Role of antiphospholipid antibodies in the diagnosis of antiphospholipid syndrome

Devreese, Katrien; Zuily, Stéphane; Meroni, Pier Luigi

doi:10.1016/j.jtauto.2021.100134

Cited by 25 publications

(25 citation statements)

References 80 publications

(135 reference statements)

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“…For now, it is unclear whether aPS/PT has additional value in APS diagnosis or risk stratification, compared to the current criteria [44,46]. aPS/PT IgG and IgM are measured with solid-phase assays but currently, only a few ELISAs are commercially available and reference standards are missing [192]. We do not recommend to routinely test for aPS/PT due to analytical restrictions, but it could provide added value for identifying false LAC negative tests in patients that show double positivity (aCL and aβ2GPI positive) [189].…”

Section: Antiphosphatidylserine/prothrombin Antibodiesmentioning

confidence: 99%

“…However, several studies failed to demonstrate value for aDI as independent risk factor as they only confirm high-risk profiles and therefore added value to current laboratory criteria for risk assessment is limited [194,195,197,202]. Some authors suggested to perform aDI testing as second-line test in patients with single positivity for aβ2GPI or double positivity to identify pathogenic aβ2GPI [189,192]. Although isolated aβ2GPI might not be associated with thrombosis [161], aDI could possibly identify a pathogenic subtype.…”

Section: Anti-domain I β2-glycoprotein I Antibodiesmentioning

confidence: 99%

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Laboratory Diagnosis of Antiphospholipid Syndrome: Insights and Hindrances

Vandevelde

Devreese

2022

JCM

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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-β2 glycoprotein I antibodies (aβ2GPI) 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 aβ2GPI 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 aβ2GPI, 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 β2 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.

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Section: Antiphosphatidylserine/prothrombin Antibodiesmentioning

confidence: 99%

Section: Anti-domain I β2-glycoprotein I Antibodiesmentioning

confidence: 99%

Laboratory Diagnosis of Antiphospholipid Syndrome: Insights and Hindrances

Vandevelde

Devreese

2022

JCM

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“…Для диагностики АФС разработаны классификационные критерии, включающие, наряду с клиническими проявлениями (тромбозы, акушерская патология), обнаружение антител к ФЛ (аФЛ), к которым относятся IgG/IgM-антитела к кардиолипину (аКЛ), IgG/IgM-антитела к β 2 -гликопротеину 1 (анти-β 2 -ГП1) и волчаночный антикоагулянт (ВА) [5,6]. Определение перечисленных аФЛ имеет значение не только для подтверждения диагноза АФС, но и для оценки риска рецидивирования тромбозов [7][8][9]. Для улучшения лабораторной диагностики АФС и стратификации риска развития тромбозов активно изучаются так называемые «некритериальные» аФЛ, к которым в первую очередь относятся антитела к домену I β 2 -гликопротеина 1 (антиβ 2 -ГП1DI) [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25].…”

Section: Discussionunclassified

“…При оценке клинических проявлений АФС специфичность была выше чувствительности: для тромбозов -84% и 54%, для акушерской патологии -94% и 53% соответственно. Предполагается также, что определение IgG антиβ 2 -ГП1DI может быть полезным тестом «второй линии» у пациентов с изолированным увеличением концентрации анти-β 2 -ГП1DI или «двойной позитивностью» по аФЛ для выявления «патогенной» популяции антиβ 2 -ГП1 [9,45], поскольку изолированное увеличение концентрации этих антител не ассоциируется с развитием тромбозов [22]. Однако, по данным ряда авторов, обнаружение IgG анти-β 2 -ГП1DI не является независимым фактором риска АФС, по сравнению с аФЛ, входящими в критерии АФС [11,12,14,19].…”

Section: Discussionunclassified

Antibodies to domain I β2 -glycoprotein 1 in patients with antiphospholipid syndrome and systemic lupus erythematosus

Cheldieva

Reshetnyak

Черкасова³

et al. 2022

Naučno-praktičeskaâ revmatologiâ

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The study of antiphospholipid antibodies (aPL), not included in the Sydney diagnostic criteria, in antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) is poorly understood.The aim of this study – to determine the clinical significance of IgG antibody testing for domain I β2 -glycoprotein 1 (β2 -GP1DI) – IgG anti-β2 -GP1DI in patients with APS with and without SLE.Materials and methods. The study included 187 patients with APS with or without SLE, 49 patients formed a comparison group, and 100 relatively healthy individuals formed a control group. IgG/IgM antibodies to cardiolipin and IgG/ IgM anti-β2 -GP1 were determined by enzyme immunoassay (ELISA) in patients with or without APS, and IgG antiβ2 -GP1DI was determined by chemiluminescence assay in all patients and controls.Results. IgG anti-β2 -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 comparison group and in none of control group. IgG anti-β2 -GP1DI was significantly associated with PAPS and SLE+APS compared with patients with SLE (p=0.0002 and p=0.0001, respectively). The association of IgG anti-β2 -GP1DI with clinical manifestations of APS (thrombosis (χ2 =9.69; p=0.001) and obstetric pathology (χ2 =4.19; p=0.04)) was detected. There was a significant association of IgG anti-β2 -GP1DI with arterial thrombosis (χ2 =8.84; p=0.002) and with late gestational obstetric pathology (χ2 =6.35; p=0.01). High specificity of IgG anti-β2 - GP1DI depending on the diagnosis and clinical manifestations of APS was noted despite low sensitivity: specificity for thrombosis was 84%, for obstetric pathology – 94%, for APS – 89%. Isolated IgG anti-β2 -GP1DI positivity was reported in 2% of 50 aPL negative patients and was not associated with APS manifestations.Conclusion. The frequency of IgG anti-β2 -GP1DI detection was higher in patients with APS compared to patients with SLE, comparison group and control (p<0.05). Positive IgG anti-β2 -GP1DI values were significantly associated with thrombotic complications and with obstetric pathology (χ2 =8.84; p=0.002 and χ2 =6.35; p=0.01). Specificity>˂ 0.05). Positive IgG anti-β2 -GP1DI values were significantly associated with thrombotic complications and with obstetric pathology (χ2 =8.84; p=0.002 and χ2 =6.35; p=0.01). Specificity of IgG anti-β2 -GP1DI for APS and its clinical manifestations (thrombosis and obstetric pathology) was higher than sensitivity: 89%, 94%, and 84%, respectively.

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“…The criteria of antibodies LA, aCL, and anti-β2GPI are strongly associated with the clinical manifestations of APS. Other non-criteria antibodies, such as anti-phosphatidylserine/prothrombin and anti-annexin V, are also currently being studied and their role in the development of thrombotic complications in the patient [ 72 ]. However, the presence of these non-criteria aPL has not yet been shown in clinical research to significantly increase thrombogenicity and cause thrombosis.…”

Section: Discussionmentioning

confidence: 99%

Determination of Thrombogenicity Levels of Various Antiphospholipid Antibodies by a Modified Thrombin Generation Assay in Patients with Suspected Antiphospholipid Syndrome

Bradacova

Slavík²,

Skoumalová³

et al. 2022

IJMS

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Antiphospholipid syndrome (APS) is a hypercoagulable state accompanied by the presence of heterogeneous antiphospholipid antibodies (aPL), which nonspecifically affect hemostasis by the presence of lupus anticoagulans (LA), anticardiolipin antibodies (aCL), antibodies against β2-glycoprotein-I (anti-β2GPI), but also non-criteria antibodies such as antibodies against β2-glycoprotein-I domain I (anti-DI), anti-phosphatidylserine/prothrombin (anti-PS/PT), anti-annexin V, and many others. The main target of the antibodies is the activated protein C (APC) system, the elimination of which can manifest itself as a thrombotic complication. The aim of this study was to determine the thrombogenicity of antibodies using a modified protein C-activated thrombin generation assay (TGA) on a group of 175 samples suspected of APS. TGA was measured with/without APC and the ratio of both measurements was evaluated (as for APC resistance), where a cut-off was calculated ≤4.5 (90th percentile) using 21 patients with heterozygous factor V Leiden mutation (FV Leiden heterozygous). Our study demonstrates the well-known fact that multiple positivity of different aPLs is a more severe risk for thrombosis than single positivity. Of the single antibody positivity, LA antibodies are the most serious (p value < 0.01), followed by aCL and their subgroup anti-DI (p value < 0.05). Non-criteria antibodies anti-annexin V and anti-PT/PS has a similar frequency occurrence of thrombogenicity as LA antibodies but without statistical significance or anti-β2GPI1 positivity. The modified TGA test can help us identify patients in all groups who are also at risk for recurrent thrombotic and pregnancy complications; thus, long-term prophylactic treatment is appropriate. For this reason, it is proving increasingly beneficial to include the determination antibodies in combination with modified TGA test.

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Role of antiphospholipid antibodies in the diagnosis of antiphospholipid syndrome

Cited by 25 publications

References 80 publications

Laboratory Diagnosis of Antiphospholipid Syndrome: Insights and Hindrances

Laboratory Diagnosis of Antiphospholipid Syndrome: Insights and Hindrances

Antibodies to domain I β2 -glycoprotein 1 in patients with antiphospholipid syndrome and systemic lupus erythematosus

Determination of Thrombogenicity Levels of Various Antiphospholipid Antibodies by a Modified Thrombin Generation Assay in Patients with Suspected Antiphospholipid Syndrome

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