Establishment of cutoff values for anti-ß2 glycoprotein I antibodies in women of reproductive age in Southwest China.

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-ß2 glycoprotein I (aß2GPI) antibodies and aimed to establish the first population-based cutoff values for aß2GPI 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-ß2GPI 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 aß2GPI 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 aß2GPI IgA, 27.54 RU/mL for aß2GPI IgM and 1.81 RU/mL for aß2GPI IgG, which indicated that the levels of aß2GPI 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 aß2GPI antibodies in all healthy controls. With the 99th percentile cutoff value, the sensitivity was 14.46% for aß2GPI IgA, 22.89% for aß2GPI IgG, and 9.64% for aß2GPI IgM in APS patients. This study established population-based cutoff values that are applicable to the local population for the accurate laboratory examination of aß2GPI antibodies in non-pregnant women of reproductive age. The study also recommends paying more attention to IgM positivity in women of reproductive age.

Antiphospholipid syndrome in children.

Antiphospholipid syndrome (APS) in children is a rare disease associated with significant morbidity and mortality. In comparison with APS in adults, pediatric APS has a more severe presentation with frequent recurrences of thrombotic events and a higher probability of life-threatening catastrophic APS. Nonthrombotic manifestations are also more common in the pediatric age group and can precede thrombosis. New classification criteria have been introduced recently and have not yet been assessed in pediatric patients with APS. In addition to anticoagulation drugs, other novel therapies have emerged including the use of B cell and complement inhibitors, especially in catastrophic APS. The purpose of this review is to provide a broad overview of aPL-related clinical manifestations in pediatric patients based on the analysis of published cohorts and data from the international pediatric APS registry. We also aim to illustrate APS in infants caused by transplacentally transferred maternal aPL, which is very rarely associated with acute thrombotic events in the perinatal period and more frequently with long-term neurodevelopmental abnormalities.

IgA is the predominant isotype of anti-ß2 glycoprotein I in patients with COVID-19.

OBJECTIVE: The aim of this research was to determine the frequency of antiphospholipid antibodies (aPL) in patients with COVID-19. METHODS: The frequency and titers of anticardiolipin antibodies (aCL) and anti-ß2 glycoprotein I antibodies (aß2GPI) were determined in sera of adult patients hospitalized with COVID-19. Immunoglobulin (Ig)G, IgA, IgM aCL, and aß2GPI were measured using enzyme-linked immunosorbent assay. RESULTS: Eighty-three patients were included in the study. The mean age of patients was 62 ± 13.9 years, ranging from 23 to 86 years. Stratification according to severity of infection divided patients in 2 groups: 45 patients with moderate infection and 38 patients with critical or severe infection. Out of the 83 patients suffering from COVID-19, aPL (aCL or aß2GPI) were detected in 24 patients (28.9%). IgG, IgA and IgM aß2GPI were positive in 2.4%, 16.9% and 8.4%, respectively. IgG, IgA and IgM aCL showed positivity in 7.2%, 0%, and 4.8%, respectively. The frequency of aPL was 36.8% in patients with critical/severe infection and 22.2% in patients with moderate infection. In critical/severe patients, the frequency of aß2GPI was significantly higher than aCL (34.2% vs 13.2%, P = .03) and aß2GPI-IgA were significantly more frequent than aß2GPI-IgG (21.1% vs 2.6%, P = .028). CONCLUSION: In this cross-sectional study, aPL and particularly aß2GPI-IgA were common in patients with COVID-19.

Antiphospholipid Antibody Testing for Anti-cardiolipin and Anti-ß2 Glycoprotein I Antibodies Using Chemiluminescence-Based Panels.

Antiphospholipid (antibody) syndrome (APS) is a prothrombotic condition with increased risk for thrombosis and pregnancy-related morbidity. In addition to clinical criteria related to these risks, APS is characterized by the persistent presence of antiphospholipid antibodies (aPL), as detected in the laboratory using a potentially wide variety of assays. The three APS criteria-related assays are lupus anticoagulant (LA), as detected using clot-based assays, and the solid-phase assays of anti-cardiolipin antibodies (aCL) and anti-ß2 glycoprotein I antibodies (aß2GPI), with immunoglobulin subclasses of IgG and/or IgM. These tests may also be used for the diagnosis of systemic lupus erythematosus (SLE). In particular, APS diagnosis/exclusion remains challenging for clinicians and laboratories because of the heterogeneity of clinical presentations in those being evaluated and the technical application and variety of the associated tests used in laboratories. Although LA testing is affected by a wide variety of anticoagulants, which are often given to APS patients to prevent any associated clinical morbidity, detection of solid-phase aPL is not influenced by these anticoagulants, and this thus represents a potential advantage to their application. On the other hand, various technical issues challenge accurate laboratory detection or exclusion of aPL. This report describes protocols for the assessment of solid-phase aPL, specifically aCL and aß2GPI of IgG and IgM class by means of a chemiluminescence-based assay panel. These protocols reflect tests able to be performed on the AcuStar instrument (Werfen/Instrumentation Laboratory). Certain regional approvals may also allow this testing to be performed on a BIO-FLASH instrument (Werfen/Instrumentation Laboratory).

Antiphospholipid antibodies in autoimmune thyroid diseases.

BACKGROUND: Antiphospholipid (aPL) antibodies have been reported in several autoimmune diseases. The aim of this study was to evaluate the frequency of aPL (anti-cardiolipin antibodies (aCL) and anti-ß2 glycoprotein I antibodies (aß2GPI)) in patients with autoimmune thyroid diseases (AITD). METHODS: One hundred and ninety-five patients with AITD (139 Hashimoto's thyroiditis (HT) patients and 56 Graves' disease (GD) patients) and 90 healthy blood donors (HBD) were studied. IgG, IgA and IgM aCL and aß2GPI were determined by ELISA. RESULTS: One hundred fifty-four AITD patients were women and 41 were men. Fifty-six healthy subjects were women and 34 were men. The median age of patients and the control group was 45 and 38.5 years, respectively. The frequency of aPL was significantly higher in patients with AITD and in patients with HT than in HBD (33.3% vs 11.1%, p < 10-3 and 38.1% vs 11.1%, p < 10-3 ). The frequency of aPL in GD was significantly lower than in HT (21.4% vs 38.1%, p = 0.025). In patients with HT, aß2GPI (34.5%) was significantly more frequent than aCL (13.6%) (p < 10-3 ). The frequency of aß2GPI was significantly higher in patients with HT than in healthy population (34.5% vs 11.1%, p < 10-3 ). In HT patients, IgA isotype of aß2GPI was significantly more common than in HBD and in GD patients (27.3% vs 7.8%, p < 10-3 and 27.3% vs 12.5%, p = 0.02, respectively). CONCLUSION: aß2GPI and not aCL were frequent in AITD. IgA was the predominant isotype of aß2GPI. aß2GPI-IgA was more frequent in HT than in GD.

Frequency of serological markers of rheumatoid arthritis in patients with IgA anti-ß2 glycoprotein I antibodies.

AIM: To determine the frequency of serological markers of RA in patients with anti-ß2 glycoprotein I antibodies (aß2GPI) of IgA isotype. MATERIAL AND METHODS: A retrospective study was conducted on 67 patients with aß2GPI-IgA. Ninety healthy blood donors (HBD) were used as a control group. IgG anti-cyclic citrullinated peptides antibodies (CCP-Ab) and rheumatoid factors (RF) IgG, IgA, and IgM were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Seventeen patients and eight HBD had CCP-Ab and/or RF (25.4% vs. 8.9%, p = 0.005, CI 95% [14.95; 35.79], odds ratio = 3.5). The frequency of CCP-Ab was significantly higher in patients than in healthy subjects (14.9% vs. 3.3%, p = 0.009). IgA isotype of RF was significantly higher in patients than in controls (7.5% vs. 0%, p = 0.02). In male patients, CCP-Ab and/or RF were more frequent than in healthy male subjects (37.5% vs. 11.8%, p = 0.02). In patients, no correlation was found between the levels of aß2GPI-IgA and CCP-Ab (r = 0.082, p = 0.51). There was no correlation between the level aß2GPI-IgA and the level of the isotypes of RF (IgG, IgA, and IgM) in patients (r = 0.1, p = 0.37; r = 0.17, p = 0.17 and r = 0.07, p = 0.59 respectively). CONCLUSION: Frequencies of CCP-Ab and RF are high in patients with aß2GPI-IgA suggesting that these patients are susceptible to developing RA.

Laboratory Diagnosis of Antiphospholipid Syndrome: Insights and Hindrances.

Diagnosis of antiphospholipid syndrome (APS) requires the presence of a clinical criterion (thrombosis and/or pregnancy morbidity), combined with persistently circulating antiphospholipid antibodies (aPL). Currently, laboratory criteria aPL consist of lupus anticoagulant (LAC), anticardiolipin antibodies (aCL) IgG/IgM, and anti-ß2 glycoprotein I antibodies (aß2GPI) IgG/IgM. Diagnosis and risk stratification of APS are complex and efforts to standardize and optimize laboratory tests have been ongoing since the initial description of the syndrome. LAC detection is based on functional coagulation assays, while aCL and aß2GPI are measured with immunological solid-phase assays. LAC assays are especially prone to interference by anticoagulation therapy, but strategies to circumvent this interference are promising. Alternative techniques such as thrombin generation for LAC detection and to estimate LAC pathogenicity have been suggested, but are not applicable yet in routine setting. For aCL and aß2GPI, a lot of different assays and detection techniques such as enzyme-linked immunosorbent and chemiluminescent assays are available. Furthermore, a lack of universal calibrators or standards results in high variability between the different solid-phase assays. Other non-criteria aPL such as anti-domain I ß2 glycoprotein I and antiphosphatidylserine/prothrombin antibodies have been suggested for risk stratification purposes in APS, while their added value to diagnostic criteria seems limited. In this review, we will describe laboratory assays for diagnostic and risk evaluation in APS, integrating applicable guidelines and classification criteria. Current insights and hindrances are addressed with respect to both laboratory and clinical implications.

IgA anti-beta-2 glycoprotein I antibodies in chronic hepatitis C.

BACKGROUND AND STUDY AIMS: Antiphospholipid antibodies (aPL) have been reported not only in various autoimmune conditions but also in other infections, such as chronic hepatitis C (CHC) infection. The aim of this study is to evaluate the frequency of aPL in patients with CHC. PATIENTS AND METHODS: Ninety-six CHC patients and 90 healthy blood donors (HBD) were studied. Fifty-three of the patients were under treatment, and 43 had not yet received any treatment. IgG, IgA, and IgM antibodies against cardiolipin (aCL) and beta-2 glycoprotein I (aß2GPI) were detected by ELISA. RESULTS: We found that the frequency of aPL (aCL and/or aß2GPI) was significantly higher in CHC patients than in controls (51% vs 11.1%, p <10-6). The frequencies of aCL and aß2GPI were significantly higher in patients than in HBD (27.1% vs 5.5%, p < 10-3, and 44.8% vs 11.1%, p < 10-6, respectively). The isotype distribution of aCL and aß2GPI demonstrated that aCL-IgG and aß2GPI-IgA were more frequent in patients than in healthy subjects (21.9% vs 2.2%, p < 10-3, and 38.5% vs 7.8%, p < 10-6, respectively). In CHC patients, the frequency of aß2GPI was significantly higher than that of aCL (44.8% vs 27.1%, p = 0.01). aß2GPI-IgA was significantly more frequent than aß2GPI-IgG (38.5% vs 7.3%, p <10-6), aß2GPI-IgM (38.5% vs 9.4%, p <10-3), and aCL-IgG (38.5% vs 21.9%, p = 0.01). No difference in aPL frequency was observed between the treated and untreated patients. CONCLUSION: On the basis of the findings of this study, aPL, particularly aß2GPI-IgA and aCL-IgG, are frequent in CHC patients.

Role of antiphospholipid antibodies in the diagnosis of antiphospholipid syndrome.

The diagnosis of antiphospholipid syndrome (APS) relies on the detection of antiphospholipid antibodies (aPL). Currently, lupus anticoagulant (LA), anticardiolipin (aCL), and antibeta2-glycoprotein I antibodies (aß2GPI) IgG or IgM are included as laboratory criteria, if persistently present. LAC measurement remains a complicated procedure with many pitfalls and interfered by anticoagulant therapy. Solid-phase assays for aCL and aß2GPI show interassay differences. These methodological issues make the laboratory diagnosis of APS challenging. In the interpretation of aPL results, antibody profiles help in identifying patients at risk. Other aPL, such as antibodies against the domain I of beta2-glycoprotein (aDI) and antiphosphatidylserine-prothrombin (aPS/PT) antibodies have been studied in the last years and may be useful in risk stratification of APS patients. Because of the methodological shortcomings of immunological and clotting assays, these non-criteria aPL may be useful in patients with incomplete antibody profiles to confirm or exclude the increased risk profile. This manuscript will focus on the laboratory aspects, the clinical relevance of assays and interpretation of aPL results in the diagnosis of APS.

Risk factors for ischemic antiphospholipid syndrome: A case-control study.

OBJECTIVE: The objective of this study was to identify clinical and laboratory risk factors for ischemic stroke (IS) in primary antiphospholipid syndrome (APS) patients. MATERIALS AND METHODS: We performed a case-control study with consecutive primary APS patients divided into two groups, those who presented with IS, vs. those with no history of stroke. Demographics, vascular risk factors, therapeutic approaches, laboratory, imaging and functional outcomes were recorded. RESULTS: Fifty-three confirmed primary APS patients with IS and sixty-six non-stroke primary APS controls were recruited. Most patients were female (65.5 %), with a median age of 33 years. The main vascular risk factors for primary APS-associated stroke were hypertension (11.3 %), diabetes (11.3 %) and hypercholesterolemia (9.4 %). Among patients with stroke, median NIHSS score was 6; 15.1 % of these patients presented a recurrent stroke, and 88.8 % had a good functional outcome at the final follow-up. Positive lupus anticoagulant (OR = 6.1, 95 %CI 2.7-13.5), anti-ß2 glycoprotein IgG (OR = 3.6, 95 %CI 1.7-7.9), and anticardiolipin IgG (OR = 2.8, 95 %CI 1.3-5.9) were more prevalent in non-stroke primary APS, with a triple-positive antibody presence in 46.4 % of controls vs. 22.2 % of patients with stroke (OR = 3.0, 95 %CI 1.3-6.7). At the time of the index event (arterial or venous), 14 known primary APS patients were using vitamin K antagonists, but only 35.7 % of them had achieved therapeutic INR. CONCLUSION: Patients with primary APS and IS have similar vascular risk factors and lower antibody positivity than those with extracranial thrombosis.

How to Interpret Antiphospholipid Laboratory Tests.

PURPOSE OF THE REVIEW: This review focuses on the laboratory tests necessary for the diagnosis of antiphospholipid syndrome (APS). For the interpretation of the results of the tests for antiphospholipid antibodies (aPL), understanding of all pitfalls and interferences is necessary. RECENT FINDINGS: Progress has been made on the standardization of aPL tests and current guidelines for detection of lupus anticoagulant (LAC), anticardiolipin antibodies (aCL), and antibeta2-glycoprotein I antibodies (aß2GPI) are useful tools. LAC measurement remains a complex procedure with many pitfalls and interference by anticoagulant therapy. Solid phase assays for aCL and aß2GPI still show inter-assay differences. Measuring LAC, aCL, and aß2GPI allows making antibody profiles that help in identifying patients at risk. Other aPL, such as antibodies against domain I of beta2-glycoprotein I (aDI) and antiphosphatidylserine-prothrombin (aPS/PT) antibodies, may be useful in risk stratification of APS patients, but are not included in the current diagnostic criteria as no added value in the diagnosis of APS has been illustrated so far. The laboratory diagnosis of APS remains challenging. LAC, aCL, aß2GPI IgG, and IgM should be performed to increase diagnostic efficacy, with an integrated interpretation of all results and an interpretative comment. A close interaction between clinical pathologists and clinicians is mandatory.

Testing for antiphospholipid antibodies: Advances and best practices.

The diagnosis of antiphospholipid syndrome (APS) relies on the detection of circulating antiphospholipid antibodies (aPL). Currently, lupus anticoagulant (LAC), anticardiolipin (aCL), and antibeta2-glycoprotein I antibodies (aß2GPI) IgG or IgM are included as laboratory criteria if persistently present. Progress has been made on the standardization of tests as guidelines on LAC testing and immunological assays for aCL and aß2GPI are published. However, LAC measurement remains a complicated procedure with many pitfalls and interfered by anticoagulant therapy. Solid-phase assays for aCL and aß2GPI still show interassay differences. These methodological issues make the laboratory diagnosis of APS challenging. In the interpretation of aPL results, antibody profiles help in identifying patients at risk. Noncriteria aPL, such as antibodies against the domain I of beta2-glycoprotein (aDI) and antiphosphatidylserine-prothrombin (aPS/PT) antibodies have been studied in the last years and may be useful in risk stratification of APS patients. But, aDI and aPS/PT are not included in the current diagnostic criteria and testing in daily practice is not recommended as these antibodies have no added value in the diagnosis of APS. This review will focus on the technical aspects of the laboratory methods, the clinical relevance of assays and interpretation of aPL results in the diagnosis of APS.

IgA is the predominant isotype of anti-ß2 glycoprotein I antibodies in rheumatoid arthritis.

BACKGROUND: The aim of this study was to determine the frequency of anti-cardiolipin antibodies (aCL) and anti-ß2 glycoprotein I antibodies (aß2GPI) among Tunisian patients with rheumatoid arthritis (RA). METHODS: Ninety RA patients with positive anti-cyclic citrullinated antibodies (anti-CCP) and 90 healthy blood donors (HBD) were studied. aCL and aß2GPI of isotype IgG, IgA and IgM were detected by ELISA. RESULT: The frequency of antiphopholipid antibodies (aPL) (aCL and/or aß2GPI) was significantly higher in patients with RA than in HBD (35.5% vs 11.1%, P = .0001). The frequencies of aCL and aß2GPI were significantly higher in patients than in healthy subjects (15.5% vs 5.5%, P = .04 and 32.2% vs 11.1%, P = .0005 respectively). aß2GPI-IgA were significantly more frequent in patients than in the control group (26.7% vs 7.8%, P = .0007). In patients, aß2GPI-IgA were significantly more frequent than aß2GPI-IgG (26.7% vs. 6.7%, P = .0003) and aß2GPI-IgM (26.7% vs 5.6%, P = .0001). In RA patients, the frequency of aß2GPI was significantly higher than that of aCL (32.2% vs 15.5%, P = .008). aß2GPI-IgA was significantly more frequent than aCL-IgA (26.7% vs 4.4%, P = .00005). The average titer of anti-CCP in aPL positive patients was significantly higher than in aPL negative patients (170.6 ± 50 RU/mL vs 147.7 ± 51 RU/mL, P = .04). Significant correlation was found between aß2GPI-IgA and anti-CCP (r = .235, P = .026). CONCLUSIONS: aPL and particularly aß2GPI-IgA are frequent in RA and are correlated with anti-CCP.

Triple Antiphospholipid (aPL) Antibodies Positivity Is Associated With Pregnancy Complications in aPL Carriers: A Multicenter Study on 62 Pregnancies.

Objective: Antiphospholipid antibodies (aPL) are risk factors for thrombosis and adverse pregnancy outcomes (APO). The management of the so called "aPL carriers" (subjects with aPL positivity without the clinical criteria manifestations of APS) is still undefined. This study aims at retrospectively evaluating the outcomes and the factors associated with APO and maternal complications in 62 pregnant aPL carriers. Methods: Medical records of pregnant women regularly attending the Pregnancy Clinic of 3 Rheumatology centers from January 1994 to December 2015 were retrospectively evaluated. Patients with concomitant autoimmune diseases or other causes of pregnancy complications were excluded. Results: An aPL-related event was recorded in 8 out of 62 patients (12.9%) during pregnancy: 2 thrombosis and 6 APO. At univariate analysis, factors associated with pregnancy complications were acquired risk factors (p:0.008), non-criteria aPL manifestations (p:0.024), lupus-like manifestations (p:0.013), and triple positive aPL profile (p:0.001). At multivariate analysis, only the association with a triple aPL profile was confirmed (p:0.01, OR 21.3, CI 95% 1.84-247). Patients with triple aPL positivity had a higher rate of pregnancy complications, despite they were more frequently receiving combined treatment of low dose aspirin (LDA) and low molecular weight heparin (LMWH) at prophylactic dose. Conclusion: This study highlights the importance of risk stratification in pregnant aPL carriers, in terms of both immunologic and non-immunologic features. Combination treatment with LDA and LMWH did not prevent APO in some cases, especially in carriers of triple aPL positivity. Triple positive aPL carriers may deserve additional therapeutic strategies during pregnancy.

Potential Roles of Antiphospholipid Antibodies in Generating Platelet-C4d in Systemic Lupus Erythematosus.

Premature, accelerated onset of atherothrombotic disease is prevalent in patients with systemic lupus erythematosus (SLE). Most, if not all, atherothrombotic diseases are likely to involve platelets and complement. Previously, we discovered that platelets bearing complement activation product C4d (P-C4d) are present in SLE patients, and are significantly associated with antiphospholipid (aPL) antibody positivity and stroke in SLE patients. The goal of the present study was to further elucidate the role of aPL and other platelet-reactive autoantibodies in the generation of P-C4d. To determine the association between P-C4d and aPL antibodies, the serum levels of aPL antibodies and P-C4d of 180 SLE patients were measured by enzyme-linked immunoassays and flow cytometry, respectively. To investigate the role of aPL antibodies, and possibly other autoantibodies as well, in mediating the generation of P-C4d, in vitro 2-step P-C4d induction experiments were performed. The results showed that the presence and levels of aPL antibodies in the serum were specifically elevated in SLE patients with positive P-C4d. The plasma and immunoglobulins purified from SLE patients who were positive for P-C4d and aPL were capable of inducing C4d deposition on normal platelets in vitro. The capacity of SLE plasma in inducing P-C4d appeared to correlate proportionately to the serum aPL levels. Collectively, the results demonstrate that both aPL and other platelet-reactive autoantibodies may participate in mediating the generation of P-C4d in SLE patients.

Association of anticardiolipin, antiphosphatidylserine, anti-ß2 glycoprotein I, and antiphosphatidylcholine autoantibodies with canine immune thrombocytopenia.

BACKGROUND: 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. RESULTS: 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-ß2 glycoprotein I antibodies (aß2GPI), 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 aß2GPI are risk factors for immune thrombocytopenia (relative risks around 2). CONCLUSIONS: 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 aß2GPI, and aPC are moderately relevant to canine immune thrombocytopenia. In contrast, aPI is not significantly associated with canine immune thrombocytopenia.

Anti Saccharomyces cerevisiae Antibodies in Patients With Anti-ß2 Glycoprotein I Antibodies.

BACKGROUND: In this study, cross-reactive epitopes on ß2 glycoprotein I and Saccharomyces cerevisiae have been described. The objective of our study was to determine the frequency of anti S. cerevisiae antibodies (ASCA) in patients with anti-ß2 glycoprotein I antibodies (aß2GPI). METHODS: A retrospective study was conducted in 77 patients with aß2GPI (aß2GPI-IgG or aß2GPI-IgA). Eighty blood donors were used as a control group. ASCA IgG and ASCA IgA were determined by Enzyme Linked Immunosorbent Assay (ELISA). RESULTS: Thirteen patients among 77 had ASCA. ASCA (IgA or IgG) was significantly more frequent in patients than in healthy subjects (16.9% vs. 3.7%, P = 0.01). The positivity of both ASCA IgG and ASCA IgA is higher in patients than in control group (6.5% vs. 0%, P = 0.02). The frequency of ASCA IgG was significantly higher in patients than in the control group (15.6% vs. 2.5%, P = 0.009). In females, the frequency of ASCA IgG was significantly higher in patients than in control group (17.5% vs. 3.7%, P = 0.03). The average titer of ASCA IgG was significantly higher in patients than in the control group (9.7 ± 23 U/ml vs. 2.2 ± 2.8 U/ml; P = 0.004). ASCA IgG was significantly more frequent than ASCA IgA in all patients (15.6% vs. 7.8%, P = 0.04). CONCLUSION: The frequency of ASCA was significantly higher in patients with aß2GPI than in the control group.

The challenges of lupus anticoagulants.

The term "lupus anticoagulant" (LA) refers to a heterogeneous group of immunoglobulins behaving as acquired in vitro inhibitors of coagulation. These antibodies, namely anti-ß2GPI and anti-prothrombin antibodies, induce the in vitro elongation of clotting time interfering with phospholipid-dependent coagulation cofactors. Positive LA is associated with thrombosis and pregnancy complications, providing one of the three laboratory criteria for the classification of the anti-phospholipid syndrome. LA is the strongest predictor of clinical events, especially when associated with other anti-phospholipid antibodies. Much more controversial is the risk conveyed by isolated and weak LA. LA detection is technically laborious, envisaging screening, mixing and confirming tests. Hopefully critical issues in LA detection, such as the interference of anticoagulants, will be overcome, in the next future.

Detection of IgG anti-Domain I beta2 Glycoprotein I antibodies by chemiluminescence immunoassay in primary antiphospholipid syndrome.

BACKGROUND: IgG anti-Domain I (anti-DI) ß2 Glycoprotein I (ß2GPI) antibodies are associated to thrombotic risk in antiphospholipid syndrome (APS), but their detection is technically difficult. In this study, a chemiluminescent immunoassay (CLIA) was used to evaluate the clinical significance of IgG anti-DI in a large cohort of patients with primary APS (PAPS). METHODS: The study population included 88 patients with PAPS, 63 ELISA-negative subjects and 166 controls. IgG anti-DI, IgG anticardiolipin (aCL) and IgG anti-ß2GPI antibodies were assayed using CLIA (HemosIL AcuStar®). RESULTS: The sensitivity and specificity of IgG anti-DI antibodies were comparable to those of IgG aCL and IgG anti-ß2GPI antibodies. There was a significant agreement, association and titre correlation between IgG anti-DI and IgG aCL as well as IgG anti-ß2GPI antibodies (p<0.001 for all). IgG anti-DI antibody showed lesser prevalence and mean titres in the pregnancy morbidity than in thrombotic and PAPS patients with both involvements (p<0.001). Regarding the conventional aPL antibody profiles, the triple positivity group had higher prevalence and mean titres than single and double positivity ones (p<0.001). CONCLUSIONS: This study provides further evidence that anti-DI antibodies can be considered a promising biomarker for risk assessment particularly in patients having vascular thrombosis and triple conventional aPL positivity.

Viral hepatitis and anti-phospholipid antibodies positivity: A systematic review and meta-analysis.

BACKGROUND: Anti-phospholipid antibodies positivity is associated with several clinical conditions, including infectious diseases. AIMS: We performed a meta-analysis evaluating the association of hepatitis B and C with anti-phospholipid antibody positivity and with anti-phospholipid antibody-related thrombotic complications. METHODS: Studies evaluating the association of viral hepatitis with anti-cardiolipin, anti-ß2 glycoprotein-I and lupus anticoagulant antibodies and anti-phospholipid antibody-related thrombotic events were systematically searched. RESULTS: 20 studies (2319 cases, 1901 controls) were included. The analyses showed that viral hepatitis is associated with the presence of anti-cardiolipin and anti-ß2 glycoprotein-I antibodies. The association with anticardiolipin antibodies was confirmed in both hepatitis B (OR 11.22, 95% CI: 6.68-18.84) and hepatitis C (OR 11.26, 95% CI: 6.82-18.59). Similarly, compared to controls, anti-ß2 glycoprotein-I antibodies were found more frequently in hepatitis B (OR 14.07, 95% CI: 3.06-64.66) and hepatitis C (OR 5.64, 95% CI: 1.69-18.77). Moreover, 11 studies (257 cases, 1079 controls) showed a higher prevalence of venous and/or arterial thrombosis in patients with hepatitis and anti-cardiolipin antibody positivity compared hepatitis alone (OR 3.29, 95% CI: 1.79-6.07). This result was consistently confirmed in hepatitis C (OR 3.64, 95% CI: 1.78-7.46) but not in hepatitis B. CONCLUSIONS: Viral hepatitis is significantly associated with anti-phospholipid antibody positivity and with anti-phospholipid antibody-related thrombotic complications.