Anticardiolipin Antibody Titers Research Articles

B cell depletion therapy for patients with systemic lupus erythaematosus results in a significant drop in anticardiolipin antibody titres

Background:B cell depletion therapy (BCDT) has recently been used with success to treat patients with rheumatoid arthritis and systemic lupus erythematosus (SLE). As antiphospholipid antibodies have been implicated in the...

In Vivo Effects of an Inhibitor of Nuclear Factor‐Kappa B on Thrombogenic Properties of Antiphospholipid Antibodies

It has been shown that endothelial cell (EC) activation and tissue factor (TF) upregulation in EC and monocytes by antiphospholipid antibodies (aPL Abs) leads to a prothrombotic state and involves translocation of nuclear factor-kappa B (NF-kappaB). Here we examined the effects of an NF-kappaB inhibitor on aPL-induced thrombosis, TF activity, and EC in vivo. We treated CD1 mice with IgG from a patient with antiphospholipid syndrome (IgG-APS) or with control IgG (IgG-NHS). The adhesion of leukocytes (number of white blood cells) to EC in cremaster muscle (as an indication of EC activation) as well as the size of an induced thrombus in the femoral vein of the mice were examined. Some mice in each group were infused with 10 microM MG132 (an inhibitor of NF-kappaB). TF activity was determined using a chromogenic assay in homogenates of carotid arteries and in peritoneal cells of mice. In vivo, IgG-APS increased significantly the number of white blood cells adhering to ECs (4.7 +/- 2.2) when compared to control mice (1.5 +/- 0.8), and these effects were significantly reduced when mice were pretreated with MG132 (0.8 +/- 0.2). IgG-APS increased significantly the thrombus size and MG132 inhibited that effect (93%). Treatment of the mice with IgG-APS also induced significantly increased TF function in peritoneal cells and in homogenates of carotid arteries. Pretreatment of the mice with MG132 abrogated those effects significantly. Mice injected with IgG-APS or with IgM-APS with or without the inhibitor had medium-high titers of anticardiolipin antibodies in serum at the time of the surgical procedures. The data show that prothrombotic and proinflammatory properties of IgG-APS and IgM-APS are downregulated in vivo by an NF-kappaB inhibitor. These findings may be important in designing new modalities of targeted therapies to treat thrombosis in patients with APS.

Benign intracranial hypertension associated to blood coagulation derangements

BackgroundBenign Intracranial Hypertension (BIH) may be caused, at least in part, by intracranial sinus thrombosis. Thrombosis is normally due to derangements in blood coagulation cascade which may predispose to abnormal clotting activation or deficiency in natural inhibitors' control. The aim of the study is to examine the strength of the association between risk factors for thrombosis and BIH.Patients and methodsThe incidence of prothrombotic abnormalities among a randomly investigated cohort of 17 patients with BIH, was compared with 51 healthy subjects matched for sex, age, body mass index, height and social background.ResultsThe number of subjects with protein C deficiency was significantly higher in patients than in controls (3 vs 1, p < .001; Fisher Exact Test). Moderate to high titers of anticardiolipin antibodies (β2-Glycoprotein type I) were found in 8 out of 17 patients.Increased plasma levels of prothrombin fragment 1+2, fibrinopeptide A (FPA), and PAI-1 were demonstrated in patients group (5.7 ± 1.15 nM vs 0.45 ± 0.35 nM; 8.7 ± 2.5 ng/mL vs 2.2 ± 1.25 ng/mL; 45.7 ± 12.5 ng/mL vs 8.5 ± 6.7 ng/mL, respectively; p < .001; Fisher Exact Test). Gene polymorphisms for factor V Leiden mutation, prothrombin mutation 20210 A/G, MTHFR 677 C/T, PAI-1 4G/5G, ACE I/D were detected in 13 patients.DiscussionIn agreement with other authors our data suggest a state of hypercoagulability in BIH associated with gene polymorphisms. Our findings also showed that mutations in cardiovascular genes significantly discriminate subjects with a BIH history. The association between coagulation and gene derangements, usually regarded to as cryptogenic, may suggest a possible pathogenetic mechanism in BIH. So, a prothrombotic tendency may exist that would, at least in part, explain some cases of BIH.Although based on a small population, these findings raise the exciting possibility of using these haemostatic factors as markers for selecting high-risk subjects in BIH disease.

High Titer of Anticardiolipin Antibody Is Associated with First-Ever Ischemic Stroke in Taiwan

Background and Purpose: The association between anticardiolipin antibody (aCL) and ischemic stroke is controversial, and there are few case-control studies of Asian populations. The aim of this study, therefore, was to determine whether aCL is an independent risk factor for ischemic stroke in Taiwanese patients over the age of 40 years. Methods: Both the IgG and IgM isotypes of aCL were measured in 273 patients (>40 years of age) hospitalized for first-ever ischemic stroke and in 181 non-stroke controls. Results were defined as: negative (<10 IgG phospholipid units [GPL] or <7.5 IgM phospholipid units [MPL]); low positive (10–20 GPL or 7.5–15 MPL); or, high positive (>20 GPL or >15 MPL). Odds ratios (OR) were estimated by logistic regression with adjustment for potential confounders. Results: A high positive IgG aCL was present in 4.4% of the stroke patients and 1.2% of the controls. Age- and sex-adjusted analysis showed a borderline association between a high positive level for aCL IgG titer and stroke, with an OR of 4.01 (95% CI 0.87–18.37; p = 0.0739). Final analysis, with adjustments for age, sex, hypertension, diabetes, tobacco smoking, atrial fibrillation, left ventricular hypertrophy and hyperlipidemia, revealed an OR of 5.25 (95% CI 1.06–25.89; p = 0.0419). Conclusions: The results of this study suggest that elevated titer of aCL IgG (>20 GPL) is associated with first-ever ischemic stroke in Taiwanese patients aged over 40 years. High positive aCL titer is related to ischemic stroke after adjustment for conventional cerebrovascular risk factors, indicating that it is probably an independent risk factor for ischemic stroke.

A re-appraisal of the normal cut-off assignment for anticardiolipin IgM tests.

Recent reports show an apparent large number of individuals with low to moderate titers of anticardiolipin antibodies (ACA), particularly of the IgM isotype with no clinical signs of antiphospholipid syndrome (APS). The significance of these results is unknown. This study examined the prevalence of low positive titers of IgM ACA antibodies in a large number (n = 982) of normal blood donors (Group 1) and in a group of 159 individuals > 60 years of age (Group 2). The effect of re-defining the currently used cut-off values for the IgM ACA tests was also examined. IgM ACA antibodies were tested in three ELISA assays: the Bindazyme Anti-IgM Cardiolipin EIA kit (assay A), an 'in-house' ACA test (assay B), and the APhL ELISA kit (assay C). THE normal range cut-offs were re-calculated using the 95th percentile of the data for Group 1 (12.4 MPL U mL(-1) for assay A, 5.4 MPL U mL(-1) for assay B and 9.5 MPL U mL(-1) for assay C) and Group 2 (9.9 MPL U mL(-1) for assay A, 5.5 MPL U mL(-1) for assay B and 13.2 MPL U mL(-1) for assay C). These values were not significantly different from the current cut-off values for each assay. The prevalence of low positive results in Group 1 relative to the re-defined cut-off for that group were: 1.0%, 1.1% and 0.9% in assay A, B and C; and in Group 2: 0.6%, 0.6% and 0.6%, respectively. An indeterminate zone (between the 95th and 99th percentile) was then established for the two groups. The prevalence in Group 1 was 3.8%, 3.9% and 3.9% for assays A, B and C, respectively, and for Group 2: 4.4% in all three assays. The data confirm that the current cut-off point for each of the three assays is correct. We suggest based on this study that the low positive range is re-assigned 'indeterminate' and recommend that samples falling in this category should be retested to confirm positivity at a later date.

Neonatal antiphospholipid syndrome

Antiphospholipid syndrome (APS) is a clinical entity characterized by arterial and venous thrombosis, adverse obstetric outcome and the presence of antibodies against phospholipids in serum or plasma. The objective of the present study is to describe a rare case of APS that occurred in a neonate born from a patient previously diagnosed as primary APS. A male, preterm born twin infant, whose mother had been diagnosed as primary APS, developed thrombocytopenia, livedo reticularis, pericardial effusion and thrombosis of the left subclavian and external jugular veins concomitantly with severe respiratory tract infection soon after his delivery, that culminated with his death two months after the birth, in spite of the large spectrum antibiotic therapy and all supportive measures. Laboratory findings included high titers of IgM anticardiolipin antibodies and moderate titers of IgG isotype and negative antinuclear antibody, configuring a case of neonatal APS. Neonatal APS is a rare clinical condition, with only a few cases described in the literature. Its occurrence may depend on the passage of antibodies through the placenta or, as it seems to have occurred in the present case, by the production of de novo antibodies by the fetus. The present case illustrates the necessity of a higher surveillance of the neonates born from mothers with primary APS or systemic lupus erythematosus (SLE) for the eventual development of such complication.

Combined Oral Contraceptives in Women With Systemic Lupus Erythematosus

The Oral Contraceptives part of the Safety of Estrogens in Lupus Erythematosus National Assessment (OC-SELENA) study was a prospective, randomized, double-blind trial carried out at 15 U.S. centers that examined the effects of oral contraceptives on disease activity in 183 premenopausal women with systemic lupus erythematosus. Initially, disease was inactive in 76% of participants and active but stable in the remaining 24%. Participants were assigned to receive 35 μg triphasic ethinyl estradiol plus 0.5, 0.75, or 1 mg norethindrone, or placebo, for 12 28-day cycles. None of the subjects had moderate to high titers of anticardiolipin antibodies, lupus anticoagulant, or a history of thrombosis. Just over one third of patients in each group failed to comply throughout the 12-month study. Only seven of 91 women given oral contraceptives and seven of 92 placebo recipients had a severe flare of disease during the study. Two flares in the active treatment group occurred when the study drug was omitted. On Cox proportional-hazards analysis, the relative risk (RR) of a severe flare occurring during OC treatment, compared with placebo, was 0.93 (95% confidence interval [CI], 0.33–2.65). The estimated difference was less than the maximum clinically acceptable difference. Participants in both groups who had active disease at the outset were likelier than those whose disease was inactive to have a severe flare. The estimated RR, adjusted for treatment, was 3.5 (95% CI, 1.23–9.99). Rates of moderate or mild flares were similar in the treatment and placebo groups. The likelihood of having at least one flare of any degree during 12 months of follow up was 76% for actively treated patients and 69% for those in the placebo group (RR, 1.09; 95% CI, 0.76–1.55). One OC-treated patient had deep venous thrombosis (DVT) and one had a clotted graft. In the placebo group, there was one case each of DVT, ocular thrombosis, and superficial thrombophlebitis, and one woman died after the trial ended. These findings endorse the use of oral contraceptives, including estrogen, as a birth control measure by women having inactive or active but stable systemic lupus erythematosus. These patients are at relatively low risk of developing thrombosis.

Toll like Receptor 4 Is Involved in In VIvo Antiphospholipid-Mediated Thrombosis and Endothelial Cell Activation.

Background: Antiphospholipid antibodies (aPL) are associated with thrombosis and pregnancy loss in patients with Antiphospholipid Syndrome (APS). aPL and bacterial lipopolysaccharide (LPS) bind to and activate endothelial cells (EC) through NFκB and p38 MAPK pathways. Recent studies suggest that aPL might interact with toll-like receptor-4 (TLR-4), the receptor for LPS.Aim: to investigate the role of TLR-4 in antiphospholipid syndrome (APS).Methods: we examined: i) the aPL effects on thrombosis and EC activation in LPS non-responsive (LPS−/−) mice that display a spontaneous mutation of TLR-4 vs LPS-responsive (LPS+/+) mice displaying wild type TLR-4, ii) the prevalence of TLR-4 Asp299gly and Thr399Ile polymorphisms - both associated with decreased response to LPS - in 110 APS patients (with arterial and/or venous thrombosis) vs 220 controls (of same ethnic background). IgGs were purified from a patient with APS (IgG-APS) and from control serum (IgG-NHS). LPS −/− and LPS +/+ mice, in groups of nine, were treated with IgG-APS or with IgG-NHS twice intraperitoneally. Size of induced thrombi and # of leukocyte (WBC) adhering to endothelial cells in the microcirculation of endothelium of the cremaster muscle of mice (as a means to measure endothelial cell activation) were determined in vivo, seventy-two hours after the first injection. TLR-4 Asp299gly & Thr399Ile polymorphisms were evaluated by Allele-Specific PCR.Results: LPS +/+ mice treated with IgG-APS produced significantly larger thrombi when compared to mice treated with IgG-NHS (2166 ± 1419 μm2 vs 1176 ± 841 μm2) and significantly larger number of WBC adherence to ECs (4.5 ± 1.9 vs 2.2 ±1.1). Thrombus size and number of adhering WBC to ECs were significantly lower in LPS −/− mice treated with IgG-APS compared to LPS +/+ mice treated with IgG-APS [thrombus size: 779 ± 628 μm2 vs 2166 ± 1419 μm2 (p<0.05) and number of adherent WBC to EC: 1.0 ± 0.5 vs 4.5 1.9 (p<0.05)], respectively. The titer of anticardiolipin antibodies in the sera of mice injected with aPL was 48.2 ± 17.1 GPL (for LPS −/− mice) and 50.8 ± 11.2 GPL (for LPS +/+ mice), respectively (NS). A significant reduction in TLR-4 Asp 299gly & Thr399Ile polymorphisms was observed in APS patients (5%) compared to controls (11.4%) (p<0.05).Conclusions: These findings strongly suggest that TLR-4 is involved in aPL interaction with endothelial cells and mediates their pathogenic effects.

Antiphospholipid syndrome in patients with systemic lupus erythematosus treated by autologous hematopoietic stem cell transplantation

AbstractSystemic lupus erythematosus (SLE) is the most common disease associated with antiphospholipid syndrome (APS). We, therefore, evaluated 46 patients with refractory SLE treated by autologous hematopoietic stem cell transplantation (HSCT) for a history of APS prior to transplantation. The prevalence of SLE-related APS in our patient population was 61% (28 of 46 patients with refractory SLE). Nineteen of 28 patients with APS had lupus anticoagulant (LA) or high titers of anticardiolipin antibodies (ACLAs), either immunoglobulin (Ig)G or IgM, when evaluated at study entry. Six of 8 evaluable LA+ patients became and remained LA–; 5 of 7 initially ACLA IgG+ patients and 9 of 11 ACLA IgM+ patients demonstrated normalization of ACLA titers when followed after HSCT. Eighteen of 22 patients refractory to chronic anticoagulation discontinued anticoagulation therapy a median of 4 months after transplantation; 78% of them remained free of thrombotic events and in complete SLE remission for up to 78 months (median, 15 months) after HSCT. There was no treatment-related mortality. Autologous HSCT may be performed safely in patients with APS and appears to be effective therapy for eliminating ALPAs and preventing thrombotic complications in patients with SLE.

Five-Year Follow-Up by Transesophageal Echocardiographic Studies in Primary Antiphospholipid Syndrome

This prospective study describes valvular abnormalities assessed by transesophageal echocardiography (TEE) in patients with primary antiphospholipid syndrome (APLS) over a 5-year follow-up. Of the 56 patients with APLS evaluated at baseline, 47 (84%) had repeat TEE examinations, including 3 patients who died before the end of the follow-up. The first TEE study showed cardiac involvement (thickening or vegetations and embolic sources) in 34 subjects (61%), with mitral valve thickening, the most common abnormality, present in 30 patients (54%). Embolic sources were found in 14 patients (25%; 9 severe spontaneous echocardiographic contrast, 5 Libman-Sacks endocarditis), associated with mitral valve thickening or stenosis in 10 patients. Over the 5-year follow-up, cardiac involvement was unchanged in 30 subjects (64%). New cardiac abnormalities were observed in 17 patients (36%), 15 (88%) with high immunoglobulin-G (IgG) anticardiolipin antibody (aCL) titers and 2 (12%) with low IgG aCL titers. In conclusion, this study showed that mitral valve thickening and embolic sources are frequently observed in patients with APLS. Anticoagulant and/or antiplatelet treatment was ineffective in terms of valvular lesion regression. New appearances of cardiac involvement are significantly related to high IgG aCL titers.

Perinuclear antineutrophil cytoplasmic antibody myeloperoxidase-positive vasculitis in association with ulcerative colitis

We describe a patient with ulcerative colitis (UC) who developed small vessel vasculitis. Perinuclear antineutrophil cytoplasmic antibody myeloperoxidase (p-ANCA-MPO) positivity was detected along with a highly elevated titer of anticardiolipin antibodies. A total proctocolectomy was undertaken and the patient, more than 5 years later, remains in very good condition. The possible causative association between the UC, the p-ANCA-MPO-positive small vessel vasculitis, and the anticardiolipin antibodies is discussed.

Antibodies against oxidized LDL and cardiolipin and mortality in patients with coronary heart disease

The association between antibodies against oxidized LDL (oxLDL) and cardiolipin and the risks of death and cardiovascular disease events were evaluated in patients with established coronary heart disease (CHD). The patients (mean age: 61 years, range: 33–74 years) were participants in the EUROASPIRE study; 108 of them had undergone coronary artery bypass surgery, 106 had balloon angioplasty, 101 had a diagnosis of acute myocardial infarction (AMI), and 98 acute myocardial ischemia. Antibodies against oxLDL and cardiolipin were measured and incidence of CHD events and deaths were followed up for 5 years in 284 men and 129 women. During the follow-up 36 patients died and 21 had AMI. After adjustment for cardiovascular disease risk factors the relative risks (RR [95% confidence interval]) of death were 1 (reference), 2.50 (0.97–6.49) and 2.21 (0.85–5.80) in increasing tertile categories of anti-oxLDL antibody titers, respectively ( P for trend 0.16). The risks of CHD-death or AMI combined were 1 (reference), 2.61 (1.02–6.65) and 1.06 (0.37–3.03) in increasing tertile categories of anticardiolipin antibody titers, respectively ( P for trend 0.03). In conclusion, the results suggest that antibodies against oxLDL and cardiolipin are not major predictors of risks of death and CHD events in patients with established CHD.

Anticuerpos antifosfolípidos en nefropatía membranosa idiopática

Antiphospholipid antibodies have been found in the sera from patients with idiopathic and secondary glomerulopathies, mainly related to lupus. No special attention has been devoted to idiopathic membranous nephropathy, a glomerular disease with a high frequency of thrombotic complications, particularly of the renal vein. To study the presence and significance of antiphospholipid antibodies in idiopathic membranous nephropathy. Anticardiolipin and anti-ss2-glycoprotein-I IgG antibodies were measured in serum samples from 21 patients with idiopathic membranous nephropathy (age range 11-75 years, 5 female). The medical records of 20 of these patients were reviewed, looking for vascular complications and nephrological evolution during a follow-up period that ranged from two to 277 months. Five patients had anticardiolipin antibody titers over the cutoff for normal values, and two others were positive for anti-ss2-glycoprotein-I, without cross-reactivity. There was no difference in the incidence of thrombotic complications in the renal vein, or other locations, between these seven patients and the remaining patients. No differences in the clinical course of the nephropathy were detected either. Antiphospholipid antibodies may be found in patients with primary membranous nephropathy. They are not related to thrombosis or a worse evolution.

Assessment of Cardiac Structure and Left Atrial Appendage Functions in Primary Antiphospholipid Syndrome

Although thromboembolic events are the major complication of primary antiphospholipid syndrome (PAPS), cardiac involvement is commonly present. Left atrial appendage (LAA) is recognized as an important source for thrombus formation and thromboembolism. The purpose of the study was to assess the structure and function of LAA with transesophageal echocardiography (TEE) in PAPS patients. Thirty-one PAPS patients (22 women, mean age 36+/-9 years) in sinus rhythm and 31 (17 women, mean age 37+/-7 years) controls with normal TEE examination were investigated. Eighty-four percent of the PAPS patients had functional and structural valvular defect predominantly in the mitral valve. Valvular lesions were especially frequent in PAPS patients with a history of cerebrovascular events, patients with history of arterial thrombosis (91.6%), and patients with high titers of IgG anticardiolipin antibodies (100%). Intracardiac thrombus was present in 5 patients and in 1 of them it was located in LAA. The structure of LAA was similar between groups. Left atrial appendix ejection fraction (51.8+/-4 versus 48.6+/-5.5%; P<0.05) and LAA peak outflow velocity (87+/-10.9 versus 80.6+/-10.3 cm/s; P=0.02) was significantly higher in PAPS group compared with controls. In PAPS patients with mitral regurgitation (MR), LAA outflow peak velocity (84.3+/-10 versus 98.6+/-6.5 cm/s; P=0.002) and LAA inflow peak velocity (67.8+/-10.5 versus 80.8+/-8.6 cm/s; P=0.009) were significantly lower compared with PAPS patients without MR. It was concluded that disease process in PAPS frequently involved cardiac valves especially mitral valve but spared LAA function. LAA function was normal, but intracardiac thrombus was present in 5 patients and 1 of them was located in LAA. MR in PAPS patients seems to impair LAA function.

IgM-Anticardiolipin Antibody and Vascular Access Thrombosis in Chronic Hemodialysis Patients

Aim: Vascular access failure is a major cause of morbidity in chronic hemodialysis (HD) patients. Elevated immunoglobulin-M anticardiolipin antibody (IgM-aCL) titer is associated with stenosis of vascular access in HD patients. The clinical significance of elevated IgM-aCL titer relative to recurrent vascular access thrombosis (VAT) in patients with HD is less clear. However, little information has been available until now about the clinical influence of elevated IgM-aCL titer with recurrent VAT in HD patients from Western countries, and no report exists for Taiwan. This study attempted to determine whether elevated IgM-aCL titer was associated with recurrent VAT in HD patients. Methods: This study enrolled 483 patients undergoing HD. IgM-aCL titer and hepatitis C marker were measured for all subjects. Results: Elevated IgM-aCL titer was present in 17.4% (84/483) of patients. There was no association recurrent VAT between elevated and normal IgM-aCL titers (P = 0.90). Presence of hepatitis C had significant differences between elevated and normal IgM-aCL titers (P = 0.027). Conclusions: We found no significant differences in recurrent VAT between elevated and normal IgM-aCL titer in chronic HD patients. Our results suggest recurrent VAT of synthetic or native fistula may not be caused by elevated IgM-aCL titer in these patients. Presence of hepatitis C may be a cofactor.

Apolipoprotein H (apoH)-dependent autoantibodies and apoH protein polymorphism in selected patients showing lupus anticoagulant activity

Apolipoprotein H (apoH) is considered to be a necessary cofactor for the binding of certain antiphospholipid antibodies to anionic phospholipids. Some apoH-dependent antiphospholipid antibodies also exert lupus anticoagulant (LA) activity, which seems to depend on antiphospholipid antibody epitope specificity. The aim of this study was to evaluate whether the presence of less frequent apoH alleles may induce structural or conformational changes in these "LA-dependent" regions that may initiate more frequent autoimmune responses in subjects. We selected patients with confirmed LA activity and none or low titers of anticardiolipin antibodies that had been sent to the laboratory for routine antiphospholipid antibody determination. Many of them had some clinical manifestation of antiphospholipid syndrome. Antibodies to apoH were determined with a commercially available anticardiolipin/apoH ELISA kit. ApoH protein polymorphism (apoH phenotype) was demonstrated by isoelectric focusing and immunoblotting. Our results showed that 47/74 (63.5%) of our selected LA-positive patients also had elevated apoH-dependent antiphospholipid antibody titers. These results point to two subgroups of patients according to the LA potency of apoH-dependent antibodies. A strong positive correlation (non-linear or linear) for apoH-dependent antibody titers and LA activity was observed in both subgroups of patients. In this study, we did not find significant differences in the distribution of apoH phenotypes among control subjects and patients with apoH-dependent/LA-positive auto- antibodies.

Antiphospholipid syndrome in a young patient with myocardial infarction, pulmonary embolism and coronary artery pearl-like lesions

Summary: Our paper presents the case of a patient, aged 34, with a previous anamnesis of three miscarriages and two normal children, transitory Raynaud phenomenon and livedo reticularis with no classical factors for coronary arterial disease, excluding smoking, who was diagnosed with myocardial infarction furthermore complicated by pulmonary embolism. The coronarography and ventriculography findings showed morphological signs of coronaritis, ostial occlusion of LAD, diffuse stenoses of RCA like a string of beads, aneurysm of the anterior wall and apex, ejection fraction of 20%, while echocardiography showed dilatative cardiomyopathy. Elevated IgM anticardiolipin (22 MPLU/mL) antibodies were found at first, and 8 weeks later both IgG (19.8 GPLU/mL) and IgM (15.6 MPLU/mL) were positive. The importance of relatively low levels of anticardiolipin antibody titres was confirmed by a positive anti-b2 GPI test. All other analyses encompassing investigations of thrombophilia, early atherosclerosis markers including Lp(a), homocysteine, immunological analyses specific for systemic diseases, antibodies against Borrelia burgdopheri, HCV, HBV, EBV, were negative. Though the one-year stabilisation of the clinical state and normalisation of acute phase reactants was achieved, along with six-time decrease in sedimentation rate, the disease ended lethally in a sudden death of the patient under home care. In compliance with our surveys, this is the first so far reported case of coexistent pearl-like pattern occurrence in coronary arteries with antiphospholipid syndrome.

Antiphospholipid Syndrome in Patients with Systemic Lupus Erythematosus Treated by Autologous Hematopoietic Stem Cell Transplantation.

The association of antiphospholipid antibodies (APLA) with either vascular thrombosis or fetal morbidity is known as the antiphospholipid syndrome (APS). Since systemic lupus erythematosus (SLE) is frequently associated with APS, we analyzed 44 patients with severe and refractory SLE involved in a larger study of autologous hematopoietic stem cell transplantation (HSCT) utilizing cyclophosphamide and antithymocyte globulin (ATG) conditioning to determine the efficacy of this treatment in eliminating APLA and preventing recurrent thrombi. The prevalence of SLE-related APS in our patient population was 63% (45% met Sapporo criteria for definite APS, and 18% had history of APLA positivity with associated clinical APS features). Nineteen patients with APS had lupus anticoagulant (LA) and/or high titers of anticardiolipin antibodies (ACLA) at the entry into study. Ten patients were positive for LA. Fourteen patients showed elevated titers of ACLA, IgG and/or IgM. When followed for up to 30 months after autologous HSCT, 70% of initially LA-positive patients became and remained negative for anticoagulant. 79% demonstrated normalization of ACLA titers during maximum of 28 months follow-up. 64% of patients refractory to chronic anticoagulation regimen were able to discontinue from anticoagulation therapy at average of 6 months post-transplant and remained thrombotic events-free and in complete SLE remission for up to 78 months after HSCT. There was no treatment-related mortality or severe adverse events, including stem cell engrafment-related hematological complications or overhelming bacterial, fungal or viral infection, in any of the 28 SLE-related APS patient. Autologous hematopoietic stem cell transplantation may be performed safely and appears to be effective therapy for eliminating SLE-related APLA and preventing further thrombotic events.

Resolution of Catastrophic Anti Phospholipid Antibody Syndrome with Acute Renal Failure after Treatment with Rituximab.

Antiphospholipid antibody syndrome (APS) is a thrombophilic disorder defined by the presence of recurrent thrombosis associated with anticardiolipin antibodies (ACA). To date, there is no effdective therapy for this condition. Rituximab, a chimeric monoclonal antibody B Cells has been shown to be effective in autoimmune disorders. Sporadic abstracts have reported the disappearance of ACA after Rituximab treatment. We have successfully treated a patient with primary catastrophic APS and renal failure with Rituximab. Case Report: A thirty seven year old male with history of DVT, ischemic cardiomyopathy and cerebrovascular accident was admitted to the Hospital for the treatment of acute renal failure and thrombocytopenia. Physical examination was significant for cognitive deficits, mild hepatomegaly, generalized livido reticulairs, and acrocyanosis. Laboratory data revealed platelet count of 97000, creatinine 3.4 mg/dl, IgG ACA titer of 43.8 and negative IgM ACA and ANA. He had proteinuria with benign urinary sediment. Kidney biopsy showed thrombotic microangiopathy. Plasmaphersis was initiated and hemodialysis for the rapidly progressing renal failure. He continued his treatment in an outpatient hemodialysis unit while on Coumadin. Four weekly cycles of Rituximab were given as an outpatient. Serial laboratory investigations showed gradual normalization of the platelet count and disappearance of the IgG ACA. Gradually renal function recovered and hemodialysis was discontinued after three months. He remains in remission with no further thrombotic events.Conclusion: Rituximab is promising in the treatment of APS and must be considered in the first;line treatment of catastrophic APS. A clinical trial is necessary to test the feasibility of discontinuing anticoagulation in these patients.PERTINENT LABORATORY DATADATEHEMOGLOBINPLATELETSCREATININEACA TITER03/21/021.411/15/0314.4973.411/21/0312.51006.243.812/01/0312.2222ON DIALYSIS16.101/01/0414.1276ON DIALYSIS20.903/17/0414.1276ON DIALYSIS05/05/0411.33303.3NEGATIVE

Significance of Anticardiolipin Antibodies on Short and Long Term Allograft Survival and Function following Kidney Transplantation

The significance of anticardiolipin antibodies (ACAs) prior to renal transplantation is unclear. We studied a cohort of 337 patients who underwent renal transplantation from 1996 to 2001. Follow-up continued until allograft loss, patient death or 31 December 2002. The primary outcome was a composite endpoint of death-censored allograft loss or a 25% reduction in estimated glomerular filtration rate (GFR) from 1-month post-transplant. Secondary outcomes were allograft loss, a 25% reduction in GFR, acute rejection and creatinine at 1 year. IgG and IgM ACA titers were positive (> or =15) in 18.1% of recipients. There were no significant differences at baseline between recipients, except coumadin therapy in those with positive ACA titers (20% vs. 7.4%). Post-transplant, there was no increase in the primary outcome in ACA-positive patients, even after adjustment for anticoagulation with coumadin (HR = 1.42 [0.68, 2.96]). There was no difference in secondary outcomes between those with or without positive titers. Two of five patients with very high titers (>50) who were not anticoagulated had early graft loss. A positive ACA titer prior to kidney transplantation was not associated with inferior renal outcomes after transplantation, although more research is required to address the prognostic significance of very high ACA titers.