Dataset Information

Influence of anticardiolipin and anti-?2 glycoprotein I antibody cutoff values on antiphospholipid syndrome classification.

ABSTRACT:

Background

Anticardiolipin (aCL) and anti-?2 glycoprotein I (a?2GPI) immunoglobulin (Ig) G/IgM antibodies are 2 of the 3 laboratory criteria for classification of antiphospholipid syndrome (APS). The threshold for clinically relevant levels of antiphospholipid antibodies (aPL) for the diagnosis of APS remains a matter of debate. The aim of this study was to evaluate the variation in cutoffs as determined in different clinical laboratories based on the results of a questionnaire as well as to determine the optimal method for cutoff establishment based on a clinical approach.

Methods

The study included samples from 114 patients with thrombotic APS, 138 patients with non-APS thrombosis, 138 patients with autoimmune disease, and 183 healthy controls. aCL and a?2GPI IgG/IgM antibodies were measured at 1 laboratory using 4 commercial assays. Assay-specific cutoff values for aPL were obtained by determining 95th and 99th percentiles of 120 compared to 200 normal controls by different statistical methods.

Results

Normal reference value data showed a nonparametric distribution. Higher cutoff values were found when calculated as 99th rather than 95th percentiles. These values also showed a stronger association with thrombosis. The use of 99th percentile cutoffs reduced the chance of false positivity but at the same time reduced sensitivity. The decrease in sensitivity was higher than the gain in specificity when 99th percentiles were calculated by methods wherein no outliers were eliminated.

Conclusions

We present cutoff values for aPL determined by different statistical methods. The 99th percentile cutoff value seemed more specific. However, our findings indicate the need for standardized statistical criteria to calculate 99th percentile cutoff reference values.

SUBMITTER: Vanoverschelde L

PROVIDER: S-EPMC6611479 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Influence of anticardiolipin and anti-β2 glycoprotein I antibody cutoff values on antiphospholipid syndrome classification.

Vanoverschelde Laura L Kelchtermans Hilde H Musial Jacek J de Laat Bas B Devreese Katrien M J KMJ

Research and practice in thrombosis and haemostasis 20190526 3

<h4>Background</h4>Anticardiolipin (aCL) and anti-β2 glycoprotein I (aβ2GPI) immunoglobulin (Ig) G/IgM antibodies are 2 of the 3 laboratory criteria for classification of antiphospholipid syndrome (APS). The threshold for clinically relevant levels of antiphospholipid antibodies (aPL) for the diagnosis of APS remains a matter of debate. The aim of this study was to evaluate the variation in cutoffs as determined in different clinical laboratories based on the results of a questionnaire as well a ...[more]

PMID: 31294336

Similar Datasets

Project description:Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by vascular thrombosis and obstetric morbidity, with accurate laboratory examination of antiphospholipid antibodies (aPLs) being crucial for diagnosis. This study focused on anti-β2 glycoprotein I (aβ2GPI) antibodies and aimed to establish the first population-based cutoff values for aβ2GPI IgA/IgM/IgG antibodies in non-pregnant women of reproductive age in Southwest China. The study cohort comprised 181 healthy women of reproductive age for study. Blood samples were collected on an early morning fast. Anti-β2GPI antibodies including IgA, IgM and IgG were measured in serum using the HOB® BioCLIA kit. According to the Clinical and Laboratory Standards Institute (CLSI) guidelines, the study used non-parametric percentile methods to calculate the 95th, 97.5th, and 99th percentiles cutoff values for aβ2GPI IgA/IgM/IgG antibodies, along with corresponding 90% confidence intervals (CI), while excluding outliers. A total of 168 independent samples were collected for verification, including 85 samples from healthy subjects and 83 samples from APS patients, in order to evaluate the analytical performance of the obtained cutoff values. The 99th percentile cutoff values were 3.36 RU/mL for aβ2GPI IgA, 27.54 RU/mL for aβ2GPI IgM and 1.81 RU/mL for aβ2GPI IgG, which indicated that the levels of aβ2GPI IgM antibodies were generally higher compared to those of IgA and IgG antibodies. Our established reference range was confirmed to be successful in validating the detected values of aβ2GPI antibodies in all healthy controls. With the 99th percentile cutoff value, the sensitivity was 14.46% for aβ2GPI IgA, 22.89% for aβ2GPI IgG, and 9.64% for aβ2GPI IgM in APS patients. This study established population-based cutoff values that are applicable to the local population for the accurate laboratory examination of aβ2GPI antibodies in non-pregnant women of reproductive age. The study also recommends paying more attention to IgM positivity in women of reproductive age.

Project description:To examine the prevalence of isolated IgA anti-?2 -glycoprotein I (anti-?2 GPI) positivity and the association of these antibodies, and a subgroup that bind specifically to domain IV/V of ?2 GPI, with clinical manifestations of the antiphospholipid syndrome (APS) in 3 patient groups and to evaluate the pathogenicity of IgA anti-?2 GPI in a mouse model of thrombosis.Patients with systemic lupus erythematosus (SLE) from a multiethnic, multicenter cohort (LUpus in MInorities, NAture versus nurture [LUMINA]) (n = 558), patients with SLE from the Hopkins Lupus Cohort (n = 215), and serum samples referred to the Antiphospholipid Standardization Laboratory (APLS) (n = 5,098) were evaluated. IgA anti-?2 GPI titers and binding to domain IV/V of ?2 GPI were examined by enzyme-linked immunosorbent assay (ELISA). CD1 mice were inoculated with purified IgA anti-?2 GPI antibodies, and surgical procedures and ELISAs were performed to evaluate thrombus development and tissue factor (TF) activity.A total of 198 patients were found to be positive for IgA anti-?2 GPI isotype, and 57 patients were positive exclusively for IgA anti-?2 GPI antibodies. Of these, 13 of 23 patients (56.5%) in the LUMINA cohort, 17 of 17 patients (100%) in the Hopkins cohort, and 10 of 17 patients (58.9%) referred to APLS had at least one APS-related clinical manifestation. Fifty-four percent of all the IgA anti-?2 GPI-positive serum samples reacted with domain IV/V of anti-?2 GPI, and 77% of those had clinical features of APS. Isolated IgA anti-?2 GPI positivity was associated with an increased risk of arterial thrombosis (P < 0.001), venous thrombosis (P = 0.015), and all thrombosis (P < 0.001). The association between isolated IgA anti-?2 GPI and arterial thrombosis (P = 0.0003) and all thrombosis (P = 0.0003) remained significant after adjusting for other risk factors for thrombosis. In vivo mouse studies demonstrated that IgA anti-?2 GPI antibodies induced significantly larger thrombi and higher TF levels compared to controls.Isolated IgA anti-?2 GPI-positive titers may identify additional patients with clinical features of APS. Testing for these antibodies when other antiphospholipid tests are negative and APS is suspected is recommended. IgA anti-?2 GPI antibodies directed to domain IV/V of ?2 GPI represent an important subgroup of clinically relevant antiphospholipids.

Project description:In humans, the presence of antiphospholipid antibodies (aPL) is frequently found in immune thrombocytopenia. The present study investigated whether aPL and any aPL subtypes are associated with canine thrombocytopenia, in particular, immune-mediated thrombocytopenia (immune thrombocytopenia) that usually manifests with severe thrombocytopenia.Sera were collected from 64 outpatient dogs with thrombocytopenia (Group I, platelet count 0 - 80?×?10(3)/uL), and 38 of which having severe thrombocytopenia (platelet count?<?30?×?10(3)/uL) were further divided into subgroups based on the presence of positive antiplatelet antibodies (aPLT) (subgroup IA, immune thrombocytopenia, n =20) or the absence of aPLT (subgroup IB, severe thrombocytopenia negative for aPLT, n =18). In addition, sera of 30 outpatient dogs without thrombocytopenia (Group II), and 80 healthy dogs (Group III) were analyzed for comparison. Indirect ELISAs were performed to compare serum levels of aPL subtypes, including anticardiolipin antibodies (aCL), antiphosphatidylserine antibodies (aPS), antiphosphatidylcholine (aPC), and anti-?2 glycoprotein I antibodies (a?2GPI), and antiphosphatidylinositol antibodies (aPI), among different groups or subgroups of dogs. Among outpatient dogs, aCL, being highly prevalent in outpatient dogs with thrombocytopenia (63/64, 98 %), is an important risk factor for thrombocytopenia (with a high relative risk of 8.3), immune thrombocytopenia (relative risk 5.3), or severe thrombocytopenia negative for aPLT (relative risk ?, odds ratio 19). In addition, aPS is a risk factor for immune thrombocytopenia or severe thrombocytopenia negative for aPLT (moderate relative risks around 2), whereas aPC and a?2GPI are risk factors for immune thrombocytopenia (relative risks around 2).Of all the aPL subtypes tested here, aCL is highly associated with canine thrombocytopenia, including immune thrombocytopenia, severe thrombocytopenia negative for aPLT, and less severe thrombocytopenia. Furthermore, aPS is moderately associated with both canine immune thrombocytopenia and severe thrombocytopenia negative for aPLT, whereas a?2GPI, and aPC are moderately relevant to canine immune thrombocytopenia. In contrast, aPI is not significantly associated with canine immune thrombocytopenia.

Project description:To investigate which serologic and clinical findings predict adverse pregnancy outcome in patients with antiphospholipid antibody (aPL) and to test the hypothesis that a pattern of clinical and serologic variables can identify women at highest risk of adverse pregnancy outcome.Women enrolled in a multicenter prospective observational study of risk factors for adverse pregnancy outcome in patients with aPL (lupus anticoagulant [LAC], anticardiolipin antibody [aCL], and/or antibody to ?2-glycoprotein I [anti-?2 GPI]) and/or systemic lupus erythematosus (SLE) were recruited for the present prospective study. Demographic, clinical, serologic, and treatment data were recorded at the time of the first study visit. The relationship between individual and combined variables and adverse pregnancy outcome was assessed by bivariate and multivariate analysis.Between 2003 and 2011 we enrolled 144 pregnant patients, of whom 28 had adverse pregnancy outcome. Thirty-nine percent of the patients with LAC had adverse pregnancy outcome, compared to 3% of those who did not have LAC (P<0.0001). Among women with IgG aCL at a level of ?40 units/ml, only 8% of those who were LAC negative had adverse pregnancy outcome, compared to 43% of those who were LAC positive (P=0.002). IgM aCL, IgG anti-?2 GPI, and IgM anti-?2 GPI did not predict adverse pregnancy outcome. In bivariate analysis, adverse pregnancy outcome occurred in 52% of patients with and 13% of patients without prior thrombosis (P=0.00005), and in 23% with SLE versus 17% without SLE (not significant); SLE was a predictor in multivariate analysis. Prior pregnancy loss did not predict adverse pregnancy outcome. Simultaneous positivity for aCL, anti-?2 GPI, and LAC did not predict adverse pregnancy outcome better than did positivity for LAC alone.LAC is the primary predictor of adverse pregnancy outcome after 12 weeks' gestation in aPL-associated pregnancies. Anticardiolipin antibody and anti-?2 GPI, if LAC is not also present, do not predict adverse pregnancy outcome.