scholarly journals Antiphospholipid Antibody Assays in 2021: Looking for a Predictive Value in Addition to a Diagnostic One

2021 ◽  
Vol 12 ◽  
Author(s):  
Pier Luigi Meroni ◽  
Maria Orietta Borghi
Keyword(s):  
Clinical Manifestations ◽  
General Rule ◽  
Antiphospholipid Antibody ◽  
Prognostic Information ◽  
Glycoprotein I ◽  
Laboratory Characterization ◽  
Antibody Assays ◽  
Quantitative Results ◽  
Epitope Characterization ◽  
Prognostic Power

Antiphospholipid antibodies (aPL) are mandatory for the diagnosis but are also a risk factor for the antiphospholipid syndrome (APS) clinical manifestations. Lupus anticoagulant (LA), anticardiolipin (aCL), and anti-beta2 glycoprotein I (β2GPI) assays are the formal laboratory classification/diagnostic criteria. Additional nonclassification assays have been suggested; among them, antiphosphatidylserine-prothrombin (aPS/PT) and antidomain 1 β2GPI antibodies are the most promising ones although not yet formally accepted. aPL represent the example of a laboratory test that moved from dichotomous to quantitative results consistent with the idea that reporting quantitative data offers more diagnostic/prognostic information for both vascular and obstetric manifestations. Although the general rule is that the higher the aPL titer, the higher the test likelihood ratio, there is growing evidence that this is not the case for persistent low titers and obstetric events. LA displays the highest diagnostic/prognostic power, although some isolated LAs are apparently not associated with APS manifestations. Moreover, isotype characterization is also critical since IgG aPL are more diagnostic/prognostic than IgA or IgM. aPL are directed against two main autoantigens: β2GPI and PT. However, anti-β2GPI antibodies are more associated with the APS clinical spectrum. In addition, there is evidence that anti-β2GPI domain 1 antibodies display a stronger diagnostic/prognostic value. This finding supports the view that antigen and even epitope characterization represents a further step for improving the assay value. The strategy to improve aPL laboratory characterization is a lesson that can be translated to other autoantibody assays in order to improve our diagnostic and prognostic power.

Antiphospholipid antibody profile: implications for the evaluation and management of patients

Lupus ◽  
2010 ◽  
Vol 19 (4) ◽  
pp. 432-435 ◽  
Author(s):  
A. Tincani ◽  
L. Andreoli ◽  
C. Casu ◽  
R. Cattaneo ◽  
P. Meroni
Keyword(s):  
Pregnancy Loss ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Diagnostic Value ◽  
Antiphospholipid Antibody ◽  
Vein Thrombosis ◽  
Glycoprotein I ◽  
Antibody Assays ◽  
Independent Risk Factors ◽  
Deep Vein

According to the classification criteria of antiphospholipid syndrome, lupus anticoagulant, anticardiolipin and anti-β2 glycoprotein I antibody assays are independent risk factors for the occurrence of vascular thrombosis and pregnancy loss. However, it is generally accepted that patients carrying multiple positivity have more a severe disease and higher recurrence rate despite treatment. On the other hand, the diagnostic value of a positive result in one only assay is more controversial, particularly in the presence of clinical manifestations such as deep vein thrombosis or early miscarriages, which are rather common in the general population. In this review we speculate on current and future strategies to interpret different antiphospholipid antibody profiles in the clinical practice. Lupus (2010) 19, 432—435.

scholarly journals Phospholipid Autoantibodies and the Antiphospholipid Antibody Syndrome: Diagnostic Accuracy of 23 Methods Studied by Variation in ROC Curves with Number of Clinical Manifestations

2002 ◽  
Vol 48 (7) ◽  
pp. 1004-1010 ◽  
Author(s):  
Jan-Christian Wasmuth ◽  
Desamparados Oliver y Miñarro ◽  
Angela Homrighausen ◽  
Ludger Leifeld ◽  
Jürgen K Rockstroh ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Clinical Manifestations ◽  
Signs And Symptoms ◽  
Roc Curves ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Test Results ◽  
Glycoprotein I ◽  
Immunoglobulin Isotypes ◽  
The Individual

Abstract Background: We analyzed the diagnostic accuracies for the diagnosis of antiphospholipid syndrome (APS) of 23 antiphospholipid antibody (APL-Ab) assays targeted at different antigen preparations and immunoglobulin isotypes. Methods: In 144 patients with suspected APS, anti-cardiolipin (aCL) and anti-β2-glycoprotein I (aβ2GPI) antibodies were measured with 23 different ELISAs from three manufacturers. Data were analyzed by ROC curves. In the absence of an accepted criterion standard, the endpoint “diagnosis of APS” was varied according to the number (two through five) of signs and symptoms of APS. Results: Although the presence of lupus anticoagulant was associated significantly with APL-Ab in 10 of 23 assays (P = 0.01–10−4) and recurrent arterial or venous occlusions were significantly associated with APL-Ab of IgM isotype in 5 of 6 assays (P = 0.02–10−4), sensitivity for detection of APS did not exceed 67%. With the exception of IgA APL-Ab, the diagnostic accuracy of the assays improved when the diagnosis of APS was based on an increasing number of simultaneous features of APS. For most methods, areas under the ROC curves were >0.8 irrespective of the method’s subclass specificity and antigen preparation (aCL or aβ2GPI), if the clinical diagnosis of APS was based on four or more signs and symptoms of APS. Conclusion: Despite considerable heterogeneity in the individual test results, a single test of IgG or IgM isotype targeted at either aCL or aβ2GPI antibodies has excellent diagnostic accuracy when the criterion for diagnosis requires four or more typical manifestations of APS.

Risky business: the interpretation, use, and abuse of antiphospholipid antibody tests in clinical practice

Lupus ◽  
2010 ◽  
Vol 19 (4) ◽  
pp. 440-445 ◽  
Author(s):  
RAS Roubey
Keyword(s):  
Risk Factors ◽  
High Titer ◽  
Clinical Manifestations ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antiphospholipid Antibody ◽  
High Concentration ◽  
Clinical Issue ◽  
Glycoprotein I ◽  
Antibody Titers ◽  
Risky Business

Antiphospholipid antibodies (aPL) are best considered as risk factors. aPL are not diagnostic tests and considering them as such can be misleading and may direct attention away from the more important clinical issue of risk modification and management. When considering aPL as risk factors, quantitative aPL tests such enzyme-linked immunosorbent assay (ELISA) for anticardiolipin (aCL) and anti-β 2-glycoprotein I (anti-β2GPI) antibodies, should be interpreted carefully. Risk for clinical manifestations appears to be associated with moderate to high levels of these autoantibodies. Lower levels may be statistically abnormal compared with a control population, but may not be associated with the risk of thrombosis or pregnancy loss. Lupus anticoagulants (LA) are generally thought to be more strongly associated with the risk of clinical manifestation of antiphospholipid syndrome (APS) than aCL and anti-β2GPI antibodies. One reason for the stronger association may be related to patients’ antibody titers. LA assays are not very analytically sensitive, i.e. a relatively high concentration of antibodies is required to prolong the clotting time in these tests. Thus, the presence of LA indicates a high titer of aPL and this, rather than the intrinsic functional characteristics of LA antibodies, may explain the high risk of clinical manifestations associated with LA.

The Interaction of β2 Glycoprotein-I and Heparin and Its Effect on β2 Glycoprotein-I Antiphospholipid Antibody Cofactor Function in Plasma

1994 ◽  
Vol 72 (04) ◽  
pp. 578-581 ◽  
Author(s):  
T McNally ◽  
S E Cotterell ◽  
I J Mackie ◽  
D A Isenberg ◽  
S J Machin
Keyword(s):  
Solid Phase ◽  
Pharmaceutical Preparations ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antiphospholipid Antibody ◽  
Biological Functions ◽  
Dermatan Sulphate ◽  
Glycoprotein I ◽  
Crossed Immunoelectrophoresis ◽  
Calcium Heparin ◽  
Cofactor Activity

Summaryβ2 glycoprotein-I (β2GPI), a cofactor for antiphospholipid antibody (aPA) binding, binds to many anionic macromolecules including heparin. The nature of this interaction with heparin is not well understood and its effect on the purported biological functions of β2GPI is unknown.We have examined the interactions of dermatan sulphate (DS) and different pharmaceutical preparations of heparin with β2GPI by crossed immunoelectrophoresis (CIE) and investigated the effect of these agents on plasma levels of p2GPI antigen (β2GPI: Ag) by a standardised enzyme linked immunosorbent assay (ELISA). P2GPI aPA cofactor activity (β2GPI:Cof) was also measured using a modified solid phase an-ti-phosphatidylserine (aPS) ELISA. CIE results confirmed a heparin-β2GPI interaction with unfractionated (UF) heparin. β2GPI:Ag levels were unaffected by any of the preparations investigated. There were no significant differences in β2GPI:Cof activities of the samples containing LMW heparins or DS but levels of β2GPI:Cof were increased in samples containing UF sodium and calcium heparin preparations (0.5 IU/ml Monoparin, p <0.05, and 10 IU/ml Liquemin and Calcipa-rine, p <0.05).

KM55 Monoclonal Antibody Staining in IgA-Dominant Infection-Related Glomerulonephritis

Nephron ◽  
2021 ◽  
pp. 1-13
Author(s):  
Minfang Zhang ◽  
Wenyan Zhou ◽  
Shaojun Liu ◽  
Liyin Zhang ◽  
Zhaohui Ni ◽  
...  
Keyword(s):  
Clinical Manifestations ◽  
Staining Intensity ◽  
Integrated Analysis ◽  
Control Group ◽  
Pathological Feature ◽  
Characteristic Analysis ◽  
Prognostic Information ◽  
Antibody Staining ◽  
Key Factor ◽  
Focal Segmental Sclerosis

Introduction: IgA-dominant infection-related glomerulonephritis (IgA-IRGN) is a unique form of IRGN, which needs to be distinguished from IgA nephropathy (IgAN), due to overlapping clinical and pathological features. The key factor in the pathogenesis of IgAN is galactose-deficient IgA1 (Gd-IgA1). However, the mechanism of glomerular IgA deposition in patients with IgA-IRGN is unclear. Therefore, we evaluated whether Gd-IgA1 could be a useful biomarker to distinguish between these 2 diseases. Methods: A case-control study was conducted to analyze the clinical and pathological characteristics of 12 patients with IgA-IRGN. The intensity and distribution of glomerular Gd-IgA1 (KM55) staining in renal biopsies were assessed. The control group consisted of 15 patients diagnosed with IgAN and an additional 17 patients with glomerulopathy involving IgA deposition. Results: The main clinical manifestations of patients with IgA-IRGN were nephrotic-range proteinuria, hematuria, acute renal injury, and hypocomplementemia. Active lesions were the leading pathological feature, while focal segmental sclerosis was rare. Half of the patients exhibited hump-shaped subepithelial deposits. Glomerular KM55 staining was negative in 7 patients, trace in 4 patients, and 2+ in 1 patient. The median intensity of KM55 staining in IgA-IRGN patients was 0 (range 0∼2+), which was significantly lower than that of primary IgAN patients (median 2+, range 1+∼3+). The receiver operating characteristic analysis demonstrated that the optimal cutoff level to identify these 2 diseases was 0.5+. Conclusions: Glomerular KM55 staining intensity might be helpful to distinguish IgA-IRGN from primary IgAN. Weak or negative staining may favor IgA-IRGN. In addition, integrated analysis including clinical data, pathological findings, and prognostic information would further improve the differential diagnosis.

scholarly journals Case of an unusual diagnosis of primary antiphospholipid syndrome with multiple clinical complications

2020 ◽  
Vol 2020 (12) ◽  
Author(s):  
Stathis Tsiakas ◽  
Chrysanthi Skalioti ◽  
Paraskevi Kotsi ◽  
Ioannis Boletis ◽  
Smaragdi Marinaki
Keyword(s):  
Antiphospholipid Syndrome ◽  
Thrombotic Event ◽  
Renal Involvement ◽  
Clinical Manifestations ◽  
Young Male ◽  
Multiple Organ ◽  
Systemic Autoimmune Disease ◽  
Antiphospholipid Antibody ◽  
Primary Antiphospholipid Syndrome ◽  
Wide Range

ABSTRACT Antiphospholipid syndrome (APS) is a systemic autoimmune disease defined by the presence of antiphospholipid antibodies in association with thrombotic events and/or obstetric complications. Renal involvement is not infrequent in both primary and secondary APS. Kidney manifestations comprise a wide range of clinical features, including hypertension, major renal vessel thrombosis or microvascular endothelial injury, also described as APS nephropathy. In the absence of a thrombotic event, clinical manifestations of APS are often non-specific. We recently encountered a case of primary APS in a young male with newly diagnosed hypertension and renal impairment. The diagnosis of APS was initially suspected by his kidney biopsy findings, when electron microscopy examination showed the features of chronic microangiopathy, and was later confirmed by a triple positive antiphospholipid antibody profile and multiple organ involvement.

Anticardiolipin and Anti-Beta2 Glycoprotein I Antibodies in Infants Born to Mothers with Antiphospholipid Antibody-Positive Autoimmune Disease: A Follow-Up Study

2006 ◽  
Vol 23 (4) ◽  
pp. 247-252 ◽  
Author(s):  
Mario Motta ◽  
Gaetano Chirico ◽  
Chiara Rebaioli ◽  
David Faden ◽  
Andrea Lojacono ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Antiphospholipid Antibody ◽  
Follow Up Study ◽  
Glycoprotein I

Missed hypereosinophilic syndrome in a critically ill patient with systemic lupus erythematosus

2021 ◽  
Vol 14 (1) ◽  
pp. e236592
Author(s):  
Ying Ling ◽  
Mary Jane Bell ◽  
Lisa Chodirker ◽  
Shirley Lake
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Hypereosinophilic Syndrome ◽  
Clinical Manifestations ◽  
Critically Ill Patient ◽  
Total Leucocyte Count ◽  
High Dose ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Systemic Lupus

A high functioning 74-year-old man with systemic lupus erythematosus presented to the emergency department with acute anxiety. He was found to have elevated cardiac enzymes and admitted to the cardiology service for investigation. In hospital, he developed an erythematous papular rash, and deteriorated to being somnolent and bedridden. He was found to have new multiterritory ischaemic strokes. It was eventually noted that he had persistent eosinophilia, present even on admission, which had been overlooked as the total leucocyte count was normal. Serology for antiphospholipid antibody syndrome (APS) was positive. He was diagnosed with hypereosinophilic syndrome (HES) secondary to new APS, and responded to high-dose steroids. This case highlights the importance of fully evaluating a leucocyte differential to make a diagnosis of HES. We discuss the definition, clinical manifestations, diagnostic approach and management of this important condition.

scholarly journals Anticardiolipin Antibodies in Patients with Chronic Hepatitis C Virus Infection: Characterization in Relation to Antiphospholipid Syndrome

2000 ◽  
Vol 7 (2) ◽  
pp. 241-244 ◽  
Author(s):  
Josep Ordi-Ros ◽  
Julieta Villarreal ◽  
Francesc Monegal ◽  
Silvia Sauleda ◽  
Ignacio Esteban ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Antiphospholipid Syndrome ◽  
Clinical Manifestations ◽  
Cross Reactivity ◽  
Healthy Controls ◽  
Glycoprotein I ◽  
Chronic Hepatitis C Virus

ABSTRACT The antiphospholipid syndrome (APS) is usually defined by the association of clinical manifestations that comprise venous and/or arterial thrombosis, recurrent fetal losses, and thrombocytopenia, along with the presence of anticardiolipin (aCL) antibodies and/or lupus anticoagulant. Various infectious diseases can induce aCL; however, these antibodies are not usually associated with thrombotic events, as happens with autoimmune diseases, in which these antibodies need the presence of β2-glycoprotein I. Levels of immunoglobulin G (IgG) and IgM aCL antibodies were determined by enzyme-linked immunosorbent assay for 243 patients with chronic hepatitis C virus (HCV) infection and 100 healthy controls. Clinical events of APS, the level of β2-glycoprotein dependence of aCL, the presence of cryoglobulins and other autoantibodies, and cross-reactivity between purified aCL and HCV were evaluated. Positive results for aCL antibodies were found more frequently (3.3%) for the patients with HCV infection than for healthy controls (0%). All positive aCL antibodies were β2-glycoprotein I independent. No significant association was found between aCL antibodies and clinical manifestations of APS, neither was one found between the presence of other autoantibodies or cryoglobulins and that of aCL. Finally, no cross-reactivity between aCL antibodies and HCV antigens was observed. As previously reported, aCL antibodies seem to be an epiphenomenon, and they do not have clinical or laboratory significance in HCV patients.

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