S. Loizou

Cardiac abnormalities in systemic lupus erythematosus. Association with raised anticardiolipin antibodies.

Two-dimensional echocardiographic studies were prospectively performed in 93 patients with systemic lupus erythematosus (SLE) to discover the incidence and spectrum of cardiac abnormalities and to relate these findings to the presence of high levels of anticardiolipin antibodies. Assessment of the intracardiac anatomy was also performed in an additional 12 patients who had increased anticardiolipin antibody levels but did not have SLE. Fifty patients (54%) with SLE had cardiac abnormalities, and 43 patients (46%) had normal hearts. Three categories of cardiac abnormalities were identified--valvular lesions, ranging from vegetations to valvular thickening, were found in 28%, pericardial effusion or thickening was found in 20%, and regional or global left ventricular dysfunction was found in 5%. High levels of anticardiolipin antibodies were detected in 50 patients (54%) with SLE. Of those, only 11 (22%) had an entirely normal heart, whereas the remaining 39 (78%) had at least one cardiac abnormality (valvular lesions in 20, pericardial effusion in 15, and myocardial dysfunction in five patients). In patients with SLE, the presence of abnormal intracardiac anatomy was strongly associated with increased levels of anticardiolipin antibodies (p less than 0.0001). The overall sensitivity and specificity of high levels of anticardiolipin antibodies in the prediction of cardiac abnormalities was 78% and 74%, respectively, with a positive predictive accuracy of 78% and a negative predictive accuracy of 74%. Eight of the 12 patients (67%) who had increased anticardiolipin antibodies but whose disease did not fulfill the American Rheumatism Association classification criteria for SLE had cardiac abnormalities similar to those in patients with SLE compared with only four (33%) who had normal hearts (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Immunoglobulin class and IgG subclass distribution of anticardiolipin antibodies in patients with systemic lupus erythematosus and associated disorders

The class and subclass distribution of an antibody response may give insight into the stimulating mechanism and likely effector functions. IgA, IgG and IgM anlicardiolipin antibodies (aCL) were quantified in a consecutive series of 200 samples sent to an autoimmune serology laboratory to determine the relationships between aCL responses of each of these antibody classes and, in particular, whether there was any utility in the measurement of IgA aCL. Positive results for one of the three aCL isotypes were found in 105 samples (53%). and in 41 samples IgA aCL was detected (21%). However, amongst these unselected samples, little additional information was obtained by measurement of IgA aCL, which was found in conjunction with IgM or IgG aCL in all but five samples, and in these the isolated elevation of IgA aCL was only slight, and showed no disease specificity. The levels of each of the four IgG subclasses of aCL were measured in a subgroup of serum samples from 28 patients with autoimmune disease and from 29 patients with syphilis. Amongst the SLE patients IgGl and lgG3 aCL were the predominant IgG subclasses, consistent with an antigen‐driven. T cell‐dependent antibody response. However, a subgroup of eight of the autoimmune subjects had predominant elevation of IgG2 aCL, possibly implying a role for T cell‐independent antibody production to cardiolipin. Amongst the syphilis patients IgG I and IgG3 aCL were also the predominant subclasses of aCL but lgG4 aCL were also detected in the majority of subjects, consistent with prolonged antigenic stimulation.

Heterogeneity of binding reactivity to different phospholipids of antibodies from patients with systemic lupus erythematosus (SLE) and with syphilis

The binding specificities were investigated of anti‐phospholipid antibodies derived from sera from 55 patients with SLE and related diseases, and from 33 patients with syphilis. Antibodies from both these groups of patients bind strongly to cardiolipin in solid‐phase immunoassays, but only anti‐phospholipid antibodies from patients with autoimmune diseases are associated with thrombotic complications and recurrent spontaneous abortions. IgG anti‐phospholipid antibodies from both groups of patients cross‐reacted with a range of negatively charged phospholipids, but binding to neutral phospholipids was largely restricted to sera from patients with syphilis. A monoclonal IgMλ anti‐cardiolipin antibody, derived from a patient with autoimmunity, was used to inhibit binding of anti‐phospholipid antibodies to cardiolipin and to phosphatidic acid. This antibody inhibited the binding of autoimmune sera to cardiolipin more strongly than sera from syphilis patients, but the converse pattern of inhibition of binding to phosphatidic acid was observed. The VDRL litre correlated with anti‐phospholipid antibody activity in sera from syphilis patients, but not from those with autoimmunity. Lupus anti‐coagulant activity correlated weakly with IgG antibody levels to each of the negatively charged phospholipids among the patients with autoimmunity. Lupus anticoagulant activity did not correlate uniquely with any anti‐phospholipid antibody specificity. These results provide further documentation of the great heterogeneity of anti‐phospholipid antibodies associated with autoimmune disease and syphilis.

Clinical and immunologic features of livedo reticularis in lupus: a case-control study.

PURPOSE We recently noticed the occurrence of both livedo and elevated anticardiolipin antibody levels in a small number of patients with lupus. The purpose of our study was two-fold: (1) to investigate whether anticardiolipin antibodies were more common in lupus patients with livedo than in those without; and (2) to determine if the features of Sneddons syndrome (livedo and cerebrovascular disease) also were found in patients with lupus. PATIENTS AND METHODS In this case-control study of lupus patients without significant renal impairment, 29 patients with livedo reticularis (cases) were compared clinically and immunologically with 29 patients without livedo (controls). RESULTS Both groups shared many disease characteristics and were similar in age and sex. However, they differed markedly in other respects. Elevated anticardiolipin antibody levels were significantly more common in the cases. Indeed, 81% of all cases from our study sample had elevated anticardiolipin levels. A history of thrombosis and thrombocytopenia--clinical associates of the anticardiolipin antibody--was also significantly more common in cases than in controls. The relative odds of livedo reticularis were 23-fold greater in those with elevated anticardiolipin levels than in those without these antibodies. The estimated proportion of livedo-positive patients with elevated anticardiolipin antibodies in a general lupus population without significant renal impairment was 0.77. CONCLUSION The association between livedo reticularis and cerebrovascular disease, originally described by Sneddon in otherwise healthy individuals, also applies to lupus patients. The presence of elevated anticardiolipin antibody levels in 10 of 11 such patients suggests that the anticardiolipin antibody may be of pathogenetic importance in the manifestations of Sneddons syndrome in lupus and also possibly in the idiopathic form of this disease.

Quantification of IgG on erythrocytes of patients and normals by a radio‐ligand‐binding assay

Summary. A monoclonal IgG anti‐human IgG, 1B12, was used in a radio‐ligand‐binding assay to quantify IgG on erythrocytes of patients and normals. The assay detected a range of 10–700 IgG molecules. Good correlation was achieved between the number of molecules and the strength of agglutination in antiglobulin tests performed in capillary tubes. The assay was capable of detecting subagglutinating immune bound IgG on erythrocytes from patients with systemic lupus erythematosus (SLE).