Luis O. Carreras

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.

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.

Pregnancy loss and autoantibodies against phospholipid-binding proteins.

Objective To evluate the relationship between anibodies against β2-glycoprotein I or prothrombin and pregnancy losses in women with antiphospholipid antibodies. Methods Women with antiphospholipid antibodies, (lupus anticoagulant and/or anticardiolipin antibodies), with (n = 41) and without (n = 61) a history of pregnancy loss were evaluated. Thirty-one out of the frty-one patients with pregnancy loss had early miscarriages (at less than 13 weeks) and ten patients had late iscarriages. Immunoglobulin (Ig)-G and IgM anti-β2-glycoprotein I and anti-linked immunosorbent assay method. Results A significant association between pregnancy loss and positive IgM anti-β2-glycoprotein I antibodies was found (odds ratio 2.6; 95% confidence interval 1.03, 6.6; P = .043). Women with late pregnancy loss had higher levels of both IgG and IgM anti-β2-glycoprotein I antibodies compared with controls (P < .05). There was a good correlation between anticardiolipin and anti-β2-glycoprotein I antibodies levels (IgG: r = 0.75; IgM: r = 0.73). In contrast, there was no correlation between the levels of anticardiolipin or anti-β2-glycoprotein I antibodies and the levels of anti-prothrombin antibodies. furthermore, the presence of antiprothrombin antibodies was not associated with a history of pregnancy loss. Conclusion The result of our study shows that there is a relationship between the presence of IgM anti-β2-glycoprotein I and previous miscarriages in women with antiphospholipid antibodies.

Occurrence of anti-prothrombin and anti-β2- glycoprotein I antibodies in patients with history of thrombosis

New evidence indicates that antibodies to beta2-glycoprotein I (anti-beta2GPI) or to human prothrombin (anti-II)(or to both of these) are specific markers of the antiphospholipid syndrome (APS). They have been mainly associated with thrombotic complications in patients with APS. However, some studies have reported that elevated levels of anti-II, but not of anfi-beta2GPI, imply a risk of venous thrombosis (VT) or arterial thrombosis (AT) in subjects with no previous thrombosis and no antiphospholipid antibodies (aPL) by ELISA. The present study Included 180 patients with a history of thrombosis, 83 of them without aPL (group I) and the remaining 97 diagnosed as having APS (group II). Anti-beta2GPI was found in only 1 of the 83 patients from group I but was found in approximately 50% of those from group II (P < .0001). In contrast, positive anti-II was detected with a high prevalence in patients from group I (VT, 22.6%; AT, 26.7%) and in those from group II (VT, 37.5%; AT, 14.6%). No statistical differences were found in the prevalence of anti-II between the two groups of patients. On the other hand, such a difference was significant when compared with results in a normal group (1/67, 1.4%, P < .0001). These data Indicate that anti-II occurs frequently in patients with previous thrombosis either with or without lupus anticoagulant activity. Accordingly, testing of anti-II might be clinically useful in the evaluation for thrombophilla.

Melatonin effect on arachidonic acid metabolism to cyclooxygenase derivatives in human platelets

Abstract: The effect of melatonin on thrombin‐induced [3H]‐arachidonic acid (AA) metabolism to cyclooxygenase derivatives was determined in platelets obtained from normal volunteers at 0830 and 2030 h. Percent conversion of radioactive AA was generally greater at 2030 h than at 0830 h for every cyclooxygenase derivative analyzed. Micromolar or greater concentrations of melatonin decreased significantly the conversion of [3H]‐AA to prostaglandin (PG) F2 and thromboxane (Tx) B2, and inhibited slightly the conversion to PGE2 and PGD2. After preincubation of platelets with 1 mM imidazole, the melatonin inhibitory effect was significant for PGF2 only. Melatonin (10−6 M) showed a significant inhibitory influence on platelet ATP release induced by phorbol‐12 myristate‐13 acetate (PMA) at 2030 h, an effect inhibited by 1 mM aspirin. These results indicate that at pharmacological concentrations melatonin inhibits human platelet cyclooxygenase.

Inhibition of human platelet aggregation and thromboxane B2 production by melatonin. Correlation with plasma melatonin levels

Abstract: Plasma melatonin concentrations and the effect of melatonin on arachidonic acid (AA)‐induced aggregation and thromboxane B2 (TxB2) production by platelet‐rich plasma (PRP) were examined in five normal male volunteers, sampled at 2 hr intervals from 21:30 to 09:30 hr. Peak plasma melatonin concentration was found at 03:30 hr. Inhibition by 10−6 M melatonin of AA‐induced PRP aggregation was observed only in samples taken at 01:30 hr. Assessment of the inhibitory effect of 10−9–10−6 M melatonin on AA‐induced TxB2 production indicated that melatonin activity was greater at 01:30 h as compared to late night. Assessed as a global effect, the inhibitory activity of melatonin on PRP TxB2 showed a maximum at 01:30 hr and minimal effects at 03:30 hr, at the time when plasma concentrations of melatonin were highest. These results indicate the existence of a nocturnal variation in sensitivity of human platelets to melatonin, with a peak that precedes the maximum in circulating melatonin levels.

Comparison of Various Screening and Confirmatory Tests for the Detection of the Lupus Anticoagulant

Several assay systems have been proposed for detection of the lupus anticoagulant (LA). We compared several screening and confirmatory tests used for the detection of LA in 108 patients. LA was detected in 52 plasmas. The activated partial thromboplastin time (APTT) and the dilute Russell viper venom time (DRVVT) were the most sensitive screening tests as compared to the kaolin clotting time (p less than 0.001). The platelet neutralization procedure in both the APTT and DRVVT systems was superior to APTT performed with high phospholipid concentration (p less than 0.01) and tissue thromboplastin inhibition (p less than 0.001) as confirmatory tests. There was an association between the presence of LA and antiphospholipid antibodies detected by the enzyme-linked immunosorbent assay (p less than 0.001). In summary, our results show that APTT may be a sensitive test for the detection of LA when an appropriate reagent is employed, and that freeze-thawed platelets are more effective than phospholipids to neutralize LA activity.

Antiphospholipid Antibodies Eicosanoids

Correspondence: L.O. Carreras, M.D., University Institute of Biomedical Sciences, Favaloro Foundation, Solís 453, 1078 Buenos Aires, Argentina In spite of considerable interest in the antiphospholipid syndrome over the past 10 years, the mechanism responsible for the association between antiphospholipid (aPL) antibodies and thrombosis or fetal wastage is not fully elucidated. Several abnormalities which have been de-