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Value of isolated IgA anti-?2 -glycoprotein I positivity in the diagnosis of the antiphospholipid syndrome.

ABSTRACT: To examine the prevalence of isolated IgA anti-?2 -glycoprotein I (anti-?2 GPI) positivity and the association of these antibodies, and a subgroup that bind specifically to domain IV/V of ?2 GPI, with clinical manifestations of the antiphospholipid syndrome (APS) in 3 patient groups and to evaluate the pathogenicity of IgA anti-?2 GPI in a mouse model of thrombosis.Patients with systemic lupus erythematosus (SLE) from a multiethnic, multicenter cohort (LUpus in MInorities, NAture versus nurture [LUMINA]) (n = 558), patients with SLE from the Hopkins Lupus Cohort (n = 215), and serum samples referred to the Antiphospholipid Standardization Laboratory (APLS) (n = 5,098) were evaluated. IgA anti-?2 GPI titers and binding to domain IV/V of ?2 GPI were examined by enzyme-linked immunosorbent assay (ELISA). CD1 mice were inoculated with purified IgA anti-?2 GPI antibodies, and surgical procedures and ELISAs were performed to evaluate thrombus development and tissue factor (TF) activity.A total of 198 patients were found to be positive for IgA anti-?2 GPI isotype, and 57 patients were positive exclusively for IgA anti-?2 GPI antibodies. Of these, 13 of 23 patients (56.5%) in the LUMINA cohort, 17 of 17 patients (100%) in the Hopkins cohort, and 10 of 17 patients (58.9%) referred to APLS had at least one APS-related clinical manifestation. Fifty-four percent of all the IgA anti-?2 GPI-positive serum samples reacted with domain IV/V of anti-?2 GPI, and 77% of those had clinical features of APS. Isolated IgA anti-?2 GPI positivity was associated with an increased risk of arterial thrombosis (P < 0.001), venous thrombosis (P = 0.015), and all thrombosis (P < 0.001). The association between isolated IgA anti-?2 GPI and arterial thrombosis (P = 0.0003) and all thrombosis (P = 0.0003) remained significant after adjusting for other risk factors for thrombosis. In vivo mouse studies demonstrated that IgA anti-?2 GPI antibodies induced significantly larger thrombi and higher TF levels compared to controls.Isolated IgA anti-?2 GPI-positive titers may identify additional patients with clinical features of APS. Testing for these antibodies when other antiphospholipid tests are negative and APS is suspected is recommended. IgA anti-?2 GPI antibodies directed to domain IV/V of ?2 GPI represent an important subgroup of clinically relevant antiphospholipids.

SUBMITTER: Murthy V

PROVIDER: S-EPMC4048705 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Value of isolated IgA anti-β2 -glycoprotein I positivity in the diagnosis of the antiphospholipid syndrome.

Murthy Vijaya V Willis Rohan R Romay-Penabad Zurina Z Ruiz-Limón Patricia P Martínez-Martínez Laura A LA Jatwani Shraddha S Jajoria Praveen P Seif Alan A Alarcón Graciela S GS Papalardo Elizabeth E Liu Jigna J Vilá Luis M LM McGwin Gerald G McNearney Terry A TA Maganti Rashmi R Sunkureddi Prashanth P Parekh Trisha T Tarantino Michael M Akhter Ehtisham E Fang Hong H Gonzalez Emilio B EB Binder Walter R WR Norman Gary L GL Shums Zakera Z Teodorescu Marius M Reveille John D JD Petri Michelle M Pierangeli Silvia S SS

Arthritis and rheumatism 20131201 12

<h4>Objective</h4>To examine the prevalence of isolated IgA anti-β2 -glycoprotein I (anti-β2 GPI) positivity and the association of these antibodies, and a subgroup that bind specifically to domain IV/V of β2 GPI, with clinical manifestations of the antiphospholipid syndrome (APS) in 3 patient groups and to evaluate the pathogenicity of IgA anti-β2 GPI in a mouse model of thrombosis.<h4>Methods</h4>Patients with systemic lupus erythematosus (SLE) from a multiethnic, multicenter cohort (LUpus in ...[more]

PMID: 23983008

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Project description: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.

Dataset Information

Value of isolated IgA anti-?2 -glycoprotein I positivity in the diagnosis of the antiphospholipid syndrome.

Publications

Value of isolated IgA anti-β2 -glycoprotein I positivity in the diagnosis of the antiphospholipid syndrome.

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