Performance Evaluation and Clinical Associations of Immunoassays That Detect Antibodies to Negatively Charged Phospholipids Other Than Cardiolipin

Castanon, Amaris; Pierre, Grant; Harris, Edward N.; Papalardo, Elizabeth; Romay-Penabad, Zurina; Schleh, Alvaro; Jajoria, Praveen; Smikle, Monica; DeCeulaer, K; Tebo, Anne E.; Jaskowski, Troy D.; Guerra, Marta; Branch, D. Ware; Salmon, Jane E.; Petri, Michelle; González, Emilio B.

doi:10.1093/ajcp/aqy003

Cited by 9 publications

(4 citation statements)

References 29 publications

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“…Additionally, aPI IgG correlated with pre-eclampsia or premature birth, and it was also significantly correlated with stroke. Castanon et al observed a high sensitivity for aPI (41.2%-59.2%) across manifestations including thrombotic and obstetric events (18). Our previous results also demonstrated a correlation between aPI IgG and thrombosis (8).…”

Section: Discussionsupporting

confidence: 73%

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Prevalence and diagnostic value of non-criteria antiphospholipid antibodies for antiphospholipid syndrome in Chinese patients

Bai

Meng

et al. 2023

Front. Immunol.

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BackgroundThe presence of antiphospholipid antibodies (aPLs) plays a pivotal role in the pathogenesis of antiphospholipid antibody syndrome (APS). This study aimed to examine the diagnostic value of a set of non−criteria aPLs and their relevance with APS-related criteria and extra-criteria manifestations.MethodsFrom a prospectively constructed database, consecutive APS patients consisting of 114 primary APS (PAPS group), 54 with APS secondary to SLE (SAPS group), 9 seronegative APS (SNAPS), as well as 209 patients with systemic lupus erythematosus (SLE) and 88 healthy controls were included in this study. Levels of criteria aPLs, baseline information, and APS-related criteria and extra-criteria features were extracted from the database. Serum levels of non-criteria aPLs including aPC IgG/IgM, aPI IgG/IgM, aPE IgG/IgM/IgA, aPG IgG/IgM/IgA, anti-phosphatidic acid (aPA) IgG/IgM, aSM IgG/IgM, and aPS/PT IgG/IgM were analyzed with AESKULISA® ELISA Test Kits.ResultsThe addition of aPC IgG/M, aPI IgG/M, aPE IgG/M/A, aSM IgG/M, and aPA IgG/M to aCL or aβ2GPI IgG/M could significantly increase diagnostic sensitivity and accuracy. A significant difference between PAPS or SAPS and HC was presented in all non-criteria aPLs except for aSM IgM and aPG IgA. Eight out of nine SNAPS patients were positive for at least 1 aPL. Pregnancy morbidity was associated with aSM IgM (r = 0.22) and aSM IgG (r = 0.15). Pre-eclampsia or premature birth was associated with aSM IgG (r = 0.16), aPI IgG (r = 0.22), aPC IgG (r = 0.16), and aPG IgG (r = 0.18). Stroke was associated with aPI IgG (r = 0.2). The clinical association was also observed in DVT with aPS/PT IgG (r = 0.17). Valve lesion was positively associated with aSM IgM (Fisher test p = 0.039), APS nephropathy was associated with aPC IgG (OR 3.797), and livedo reticularis was associated with aPE IgM (OR 15.391).ConclusionAdditional detection of non-criteria aPLs including aPC IgG/M, aPE IgG/M/A, aPI IgG/M, aSM IgG/M, and aPA IgG/M could assist in APS diagnosis. The positivity of certain aPLs was statistically associated with both criteria and extra-criteria APS clinical manifestations.

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Section: Discussionsupporting

confidence: 73%

“…Castanon et al. observed a high sensitivity for aPI (41.2%-59.2%) across manifestations including thrombotic and obstetric events ( 18 ). Our previous results also demonstrated a correlation between aPI IgG and thrombosis ( 8 ).…”

Section: Discussionmentioning

confidence: 99%

Prevalence and diagnostic value of non-criteria antiphospholipid antibodies for antiphospholipid syndrome in Chinese patients

Bai

Meng

et al. 2023

Front. Immunol.

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“…The anti-LBPA antibodies were demonstrated in a significant number of patients with APS, however, sensitivity and specificity were lower than in aCL and anti-β2GPI [63]. Castanon et al [64] examined various aPL IgMs and IgGs in 548 serum samples using the ELISA method. Comparison of two groups of APS/healthy donors demonstrated the presence of APhL in 89.7/0%, anti-PI in 89.7/32.1%, anti-PS in 86.2/7.1%, aCL in 93.1/32.1%, and anti-β2GPI in 86.2/0%.…”

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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“…Beyond the criteria anti-phospholipid antibodies (aPL) aCL and aβ2-GPI, aPL against several other anionic phospholipids (PLs) (e.g., phosphatidic acid, phosphatidyl-serine, -glycerol, -inositol), neutral PL (e.g., phosphatidyl-choline,–ethanolamine), and PL-binding proteins (e.g., annexin V, prothrombin) have been observed in APS [4, 5]. Their pathogenic role and clinical significance is not well understood and still a matter of debate [6–8]. These non-criteria aPL are also commonly detected with ELISA-based methods [5], which are generally less well evaluated than those for the criteria aPL [7, 9].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the sensitivity and specificity of a novel line immunoassay for the detection of criteria and non-criteria antiphospholipid antibodies in comparison to established ELISAs

et al. 2019

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Background Persistent antiphospholipid antibodies (aPL) constitute the serological hallmark of the antiphospholipid syndrome (APS). Recently, various new assay technologies for the detection of aPL better suited to multiplex reaction environments than ELISAs emerged. We evaluated the diagnostic performance of such a novel line immunoassay (LIA) for the simultaneous detection of 10 different aPL. Methods Fifty-three APS patients and 34 healthy controls were investigated for criteria (antibodies against cardiolipin [aCL], β2-glycoprotein I [aβ2-GPI]) and non-criteria aPL (antibodies against phosphatidic acid [aPA], phosphatidyl-choline [aPC], -ethanolamine [aPE], -glycerol [aPG], -inositol [aPI], -serine [aPS], annexin V [aAnnV], prothrombin [aPT]) IgG and IgM by LIA. Criteria aPL were additionally determined with the established Alegria (ALE), AcuStar (ACU), UniCap (UNI), and AESKULISA (AES) systems and non-criteria aPL with the AES system. Diagnostic performance was evaluated with a gold standard for criteria aPL derived from the results of the four established assays via latent class analysis and with the clinical diagnosis as gold standard for non-criteria aPL. Results Assay performance of the LIA for criteria aPL was comparable to that of ALE, ACU, UNI, and AES. For non-criteria aPL, sensitivities of the LIA for aPA-, aPI-, aPS-IgG and aPA-IgM were significantly higher and for aPC-, aPE-, aAnnV-IgG and aPC- and aPE-IgM significantly lower than AES. Specificities did not differ significantly. Conclusions The LIA constitutes a valuable diagnostic tool for aPL profiling. It offers increased sensitivity for the detection of aPL against anionic phospholipids. In contrast, ELISAs exhibit strengths for the sensitive detection of aPL against neutral phospholipids.

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Performance Evaluation and Clinical Associations of Immunoassays That Detect Antibodies to Negatively Charged Phospholipids Other Than Cardiolipin

Abstract: Increasing titers of APhL, anti-PS, and anti-PI antibodies could indicate an increased risk of thrombotic and/or obstetric aPL-related manifestations. These assays may be promising biomarkers for particular APS manifestations.

Cited by 9 publications

References 29 publications

Prevalence and diagnostic value of non-criteria antiphospholipid antibodies for antiphospholipid syndrome in Chinese patients

Prevalence and diagnostic value of non-criteria antiphospholipid antibodies for antiphospholipid syndrome in Chinese patients

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

Evaluation of the sensitivity and specificity of a novel line immunoassay for the detection of criteria and non-criteria antiphospholipid antibodies in comparison to established ELISAs

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