the fetus being affected, and steroids have been used to reduce the inflammatory reaction in the heart. In many cases the underlying pathology of the immune system adversely affects utero-placental function requiring careful monitoring of fetal well-being. CCHB renders fetal heart rate monitoring virtually useless, in the antenatal and intrapartum periods. Alternatives are explored.     

Antinuclear antibodies in scleroderma,mixed connective tissue disease and “primary” Raynaud's phenomenon

Summary The diversity of antibodies in patients with scleroderma, mixed connective tissue disease or primary Raynaud's phenomenon could be used as a laboratory aid in the clinical diagnosis. In serum samples of 75 patients we screened for antinuclear antibodies (HEp 2 cells), anti DNA, soluble nucleoprotein and extractable nuclear antigens (Sm, rRNP, Ul-nRNP, SSA/Ro, SSB/La and Scl-70). Distinctive antinuclear antibodies pattern was identified in each group of patients. This immunologic profile is valuable for clinical diagnosis and the preferential association of certain autoantibodies with some diseases and not with others, suggest an antigen-driven stimulus for its production.     

靶向B细胞治疗系统性红斑狼疮研究进展

系统性红斑狼疮(Systemic lupus erythematosus, SLE)是一种慢性、全身多系统受累的自身免疫性疾病。其病因和发病机制尚未完全明确,有研究表明B细胞过度增殖、活化是SLE发病至关重要的环节,也是造成全身多脏器损害的病理基础。因此B细胞成为SLE治疗的新型靶点,本综述主要围绕B细胞相关靶向治疗进展进行讨论,包括靶向B细胞表面抗原、靶向B细胞因子、共刺激阻断、酪氨酸蛋白激酶抑制剂等方面,重点介绍其已经结束或正在进行的临床试验以及实际上市后的临床应用。     

Plasminogen activation in plasma of patients with systemic lupus erythematosus

Summary We measured ₂-plasmin inhibitor-plasmin complexes (PI-PC) in plasma of patients with systemic lupus erythematosus (SLE) to examine the plasminogen activation in SLE. The plasma PI-PC level in 23 patients with SLE was significantly higher than that in 18 normal subjects (P<0.001) and the SLE patients with nephrotic syndrome had higher plasma PI-PC levels than those without nephrotic syndrome (P<0.01). In addition, the plasma PI-PC level was significantly correlated with the level of plasma C3 breakdown products (iC3b/C3dg) in the patients with SLE (r=0.53, P<0.01). These results suggest that plasminogen is activated in plasma of patients with SLE and that the plasminogen activation may be associated with the activation of complement in SLE.     

Assessment of class-specific antibodies against denatured DNA in patients with systemic lupus erythematosus

In this retrospective study 103 serum samples from 16 females with systemic lupus erythematosus (SLE), obtained during a mean follow-up time of 2 years, were investigated for the presence of anti-denatured [single-stranded (ss)] DNA antibodies of the IgG, IgM, and IgA classes. The anti-ssDNA antibodies were determined by an enzyme-linked immunosorbent assay (ELISA), and the results were expressed in three ways: as units derived from a single serum dilution and as two parameters,E andA, calculated from the dose-response curve,E being an estimate of the effective amount of antibodies andA a function of the reaction constant between the antigen and the antibody. The simultaneous occurrence of anti-ssDNA antibodies of all three immunoglobulin classes was seen most often in the patients with the shortest duration of the disease. Clinically active disease was found to correlate with high reaction constants of the IgA anti-ssDNA antibodies. There was also an association between the IgA anti-ssDNA antibody levels and the presence of nephritis. Great fluctuations in the amounts of effective antibodies of the IgG class were seen in seven patients, in six of whom changes in the disease activity also were seen. Changes in the disease activity were unaccompanied by fluctuations in the IgG anti-ssDNA levels in four patients; two of these patients were positive for antibodies against extractable nuclear antigens. We conclude that it is of value to express the results of the anti-ssDNA ELISA as a function of the dose-response curve when monitoring patients with SLE and that immunoglobulin class-specific determinations of anti-ssDNA antibodies may provide information about the disease activity in many patients with SLE.     

Interleukin-10 (IL-10) secretion in systemic lupus erythematosus and rheumatoid arthritis: IL-10-dependent CD4+CD45RO+ T cell-B cell antibody synthesis

Interleukin-10 (IL-10) is a major immunoregulatory cytokine and has a multitude of immunomodulatory effects in the immune system. In this study, we have examined the secretion andin vitro function of IL-10 in B cell hyperactivity in antibody production in two common autoimmune diseases, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). IL-10 was detectable in serum of all active SLE and serum and synovial fluid samples of all RA patients but in none of the normal controls. B cells and CD4+CD45RO+ memory T cells secreted highly enhanced levels of IL-10 in SLE and RA versus normals. Increased IgM and IgG production by B cells-CD4+CD45RO+ T cells in SLE and RA was IL-10 dependent, since neutralization of IL-10 cytokine by anti-IL-10 antibody drastically reduced Ig synthesis in these coculture experiments. B cell hyperactivity in autoantibody production in SLE and RA may be a function of IL-10-dependent CD4+CD45RO+ Th2 cell activation. Therefore, IL-10 may play an important role in highly disturbed immune system and B cell-T cell function in these immune disorders.