How to Interpret Antiphospholipid Laboratory Tests

Devreese, Katrien

doi:10.1007/s11926-020-00916-5

Cited by 27 publications

(32 citation statements)

References 85 publications

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“…Although both IgG and IgM aPL have been included in the laboratory classification criteria ( 1 ), the IgG isotype has displayed a higher diagnostic and prognostic value than the IgM one for both the vascular and the obstetric manifestations of the syndrome since the beginning of the APS story ( 27 , 28 ). More recently, several groups suggested that IgA aPL may offer a good diagnostic/prognostic profile as well.…”

Section: Laboratory Perspectivesmentioning

confidence: 99%

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

Meroni

Borghi

2021

Front. Immunol.

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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.

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Section: Laboratory Perspectivesmentioning

confidence: 99%

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

Meroni

Borghi

2021

Front. Immunol.

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“…Compared to similar studies, the sensitivity for some autoantibodies is not very high, which may influence the results of sequence comparison. Since different detection methods and manufacturers vary greatly in antibody measurement, contradictory results could arise (36). In the future, quantitative/semi-quantitative detection methods such as chemiluminescence analysis (CLIA) could be applied to reduce systemic detection error.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Diagnostic Value of Non-criteria Antibodies for Antiphospholipid Syndrome Patients in a Chinese Cohort

Xie

et al. 2021

Front. Immunol.

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ObjectiveAlthough specific anti-phospholipid antibodies (aPLs) have been used in the diagnosis of the antiphospholipid syndrome (APS) for years, new biomarkers are required to increase its diagnostic and risk-predictive power. This study aimed to explore the value of several non-criteria aPLs in a Chinese cohort.MethodsA total of 312 subjects, namely, 100 patients diagnosed with primary APS, 51 with APS secondary to SLE, 71 with SLE, and 90 healthy controls, were recruited. Serum anticardiolipin (aCL) IgG/IgM/IgA, anti-β2-glycoprotein I (aβ2GPI) IgG/IgM/IgA, anti-phosphatidylserine/prothrombin antibodies (aPS/PT) IgG/IgM, and anti-annexin A5 antibodies (aAnxV) IgG/IgM were tested using ELISA kits.ResultsOf the total number of patients, 30.46% and 6.62% with APS were positive for aCL or aβ2GPI IgA, respectively, while 39.07% and 24.50% were positive for aAnxV or aPS/PT for at least one antibody (IgG or IgM). The addition test of aCL IgA and aAnxV IgM assists in identifying seronegative APS patients, and IgG aPS/PT was linked to stroke.ConclusionDetection of aCL IgA, aβ2GPI IgA, aAnxV IgG/M, and aPS/PT IgG/M as a biomarker provides additive value in APS diagnosis and would help in risk prediction for APS patients in medical practice.

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“…The traditional procedure of the LA examination is performed in three basic steps: 1-screening, 2-mixed tests, and 3-confirmation [68]. The LA results are interpreted according to ISTH SSC as positive/negative based on the normalized ratio (NR) calculation (NR = patient/polled normal plasma (PNP)) [69]. With regard to the use of different analyzers and reagents, each laboratory should determine its own cut-off for LA (99th percentile) by measuring ideally 120 (minimally 40) healthy controls [47,70,71].…”

Section: Antibodies Against Phospholipid Antigensmentioning

confidence: 99%

Current Promising Biomarkers and Methods in the Diagnostics of Antiphospholipid Syndrome: A Review

et al. 2021

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Antiphospholipid syndrome (APS) is a hypercoagulation condition associated with the incidence of heterogenic antiphospholipid antibodies (aPLs), which non-specifically affect hemostasis processes. APS is clinically manifested by recurrent arterial and venous thromboses and reproduction losses. The aPL antibodies, which may induce clinical manifestations of APS, include criteria antibodies anti-cardiolipin, anti-β2-glycoprotein-I, and lupus anticoagulant, but also non-criteria antibodies, for example anti-β2-glycoprotein-I domain I, anti-phosphatidylserine/prothrombin, anti-annexin V, and many others. APS occurs mostly in patients of younger and middle age, most frequently in females. Laboratory diagnostics of APS are quite difficult, as they include a wide spectrum of examining methods, which are based on various principles of detection and are performed using various laboratory techniques. The objective of the review is to describe the current state of potentially examined biomarkers and methods in APS diagnostics. The aforementioned biomarkers are lupus anticoagulant, anti-β2-glycoprotein-I, anti-cardiolipin, anti-β2-glycoprotein-I domain I, anti-phosphatidylserine/prothrombin, anti-β2-glycoprotein-I IgA, anti-cardiolipin IgA, anti-annexin V and II, anti-prothrombin, anti-cardiolipin/vimentin, anti-protein S/protein C, and antibodies against phospholipid antigens for whose diagnostics we may use some of the methods established for a long time and some of the modern methods—the coagulation method for the determination of lupus anticoagulant (LA), enzyme-linked imunosorbent assay (ELISA), chemiluminescence analysis (CLIA), multiplex fluorescence flow immunoassay (MFFIA), fluorescence enzyme immunoassay (EliA), line immunoassay (LIA), multiline dot assay (MLDA), and thin-layer chromatography (TLC). Conclusion: Antibodies against phosphatidylethanolamine, phosphatidic acid, phosphatidylserine, phosphatidylinositol, cardiolipin/vimentin complex, and annexin V are currently the most studied new markers. However, these assays have not been standardized until now, both from the laboratory and clinical point of view. In this review we summarize the evidence of the most studied aPL markers and their potential clinical significance in seronegative APS (SN-APS).

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How to Interpret Antiphospholipid Laboratory Tests

Cited by 27 publications

References 85 publications

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

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

Evaluation of the Diagnostic Value of Non-criteria Antibodies for Antiphospholipid Syndrome Patients in a Chinese Cohort

Current Promising Biomarkers and Methods in the Diagnostics of Antiphospholipid Syndrome: A Review

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