E. N. Harris

ANTICARDIOLIPIN ANTIBODIES: DETECTION BY RADIOIMMUNOASSAY AND ASSOCIATION WITH THROMBOSIS IN SYSTEMIC LUPUS ERYTHEMATOSUS

A new solid-phase radioimmunoassay for the detection of anticardiolipin antibodies is 200-400 times more sensitive than the precipitation method used in the Venereal Disease Reference Laboratory test. 61% of serum samples from patients with systemic lupus erythematosus (SLE) had high levels of anticardiolipin antibodies of at least one immunoglobulin class. There were strong correlations between raised anticardiolipin levels and the lupus anticoagulant, venous and arterial thrombosis, and thrombocytopenia, but no correlation with anti-DNA antibody levels. Of the 15 patients with the highest anticardiolipin titres, 6 had a history of venous thrombosis, 5 cerebral thrombosis, 5 thrombocytopenia, and 2 each pulmonary hypertension and multiple abortions. This simple immunoassay appears to have predictive value for thrombosis in SLE and related disorders.

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 Sjögrens 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 < 0.001) and IgM (P < 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.

Immune mediated mechanism for thrombosis: antiphospholipid antibody binding to platelet membranes.

Because thrombocytopenia occurs frequently in patients with anticardiolipin (aCL) antibodies and thrombosis, some investigators have proposed that aCL antibodies may play a direct part in thrombosis by binding and activating platelets. To test this proposal experiments were performed to determine whether aCL antibodies can bind platelets. Preincubation of aCL positive sera with freeze-thawed platelets caused significant inhibition of aCL activity in four serum samples tested. Antibodies with cardiolipin binding activity were subsequently eluted from these platelets. Total phospholipids extracted from platelets inhibited aCL activity, and the specific phospholipids bound were shown to be phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol. It is concluded that aCL antibodies can bind phospholipids in platelet membranes but pertubation of the membrane must first occur.

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.

Antibody to phosphatidylethanolamine in a patient with lupus anticoagulant and thrombosis.

Most patients with lupus anticoagulant (LA) activity have coincident antibodies to a group of negatively charged phospholipids, and its is suggested that LA and anticardiolipin tests detect antibodies with overlapping specificities. Some discordance between the two assays has been described, however. One patient presenting with severe thrombotic disease (recurrent deep vein thrombosis, pulmonary embolism, inferior venocaval obstruction, myocardial infarction, and digital gangrene) showed strong LA activity in February 1987. An enzyme linked immunosorbent assay (ELISA) showed no binding to the negatively charged phospholipids cardiolipin, phosphatidylserine, and phosphatidic acid, but binding to zwitterionic phosphatidylethanolamine (PE) was demonstrated. Inhibition studies and affinity purification confirmed this finding. Interestingly, the serum did not bind to the kaolin cephalin clotting time reagent when used as antigen in an ELISA. The pathogenic significance of anti-PE antibodies and their relation to LA remains to be clarified. Further studies of the occurrence of anti-PE antibodies in patients with LA activity who have negative anticardiolipin tests are suggested.

Lupoid sclerosis: a possible pathogenetic role for antiphospholipid antibodies.

The case of a 45-year-old woman is described who developed transverse myelitis over a one-year period. Serological tests suggested a lupus-like illness. Antibodies to cardiolipin of the IgM class were detected in high titres in her serum. These may have played a part in the pathogenesis of her disease.

IgG subclass and light chain distribution of anticardiolipin and anti-DNA antibodies in systemic lupus erythematosus.

The IgG subclass and light chain distribution of anticardiolipin and anti-DNA antibodies were determined in serum samples from patients with systemic lupus erythematosus. With an enzyme linked immunosorbent assay (ELISA) and mouse monoclonal antibodies to individual subclasses, significant differences in the distributions of IgG2, IgG3, and IgG4 subclasses were observed between anticardiolipin and anti-DNA antibodies. Whereas anti-DNA antibodies were predominantly IgG1 and IgG3, all subclasses of anticardiolipin were detected with a prevalence ranging from 34% (IgG3) to 57% (IgG1). Clinical complications were found slightly more frequently (83%) in patients with sera containing the non or weak complement fixing subclasses (IgG2 and IgG4) than in patients with sera containing complement fixing (IgG1 and IgG3) subclasses (62%). Light chain analysis by ELISA showed a trend towards use of kappa chains for anti-DNA and lambda chains for anticardiolipin antibodies. These findings further emphasise the differences between anti-DNA and anticardiolipin antibodies in terms of their origins and potential mechanisms for producing tissue injury.

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

SummaryA 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.