B. Alonso

Different Types of Antiphospholipid Antibodies in AIDS: A Comparison with Syphilis and the Antiphospholipid Syndrome

Alloimmune antiphospholipid antibodies react with phospholipids and are an epiphenomenon of an infectious disease. Most autoimmune antiphospholipid antibodies recognise phospholipid-protein complexes or proteins, such as beta2 glycoprotein I or prothrombin and are related to the clinical features of the antiphospholipid syndrome. Lupus anticoagulant, anticardiolipin antibodies, antiprothrombin, and anti-beta2 glycoprotein I antibodies were studied in 61 human immunodeficiency virus (HIV) patients, 55 syphilis patients, and 45 selected patients with antiphospholipid syndrome. Lupus anticoagulant was present in 72% of HIV and 81% of antiphospholipid syndrome patients. None of the syphilis patients had lupus anticoagulant. Anticardiolipin antibodies were found at comparable prevalence in the three groups (HIV 67%, syphilis 67%, antiphospholipid syndrome 84%). HIV had more frequently anti-beta2 glycoprotein I (13%) and antiprothrombin (12%) antibodies than syphilis (0 and 4%, respectively), but significantly less than antiphospholipid syndrome (61 and 40%, respectively). Autoimmune antiphospholipid antibodies in HIV without clinical features of antiphospholipid syndrome might be a reflex of the immunological chaos and/or the constant antigenic virus stimulus.

Endothelial markers and HIV infection in the era of highly active antiretroviral treatment

Many circumstances can induce activation and/or injury of the endothelium that plays a role in the development of vascular complications. Raised plasma levels of endothelial markers such as von Willebrand factor (vWF), soluble thrombomodulin (sTM) and soluble vascular cell adhesion molecule-1 (sVCAM-1) have a prognostic and/or diagnostic value. Human immunodeficiency virus-infected patients (HIV+) have a clustering of conditions that activate or injure the endothelium. Highly active antiretroviral treatment produces adverse effects such as dyslipemia, insulin resistance (IR) and body fat changes (named lipodystrophy syndrome) which may contribute to aggravate their endothelial perturbation. The aim of this study was to measure lipid profile, insulin resistance status, and endothelial markers in 38 HIV+ naive of antiretroviral treatment and 63 HIV+ under highly active antiretroviral treatment (33 with lipodystrophy syndrome and 30 without it). Body fat distribution was also evaluated by dual-energy X-ray absorptiometry (DEXA) analysis. Thirty-one HIV negative subjects were used as controls. We looked for association between variables. Insulin resistance status was a common finding in the four groups. Lipodystrophic patients presented an atherothrombotic lipid profile [elevated levels of triglycerides (TG), low-density lipoprotein cholesterol (LDL-chol) and apolipoprotein-B (APO-B)] and a strong loss of fat in legs and arms (lipoatrophy). All endothelial markers evaluated in our naive patients were higher as compared to control group. sVCAM-1 in HIV+ under therapy without lipodystrophy syndrome showed significantly decreased levels as compared to naive group (487 vs. 666 ng/ml) and vWF and sTM tended to diminish although they did not show a significant difference (130% vs. 170%, 41 vs. 45 ng/ml, respectively). Lipodystrophic patients showed a tendency to increased levels of endothelial activation markers (sVCAM-1: 500 ng/ml and vWF: 154%) together with significantly increased levels of an endothelial injury marker (sTM: 50 ng/ml) with respect to HIV+ under therapy without lipodystrophy syndrome. Plasma levels of sTM, as an endothelial injury marker, correlated with peripheral lipoatrophy (rho = -0.357) in lipodystrophic patients. In conclusion, despite the beneficial immunology effect of highly active antiretroviral treatment and the apparent decrease in the endothelial perturbation, the patients who develop lipodystrophy present altered endothelial markers and other risk factors, such as IR and dyslipemia, which turn them into a high atherothrombotic risk group.

High prevalence of antiphospholipid antibodies in leprosy: evaluation of antigen reactivity.

Antiphospholipid antibodies (aPL) have been reported not only in autoimmune disorders but also in various infectious diseases. Accumulating evidence indicates that b2 glycoprotein I (b2GPI) and prothrombin are the main proteins to which autoimmune aPL bind. The aim of this study was to evaluate the prevalence of different aPL in patients with leprosy. We included 51 outpatients (42 lepromatous and 9 borderline leprosy) without any clinical feature of the antiphospholipid syndrome (APS). 35 had lupus anticoagulant and 31 had anticardiolipin antibodies (aCL). Anti-β2GPI antibodies were highly positive in 29=51 and anti-prothrombin antibodies (anti-II) were detected in 23=51. Almost all aCL and anti-b2GPI were of IgM isotype, while IgG isotype was more frequent among anti-II. No statistical difference was found when aPL were evaluated in patients grouped according to their bacteriological status. Furthermore, patients under treatment (n ‘ 33) had a similar frequency of positive aPL compared to patients in vigilance (n ‘ 14). Assessing the specificity of antibody binding to CL and b2GPI in ELISA by means of inhibition studies with cardiolipin-b2GPI liposomes, leprosy and APS sera showed a similar behaviour. Comparable results were also found in both groups of patients when inhibition experiments with lysate of Mycobacterium leprae were carried out. In summary, leprosy-related aPL resemble those found in patients with APS but the immunoglobulin isotype is different, with IgM much more prevalent in leprosy patients.

Insulin resistance status is an important determinant of PAI-1 levels in HIV-infected patients, independently of the lipid profile.

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Soluble thrombomodulin levels among women with a history of recurrent pregnancy loss, with or without antiphospholipid antibodies

The endothelial cells produce substances whose elevated plasma levels acquire predictive value for the development of events. For instance, soluble thrombomodulin (sTM) levels evidence endothelial cell injury. Under specific clinical conditions the levels of sTM are raised, such as in patients with certain autoimmune disorders, pre-eclampsia or antiphospholipid syndrome. The levels of sTM, as an endothelial injury marker, were evaluated in 65 women with a history of recurrent pregnancy loss (12 with autoimmune disorders, 19 pregnant women and nine with a history of gestational hypertension or pre-eclampsia or eclampsia); 13 of them had antiphospholipid antibodies. sTM levels could be used as a predictor of pregnancy loss in future prospective studies. We compared those levels with the levels found in control groups without recurrent pregnancy loss (20 healthy women and 14 women with autoimmune disorder). There were no statistically significant differences (P = 0.729) in the levels of sTM between the recurrent pregnancy loss group (31.1 ng/ml) and the healthy control group (31.4 ng/ml) or between the different subgroups with recurrent pregnancy loss (P = 0.873) and the healthy control group or the control group with autoimmune disorder (28.0 ng/ml). There were no statistically significant differences (P = 0.605) in the levels of sTM among the patients with recurrent pregnancy loss, with or without moderate or high antiphospholipid antibodies (32.0 versus 23.3 ng/ml). Consequently, the levels of sTM would not seem to be a useful tool, as an endothelial injury marker, in women with a history of recurrent pregnancy loss with or without antiphospholipid antibodies.

Association between the acquired free protein S deficiency in HIV-infected patients with the lipid profile levels

prothrombin gene mutation G20210A who also had a history of poor pregnancy outcome. At this time, management of women with these inherited thrombophilic conditions is based upon the results of small studies, and expert opinion [15]. An adequate randomized placebo controlled trial is urgently needed to determine whether antenatal heparin administration improves the pregnancy outcome of women with these inherited thrombophilias and prior adverse pregnancy outcomes.