Evidence for direct anti-heparin-sulphate reactivity in sera of SLE patients.

Recently it has been suggested that anti-ds-DNA antibodies (Abs) promote tissue damage in systemic lupus erythematosus (SLE) by cross-reactivity with highly negatively charged tissue components such as heparan sulphate (HS), the major glycosaminoglycan of the glomerular basement membrane (GBM). Other authors, however, support the theory of DNA-anti-dsDNA immune complex deposition in situ. To further elucidate the possible role of HS antibodies, we developed a new ELISA system with heparan sulphate bound to solid phase. SLE patients (n = 40) showed a higher reactivity against HS (mean = 28.4, SD = 34.3) as compared to normal donors (n = 28, mean = 15.2, SD = 6.3) and patients with rheumatoid arthritis (n = 35, mean = 14.3, SD = 6.4). The addition of native dsDNA or HS to SLE sera was followed by a dose-dependent reduction in anti-HS reactivity. In contrast, in an anti-dsDNA ELISA, no reduction was observed when HS was added to SLE sera. An increase in reactivity was observed when SLE sera with and without a prior incubation with dsDNA were digested with DNAse I or II. After the purification of serum samples by protein A sepharose under dissociative conditions, seven out of eight SLE patients showed an increase in anti-HS reactivity. No correlation of the anti-HS Abs was found with organ involvement or other serological parameters. We concluded, that there is evidence for a direct anti-HS Ab reactivity in SLE sera. A part of these antibodies seems to show low avidity anti-dsDNA cross-reactivity.

Single-photon-emission computed tomography analysis of cerebral blood flow in the evaluation of central nervous system involvement in patients with systemic lupus erythematosus.

OBJECTIVE: Single-photon-emission computed tomography (SPECT) scanning was used to detect potential central nervous system (CNS) involvement in patients with systemic lupus erythematosus (SLE), by determining cerebral blood flow abnormalities. METHODS: SPECT scans were performed on 35 SLE patients, grouped into 3 categories: those without neuropsychiatric symptoms (n = 10), those with definite neurologic or psychiatric disorders (n = 10), and those with mild symptoms such as headache or memory disturbances (n = 15). SPECT scan features were classified as normal or as focal or diffuse defects in uptake. RESULTS: SPECT findings were normal in 9 of the 10 patients without CNS symptoms, and abnormal in 9 of the 10 patients with overt neuropsychiatric disease (with motor or sensory deficits). Interestingly, only 4 of the 15 patients (26.7%) with mild symptoms suggestive of CNS disease had normal SPECT findings; the 11 remaining patients showed focal (53.3%) or diffuse (20%) uptake defects. An association between SPECT findings and disease duration was also observed, but there was no correlation of SPECT results with overall disease activity, serologic findings, or medications used. CONCLUSION: Our data suggest that in a substantial proportion of patients, SPECT analysis may provide additional information on potential CNS involvement, and may therefore be useful in therapeutic decision-making and disease monitoring in order to prevent CNS damage.

A soluble form of the human transferrin receptor is released by activated lymphocytes in vitro.

Soluble transferrin receptors (sTfR) were detected in culture supernatants of activated human peripheral blood mononuclear cells (PBMC) using a sandwich ELISA technique with two non-cross-reacting TfR MoAbs. Mitogenic stimulation of lymphoid cells induced both up-regulation of TfR surface density and release of sTfR to the medium. Peak levels of sTfR in culture supernatants occurred at day 4 after activation, 1 day later than maximum expression of TfR in the plasma membrane. Production of sTfR was independent of proliferation, as demonstrated by measuring sTfR release by PBMC, which had been irradiated with a dose of 20 Gy before activation. In addition to these in vitro experiments, we tested the sera of 85 patients with systemic lupus erythematosus (SLE), an autoimmune disease accompanied by in vivo activation of lymphocytes, for their sTfR levels. No correlation of these data was detectable to serum concentrations of the soluble alpha-chain of the IL-2 receptor, an unequivocal marker of lymphocyte activation. However, they correlated negatively to the haemoglobin content of the patients' erythrocytes, indicating that erythroid progenitors are the predominant source of sTfR in SLE patients' sera.

[Intravenous administration of immunoglobulins in systemic lupus erythematosus: review of the literature and initial clinical experiences]. / Intravenös verabreichte Immunoglobuline beim systemischen Lupus erythematodes: Literaturübersicht und erste klinische Erfahrungen.

About 10 years ago, the first reports about the successful treatment of autoimmune thrombocytopenia with high-dose intravenously administered immunoglobulins (ivIg) were published. Since this time ivIg have been tried for treating almost any autoimmune disease. However, reports about this treatment modality are only anecdotal. So far, ivIg are a widely used and accepted treatment only for autoimmune thrombocytopenia and Kawasaki disease. During the last years many groups tried to gain a better understanding of the mechanisms by which ivIg exert their effects in autoimmune diseases. In systemic lupus erythematosus (SLE) only case reports are available which describe encouraging positive effects of ivIg especially in patients with cytopenia and vasculitis. However in some cases a serious impairment of renal function after ivIg therapy has been reported. This was seen mainly in SLE patients who already had renal involvement before ivIg therapy was started. Therefore, extreme caution should be exercised in these patients until we know more about the pathophysiology of this side effect. We have treated 6 SLE patients with high-dose ivIg (400 mg/kg, 5 days). One patient had a remission for 6 months, another patient for 36 months; in 2 patients with preexisting reduced renal function we observed two acute renal failures and in 1 patient a decrease of the renal function 1 month after ivIg treatment. These preliminary data demonstrate the necessity of controlled clinical trials to prove the effectiveness, to define indications, to find the optimal dosage, and to study the possible mechanisms of action.(ABSTRACT TRUNCATED AT 250 WORDS)

Pregnancy course and complications in patients with systemic lupus erythematosus.

Among 165 patients with systemic lupus erythematosus (SLE), we observed 21 pregnancies in 19 patients since 1987. The mean duration of disease at the time of pregnancy was 4.5 +/- 3 years. All but three patients required immunosuppressive treatment before and during pregnancy. The effect of pregnancy on the course of SLE was studied. Severe disease exacerbations were rare and largely confined to patients with renal involvement. Most patients showed elevated titers of dsDNA antibodies during pregnancy but clinical activity of disease was usually mild. Complement C3 decrease appeared to be the most sensitive marker for pregnancy-related complications. The detection of antibodies to phospholipids was frequent during pregnancy in contrast to a low prevalence before and after pregnancy. Their presence could be associated with intrauterine growth retardation. Preterm delivery before the 37th week of pregnancy had to be performed in the majority of patients. None of the patients experienced abortion although three patients had to delivered in the 29th week of pregnancy because of increasing symptoms of pre-eclampsia. Two of these children died and the third child suffered from intracranial hemorrhage in the early postpartum period. Our data demonstrate that successful pregnancy outcome was related to a gestational age of more than 32 weeks, making careful monitoring and appropriate therapeutic management necessary.

[Systemic lupus erythematosus and pregnancy]. / Systemischer Lupus erythematodes und Schwangerschaft.

Our study strengthens the view that successful pregnancy outcome can be achieved in most patients with SLE, although premature delivery and pregnancy-related complications are common. For the differential diagnosis of preeclampsia and lupus flare in pregnancy, levels of anti-DNA antibodies and complement C3 are valuable parameters. In patients with antibodies to phospholipids, no major clinical problems occurred provided that patients were treated with corticosteroids and low-dose aspirin. However, none of our patients with renal involvement of SLE had an uncomplicated pregnancy course.

[Significance of ultraviolet light in the pathogenesis of systemic lupus erythematosus: case report and discussion of the literature]. / Bedeutung des UV-Lichtes in der Pathogenese des SLE: Kasuistik und Diskussion der Literatur.

A 33-year-old woman with a 9-year history of psoriasis developed a severe SLE with no signs of visceral involvement during a 3-week exposure to PUVA (psoralen and UVA) therapy. The patient fulfilled the criteria of the American Rheumatism Association (25) for the diagnosis of SLE. She showed dermatological lesions including facial erythema, photo-sensibility arthritis, hematological disorders including leuko-, lympho-, thrombocytopenia, antinuclear antibodies, and dsDNA antibodies. With a therapy that included corticosteroids, chloroquine, and azathioprine the disease could be controlled. The coincidence of a PUVA therapy and the first flare-up of an SLE demonstrates a possible pathogenic role of UV light in SLE.

Expression of the CD2 activation epitope T11-3 (CD2R) on T cells in rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and Lyme disease: phenotypic and functional analysis.

CD2R is an activation-associated epitope unmasked by a conformational change of the CD2 cell-surface glycoprotein. In spite of elaborate studies on the role of CD2 and CD2R in adhesion and stimulation of T cells in vitro, no instances of CD2R expression in vivo were known to date. We report high levels of CD2R observed on blood and synovial fluid T cells in rheumatoid arthritis and on peripheral blood T cells in juvenile rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and Lyme disease. In vivo, expression of CD2R was restricted to T cells, not limited to a particular T-cell subset and not correlated with the expression of p55 interleukin 2R (IL-2R) (CD25) or major histocompatibility complex (MHC) class II molecules. When stimulated to proliferation via CD2 or CD3, ex vivo CD2R+ T cells showed the same basic activation requirements as CD2R-T cells.

Immunoglobulin allotypes in systemic lupus erythematosus--results of a central European multicenter study. SLE Study Group.

Immunoglobulin heavy chains (G1m, G2m, G3m, A2m) and kappa light chain (Km) allotype and phenotype frequencies were examined in 323 central European Caucasian patients with systemic lupus erythematosus (SLE). No significant differences were found between the different allotype or phenotype frequencies of the SLE patients and a control group of healthy individuals. Our results indicate that Gm, A2m and Km allotypes do not represent susceptibility factors for SLE in Caucasians.

Immunoglobulin allotypes are not associated with HLA-antigens, autoantibodies and clinical symptoms in systemic lupus erythematosus. Members of the SLE Study Group.

Immunoglobulin heavy chain (G1m, G2m, G3m, A2m) and kappa light chain (Km) allotype and phenotype frequencies of 323 central European Caucasian patients with systemic lupus erythematosus (SLE) were examined and correlated with various genetic, serologic and clinical markers of SLE. No significant associations were found between immunoglobulin allotypes or phenotypes and all 20 parameters tested (nephritis, vasculitis, arthralgias, photosensitivity, discoid lesions, central nervous system disease, Raynaud's phenomenon, sex, anti-Ro, anti-La, anti-nRNP, HLA-DR1-DR7, HLA phenotypes B8-DR3, B7-DR2). It could therefore be assumed that Gm, A2m and Km allotypes were not associated with HLA-antigens and had no influence on the serologic and clinical expression of SLE.

[Long-term remission after i.v. immunoglobulin therapy in acquired antihemophilic factor hemophilia with systemic lupus erythematosus]. / Langzeitremission nach i.v. Immunglobulintherapie bei erworbener Hemmkörperhämophilie im Rahmen eines systemischen Lupus erythematodes.

A 27-year-old female with severe systemic lupus erythematosus with renal involvement developed extensive cutaneous hemorrhages 5 years after diagnosis. Routine coagulation tests confirmed a prolongation of activated partial thromboplastin time to 77 s. This was attributed to a marked reduction of factor VIII activity to less than 3%. An inhibitor with an activity of 1.4 Bethesda units against factor VIII was determined. Immunosuppressive therapy (steroids, azathioprin, cyclophosphamide, cyclosporine) had no influence on the hemorrhages. Later in the course of disease a life-threatening vaginal hemorrhage occurred in parallel with a flare-up of lupus activity. During that period a therapy of 7 S i.v. immunoglobulins (120 g within 5 days) was started. This led to an instant cessation of the bleeding. Factor-VIII activity rose from 3% ot 480% within 7 days and the ds-DNA-antibodies fell from 122 U/ml to 19.7 U/ml. Nine months later, under immunosuppressive therapy with cyclophosphamide and steroids, factor-VIII activity is still within the normal range and no bleeding episodes have occurred. This confirms the effectively of high-dose immunoglobulin therapy for hemophilia, due to acquired factor VIII antibodies, also in patients with severe SLE.