Antibodies to Domain I ß2-Glycoprotein 1 in Patients with Antiphospholipid Syndrome and Systemic Lupus Erythematosus.

The role of antiphospholipid antibodies (aPL), which are not included in the Sydney diagnostic criteria, in antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) is poorly understood. The aim of this study was to determine the clinical significance of IgG antibodies for domain 1 of ß2-glycoprotein 1 (ß2-GP1), IgG anti-ß2-GP1DI, in patients with APS with and without SLE. The study included 187 patients with APS with or without SLE, 49 patients formed the comparison group, and 100 apparently healthy individuals formed the control group. IgG/IgM antibodies to cardiolipin (aCL) and IgG/IgM anti-ß2-GP1 were determined by enzyme immunoassay (ELISA) in patients with or without APS, and IgG anti-ß2-GP1DI was determined by chemiluminescence assay (CLA) in all patients and controls. IgG anti-ß2-GP1DI was detected in 37 (71%) of 52 patients with primary APS (PAPS), in 6 (50%) of 12 patients with probable APS, in 42 (71%) of 59 patients with SLE + APS, in 17 (26%) of 64 patients with SLE, in 1 (2%) of the comparison group, and in none of the control group. IgG anti-ß2-GP1DI was significantly associated with PAPS and SLE + APS compared with the patients with SLE (p = 0.0002 and 0.0001, respectively). The association of IgG anti-ß2-GP1DI with clinical manifestations of APS (thrombosis (p = 0.001) and obstetric pathology (p = 0.04)) was detected. There was a significant association of IgG anti-ß2-GP1DI with arterial thrombosis (p = 0.002) and with late gestational obstetric pathology (p = 0.01). High specificity of IgG anti-ß2-GP1DI depending on the diagnosis and clinical manifestations of APS despite low sensitivity was noted: specificity was 84% for thrombosis, 94% for obstetric pathology, and 89% for APS. Isolated IgG anti-ß2-GP1DI positivity was reported in 2% of 50 aPL-negative patients and was not associated with APS manifestations. The frequency of IgG anti-ß2-GP1DI detection was higher in the patients with APS compared to the patients with SLE, comparison group, and control (p < 0.05). Positive IgG anti-ß2-GP1DI values were significantly associated with thrombotic complications and with obstetric pathology (p = 0.002 and p = 0.01, respectively). Specificity of IgG anti-ß2-GP1DI for APS and its clinical manifestations (thrombosis and obstetric pathology) was higher than sensitivity (89, 94, and 84%, respectively).

Antiphospholipid Antibodies Increase the Risk of Fetal Growth Restriction: A Systematic Meta-Analysis.

Objective: Antiphospholipid syndrome (APS) is a chronic autoimmune disease with a high prevalence in females. Published data have identified pregnant women with APS may suffer from recurrent miscarriage, fetal death. However, the association between antiphospholipid antibody (aPL) and fetal growth restriction (FGR) remains controversial. This study aims to systematically review the literature on population-based studies investigating an association between aPL and FGR. Methods: The literature was searched on 1 November, 2021, using Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL), following the MOOSE checklist. Study inclusion criteria focused on peer-reviewed published articles that reported an association between aPL and FGR. Quality assessment was performed based on the Newcastle-Ottawa scale. The between-study heterogeneity was assessed by the Q test. Publication bias was assessed by funnel plots. Results: Twenty-two studies (with 11745 pregnant women) were included in the final analysis. Pooled odds ratio for association of aPL, anticardiolipin antibodies (ACA), anti-beta2 glycoprotein 1 antibodies (ß2GP1), and FGR was 1.26 (95%CI 1.12, 1.40), 2.25 (95%CI 1.55, 2.94), and 1.31 (95% CI 1.12, 1.49), respectively. Lupus anticoagulant (LA) did not increase the chance of FGR (OR 0.82, 95%CI 0.54, 1.10). Conclusions: Our meta-analysis showed that aPL increased the risk of FGR. The risk of FGR varies with the aPL types. ACA and ß2GP1 are strongly associated with FGR. There are currently insufficient data to support a significant relationship between LA and FGR.

Analysis of Serbian Primary Antiphospholipid Syndrome Patients Confirmed a Strong Association Between Livedo Reticularis and Arterial Thrombosis: A National Cross-Sectional Cohort Study.

BACKGROUND: Antiphospholipid syndrome (APS) is characterized by antiphospholipid antibodies (aPLs) associated with thrombosis (arterial and/or venous) and/or obstetrical manifestations. However, various manifestations, which are considered to be noncriteria manifestations, are frequently found in APS. AIM: The purpose of this study was to evaluate whether noncriteria manifestations may be found more frequently in subjects with thrombotic and/or obstetrical APS ("criteria" manifestations) in a population of patients with primary APS (PAPS). This study presents the results from our national cohort. PATIENTS AND METHODS: This is a cross-sectional study of 360 PAPS patients. Data regarding the presence of thrombocytopenia, livedo reticularis, chorea, and valvulopathy were analyzed. The aPL analysis included the detection of anticardiolipin antibodies (aCLs: immunoglobulin G [IgG]/IgM), anti-ß 2 glycoprotein I (IgG/IgM), and lupus anticoagulant positivity. RESULTS: In our cohort, livedo reticularis was significantly related to arterial thromboses in the same way as valvular manifestations (valvular vegetations and valvular thickening and dysfunction not related to age) ( p = 0.0001, p = 0.013, respectively). Age was strongly related to all the noncriteria manifestations analyzed. Thrombocytopenia was significantly related to ß 2 glycoprotein I IgG and lupus anticoagulant positivity ( p = 0.043, p = 0.030, respectively), as well as to double and triple aPL positivity ( p = 0.041, p = 0.013 respectively). Moreover, in a multivariate model, livedo reticularis was strongly and independently related to arterial thrombosis in our cohort (odds ratio, 2.010; confidence interval, 1.229-3.288; p = 0.005). CONCLUSION: This cross-sectional analysis of a large cohort of Serbian PAPS patients confirmed a strong relationship between livedo reticularis and arterial thrombosis, suggesting a more cautious approach regarding the presence of noncriteria manifestations, especially livedo reticularis, in APS.

[The analysis to data from Chinese Rheumatism Data Center external quality assurance program for autoantibodies in 2021].

To evaluate the data obtained from the external quality assurance program initiated by Chinese Rheumatism Data Center (CRDC-QAP) for autoantibodies detection in 2021, so as to assess the consensus and differences in cross-laboratory testing to autoantibodies in China. This is a retrospective study. After collecting data from the first half year (from May 15th to July 10th) and the second half year (from August 15th to November 19th) of CRDC-QAP program for autoantibody detection in 2021, it firstly analyzed the qualitative consensus of the cross-laboratory results. Secondly, it compared the positivity grade of numeric results according to the Sample to cut-off ratio (S/CO ratio) calculation. Finally, the mean and coefficient variation (CV) of numeric results from three major manufacturers were calculated. A total of 303 and 332 clinical labs voluntarily participated in the first half year and the second half year of CRDC-QAP program for autoantibody detection in 2021, respectively. Except for anti-ß2 glycoprotein type I (aß2-GPI) IgM, the cross-laboratory consensus of qualitative results for the other autoantibodies is greater than 96%. As for anti-cyclic citrullinated peptide antibody (anti-CCP) and anti mitochondrial antibody-M2 (AMA-M2), the numeric results from more than 90% laboratories showed the same positivity grade. More than 50% of laboratories used chemiluminescence immunoassay (CLIA) for quantitative evaluation of autoantibody. The CV of numeric results from different manufacturers showed certain differences(P<0.01) with the range from 0 to 238%. Although high consensus can be observed in term of qualitative result for autoantibody detection in cross-laboratory, there are still certain differences in numeric results in term of positivity grade and manufacturer-based CV.

Revisiting the Phadia/EliA cut-off values for anticardiolipin and anti-ß2-glycoprotein I antibodies: a systematic evaluation according to the guidelines.

Background Phadia/EliA fluorescence enzyme immunoassays are widely used automated assays for anticardiolipin (aCL) and anti-ß2-glycoprotein I (aß2GPI) antibodies. To date, cut-off values for these assays have not been evaluated systematically and the evidence behind manufacturer's recommended cut-off values is not clear. Objective To determine Phadia/EliA cut-off values for antiphospholipid antibodies (aPL) according to the procedures suggested by guidelines. Methods A total of 266 blood donors (135 females and 131 males) were included. The pre-handling and analysis of the samples were performed according to the International Society on Thrombosis and Hemostasis (ISTH) guideline for solid phase aPL assays. Cut-off values and corresponding 90% confidence intervals (CI) for each antibody were established and outliers were handled according to the Clinical and Laboratory Standards Institute (CLSI) guideline for reference intervals. Samples from 377 consecutive patients, referred to our thrombophilia center with evidence of thrombosis or pregnancy morbidity were included for aPL testing. Results The in-house 99th (97.5th) percentile cut-off values were 11 (8.7), 12 (6.9) 8.5 (5.0) AU/mL for aß2GPI IgG, IgM and IgA, and 21 (13) GPL-U/mL and 41 (25) MPL-U/mL for aCL IgG and IgM, respectively. The prevalence of positive results (%) defined by these cut-off values in patients with evidence of thrombosis or pregnancy morbidity was 9.5 (12.2), 1.6 (2.9), and 7.0 (9.9), and 0.8 (3.8) for aß2GPI IgG, IgM, and aCL IgG and IgM respectively. The use of in-house 99th percentile cut-off values compared to the manufacturer suggested cut-off values resulted in 1 and 39 fewer samples for aß2GPI and aCL to be classified as positive for aPL, respectively. Conclusions We present Phadia/EliA cut-off values with 90% CI for aPL determined systematically according to the ISTH and CLSI guidelines. These values are different from values previously determined, suggesting variation of aPLs in different populations. Our findings indicate the need for each laboratory to determine/validate assay specific cut-off values for aPL.

Non-Criteria or Seronegative Obstetric Antiphospholipid Syndrome?

BACKGROUND: Obstetric antiphospholipid syndrome (Obs-APS) is one of the most commonly identified causes of recurrent pregnancy loss and its accurate diagnosis is a requirement for optimal treatment. Some patients do not fulfill the revised Sapporo classification criteria, the original APS classification criteria, and are considered to be non-criteria Obs-APS. In these patients with non-criteria, there is controversy about their inclusion within the spectrum of APS and eventually their treatment as having Obs-APS. A subset of patients may also have clinical characteristics of Obs-APS even though lupus anticoagulant (LA), anticardiolipin antibodies, and anti-ß2-glycoprotein I (aß2GPI) antibodies are consistently negative. These patients are recognized as seronegative Obs-APS. We reviewed evidence of non-criteria Obs-APS and discuss a case of a woman with a diagnosis of active systemic lupus erythematosus (SLE) and non-criteria Obs-APS with four consecutive pregnancy losses. After an accurate diagnosis the patient received prenatal counseling and benefited from the optimal treatment of Obs-APS that led to a successful pregnancy. The applicability of this successful experience about outcomes in women with non-criteria, or seronegative, Obs-APS is also evaluated.

Validation of a New Panel of Automated Chemiluminescence Assays for Anticardiolipin Antibodies in the Screening for Antiphospholipid Syndrome.

BACKGROUND: Antibodies anticardiolipin (aCL) and anti-ß2-glycoprotein I (aß2GPI) are two of three laboratory criteria of antiphospholipid syndrome (APS). All of assays of antiphospholipid antibodies (aPL), coagulation assays as well as ELISAs, show methodological shortcomings, that affect their sensitivity and specificity. Therefore, we decided to validate these parameters for a new chemiluminescent examination (CLIA). METHODS: aCL and aß2GPI antibodies were measured by ELISAs (AIDA, Bad Kreuznach, Germany) and aß2GPI with CLIA kits (Werfen, Barcelona, Spain). RESULTS: When we evaluated both assays, the coefficient of variation for CLIA was slightly lower (9.04 - 12.74%) than for ELISA (11.05 - 15.3%) and the LOD was 0.2 U/L. The dilution series showed significant linearity for all CLIA methods, aCL IgG, aCL IgM, aß2GPI IgG, and aß2GPI IgM (0 - 3000 U/L), and method comparison studies revealed good agreement with the currently used ELISA (Kappa values ranging 0.534 - 0.936) without determination of aß2GPI IgG. The determination aß2GPI IgG by CLIA method shows higher positivity in 31 samples. These new aCL IgG, aCL IgM, aß2GPI IgG, and aß2GPI IgM tests have excellent analytical characteristics and allow fully automated and simultaneous analysis on an analyzer. CONCLUSIONS: Chemiluminescent determination of an automated analyzer can improve the fundamental parameters of tests such as reproducibility between laboratories.

Differences between clinical and laboratory findings in patients with recent diagnosis of SLE according to the positivity of anti-dsDNA by the Crithidia luciliae method.

BACKGROUND: Of all anti-dsDNA antibody detection methods, the Crithidia luciliae immunofluorescence test (CLIF) is considered to have the highest specificity for systemic lupus erythematosus (SLE). OBJECTIVE: The objective of this report is to evaluate whether the presence of anti-dsDNA antibodies detected by the CLIF method is associated with a specific clinical phenotype in recently diagnosed SLE. METHODS: This retrospective cross-sectional study included all patients with newly diagnosed SLE between 1990 and 2011 and followed up in our institution. Demographic, clinical and laboratory findings were assessed. Correlations between positivity of anti-dsDNA by the CLIF method, clinical and laboratory data were analyzed. RESULTS: A total of 104 patients were included in the analysis. Patients who were positive for anti-dsDNA by the CLIF method at the time of diagnosis had (statistically) significantly higher titers of anti-dsDNA by the ELISA method, antinuclear (ANA) and anticardiolipin antibodies, lymphopenia and complement consumption compared with the other two groups. Also they presented significantly more musculoskeletal symptoms at baseline. CONCLUSION: The presence of anti-dsDNA by the CLIF method in newly diagnosed SLE was associated with certain markers of increased disease activity. Its use could be a useful biomarker for a specific clinical phenotype suggestive of a more severe involvement at the time of the diagnosis.

Real-world practice of obstetricians in respect of assays for antiphospholipid antibodies.

OBJECTIVE: The international classification criteria (CC) for definite antiphospholipid syndrome (APS) recommend confirmation of the sustained presence, for at least 12 weeks, of both lupus anticoagulant (LA), as determined by aPTT and RVVT, and anti ß2glycoprotein I (ß2GPI) or anticardiolipin (aCL) IgG and/or IgM. However, it remains unclear whether obstetricians comply with the aforementioned CC for the diagnosis of APS in daily clinical practice. We performed a nationwide survey to examine the attitudes of Japanese obstetricians toward the use of assays for antiphospholipid antibodies (aPLs). METHODS: A questionnaire was sent to 2,700 obstetric facilities where maternity checkups are carried out. The types of assays conducted for aPLs, ascertainment of persistence of the antibodies for at least 12 weeks, and the cutoff points used for the assays were examined. RESULTS: Of the facilities surveyed, 61.5% carried out the assay(s) only once. In regard to the type of assay performed, 97.1% carried out the assay for aCL IgG and/or ß2GPI-dependent aCL, while 67.9% performed the LA-aPTT and/or LA-RVVT assay. Only 8.8% carried out assays for both LA. As for the cutoff points used, 98% of the facilities used lower cutoff points described in the manufacturers' manuals rather than the cutoff values recommended in the CC. CONCLUSION: Thus, only a limited number of facilities adhered precisely to the CC for the diagnosis of APS. Inappropriate treatment and unnecessary expense are potentially major concerns when facilities overdiagnose APS using lower cutoff points or without ascertaining the persistence of the antibodies for at least 12 weeks. On the other hand, some patients miss the opportunity to be treated for APS because of the absence of testing for LA.

A new Eu(3+)-labeled method for anticardiolipin antibody IgM.

BACKGROUND: The anticardiolipin antibodies (aCL) test has become a laboratory standard for the clinical diagnosis of antiphospholipid syndrome (APS). To better the quantitative detection of aCL-IgM so as to classify patients correctly and timely as APS positive, we established herein a new immunoassay based on a time-resolved fluoroimmunoassay (TRFIA). METHODS: The complex of cardiolipin plus bovine anti-ß2 glycoprotein-I was used as antigen fixed on microtiter plates to detect serum aCL-IgM, and Eu(3+) -labeled rabbit antihuman IgM was used as conjugate. The precision, sensitivity, specificity, coefficient of recovery, and stability of the assay were evaluated, and comparison with the traditional, classical enzyme-linked immunosorbent assay (ELISA) was also made. RESULTS: The detection limit of the aCL-IgM TRFIA kit we established was 0.1 MPL U/ml, with a wider detectable range than commercial ELISA ones when a strong-positive specimen was diluted from 2,630.9 to 0.08 MPL U/ml. There was a good liner range within 0.16 to 2,630.9 MPL U/ml, whereas it was within 5.14 to 328.86 MPL U/ml when using three commercial ELISA ones. The average intra- and interassay variability was 3.19 and 3.70%, respectively. The mean recovery rate was 101.95%. The clinical diagnostic specificity was 98%. Additionally, the established assay kit presented good characteristics of stability and correlated well with the ELISA, and the correlation coefficient was 0.955. CONCLUSION: The aCL-IgM TRFIA provides an approach to a more sensitive and reliable diagnosis of APS. Further validation of its use is required.

Clinical manifestations and anti-phospholipid antibodies in 712 patients with systemic lupus erythematosus: evaluation of two diagnostic assays.

OBJECTIVES: To evaluate the agreement and performance of two tests for aPLs with regard to association with manifestations of the APS in patients with SLE. METHODS: We investigated 712 SLE patients and 280 population controls. Cardiolipin and ß(2) glycoprotein-I antibodies were measured with routine ELISA and a new automated method. Three positivity cut-offs (99%, 90% of controls and recommended cut-off by manufacturers) were used. Associations with previous thrombotic events, thrombocytopenia and, in a subgroup of patients, obstetric morbidity (n = 296) were evaluated. Results were compared with the LA test, performed in 380 patients. RESULTS: Inter-test agreement was moderate (demonstrated by κ-values 0.16-0.71). Performance of the two tests was similar: at the 99th percentile cut-off, sensitivity for any thrombotic event ranged from 3.7% to 24.8%, while specificity was 84.7-97.7%. Regardless of assay, IgG isotypes were associated with venous thrombosis and ischaemic cerebrovascular disease, whereas aPLs of IgM isotype were weakly associated with ischaemic heart disease. Associations were greatly affected by aPL level. LA performed better than the specific aPL tests. LA was associated with any thrombotic event, odds ratio 5.4 (95% CI 3.1, 9.4), while the specific aPL tests ranged from non-significant to an odds ratio of 1.9 (95% CI 1.03, 3.4) using criteria cut-off. LA was also convincingly associated with other APS manifestations. CONCLUSION: In relation to thrombotic manifestations, there was moderate agreement but no clear advantages when comparing a routine aPL ELISA with an automated method. APL isotype and titre as well as LA positivity are important for risk assessment in SLE patients.

Clinical significance of IgA anti-cardiolipin and IgA anti-ß2glycoprotein I antibodies.

IgA antiphospholipid antibodies (aPL) are not currently recognized as formal laboratory criteria for the Antiphospholipid Syndrome (APS). This is mainly due to methodological issues (different study designs, use of various non-standardized IgA assays). However, there are experimental data showing the pathogenic role of IgA anti-cardiolipin antibodies (aCL) and IgA anti-ß2glycoprotein I antibodies (anti-ß2GPI). Isolated IgA aCL are not very common, therefore their testing could be useful in the case of strong suspicion of APS but negative results for other aPL tests. IgA anti-ß2GPI seem to be the most prevalent isotype in patients with Systemic Lupus Erythematosus (SLE), with a significant association with thrombotic events. Such a clinical relevance has been recently recognized by the inclusion of these autoantibodies among the aPL tests in the novel SLICC classification criteria for SLE. Emerging interest has been raised by IgA anti-ß2GPI against domain 4/5 as a novel subgroup of clinically relevant aPL.

Anti-ß2 glycoprotein I antibodies and pregnancy outcome in antiphospholipid syndrome.

The relation between pregnancy outcome and single- or double-positivity of anticardiolipin (aCL) and ß2 glycoprotein I (aß2GPI) 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(+) /aß2GPI(-) ; aCL(+) /aß2GPI(+) ; aCL(-) /aß2GPI(+) . 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(+) /aß2GPI(-) group (46.2% vs. 22.1%, p < 0.05); the miscarriage rate in the aCL(-) /aß2GPI(+) 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 aß2GPI antibody may be a better prognostic marker than aCL antibody for pregnancy outcome.

Internal quality control and external quality assurance in testing for antiphospholipid antibodies: Part I--Anticardiolipin and anti-ß2-glycoprotein I antibodies.

Over 30 years since it was first described as a discrete clinical entity, the antiphospholipid antibody syndrome (APS) remains a challenge for both laboratory workers and clinicians in a wide range of specialties. In addition to the presence of appropriate clinical features, the diagnosis of APS also fundamentally requires the finding of positive antiphospholipid antibody (aPL) test result(s), which comprise clot-based assays for the identification of lupus anticoagulant (LA) and immunologic ("solid-phase") assays such as anticardiolipin antibodies (aCL) and anti-ß2-glycoprotein I antibodies (aß2GPI). This article is the first of two that review the process for, and provides recommendations to improve, internal quality control (IQC) and external quality assurance (EQA; or proficiency testing) for aPL assays. These processes are critical for ensuring the quality of laboratory test results and thence the appropriate clinical diagnosis and management of APS. This article covers aCL and aß2GPI testing. In brief, IQC is a process that helps control the quality of laboratory test results on a test-by-test basis; IQC should include samples that provide values around the assay critical cut-off values, and there is added value in the inclusion of non-kit assay controls. EQA is a process that helps laboratories assess their performance against those of their peers. For aCL and aß2GPI testing, we provide some updated findings from the Royal College of Pathologists of Australasia Immunology Quality Assurance Program, and covering testing for the past 3 years (2009 to 2011 inclusive). Findings show similar trends to past years, indicating limited improvement in cross-laboratory test results and interpretations. In summary: (1) EQA participants reported greatly varying numerical test data for both aCL and aß2GPI, with interlaboratory coefficients of variation > 50% with most test challenges; (2) there was considerable overlap in the interpretation (negative, positive, low positive, moderate positive, strong positive) that different participants ascribed to identical numerical test results; and (3) there was limited consensus among participants as to whether test results for individual EQA specimens were either positive or negative for aCL and/or aß2GPI.

Reevaluation of predictive value of ACL and anti-ß2GP1 antibody for thrombosis in patients with systemic lupus erythematosus: from a perspective of a practical world.

Detection of ACL (anticardiolipin, ACL) and anti-ß2GP1 (beta2 glycoprotein1, ß2GP1) antibody has been widely used, and the criteria of APS (Antiphospholipid syndrome, APS) have been used for the prediction of thrombosis in patients with SLE. What is the exact predictive value of these two antibodies? Is it really necessary to apply the criteria of APS to each patient just for the purpose of prediction of thrombosis? The aim of this retrospective study is to reevaluate the predictive value of different combination of ACL and anti-ß2GP1 antibody for thrombosis formation in Chinese patients with SLE. Patients fulfilling the 1997 ACR classification criteria for SLE were enrolled and retrospectively analyzed. Thrombosis was confirmed by ultrasound, cerebral MRI, computed tomography pulmonary angiogram and angiography. Both IgG and IgM isotype of ACL and anti-ß2GP1 antibody were detected with ELISA kit. ROC curves and other parameters of diagnostic test for different combination of ACL and anti-ß2GP1 were analyzed and compared. 175 patients were recruited and thrombosis was diagnosed in 49 patients. In patients with thrombosis, 95.9% had been treated with glucocorticoids before detection of the two antibodies, 44.9% had hypertension and 53.1% had hyperlipidemia. ACL was positive in 28 patients (16%), and anti-ß2GP1 antibody was positive in 21 patients (12%). The presence of a low or higher titer of either ACL (>12 RU/ml) or anti-ß2GP1 antibody (>20 RU/ml) once has the highest predictive accuracy. The sensitivity, the specificity, the Youden's index and the area under ROC curve are 61.11%, 81.11%, 0.4222 and 0.711 respectively. A transient low or higher titer of ACL or anti-ß2GP1 antibody had a good predictive value for thrombosis in patients with SLE, especially in those with other traditional risk factors for thrombosis and those treated with glucocorticoids.

Intravenous immunoglobulin increases plasma viscosity without parallel rise in blood pressure.

WHAT IS KNOWN AND OBJECTIVE: Intravenous immunoglobulin (IVIg) is a commonly used therapy for autoimmune disease, but may cause chronic hypertension and thrombosis. We determined whether: (i) IVIg systematically affects blood pressure in the short term; (ii) acute changes in plasma viscosity because of IVIg correlate with blood pressure effects; (iii) effects of IVIg on acute blood pressure are related to baseline blood pressure or hypertension status and (iv) IVIg influences plasma markers of inflammation, anticardiolipin antibodies and homocysteine as additional putative prothrombotic risk factors. METHODS: Twenty adults with autoimmune neurological disease who received a course of IVIg were evaluated immediately before and after each infusion, on every day of the course. Blood pressure, pulse and the following haematological parameters were determined: plasma viscosity, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), haematocrit, fibrinogen, interleukin-6 (IL-6), homocysteine and anticardiolipin positivity. RESULTS: Intravenous immunoglobulin caused both acute and cumulative rises in plasma viscosity across a treatment course, but no concordant changes in blood pressure. There was also no correlation between individual blood pressure changes and viscosity, baseline blood pressure or hypertension status. Levels of IL-6 rose across the course of therapy, but the acute-phase reactants CRP and fibrinogen did not. One patient developed anticardiolipin antibodies during therapy. WHAT IS NEW AND CONCLUSION: Individual courses of IVIg do not systematically raise blood pressure. Where IVIg is found to cause hypertension, this does not appear to be due to a direct effect of IVIg on plasma viscosity.

Antiphospholipid antibodies and osteonecrosis in systemic lupus erythematosus: a meta-analysis.

Objectives: The present meta-analysis aimed to assess the relationship between antiphospholipid antibodies (aPLs) or antiphospholipid antibody syndrome (APS) and the incidence of osteonecrosis (ON) in systemic lupus erythematosus (SLE) patients.Methods: MEDLINE/Pubmed, EMBASE, Web of science, the Chinese Biomedical Literature Database (CBM), the Wan-Fang Database, and the China National Knowledge Infrastructure (CNKI) were searched from their inception up until 26 December 2020. Studies in English were included. Case-control studies and cohort studies were included. Studies pertaining to the link between aPLs or APS and ON patients were slated for inclusion in the current analysis.Results: Twenty-two studies involving a total of 3054 SLE patients were included. The positivities of anticardiolipin antibody (ACL), IgG ACL, IgM ACL, LA and APS in SLE is not associated with ON. One study showed that IgG or IgM ß2GP1 had no association with ON. No publication bias was detected. The quality of this evidence was low because of the high risk of bias across studies, and therefore robust inferences cannot be made.Conclusion: SLE patients demonstrated a weak association between aPLs and ON. The nature of the association between aPLs and ON in SLE needs to be investigated in-depth in future research.

[Seronegative antiphospholipid syndrome: Myth or reality?] / Syndrome des antiphospholipides « séronégatif ¼ : mythe ou réalité ?

The antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis and/or obstetrical manifestations and the persistent presence, at least 12 weeks apart, of antiphospholipid antibodies (aPL) such as lupus anticoagulant (LA) and/or anticardiolipin antibodies (ACL) and/or anti-ß2 glycoprotein I antibodies (aß2GPI). The finding of patients with clinical profile highly suggestive of APS but who are negative for conventional biological criteria has led to the concept of seronegative APS. In the last few years, new antigen targets and methodological approaches have been employed to more clearly identify this syndrome in patients with thrombosis or obstetrical complications without conventional aPL. Although seronegative APS is still controversial, there is increasing recognition of the existence of this subgroup. However, clinical relevance of non conventional aPL need to be confirmed by efforts toward standardizing new biological tools and longitudinal studies involving large cohort of patients.

[Concetration of anticardiolipin antybodies in peritonel fluid and in fluid from lymphocytes culture in women with endometriosis]. / Stezenie przeciwcial antykardiolipinowych w plynie otrzewnowym i w plynie z hodowli limfocytów kobiet z endometrioza.

AIM: The aim of our work was to study both the concentration of anticardiolipin antibodies (aCL) in peritoneal fluid in women with endometriosis and to examine peritoneal lymphocyte ability to produce anticardiolipin antibodies. MATERIAL AND METHODS: Study group included 30 women with endometriosis. The clinical stages of the disease were assessed by the revised American Fertility Society (rAFS) classification. Reference group included fifteen healthy women, with excluded endometriosis and other pathological disorders within the pelvis. The concentration of aCL in the peritoneal fluid and in fluid from lymphocyte culture was measured by enzyme-linked immunosorbent ELISA assay. RESULTS: Statistical analysis showed significantly increased mean concentration of aCL in peritoneal fluid in women with endometriosis compared to women from the reference group (p<0.0001). The concentration of aCL in fluid from lymphocyte culture was also significantly higher in samples from women with endometriosis than from the reference group (p<0.0001). The highest mean levels of aCL in peritoneal fluid and in fluid from lymphocyte culture were observed in samples from women with stage I of the disease. CONCLUSIONS: An increased level of anticardiolipin antibodies in peritoneal fluid in women with endometriosis and increased antibodies production by lymphocytes may suggest an impairment of humoral immunity and its intensification in the early stages of the disease.

Brain stem infarction in a 6-year-old boy with Down syndrome.

Infarct locations in children with arterial ischemic stroke have primarily been reported to be lobar or in the basal ganglia, and those in patients with Down syndrome (DS) and antiphospholipid syndrome (APS) are typically wide and multiple. No solitary brain stem infarctions have ever been reported in children with DS until now. Here, we report a case of brain stem infarction in a 6-year-old boy with DS who had no cardiac, renal, or intestinal complications. He exhibited ataxic gait and medial longitudinal fasciculus (MLF) symptoms at first presentation. Neuroimaging revealed a localized and isolated lesion in the midbrain. Although he did not satisfy the diagnostic criteria of APS, he showed persistently elevated levels of anticardiolipin antibody (21 U/mL; normal value <10 U/mL). Although he had the risks of a multiple vascular systems disorder, DS, and persistently elevated levels of antiphospholipid antibodies, his lesion was not similar to any of the previously reported cerebral infarctions in DS or in APS. To our knowledge, this is the first report of limited solitary brain stem infarction in a child with DS.