A monoclonal Ro‐antibody and the serum of a Ro‐positive patient with subacute cutaneous lupus erythematosus (SCLE) react with basal layers of human epidermis

Mayet, W J; Bachmann, Michael; Pfeifer, Karin; Schröder, Heinz C.; Müller, Wernér E.G.; Gudat, W.; Korting, G. W.; Büschenfelde, K H Meyer zum

doi:10.1111/j.1365-2362.1988.tb01041.x

Cited by 18 publications

(8 citation statements)

References 43 publications

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“…Antibodies to Ro/SSA and La/SSB components of the small nuclear and cytoplasmic ribonucleoproteins are encountered frequently in autoimmune diseases. Among these, the most common are Sjogren's syndrome, SLE, and subacute cutaneous lupus erythematosus (3)(4)(5)(6). cDNAs encoding three different Ro peptides have been cloned, with molecular masses ranging from 46 to 60 kD (7)(8)(9), but fusion proteins ofonly two ofthese peptides (the 52 and 60 kD) have been shown to react with anti-Ro-positive sera from SLE and Sjogren's syndrome patients.…”

Section: Introductionmentioning

confidence: 99%

Cellular mechanism of the conduction abnormalities induced by serum from anti-Ro/SSA-positive patients in rabbit hearts.

Garcia

Nascimento²,

Bonfá³

et al. 1994

J. Clin. Invest.

141

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In this study, IgG fractions from sera of SLE patients with anti-Ro/SSA or anti-Ro/ SSA and anti-La/SSB activity were tested in Langendorff preparations of adult rabbit hearts, aiming to reproduce the cardiac manifestations observed in neonatal lupus in an experimental model. The hearts were perfused with normal Tyrode's solution for 30 min, followed by perfusion with Tyrode's containing 0.3 mg/ml of anti-Ro / SSA-(or antiRo/La-) positive IgG (nine sera), anti-ribonucleoprotein (RNP)-positive IgG (five sera), or IgG fractions from normal donors (five sera). In one third of the experiments done with anti-Ro/La-positive IgG, heart block was observed. With the remaining fractions, a decrease in heart rate of 17.1% was observed, but normal sinus rhythm was maintained. The IgG fractions with anti-RNP activity (five experiments) and from normal sera (six experiments) reduced heart rates by 12.9 and 3.3%, respectively, but heart block was not observed.To further characterize the cellular mechanisms involved in the conduction disturbances observed in the whole rabbit hearts, we conducted experiments with ventricular myocytes isolated from young rabbit hearts, studied by whole cell patchclamp technique. In these experiments, the slow inward currents were analyzed during the superfusion of the cell with normal Tyrode's solution and 5 min after superfusion with Tyrode's solution containing 0.3 mg/ml of anti-Ro/SSA-(or anti-Ro/La-) positive IgG (five sera), anti-RNP-positive IgG (three sera), or IgG from normal donors (four sera). Resting and action potential amplitudes were not affected by any of the sera used. The anti-Ro/SSA IgG fraction induced a mean reduction in the peak slow inward current of 31.6%. IgG fractions with anti-RNP activity reduced slow inward current by 4.4%, whereas IgG fractions from normal donors increased this current by 3.3%. IgG-free fractions from sera of patients with anti-Ro/SSA activity did not alter the peak slow inward current. These results show, for the first time, that the presence of anti-Ro/SSA or anti-Ro/SSA and anti-La/SSB antibody activity in IgG fractions from lupus patients' sera can induce cardiac conduction disorders similar to those observed in neonatal lupus. (J. Clin. Invest. 1994.93:718-724.)

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Section: Introductionmentioning

confidence: 99%

Cellular mechanism of the conduction abnormalities induced by serum from anti-Ro/SSA-positive patients in rabbit hearts.

Garcia

Nascimento²,

Bonfá³

et al. 1994

J. Clin. Invest.

141

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“…Several antigen preparations served as antigens: alpha-extract of human neutrophils, purified PR3, myeloperoxidase, cathepsin G and elastase [7]. ELISAs were performed as described earlier [8]. PAGE and Western blotting were performed as described previously [9].…”

Section: Antibody Testingmentioning

confidence: 99%

Antibodies to proteinase 3 mediate expression of vascular cell adhesion molecule-1 (VCAM-1)

Mayet¹,

Schwarting²,

Orth³

et al. 1996

Clinical and Experimental Immunology

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VCAM‐1 was first identified as an adhesion molecule induced on human endothelial cells (HEC) by inflammatory cytokines such as IL‐1, tumour necrosis factor (TNF), and lipopolysaccharide (LPS). The molecule binds to a variety of leucocytes, including B cells, T cells, basophils, eosinophils and monocytes. Vascular expression of VCAM‐1 has been associated with a number of disease states, including rheumatoid arthritis and vasculitis. The detection of antineutrophil cytoplasmic antibodies (ANCA), especially to proteinase 3 (PR3), has become important in the diagnosis of Wegener’s granulomatosis (WG) and related vasculitides. Recently we were able to demonstrate a direct effect of anti‐PR3 antibodies on neutrophil–endothelial interactions (Blood 1993; 82:1221). Binding of anti‐PR3 antibodies to their antigen translocated into the membrane of HEC leads to an enhanced adhesion of neutrophils via induction of E‐selectin (Clin Exp Immunol 1993; 94:440). The aim of this study was to investigate the effect of anti‐PR3 antibodies on the expression of VCAM‐1. HEC was isolated from umbilical vein and cultured on microtitre plates. After preincubatiion with purified anti‐PR3 antibody, purified control antibodies (SS‐A, SS‐B, RNP) (IgG and F(ab′)2 fragments) or different cytokines (controls), VCAM‐1 was detected on the surface of unfixed HEC by cyto‐ELISA and polymerase chain reaction analysis. Incubation of HEC with anti‐PR3 antibodies led to a marked increase of endothelial VCAM‐1 expression with a peak after 8 h. Incubation with TNF‐α also led to maximal VCAM‐1 expression after 4–6 h (control). Increased adhesion of T lymphocytes to HEC after binding of anti‐PR3 antibodies to their antigen could be confirmed by performing adherence assays. This effect could be inhibited by antibodies to VLA‐4. In conclusion, we have been able to show that cytokine‐like effects of anti‐PR3 antibodies on HEC are not limited to induction of neutrophil adhesion. Anti‐PR3 antibodies may thus contribute to the regulation of T lymphocyte migration from the blood by HEC in ANCA‐related vasculitides.

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“…Several antigen preparations served as antigens; alpha-extract of human neutrophils [6|, purified PR-3 [7]. myeloperoxidase.cathepsinG and elastase |8|, ELlSAs were performed as described earlier [9). PAGE and Western blotting were performed as described previously [lO.I I).…”

Section: Antibody Testingmentioning

confidence: 99%

Antibodies to proteinase 3 increase adhesion of neutrophils to human endothelial cells

Mayet¹,

Büschenfelde²

1993

Clinical and Experimental Immunology

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SUMMARY The detection of anti‐neutrophil cytoplasmic antibodies (ANCA), especially those with specificity for proteinase 3, is important in the diagnosis and in monitoring disease activity of Wegener's granulomatosis and related vasculitides. An ubiquitous feature of all ANCA‐associated acute vascular injury is lytic necrosis. Adhesion of neutrophils to endothelium is a fundamental early step of the inflammatory response. Recently we were able to show that ANCA recognize their target antigen (proteinase 3) translocated into the membrane of human endothelial cells. The aim of this study was to investigate the effect of ANCA on the adhesion of neutrophils to human endothelial cells. Incubation of endothelial cells with affinity‐purified antibodies to proteinase 3 (IgG‐ and F(ab')2‐fractions) led to a marked increase of neutrophil adhesion, with a peak after 4 h and a rapid decrease after 8 h. This effect could be inhibited by preincubation of the endothelial cells with an antibody to endothelial leucocyte adhesion molecule‐1 (ELAM‐1). Incubation with antibodies to proteinase 3 also led to an incrcase of endothelial ELAM‐1 expression as measured in a cyto‐ELISA and by flow cytometry. Our data demonstrate a direct effect of ANCA on neutrophil endothelial interactions. The enhanced adhesion of neutrophils occurs time‐dependently via induction of ELAM‐1 expression on the surface of endothelial cells. Our data give a hint of an ANCA‐mediated mechanism of endothelial injury via induction of neutrophil adhesion to vascular endothelium in Wegener's granulomatosis and other ANCA‐related vasculitides.

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A monoclonal Ro‐antibody and the serum of a Ro‐positive patient with subacute cutaneous lupus erythematosus (SCLE) react with basal layers of human epidermis

Cited by 18 publications

References 43 publications

Cellular mechanism of the conduction abnormalities induced by serum from anti-Ro/SSA-positive patients in rabbit hearts.

Cellular mechanism of the conduction abnormalities induced by serum from anti-Ro/SSA-positive patients in rabbit hearts.

Antibodies to proteinase 3 mediate expression of vascular cell adhesion molecule-1 (VCAM-1)

Antibodies to proteinase 3 increase adhesion of neutrophils to human endothelial cells

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