Our data demonstrate a high prevalence of aPL in young adults with cerebral ischemia of undetermined cause. PI was the specificity with highest prevalence, suggesting that anti-PI antibodies may be an immunological marker in young patients with cerebrovascular disease.

The specificity and immunoglobulin isotype distribution of antiphospholipid (aPL) antibodies have been evaluated in 68 patients with systemic lupus erythematosus (SLE) by ELISA which employed a panel of 7 different PL antigens. A total of 49 patients (72%) were positive for aPL antibodies of different isotypes and directed to one or more PL epitopes. Prevalence of IgG anticardiolipin (aCL, 37%) was similar to that of the other negatively charged PLs phosphatidylserine (PS, 35%), phosphatidylinositol (PI, 35%), phosphatidylglycerol (PG, 35%) and phosphatidic acid (PA, 40%); prevalence reduced to 9-12 % and 7-16 % respectively for IgM and IgA isotypes to the same antigens. aPL antibodies to the zwitterionic PLs phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were also observed, though their prevalence was lower than that demonstrated for negatively charged PLs. Of the 36 SLE patients who were aCL negative (53%), 17 (25% of all patients and 47% of aCL-negative patients) were positive for aPL antibodies of different isotypes to one or more non-CL epitopes. During a mean follow-up period of 30 months, 10 patients had deep vein thrombosis (DVT) with a total of 21 events. By χ² test, a significant correlation was found between DVT and IgG aCL (p = 0.03) and between this event and the presence of lupus anticoagulant (LA) antibody (p = 0.04). However, stronger correlations were demonstrated between DVT and IgA aCL (p = 0.007), IgG anti-PS (p = 0.02), and IgA anti-PC, -PI and -PG (p = 0.02,0.003 and 0.02, respectively), whereas no correlation was found between thrombotic events and aPL antibodies with PE and PA specificities. In contrast, a significant correlation was demonstrated between aPL antibodies to the latter antigen and thrombocytopenia (p = 0.02). Moreover, a significant correlation was observed between the presence of LA and IgG and IgM aCL antibodies, IgG and IgM anti-PS, IgG anti-PI and IgG and IgA anti-PA, suggesting the possibility that LA activity could be mediated by different subsets of aPL antibodies heterogeneous for specificity and isotype. The complexity of our data indirectly explains some of the discrepancies often observed between solid-phase immunoassays and coagulation studies employed for aPL antibody detection and indicate the importance of aPL antibodies directed to non-CL epitopes as additional parameters to predict the occurrence of thrombotic events in SLE patients.

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Essential mixed cryoglobulinemia (EMC) is a rheumatic disorder characterized by widespread vasculitis. To better define the nature of the vasculitic process and to possibly outline assessment methods reliable for using in a clinical context, we studied plasma levels of three endothelial related peptides: fibronectin (FN), von Willebrand factor (vWF) and tissue plasminogen activator (t-PA), and those of thrombin-antithrombin IIIcomplexes (TAT) as markers of activation of the coagulation in 21 patients and in 16 controls. In EMC we found a picture consisting of reduced FN and increased vWF, t-PA, and TAT levels, suggesting a condition of endothelial cell damage with thrombin formation in vivo. Since we previously demonstrated the presence of chronic disseminated intravascular coagulation in these patients, we may assume that endothelial cells stressed by cryoprecipitation or stimulated by soluble mediators may be actively involved in the vasculitic process and possibly express procoagulant properties. This is a good example of the complex interplay existing between autoimmunity and coagulation mechanisms. We also suggest that FN, vWF, t-PA and TAT should be considered as additional clinical parameters when evaluating patients with EMC.

Tumor necrosis factor alpha (TNF-alpha) is a cytokine that affects endothelial cells' function by changing their antithrombotic potential to a net procoagulant effect. Only a few data have so far been reported for the pathophysiologic role of TNF in vascular diseases in the involvement of microvessels and/or macrovessels and a prothrombotic state. In the present study the authors evaluated plasma TNF (and interleukin-1) levels in 20 patients with chronic arterial obstructive disease (CAOD) with intermittent claudication and 10 CAOD patients with more severe disease (pain at rest/skin ulcers). In addition, they studied 10 patients with Raynaud's phenomenon (RP), suspected to be secondary to a collagen disease. The control group consisted of 20 subjects matched for sex and age with the three groups of patients. TNF levels were assayed by enzyme-linked immunosorbent assay. The antigen levels of von Willebrand factor (vWF), tissue plasminogen activator (t-PA), and its inhibitor (PAI) were also determined as markers of release from the endothelium, while the fragment 1 + 2 of prothrombin (F1 + 2) and thrombin-antithrombin III (TAT) complexes were assessed as indexes of systemic thrombin generation. TNF levels were significantly higher in both groups of CAOD patients than in controls or RP patients, and the same was true for vWF. t-PA was significantly higher only in the CAOD subjects with more severe disease. No differences among groups were seen in PAI antigen/activity or thrombin generation. When data were corrected for age, TNF no longer differentiated CAOD patients from controls and RP subjects.(ABSTRACT TRUNCATED AT 250 WORDS)