Histopathological findings in placentae from patients with intra-uterine fetal death and anti-phospholipid antibodies.

Anti-phospholipid antibodies are associated with first trimester abortions and late intra-uterine fetal death. The histopathology of 47 placentae from 45 women with intra-uterine fetal death, including 16 patients with anti-phospholipid antibodies, was studied in order to detect potential differences between placentae from women with and without these antibodies. Thirteen patients had systemic lupus erythematosus or lupus-like disease, including 6 women with anti-phospholipid antibodies.

Prevalence of antiphospholipid antibodies in patients with fetal loss.

The prevalence of antiphospholipid and antinuclear antibodies in 102 patients with at least three unexplained miscarriages before a gestational age of 12 weeks, or at least one intrauterine fetal death after 12 weeks, was investigated and compared with the prevalence in 102 normal pregnant controls. Six patients had a history of thrombosis and six had 'lupus-like' disease. Twenty one patients had anticardiolipin antibodies compared with 10 controls.

Anti-phospholipid antibodies and pregnancy loss.

Anti-phospholipid antibodies such as the lupus anticoagulant and anti-cardiolipin antibodies, are antibodies directed at negatively charged phospholipids and have received much attention in the last decade. Their presence has been associated with a thrombotic tendency, leading to a variety of clinical symptoms. In the pregnant woman, the presence of these antibodies may have consequences for management, since retrospective reports have established a correlation between the lupus anticoagulant or anti-cardiolipin antibodies with intrauterine fetal death, probably due to placental thrombosis.

Antibodies to platelets in patients with anti-phospholipid antibodies.

Binding of anti-phospholipid antibodies to circulating platelets and its consequences on platelet activation and aggregation was investigated in 11 patients with anti-phospholipid antibodies. Seven patients had mild thrombocytopenia. Nine healthy donors served as controls.

Somatic mutations in the variable regions of a human IgG anti-double-stranded DNA autoantibody suggest a role for antigen in the induction of systemic lupus erythematosus.

The processes that govern the generation of pathogenic anti-DNA autoantibodies in human systemic lupus erythematosus (SLE) are largely unknown. Autoantibodies may arise as a consequence of polyclonal B cell activation and/or antigen-driven B cell activation and selection. The role of these processes in humoral autoimmunity may be studied by molecular genetic analysis of immunoglobulin (Ig) variable (V) regions of antibodies that are characteristic of SLE.

Treatment of systemic lupus erythematosus: which options do we have for therapy regimens?

The prognosis of systemic lupus erythematosus has improved markedly. This has been due to various factors: improved serological testing leading to better diagnosis, better understanding of secondary complications, and the possibility of treating these. How much has improved treatment of the primary disease process contributed to the improvement in prognosis? We have evaluated the clinical outcome of 56 patients with lupus nephritis proven by biopsy, followed at out hospital over the past 16 years.

Systemic lupus erythematosus and pregnancy.

This article critically analyses the data in the literature on pregnancy in women with systemic lupus erythematosus. Based on the results of recent controlled prospective studies, it is apparent that the long-standing opinion that pregnancy induces exacerbation of the disease should be revised. The presence of active disease and/or a significant loss of renal function at conception are not only associated with a high risk of maternal complications, but also with high frequencies of loss of the fetus, as well as pre- and dysmaturity.

A prospective study on antiribosomal P proteins in two cases of familial lupus and recurrent psychosis.

In two siblings with systemic lupus erythematosus (SLE), who experienced two episodes of psychosis each, a longitudinal study of autoantibodies, including antibodies to ribosomal P proteins, is described. In two of three evaluable periods of 15 weeks antedating psychosis a rise followed by a spontaneous drop in anti-P levels was recorded. In the third period antibodies to ribosomal protein P were absent.

Crossreactivity of antibodies directed against cardiolipin, DNA, endothelial cells and blood platelets.

The interrelationship of antibodies directed against cardiolipin (CL), double stranded DNA (dsDNA), endothelial cells (EC) and blood platelets was investigated. IgG fractions, reactive with these antigens, were isolated from the plasmas from 8 patients with systemic lupus erythematosus and tested for crossreactivity with anionic phospholipids (CL, phosphatidylserine, phosphatidylinositol), zwitterionic phospholipids (phosphatidylethanolamine, phosphatidylcholine), dsDNA, EC and platelets by enzyme-linked immunosorbent assays and for lupus anticoagulant (LAC) activity with a coagulation assay. Our results demonstrate the frequent occurrence of crossreactivity between antibodies to anionic phospholipids, EC and platelets.

In vivo antinuclear antibody of the skin: diagnostic significance and association with selective antinuclear antibodies.

Immunofluorescence microscopy of the skin has disclosed antibodies bound to epidermal cell nuclei in several connective tissue disorders. To establish the diagnostic potential of this phenomenon the results of immunofluorescence microscopy of biopsy specimens from 1651 subjects with various diseases and from 315 patients with systemic connective tissue disorders and related diseases were reviewed. It was found that the predictive value of the phenomenon for the presence of a systemic connective tissue disorder was, in general, 88%.

Heat treatment of serum and plasma induces false positive results in the antiphospholipid antibody ELISA.

We found that levels of antiphospholipid antibodies (aPLA), measured with an ELISA increase if serum or plasma samples are heated. The phenomenon is dependent on duration and degree of heating, optimum levels being reached at 3 h at 56 degrees C. Negative samples become positive after heating.

Fluctuations of anticardiolipin antibody levels in patients with systemic lupus erythematosus: a prospective study.

In 53 patients with systemic lupus erythematosus sequential blood samples obtained during a four year period (range 6-47 months) were screened for anticardiolipin antibodies (ACAs). Disease activity and treatment with prednisone were also assessed and related to ACA concentrations. During follow up only 21 patients for ACA IgG (40%) and 25 for ACA IgM (47%) remained in the ACA category (negative, low positive, high positive) found at the first sample taken at entrance.

Risk factors for thrombosis in lupus patients.

Lupus anticoagulant, concentrations of anticardiolipin antibodies, antithrombin III, plasminogen, (free) protein S, protein C, prothrombin, platelet counts, and bleeding times were determined in 74 lupus patients (58 with systemic lupus erythematosus; 16 with lupus-like disease) to establish the presence of risk factors for thrombosis in these patients. Of the variables evaluated, lupus anticoagulant had the strongest association with a history of thrombosis. Both positive anticardiolipin antibody concentrations and the presence of (mild) thrombocytopenia were significantly associated with a history of thrombosis and the presence of lupus anticoagulant.

The "primary" antiphospholipid syndrome: major clinical and serological features.

The antiphospholipid syndrome--the association of venous and/or arterial thromboses, often accompanied by thrombocytopenia in the presence of the antiphospholipid antibodies ("lupus anticoagulant" antibodies to cardiolipin)--is seen mainly in patients with systemic lupus erythematosus (SLE) and the closely related "lupus-like" disease, i.e., lupus patients not conforming to the 1982 revised American Rheumatism Association classification for SLE.

Synergistic effect of low doses of tumor necrosis factor and sera from patients with systemic lupus erythematosus on the expression of procoagulant activity by cultured endothelial cells.

The effect of 15 antiphospholipid antibody (APA) positive SLE sera, 13 APA negative SLE sera, 10 APA negative sera from patients with other connective tissue diseases (CTD) and 15 control sera on the expression of endothelial procoagulant activity (PCA) was studied. Endothelial cells (EC) were stimulated with tumor necrosis factor (TNF) and 20% serum for 4 hr and the surface PCA expression was measured. Without TNF, none of the sera stimulated PCA expression.

Plasma exchange in rhabdomyolysis.

The effect of plasma exchange (PE) was evaluated in 4 patients with rhabdomyolysis. A single 21 PE produced a transient fall of creatinine phosphokinase and did not prevent renal failure. Theoretically PE would need to be performed very frequently to remove toxins in appropriate amounts.

Coagulation screen is more specific than the anticardiolipin antibody ELISA in defining a thrombotic subset of lupus patients.

In 111 lupus patients we compared the potential of the IgG and IgM anticardiolipin antibody (ACA) enzyme linked immunosorbent assay (ELISA) and four different lupus anticoagulant (LAC) assays (partial thromboplastin time (PTT) of a 1:1 mixture of patient and control plasma with phospholipids from animal (PTT-st) or human brain (PTT-HB); PTT with dilutions of human brain phospholipids (PL dilution); and kaolin clotting time of mixtures of patient and control plasma (KCT] to identify patients with thrombosis (26/111), fetal loss (19/46), and/or thrombocytopenia (11/106). The highest specificity for thrombosis (87%) was found with PTT-HB and PL dilution (sensitivity 65%, detection rate 61%); for fetal loss (93%) with PL dilution (sensitivity 47%; detection rate 82%), and for thrombocytopenia (83%) with KCT (sensitivity 82%; detection rate 36%). Compared with LAC assays, the sensitivity of ACA-ELISA was high (greater than or equal to 77%), but specificity (less than or equal to 51%) and detection rate (less than or equal to 52%) were low.