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Detection of annexin A8 antibodies in serum of patients with antiphospholipid syndrome.

ABSTRACT: Introduction:Antibodies specific for annexin A8 (AnxA8) have not been investigated in patients suffering from antiphospholipid syndrome (APS) yet. The aim of this study was to compare the presence of AnxA8 antibodies in serum of APS patients with that of age-matched healthy controls and to investigate whether AnxA8 antibodies are potential biomarkers for APS. Materials and methods:We enrolled 22 APS patients and 22 healthy controls in this case-control study. We used sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblot to investigate the presence of AnxA8 antibodies, and we applied enzyme-linked immunosorbent assay to investigate the presence of cardiolipin (CL) and beta-2-glycoprotein I (ß2GPI) antibodies. Results:The serum of 9/22 APS patients showed AnxA8 IgG isotype antibody reactivity compared to serum of 2/22 healthy controls (P = 0.034). When we also included weak immunoblot signals, 12/22 APS patients exhibited AnxA8 IgG isotype antibody reactivity compared to 3/22 healthy controls (P = 0.005). We also investigated the presence of AnxA8 IgM isotype antibodies in the serum of APS patients but found no statistically significant difference between the APS patient group and healthy control group (P = 0.500). We further investigated the presence of ß2GPI and CL IgG and IgM isotype antibodies. AnxA8 IgG isotype antibodies were present in APS patients in a similar frequency as the APS "criteria" antibody against CL (P = 0.764). Conclusion:We demonstrated that AnxA8 IgG isotype antibodies are potential biomarkers for the diagnosis of APS.

SUBMITTER: Scholz P

PROVIDER: S-EPMC6214702 | biostudies-other | 2018 Oct

REPOSITORIES: biostudies-other

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Detection of annexin A8 antibodies in serum of patients with antiphospholipid syndrome.

Scholz Philipp P Auler Markus M Ruthard Johannes J Brachvogel Bent B Klatt Andreas R AR Streichert Thomas T

Biochemia medica 20181001 3

<h4>Introduction</h4>Antibodies specific for annexin A8 (AnxA8) have not been investigated in patients suffering from antiphospholipid syndrome (APS) yet. The aim of this study was to compare the presence of AnxA8 antibodies in serum of APS patients with that of age-matched healthy controls and to investigate whether AnxA8 antibodies are potential biomarkers for APS.<h4>Materials and methods</h4>We enrolled 22 APS patients and 22 healthy controls in this case-control study. We used sodium dodecy ...[more]

PMID: 30429671

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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.

Project description:APS is the association of antiphospholipid antibodies (aPL) with thromboses and/or recurrent pregnancy loss (RPL). Among patients with SLE, one-third have aPL and 10-15% have a manifestation of secondary APS. Animal studies suggested that complement activation plays an important role in the pathogenesis of thrombosis and pregnancy loss in APS. We performed a cross-sectional study on complement proteins and genes in 525 patients with aPL. Among them, 237 experienced thromboses and 293 had SLE; 111 had both SLE and thromboses, and 106 had neither SLE nor thrombosis. Complement protein levels were determined by radial immunodiffusion for C4, C3 and factor H; and by functional ELISA for mannan binding lectin (MBL). Total C4, C4A and C4B gene copy numbers (GCN) were measured by TaqMan-based realtime PCR. Two to six copies of C4 genes are frequently present in a diploid genome, and each copy may code for an acidic C4A or a basic C4B protein. We observed significantly (a) higher protein levels of total C4, C4A, C4B, C3, and anticardiolipin (ACLA) IgG, (b) increased frequencies of lupus anticoagulant and males, and (c) decreased levels of complement factor H, MBL and ACLA-IgM among patients with thrombosis than those without thrombosis (N = 288). We also observed significantly lower GCNs of total C4 and C4A among aPL-positive patients with both SLE and thrombosis than others. By contrast, aPL-positive subjects with SLE had significantly reduced protein levels of C3, total C4, C4A, C4B and ACLA-IgG, and higher frequency of females than those without SLE. Patients with thrombosis but without SLE (N = 126), and patients with SLE but without thrombosis (N = 182) had the greatest differences in mean protein levels of C3 (p = 2.6 × 10-6), C4 (p = 2.2 × 10-9) and ACLA-IgG (p = 1.2 × 10-5). RPL occurred in 23.7% of female patients and thrombotic SLE patients had the highest frequency of RPL (41.0%; p = 3.8 × 10-10). Compared with non-RPL females, RPL had significantly higher frequency of thrombosis and elevated C4 protein levels. Female patients with homozygous C4A deficiency all experienced RPL (p = 0.0001) but the opposite was true for patients with homozygous C4B deficiency (p = 0.017). These results provide new insights and biomarkers for diagnosis and management of APS and SLE.

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Detection of annexin A8 antibodies in serum of patients with antiphospholipid syndrome.

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Detection of annexin A8 antibodies in serum of patients with antiphospholipid syndrome.

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