Antibodies aCL Research Articles

IgA anticardiolipin and IgA anti-β2 glycoprotein I antibody positivity determined by fluorescence enzyme immunoassay in primary antiphospholipid syndrome

Primary antiphospholipid syndrome (PAPS) is an autoimmune disease characterized by thrombosis and/or pregnancy morbidity as well as blood antiphospholipid (aPL) antibodies such as anticardiolipin (aCL), anti-β2 glycoprotein I (anti-β2GPI) antibodies of the IgG/IgM isotype and lupus anticoagulant (LA). The clinical significance of aCL and anti-β2GPI antibodies of the IgA isotype in PAPS is still a controversial issue. Sera and plasma were collected from 84 PAPS patients (54 with thrombosis and/or pregnancy morbidity and 30 with pregnancy morbidity alone), 66 seronegative patients (subjects with clinical manifestations of PAPS although with negative results on conventional antiphospholipid antibody testing), and 78 healthy blood donors. IgA aCL and IgA anti-β2GPI were determined using fluorescence enzyme immunoassay (FEIA), (EliATM, Phadia AB, Uppsala, Sweden). For comparison purposes, the sera were also tested for IgG/IgM aCL/anti-β2GPI antibodies using the same immunoassay method. LA was assayed following internationally accepted guidelines. Present respectively in 19% and 50% of the PAPS patients studied, IgA aCL and IgA anti-β2GPI antibody frequencies were both statistically significant (p=0.001 and p<0.001, respectively). The mean titers of both IgA aCL and IgA anti-β2GPI antibodies were higher in the thrombotic patients, but only the latter were significantly associated with thrombosis. Isolated IgA anti-β2GPI antibody positivity was significantly prevalent (p=0.04) in seven (10.6%) of the seronegative patients. Positivity to IgA anti-β2GPI antibody detected using FEIA was found to be clinically relevant in PAPS patients. Moreover the prevalence of isolated IgA anti-β2GPI antibody positivity was significant in the seronegative patients.

Bouquet variety of antiphospholipid antibodies in recurrent pregnancy loss.

Seventy-six female patients with two or more recurrent pregnancy losses (RPL) during the 1st trimester were studied. Based on the results of the aCL and aB2GPI antibodies testing, patients were divided in two groups: 22 patients with RPL and elevated immunoglobulin (Ig) G/IgM aCL and/or aB2GPI [RPL + antiphospholipid syndrome (APS)] and 54 patients with RPL alone (without high antibodies). Immunoglobulin G aPS and IgG a-AnV in patients with RPL + APS were higher than in controls and IgG aPS were higher in RPL + APS than in RPL alone. Additionally IgG a-AnV and IgM aPE are higher in RPL alone than in controls. In 18/22 (81%) patients with RPL + APS and 29/54 (54%) patients with RPL alone, there were one or more positive antibodies: aPS, aPT, a-AnV or aPE. These results raise a question whether or not these antiphospholipid antibodies should be routinely tested in women with RPL and especially in the context of the so-called “seronegative APS”.

Analysis Of a Single Institutional Cohort Of 20,593 Patients Tested For Antiphospholipid Antibodies Indicates Significant Prospective Risk For Thrombosis

BackgroundQuantification of the risk associated with positive antiphospholipid (aPL) antibodies has been problematic since previous assessments have relied on observing relatively small study populations or meta-analyses of collected larger groups. There would be a significant benefit to a tool that would permit analysis of clinical outcomes of large patient cohorts. We applied a novel analytical information system, named “Clinical Looking Glass” (CLG), which aggregates clinical, diagnostic, therapeutic and outcomes data from a single large academic health care center to address this question. MethodsCLG was employed to collect all patients at a large tertiary care institution for whom antiphospholipid antibodies including lupus anticoagulant (LAC), anticardiolipin (aCL) antibodies and anti- β2-glycoproteinI (aβ2GPI) were performed. The immunoassays were grouped by isotype and values of >30U/L (>99th percentile) were considered positive. An untested control group was derived from outcomes data on all institutional Pioneer Accountable Care Organization patients, a cohort, whose coordinated care is managed by a single institution, permitted accurate and robust follow-up data. We used the CLG to track patients for a period of 583 days (maximum data available for control group) following their individual test results to identify a predefined thrombotic outcome. The outcome was defined by any encounter (inpatient, outpatient or ED), subsequent to the initial lab value date, which demonstrated a new thrombotic event. ResultsUsing CLG we were able to evaluate 20,593 unique patients who had some form of LA testing performed. The aCL assays were performed on the greatest number of patients (18,201) followed by the LAC (11,267) with the fewest number of patients tested for aβ2GPI (7,914). A total of 5,660 patients had testing for all three. Of all 11,267 patients having LAC testing performed, 754 patients had at least one positive result. Of these 25.9% went on to develop a thrombotic event during the follow-up period compared to 15.0% of LAC negative patients (p value <0.001) and only 1.64% of the ACO control group suffering an event (p value <0.001). The relative risk associated with LAC positivity over the control group was 14.75 (95% CI 13.6-19.1). All other APL antibodies also demonstrated statistically increased risk of thrombosis over the examined cohort control (RR ranging from 6.6-11.2), but each of these to a significantly lesser degree than when compared directly to the LAC (results summarized in adjoining table and graph). ConclusionsThis first large study of aPL assays with prospective data from a single clinical information system confirms previous observations from smaller studies that LAC is the most significant laboratory predictor of future thrombotic events. However, in contrast to previous studies, all aPL antibodies, including IgA, demonstrated a statistically increased risk over a control population with LAC positivity having statistically greater risk than all others. Interestingly, aCL IgM was the weakest predictor of a future thrombotic event. Additionally we demonstrate the utility of clinical analytical software tools to offer very powerful ways to test prior assumptions and obtain novel results on large cohorts of patients in “real world” settings. [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Antiphospholipid antibody syndrome presenting with psychosis

Antiphospholipid antibody syndrome presenting with psychosis

Clinical significance of phospholipid-cofactor antibodies in patients with systemic lupus erythematosus-associated antiphospholipid syndrome

To establish whether antibodies directed against phospholipid-binding plasma proteins such as β2-glycoprotein I (β2GPI), prothrombin (PT), and Annexin V (AnxV) constitute a risk factor for thrombosis in patients with systemic lupus erythematosus (SLE)-associated antiphospholipid syndrome (SLE/APS). A group of SLE patients (with and without APS) and patients with primary APS (PAPS) were included in this study. Fifteen patients with deep vein thrombosis but without antiphospholipid (aPL) antibodies, and another 15 age-matched and sex-matched apparently healthy individuals served as a control group. All patients were investigated for lupus anticoagulants and detection of anticardiolipin (aCL) immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies. Antibodies against β2GPI (IgG and IgM), PT (IgG and IgM), and AnxV (IgG) were also measured using the respective enzyme-linked immunosorbent assays. The study included 58 SLE patients (18 SLE/APS patients and 40 patients without APS) as well as 40 patients with PAPS, mean age 43 years (range: 18–74 years). IgG and/or IgM aCL antibodies were detected in all patients with PAPS (100%), whereas the prevalence rates of aPL-cofactor antibodies were as follows: 75% anti-β2GPI, 70% anti-PT, and 25% anti-AnxV antibodies. In SLE patients without APS, aCL antibodies were detected in 17.5%, anti-β2GPI antibodies in 20%, anti-AnxV antibodies in 20%, and anti-PT antibodies in 10% of patients. None of the antibodies measured were detected in deep vein thrombosis cases or healthy controls. Measurement of antiphospholipid-cofactor antibodies in addition to the more widely used aCL and anti-β2GPI antibodies could be a useful prognostic marker for the risk of thrombosis in SLE/APS patients.

Antiphospholipid antibodies and coronary atherosclerosis: the antiphospholipid syndrome patients

Background: In recent years it became apparent that mortality in patients with generalized autoimmune diseases like Antiphospholipid Syndrome (APS) and/or Systemic Lupus Erythematosus (SLE) is mainly due to severe cardiovascular complications. Conventional risk factors for coronary artery disease do not explain this increased risk. Suggested non-coventional factors include, among others, the presence of Antiphospholipid antibodies (aPL). Their elevated levels have been associated with arterial and microvascular thrombosis. Aims: To evaluate possible influence of aPL on myocardial ischaemia assessed by Single-Photon Emission Computerized Tomography (SPECT) and coronary atherosclerosis assessed by Multidetector Computerized Tomography (MDCT) in APS patients. Methods: SPECT (Tc 99m sestamibi) and MDCT-based coronary calcium scoring were performed in consecutive APS patients (12 females, 4 males, aged 28-62, mean 47,3) without clinical signs of heart disease. Anticardiolipin (aCL) and anti-beta2 Glycoprotein I (abeta2GPI) antibodies (IgG and IgM class) were measured by ELISA and Lupus Anticoagulant (LA) according to ISTH guidelines. Results: SPECT revealed myocardial perfusion defects in 12 (75%) patients: in 3 (19%) exercise-induced, and in 9 (56%) persistent. MDCT revealed coronary calcifications in 5 (31%) patients. The number of plaques ranged from 1 to 11 (median 2), volume 3-201,7 mm3 (median 7), calcium scores 1,3-202,6 (median 5,7). In patients with perfusion defects or coronary calcifications (n=12), as compared to patients without these pathologies (n=4) the levels of IgG aCL and/or IgG abeta2GPI antibodies were significantly higher and LA present more often (IgG aCL: 63,25±23,1 vs. 19,22±8,8, p=0,05; IgG abeta2GPI: 44,05±21,3 vs. 11,25±5,3, p=0.05; LA: 10/12 (83%) vs. 2/4 (50%), respectively). No such association was seen for IgM-class antibodies. Conclusions: In many symptom-free, relatively young APS patients SPECT shows myocardial perfusion defects and, in one third of them, coronary calcifications. These well-known cardiovascular risk markers were associated with the presence of LA and higher levels of aCL and abeta2GPI antibodies. In such patients advanced search for cardiovascular risk factors and proper preventive measures are warranted.

AB0726 The utility of IGA antiphospholipid antibodies for prediction of thrombotic complications in secondary antiphospholipid syndrome

BackgroundAt present we use modified classification criteria (Sydney 2006) for a diagnosis of antiphospholipid syndrome (APS) (1). These criteria do not include IgA class anticardiolipin (aCL) or antiβ2-glycoprotein I (antiβ2GPI)...

FRI0269 Microthrombotic renal vascular lesions are associated to increased renal inflammatory infiltration in a mouse model of lupus nephritis

BackgroundPresence of vascular microthrombotic lesions in lupus nephritis (LN), with or without antiphospholipid antibodies (aPL), may relate to worse renal outcome. Whether microthrombotic lesions are a consequence of renal inflammation...

Adalimumab-associated antiphospholipid syndrome: a case report and review of the literature

This study aims for the presentation of the first reported case of adalimumab-associated antiphospholipid syndrome (APS) and review of the literature on adalimumab-induced vasculitis and APS. A case of APS associated with adalimumab use in a 67-year-old woman is reported. The English medical literature was reviewed for antitumor necrosis factor (TNF) agents and their association with APS and vasculitis. Adalimumab is a fully humanized monoclonal antibody targeted against TNF alpha that is widely used in the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, and Crohn's disease. Literature review reveals several cases of anti-TNF-induced vasculitis including cases associated with adalimumab. We report the first case of adalimumab-induced APS in a 67-year-old woman who developed APS and vasculitis associated with de novo positive anti-cardiolipin (aCL) antibody following the third dose of adalimumab therapy for the treatment of spondyloarthropathy. This is the first case demonstrating that a short course of adalimumab therapy may induce immunoglobulin M aCL autoantibodies leading to APS. With the growing use of anti-TNF medications in immune-mediated and inflammatory diseases, adalimumab and other anti-TNF medications should be considered as a possible explanation for APS.

Immunoglobulin G Anticardiolipin Antibodies and Progression to Q Fever Endocarditis

Immunoglobulin G (IgG) anticardiolipin (aCL) antibodies are associated with valvulopathy and endocarditis in patients with lupus and other diseases. During acute Q fever, high IgG aCL prevalence has been reported, but the clinical significance remains unknown. To test if increased IgG aCL at acute Q fever diagnosis is associated with an increased risk of progression to endocarditis, all patients diagnosed in the French National Referral Center for Q fever from January 2007 to December 2011 were included and followed regularly until January 2013 in a 5-year prospective cohort study. Q fever endocarditis was defined according to recently updated criteria. Seventy-two patients were followed for a median time of 31 months (interquartile range, 18-47 months). Of these, 13 patients with valvulopathy without antibiotic prophylaxis progressed to endocarditis. IgG aCL levels were highly prevalent (57%) and significantly higher in the presence of a valvulopathy (P = .005). Using Cox regression analysis, highly increased levels of IgG aCL (adjusted hazard ratio [AHR], 12.95; 95% confidence interval, 2.85-58.95; P = .001) and high levels of phase II immunoglobulin M (IgM; AHR, 6.59; 95% CI, 1.37-31.62; P = .018) were the only independent predictors of progression to endocarditis. Rapid progression from acute Q fever to endocarditis is associated with high levels of IgG aCL and high levels of phase II IgM, findings that should be critical in the prevention of endocarditis.

Antiphospholipid Syndrome Antibodies — Snippets from the Laboratory

Antiphospholipid (aPL) antibodies refer to antibodies associated with the clinical syndrome of vascular thrombosis and/or pregnancy morbidity, termed as aPL syndrome (APS). aPL antibodies include lupus anticoagulants (LA), anticardiolipin (aCL) antibodies and anti-β2-glycoprotein 1 (anti-β2GP1). aCL antibody is more sensitive than LA and anti-β2GP1 even though the latter are more specific for APS. Interpretation of aPL results should be done collectively together with the clinical presentation of each individual. The latest recommendations and consensus on aPL antibody testings should be closely adhered to by laboratories in order to achieve an accepted standard and to ensure accuracy of test results.

Analysis of 14 young cerebrovascular accident cases with positive anti-phospholipid antibody

Aims and Objectives: To study of clinical and laboratory findings of 14 young (< 45 years) patients with cerebro vascular accident who were positive for anti-phospholipid antibodies (aPLs). Materials and Methods: The clinical, laboratory, and radiologic findings in 14 young patients with cerebrovascular accident and positive tests for aPLs referred to Shohada Hospital were studied. The analysis for aPLs included estimation of lupus anticoagulant (LA) test, anticardiolipin (aCL) antibodies and anti beta2 glycoprotein 1 antibodies. Other relevant tests included anti-nuclear antibody, human immunodeficiency virus, Venereal Diseases Research Laboratory, platelet count, echocardiography and carotid Doppler. aPL positive strokes were those cases where either the immunoglobulin G (IgG) and/or immunoglobulin M (IgM) were raised or LA or anti beta2 glycoprotein 1 antibodies was positive and other known causes were excluded. Results: Levels of IgG aCL antibody was raised in nine cases and IgM aCL antibody was elevated in 11 cases. Three cases were positive for LA test. Only one patient was positive for anti beta2 glycoprotein 1 test. Seven patients showed small multiple bilateral cerebral infarcts on computerized tomography (CT) scan. Four patients had a history of recurrent strokes. Hemiparesis was more frequent than hemiplegia. One of patient presented with dense hemiplegia. Eleven patients recovered to normal functional capacity and did not have a recurrence on drugs. Conclusion: Cerebrovascular accident in young patients with positive tests for aPL showed certain clinical and radiological features, mild to moderate stroke, pre-treatment recurrences, and multiple smaller infarcts on CT, which could be clustered in a subgroup of stroke in young. These patients showed a better prognosis in terms of long-term outcome.

The clinical significance of anticardiolipin antibody levels in patients with acute myocardial infarction: a regional study

IntroductionAcute myocardial infarction (AMI) will probably remain the most important cause of death over the next decades. Traditional risk factors of atherosclerosis could not exactly explain the development of acute coronary events such as AMI. Antiphospholipid antibody syndrome is a disorder characterized by the development of arterial and venous thrombosis.AimIn this study, we investigated the relations between acute myocardial infarction and anti-phospholipid antibody syndrome in our population representing Aegean Region people characteristics.Material and methodsOne hundred patients with acute myocardial infarction were consecutively included in the study (group I) and one hundred age and sex matched people with similar risk factors were enrolled in the study as a control group (group II). Anticardiolipin antibody (aCL) IgM and IgG levels were measured in the two groups. Levels of aCL IgG ≥ 48 U/ml and/or aCL IgM ≥ 44 U/ml were accepted as positive and significant.ResultsIn patients with acute myocardial infarction, 5 patients (5%) had positive IgM levels and 8 patients (8%) were found to have positive IgG levels. All cases in the control group had negative aCL IgM and IgG antibody levels. These results were accepted as significant for both aCL antibodies between patients and controls (p < 0.001).ConclusionsWe concluded that aCL antibody levels are also higher in a small proportion of patients with acute myocardial infarction than controls in our region, also, and these results suggest that there may be an immune stimulus in the pathogenesis of acute coronary events.

Dr. Vlachoyiannopoulos replies

Dr. Korkmaz raises the following issues: (1) the fluctuation of the aCL antibody titers, either spontaneous or modified by prednisone treatment, might be responsible for the upregulation of aPL antibodies after CYC treatment and not CYC itself; (2) his personal experience from 4 patients with SLE treated either with CYC orAZA alone or with prednisone is opposite to our own1; (3) the diagnosis of some patients with APS may not be accurate; and (4) renal biopsy findings of a patient with APS nephropathy are missing. Fluctuation of aCL antibody titers was observed in both treatment groups. However, high antibody titers (absorbance higher than the 99th percentile of 100 normal individuals in ELISA) obtained on 2 occasions 12 weeks apart were commonly detected in the CYC-treated group and constituted the criterion for seroconversion. Patients with high aCL titers tended to be permanently positive for aCL. The patients from both groups were evaluated for aCL antibodies with the same frequency over time. The … Address reprint requests to Dr. Vlachoyiannopoulos; E-mail: pvlah{at}med.uoa.gr

Anti‐β2 glycoprotein I antibodies and pregnancy outcome in antiphospholipid syndrome

The relation between pregnancy outcome and single- or double-positivity of anticardiolipin (aCL) and β2 glycoprotein I (aβ2GPI) in antiphospholipid syndrome (APS) has yet to be clearly documented. In this article, a total of 191 lupus anticoagulant-negative pregnant women with primary APS were retrospectively divided into three groups: aCL(+) /aβ2GPI(-) ; aCL(+) /aβ2GPI(+) ; aCL(-) /aβ2GPI(+) . All women had received medical therapy consisting of prednisone (10-15 mg/day), low-dose aspirin (50 mg/day), and low molecular weight heparin (40 mg/day). The miscarriage rate in the double-positive group was significantly higher than that in the aCL(+) /aβ2GPI(-) group (46.2% vs. 22.1%, p < 0.05); the miscarriage rate in the aCL(-) /aβ2GPI(+) group (36.4%) was not significantly different from the rates of the other two groups (p > 0.05). Thus, double-positivity may be a risk factor for pregnancy loss and aβ2GPI antibody may be a better prognostic marker than aCL antibody for pregnancy outcome.

Clinical and serological risk factors of systemic lupus erythematosus outcomes during pregnancy

IntroductionSLE is an important risk factor for mother and fetus during pregnancy. Aim of the workTo identify clinical and serological risk factors that may cause poor maternal and fetal outcomes in pregnant systemic lupus erythematosus (SLE) patients. Patients and methodsForty selected SLE pregnant women (group A) versus 35 non-pregnant SLE patients (group B). SLE disease activity index (SLEDAI) and flares were evaluated for both groups. Laboratory investigations included double stranded DNA, anticardiolipin antibodies (aCL), and complements (C3 & C4). SLE pregnant patients were followed up in the second and third trimesters by ultrasonography and fetal Doppler were done to assess fetal outcome. Risk factors for poor maternal and fetal outcome were recorded. ResultsSLEDAI was increased in both groups more in group A. Lupus flares were increased during pregnancy as it occurred in (62.5%) of group A compared to (37.14%) in group B where severe flares were more frequent in group A. Gestational hypertension and active SLEDAI were found statistically significant for poor maternal outcome. Fetal outcome included full term 37.5%, prematurity 25%, intra-uterine growth retardation (IUGR) 22.5%, stillbirth 12.5%, abortion 7.5% and congenital heart block (CHB) 2.5%. Factors significantly associated with poor fetal outcome were severe flares and active renal disease where fetal loss significantly associated with aCL antibodies. Full term was more common in patients with no flares. ConclusionThese data demonstrate that pregnancy in SLE patients should be considered as a high-risk pregnancy and conception should be planned during a quiescent period. Close monitoring for optimal disease control of flares, lupus nephritis, gestational hypertension and aCL antibodies is recommended.

Standardization of antiphospholipid antibody assays. Where do we stand?

The laboratory criteria (lupus anticoagulants (LA), and/or anti-cardiolipin (aCL) antibodies and/or anti-β2-glycoprotein I antibodies (aβ2GPI)) that define patients with antiphospholipid syndrome (APS) were set in the Sapporo and Sydney criteria published in 1999 and 2006, respectively, and led to a substantial improvement in the recognition of APS. In addition, guidelines for LA detection were published by the Scientific Standardisation Subcommittee (SSC) of the International Society of Thrombosis and Haemostasis (ISTH) in 2009. However, a number of questions on this respect remain unresolved. Recommendations for the aCL and aβ2GPI assays intended to ameliorate the performance of these solid-phase assays. Despite efforts over the years, standardization has not been reached. This review will focus on methodological issues of the three antiphospholipid antibody (aPL) subtypes that are the subject of debate. The use of an international standard for aPL detection might help solve many of the problems caused by a lack of standardization of these assays.

Guidelines on the investigation and management of antiphospholipid syndrome

This guidance updates and replaces the previous guideline on the investigation and management of antiphospholipid syndrome (APS) published in 2000 (Greaves et al, 2000), though where there have not been changes we refer back to them when appropriate. The guidance is updated with reference to relevant publications since 2000. Publications known to the writing group were supplemented with additional papers identified by searching PubMed for publications in the last 11 years using the key words: lupus anticoagulant, anticardiolipin, antiphospholipid, b2–glycoprotein I, antiprothrombin and limits (clinical trial, randomized control trial, meta-analysis, humans, core clinical journals, English language). The writing group produced the draft guideline, which was subsequently revised by consensus by members of the Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology. The guideline was then reviewed by a sounding board of approximately 50 UK haematologists, the Royal College of Obstetricians and Gynaecologists (RCOG), and the British Committee for Standards in Haematology (BCSH) Committee and comments incorporated where appropriate. The ‘GRADE’ system was used to quote levels and grades of evidence, details of which can be found at http://www.bcshguidelines.com/BCSH_PROCESS/EVIDENCE_LEVELS_AND_GRADES_OF_RECOMMEN DATION/43_GRADE.html. The objective of this guideline is to provide healthcare professionals with clear guidance on the diagnosis and management of patients with antiphospholipid syndrome though individual patient circumstances may dictate an alternative approach.

Focal Segmental Glomerulosclerosis Associated Seronegative Antiphospholipid Syndrome

Secondary Focal Segmental Glomerulosclerosis (FSGS) from thrombotic microangiopathies including Antiphospholipid Antibody Syndrome (APS), is well documented. We present a case with clinical features of APS but consistently negative serologies, suggesting ‘Seronegative APS (SNAPS)’. The patient was evaluated at the Division of Nephrology, University of Connecticut Health Center for progressive Chronic Kidney Disease (CKD). A renal biopsy exhibited thrombotic microangiopathy and associated FSGS. Systemic thrombophilia can be primary or secondary and has an extensive list of differential diagnoses. Distinct clinical features and serologic markers characterize a particular etiology. Antiphospholipid Syndrome (APS) is the most common acquired thrombophilia. Serologic evidence of APS is the presence of commonly recognized antibodies to phospholipids in this syndrome i.e. anticardiolipin (aCL) antibodies, Lupus Anticoagulant (LA) and β2-glycoprotein 1 (β2GPI) antibodies. Rarely a patient with classic clinical features of APS does not exhibit any of the above antibodies, suggesting ‘Seronegative APS (SNAPS)’.

Plasma exchange and immunoadsorption effectively remove antiphospholipid antibodies in pregnant patients with antiphospholipid syndrome

Conventional therapy with aspirin and/or heparin is at times incapable of preventing complications in high risk pregnancies of patients with antiphospholipid syndrome (APS). In those cases, a so-called second-line treatment protocol is used in addition to conventional therapy strategies. This manuscript is a report on three APS pregnant patients who were successfully treated with plasma exchange (PE) (two cases) or with immunoadsorption (IA) (one case) as a second-line treatment strategy. The efficacy of these procedures in removing anticardiolipin (aCL) and anti-β(2)glycoprotein I (aβ(2)GPI) antibodies from blood was evaluated. Serum samples were collected before and after 87 apheretic treatment sessions. Serum IgG/M aCL and IgG/M aβ(2)GPI antibodies were determined using an "in-house" enzyme-linked immunosorbent assay and showed that all three patients had medium/high IgG aCL and aβ(2)GPI titers. All three women had a successful pregnancy. A significant decrease in IgG aCL (P = 0.0001) and aβ(2)GPI (P = 0.0001) antibody titers was observed after PE and IA sessions. There was moreover a significant, steady fall in serum IgG aCL pretreatment levels during the course of all three pregnancies (P = 0.0001, P = 0.0001, P = 0.001). The fall in IgG aβ(2)GPI was significant in two of the patients (P = 0.0001, P = 0.0001) both with high antibody titers, but not in one with medium antibody titers, who was treated with PE (P = 0.17).