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Biomedical subjects

E N Harris

Publications and source records attributed to E N Harris.

At least 127 records · Page 7Linked to original sources

Thrombosis, recurrent fetal loss, and thrombocytopenia. Predictive value of the anticardiolipin antibody test.

To determine the predictive value of the IgG anticardiolipin antibody (ACA) test for thrombosis, recurrent fetal loss, and thrombocytopenia, the clinical features of 121 patients with varying antibody levels were studied. When patients were grouped into high-positive, low-positive, and normal groups according to their ACA levels, there were strong statistical correlations with arterial thrombosis, venous thrombosis, fetal loss, thrombocytopenia, and a positive Coombs' test. At levels of 7 SD and above, the test was highly specific (greater than 80%) and predictive (greater than 70%) for thrombosis, thrombocytopenia, and recurrent fetal loss. This study suggests that the IgG ACA test may be a useful predictor for thrombosis, recurrent fetal loss, and thrombocytopenia in patients with autoimmune disorders.

Abortion, Habitual↗

Large vessel occlusion and gangrene in systemic lupus erythematosus and "lupus-like" disease. A report of six cases.

Six patients are presented, all of whom had systemic lupus erythematosus or a "lupus-like" disease and who developed major thromboses with gangrene of the extremities. Four of the 6 patients had circulating antiphospholipid antibodies at some point during the course of their illness. These serological markers, which have been associated with a tendency to thrombosis, may have contributed to the development of gangrene in these patients. Histological examination of affected arteries in 4 patients did not show any evidence of vasculitis. One patient in whom antiphospholipid antibodies were negative showed healing vasculitis on histology.

Adult↗

Multiple venous and arterial thromboses associated with the lupus anticoagulant and antibodies to cardiolipin in the absence of SLE.

A 53-year-old man with a history of multiple venous thromboses presented with widespread occlusions of the abdominal arterial system associated with the presence of the "lupus anticoagulant" and antibodies to cardiolipin in serum. There was no serological evidence of systemic lupus erythematosus and vasculitis of the affected vessels was not evident on post mortem examination. The presence of these antibodies, associated with a tendency to thrombosis, positive anti nuclear factor and cryoglobulinaemia were the only indicators of an "auto-immune" disturbance in this patient.

Abdomen↗

Thrombocytopenia in SLE and related autoimmune disorders: association with anticardiolipin antibody.

Anticardiolipin antibody levels were determined in 116 patients with systemic lupus erythematosus and related autoimmune disorders. Forty-three of these patients had a history of thrombocytopenia--36 of whom had SLE, three primary Sjögren's syndrome, two rheumatoid arthritis and two mixed connective tissue disease. IgG anticardiolipin antibody levels were raised in 31 (72%) of the 43 patients and IgM anticardiolipin antibody levels were raised in 19 (44%). There was a strong statistical correlation between thrombocytopenia and raised anticardiolipin antibody levels of both the IgG (P less than 0.001) and IgM (P less than 0.01) immunoglobulin classes. Of the 20 patients with the highest IgG anticardiolipin antibody levels 16 had a history of thrombocytopenia. We suggest that anticardiolipin antibodies may play a direct role in mediating platelet destruction in autoimmune disorders.

Antibodies↗

Anticardiolipin antibodies in autoimmune thrombocytopenic purpura.

Using a recently devised solid phase radioimmunoassay to detect anticardiolipin antibodies, we report the presence of these antibodies in 30 of 96 patients with chronic autoimmune thrombocytopenic purpura (AITP). IgG anticardiolipin antibody levels were elevated in 14 patients and IgM anticardiolipin antibody levels were elevated in 27 patients. We suggest that these antibodies may mediate peripheral platelet destruction by binding to phospholipids in the platelet membrane. It is also conceivable that the presence of anticardiolipin antibodies may select a subpopulation of patients with chronic AITP who may go on to develop other autoimmune disorders, such as systemic lupus erythematosus.

Antibodies↗

Anticardiolipin antibody, recurrent thrombosis, and warfarin withdrawal.

Antibodies to cardiolipin, closely related to the 'lupus anticoagulant', are strongly implicated in the pathogenesis of thrombosis. We record six patients, all with high titres of these antibodies (greater than SD) in serum, who developed recurrent vascular occlusions six to 12 weeks after warfarin withdrawal. Five of the six had deep vein thrombosis, while the sixth suffered a myocardial infarction. To minimise the risk of 'recurrent' thrombosis it is strongly suggested that such patients remain on long-term anticoagulation, pending the reduction of high antibody levels.

Adolescent↗

Crossreactivity of antiphospholipid antibodies.

Using a solid phase radioimmunoassay to detect anticardiolipin antibodies, the crossreactivity of these antibodies with phospholipids and DNA was tested in 10 patients with autoimmune disorders and 1 patient with secondary syphilis. The crossreactivity of anti-ds DNA and anti-ss DNA antibodies with cardiolipin was tested in 10 additional patients with SLE. In the 10 sera tested with high anticardiolipin antibody levels, there was marked inhibition of anticardiolipin antibody activity by negatively charged phospholipids. The zwitterionic phospholipids inhibited anticardiolipin antibody activity in some sera, and in instances where this occurred, inhibition was less than that obtained for the negatively charged phospholipids. There was minimal inhibition of anticardiolipin antibody by ss DNA in only 2 of 10 sera tested and no inhibition by ds DNA in any sera tested. Conversely, cardiolipin inhibited anti-ss DNA antibody activity in 2 of 10 sera, and anti-ds DNA antibody activity in 2 of 10 sera tested. There was no correlation between anticardiolipin antibody levels and either anti-ds DNA or anti-ss DNA antibody levels. These results suggest that antiphospholipid and anti-DNA antibodies are largely separate groups of antibodies. On the basis of these studies, we suggest that there may be various groups of antiphospholipid antibodies in patients with SLE and other autoimmune disorders.

Autoantibodies↗

[Systemic lupus erythematosus. A new look].

The systemic lupus erythematosus is a chronic inflammatory condition in which many abnormalities of the immune system have been described. Recent work has shown a subset of antiphospholipid antibodies which are apparently independent of the classical antinuclear antibodies. Their association with the false positive VDRL and the lupus "anticoagulant" is statistically significant. Clinically, these antibodies are associated with thrombosis, thrombocytopenia, thrombotic and demyelinating neurological features.

Autoantibodies↗

Affinity purified anti-cardiolipin and anti-DNA antibodies.

Recent studies have raised questions concerning the specificity of anticardiolipin antibodies and their relationship to anti-DNA antibodies, the lupus anticoagulant, the biological false positive test for syphilis, and reagin, the antibody detected in syphilis. In an attempt to answer some of these questions, 3 IgG and 2 IgM affinity purified anticardiolipin antibodies, as well as 3 affinity purified anti-DNA antibodies were studied. Affinity purified anti-cardiolipin antibodies showed high binding to negatively charged phospholipids but not to ssDNA by solid phase radioimmunoassay. On the other hand, affinity purified anti-DNA antibodies did not bind cardiolipin. Inhibition experiments showed that negatively charged phospholipids and VDRL liposomes inhibited the binding of anticardiolipin antibodies to phosphatidylserine, but ssDNA, alpha-glycerol phosphate and hyaluronic acid did not. Similar studies of sera from patients with high anticardiolipin antibody levels supported the results obtained with affinity purified anticardiolipin antibodies. These results suggest that anticardiolipin antibodies bind negatively charged phospholipids and there appears to be little crossreactivity with DNA or unrelated negatively charged polymers such as hyaluronic acid. Both the negatively charged phosphodiester group and glyceride portions of the phospholipid molecules appear important for their antigenicity. Four of the 5 affinity purified anti-cardiolipin antibodies had lupus anticoagulant activity providing further evidence to suggest that these 2 groups of antibodies have the same or very similar specificities. Studies of sera from 3 patients with syphilis showed that VDRL liposomes inhibited reagin activity to a greater extent than did cardiolipin. On the other hand, in patients with autoimmune disorders, cardiolipin inhibited anticardiolipin antibody activity to a greater extent than did VDRL liposomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗

Measurement of anti-cardiolipin antibodies by an enzyme-linked immunosorbent assay (ELISA): standardization and quantitation of results.

We describe the development of a simple and highly sensitive double antibody sandwich enzyme-linked immunosorbent assay (ELISA) for measuring IgG and IgM anticardiolipin antibodies (ACA). Microtitre plates were coated with cardiolipin at a concentration of 45 micrograms/ml by evaporation under nitrogen. Non-specific binding of diluted sera was eliminated by blocking of plates with 10% fetal calf serum in phosphate buffered saline (PBS/FCS) for 2 h. Then sera (100 microliters) at a dilution of 1:100 were incubated in the wells for 1 h. Affinity purified goat anti-human IgG or IgM (100 microliters) at a concentration of 1 microgram/ml was subsequently added and allowed to incubate for 1 h; detection of ACA was achieved using an alkaline phosphatase conjugated rabbit anti-goat IgG reagent by reading the colorimetric yield at 405 nm after incubation with substrate. Reference serum pools were established to study reproducibility of the assay throughout its sensitivity range, and Standard curves were established. The quantitative normal range was 0-9.0 Anticardiolipin ELISA Units (AEU) for IgG and 0-8.0 (AEU) for IgM-ACA. A strong correlation was found between the ELISA and radioimmunoassay methods for measuring ACA of both IgG and IgM classes. Results from 65 patients with systemic lupus erythematosus (SLE) and 45 patients with seropositive rheumatoid arthritis are also reported. The advantages of the ELISA method for quantitative determination of ACA levels, should make it a useful and reliable method for clinical and experimental monitoring of patients with SLE and associated autoimmune disorders.

Arthritis, Rheumatoid↗

Degos' disease: association with anticardiolipin antibodies and the lupus anticoagulant.

A woman presented with multiple cerebral thromboses and skin lesions characteristic of Degos' disease. Her serum contained high titres of anticardiolipin antibodies and showed lupus anticoagulant activity, both known to be strong markers of a thrombotic tendency in systemic lupus erythematosus. This finding may have therapeutic implications for this usually fatal disease.

Adult↗