The renal pathology of primary antiphospholipid syndrome: a distinctive form of endothelial injury. (57/684)

Some features of the vascular and glomerular pathology of primary antiphospholipid syndrome (APS) are well recognized, but we describe novel glomerular ultrastructural changes that we consider to be pathognomonic of APS. Renal biopsies from eight patients with APS were examined by light and electron microscopy. All had anti-cardiolipin antibodies, and the clinical presentation ranged from fulminant multi-system disease to isolated proteinuria. By light microscopy, the hexamine silver stain showed a combination of glomerular basement membrane wrinkling and reduplication. By electron microscopy, redundant, wrinkled segments of basement membrane were accompanied by a 'new' straighter thin basement membrane adjacent to the endothelium. In two cases the presence of these antibodies was not suspected clinically, and there was no clinical history or evidence of a thrombotic microangiopathy. We describe a distinctive glomerular lesion that represents an unexplained form of endothelial injury in this syndrome.  (+info)

Antiphospholipid syndrome with acute myocardial infarction and portal vein occlusion: a case report. (58/684)

A 62-year-old woman was admitted to hospital because of chest oppression and abdominal discomfort. Coronary arteriography revealed that the proximal left anterior descending artery had a large thrombus with TIMI (Thrombolysis in Myocardial Infarction) Grade 3 flow. On the second hospital day, she had sudden hematemesis because of esophageal varices. Her general condition became stable with conventional therapy. On the 20th hospital day, coronary arteriography and arterial portography showed that the thrombus had diminished. Arterial portography also revealed total occlusion of the portal vein as well as giant gastric varices. She was diagnosed as antiphospholipid syndrome, based on the presence of lupus anticoagulant. The treatment of this case was very complicated because of the bleeding from the esophageal varices induced by the anticoagulant therapy for the thrombus. Prednisolone was administered for 1 month, but no remarkable effects were observed. Therefore, she was treated with endoscopic sclerotherapy for the esophageal varices and anticoagulant therapy for prevention of thrombosis.  (+info)

Antiphospholipid syndrome with cortical blindness resulting from infarction around the posterior cerebral artery in an elderly woman. (59/684)

An 87-year-old woman with antiphospholipid syndrome accompanied by cortical blindness and thalamic syndrome resulting from infarction of the posterior cerebral artery is reported. She was hospitalized because of laceration of the head. Two months later, she complained of loss of visual acuity, sharp pain and numbness involving the left half of the body except her face. New right posterior lobe infarction and the existence of old left infarctions were confirmed by serial CT scans. Helical CT scan revealed embolization of the posterior cerebral artery with atherosclerotic stenosis. Serological examination showed biologically false-positive and positive findings for lupus anticoagulant. She was treated with warfarin potassium and clonazepam.  (+info)

Anti-beta 2-glycoprotein I antibodies and anti-endothelial cell antibodies induce tissue factor in endothelial cells. (60/684)

Anti-beta 2-glycoprotein I antibodies bind to endothelial cells through beta 2-GPI. The antibodies are present in patients with systemic lupus erythematosus and antiphospholipid syndrome and are associated with the pathogenesis of the disease. Anti-endothelial cell antibodies that react with constitutive antigens on ECs are present in patients with vasculiditis and other diseases. Both types of antibodies can activate ECs. Frequent findings in APLS and vasculitis are fibrin deposits and thromboembolic phenomena. These indicate that the coagulation system is activated. However, the mechanism of activation is not clear. ECs generate tissue factor upon stimulation with various substances. In the present study we report that monoclonal anti-beta 2-GPI antibodies and AECAs, derived from a patient with primary APLS and a patient with Takayasu's arteritis, respectively, induce a potent tissue factor in ECs. The production of TF activity, TF antigen and TF mRNA is dose and time dependent. The TF activity was induced also by F(ab)2 but not by Fc fragments and was abolished completely by pre-incubation with ant-TF antibodies. The TF that is induced in ECs by AECAs with and without beta 2-GPI specificity may activate the coagulation and thereby play a major role in the pathogenesis of fibrin deposition and thrombus formation in diseases that are associated with the presence of these antibodies.  (+info)

Prognostic factors and clustering of serious clinical outcomes in antiphospholipid syndrome. (61/684)

We assessed whether initial clinical presentations suggestive of antiphospholipid syndrome (APS) predicted the subsequent rate and type of serious clinical outcomes. Eighty-two consecutive patients with anticardiolipin antibodies or lupus anticoagulant were followed for 814 person-years after a first event suggestive of APS (livedo reticularis, thrombocytopenia, autoimmune haemolysis, thrombosis, central nervous system manifestations, recurrent abortions). The hazard of developing a second event was largest in patients with antibodies recognizing beta2 glycoprotein I who had autoimmune haemolysis as the first event (hazard ratio HR 2.70, p=0.018) and smallest in patients without such antibodies who had recurrent abortions as their first event (HR 0.37, p=0.028). Subsequent serious events in patients with venous and arterial thromboses, recurrent abortions, central nervous system manifestations and autoimmune haemolytic anaemia were likely to be of the same type as the presenting event (odds ratio (OR) 3.76, 5.90, 77.7, 6.92, and 7.13, respectively. Adjusting for therapy, the rate of subsequent serious events was 6.86-fold higher (p=0.0001) in patients presenting with two events, 1.56-fold higher (p=0.038) in autoimmune haemolysis presentations, 1.69-fold higher (p=0.004) in patients with anti-beta2-glycoprotein-I antibodies, and 46% (p=0.063) lower in thrombocytopenia presentations. Initial clinical features determine the long-term evolution of APS, and specific types of clinical manifestations cluster during the course of the disease.  (+info)

Renovascular hypertension observed in a patient with antiphospholipid-antibody syndrome. (62/684)

The antiphospholipid-antibody syndrome is associated with an increased incidence of arterial and venous thrombosis. Although renal infarction has been observed in these patients, stenotic lesions of the renal artery associated with the antiphospholipid-antibody syndrome have not been reported. A 47-year-old male with a history of hypertension for 7 years developed blurred vision secondary to thrombotic occlusion of the central retinal artery. Laboratory and radiologic examinations revealed renal dysfunction, a positive anticardiolipin antibody, and narrowing of the right renal artery. Successful percutaneous transluminal renal artery angioplasty resulted in normalization of the blood pressure and recovery of renal function.  (+info)

SR proteins are autoantigens in patients with systemic lupus erythematosus. Importance of phosphoepitopes. (63/684)

OBJECTIVE: To determine whether members of the highly phosphorylated SR protein family are autoantigens and, if so, to determine the frequency and molecular basis of antigen recognition. METHODS: Native human SR proteins were purified to homogeneity from HeLa cells, and an enzyme-linked immunosorbent assay (ELISA) was developed. Further studies employed immunoblotting of both phosphorylated and dephosphorylated SR proteins. RESULTS: Anti-SR protein reactivity was frequently detected in the sera of patients with systemic lupus erythematosus (SLE). Sera from 52% of the SLE patients in a group of patients with a variety of autoimmune and other disorders (n = 137) and from 50% of the SLE patients in a separate group (n = 102) were positive in an ELISA. In contrast, sera from patients with other disorders, such as rheumatoid arthritis and primary antiphospholipid syndrome, reacted infrequently. Reactivity with double-stranded DNA (dsDNA), used in the diagnosis of SLE, did not correlate with SR protein reactivity. Anti-SR autoantisera did not bind highly charged unphosphorylated peptides related to the SR domain, which is rich in arginine and phosphoserine residues. Surprisingly, many of the epitopes were influenced by the presence or absence of SR protein phosphorylation. In immunoblots, some patient sera lost reactivity upon SR protein dephosphorylation, while others significantly gained reactivity. CONCLUSION: We have identified a novel set of autoantigens in SLE, the SR protein family of non-small nuclear RNP pre-messenger RNA splicing factors. Anti-SR autoantibodies are distinct from those which bind dsDNA. The identification of this new set of autoantigens and the observation that the auto-epitope(s) involves posttranslational modification offer new possibilities for understanding autoimmunity and its development.  (+info)

Primary antiphospholipid syndrome presenting with cerebral ischemia, thrombocytopenia, anemia and proteinuria successfully treated with warfarin potassium. (64/684)

A 30-year-old woman with primary antiphospholipid syndrome (PAPS) presented with cerebral ischemia, thrombocytopenia, anemia and proteinuria. Administration of warfarin potassium, without concomitant corticosteroid administration, significantly improved all of these symptoms along with a decrease in the titers of antiCL-beta2-GP-I antibodies and a shortening of prolonged APTT. Therefore, the antiphospholipid antibodies in this patient could have been evoked by vitamin-K-dependent coagulation factors or plasma proteins which are assumed to undergo conformational changes exposing cryptic epitopes. This case report provides clues to the mechanisms underlying the production of antiphospholipid antibodies in patients with PAPS.  (+info)