Factor XI in Carriers of Antiphospholipid Antibodies: Elevated Levels Associated with Symptomatic Thrombotic Cases, While Low Levels Linked to Asymptomatic Cases
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SUBMITTER: Pagan-Escribano J
PROVIDER: S-EPMC10670960 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
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Project description:Antiphospholipid antibodies (aPL) can be detected in asymptomatic carriers and infectious patients. The aim was to investigate whether a novel line immunoassay (LIA) differentiates between antiphospholipid syndrome (APS) and asymptomatic aPL+ carriers or patients with infectious diseases (infectious diseases controls (IDC)).Sixty-one patients with APS (56 primary, 22/56 with obstetric events only, and 5 secondary), 146 controls including 24 aPL+ asymptomatic carriers and 73 IDC were tested on a novel hydrophobic solid phase coated with cardiolipin (CL), phosphatic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, beta2-glycoprotein I (?2GPI), prothrombin, and annexin V. Samples were also tested by anti-CL and anti-?2GPI ELISAs and for lupus anticoagulant activity. Human monoclonal antibodies (humoAbs) against human ?2GPI or PL alone were tested on the same LIA substrates in the absence or presence of human serum, purified human ?2GPI or after CL-micelle absorption.Comparison of LIA with the aPL-classification assays revealed good agreement for IgG/IgM aß2GPI and aCL. Anti-CL and anti-ß2GPI IgG/IgM reactivity assessed by LIA was significantly higher in patients with APS versus healthy controls and IDCs, as detected by ELISA. IgG binding to CL and ß2GPI in the LIA was significantly lower in aPL+ carriers and Venereal Disease Research Laboratory test (VDRL)?+?samples than in patients with APS. HumoAb against domain 1 recognized ?2GPI bound to the LIA-matrix and in anionic phospholipid (PL) complexes. Absorption with CL micelles abolished the reactivity of a PL-specific humoAb but did not affect the binding of anti-?2GPI humoAbs.The LIA and ELISA have good agreement in detecting aPL in APS, but the LIA differentiates patients with APS from infectious patients and asymptomatic carriers, likely through the exposure of domain 1.
| S-EPMC4875598 | biostudies-literature
Project description:Our aim was to investigate the patterns and trajectories of white matter (WM) diffusion abnormalities in microtubule-associated protein tau (MAPT) mutations carriers. We studied 22 MAPT mutation carriers (12 asymptomatic, 10 symptomatic) and 20 noncarriers from 8 families, who underwent diffusion tensor imaging (DTI) and a subset (10 asymptomatic, 6 symptomatic MAPT mutation carriers, and 10 noncarriers) were followed annually (median = 4 years). Cross-sectional and longitudinal changes in mean diffusivity (MD) and fractional anisotropy were analyzed. Asymptomatic MAPT mutation carriers had higher MD in entorhinal WM, which propagated to the limbic tracts and frontotemporal projections in the symptomatic stage compared with noncarriers. Reduced fractional anisotropy and increased MD in the entorhinal WM were associated with the proximity to estimated and actual age of symptom onset. The annualized change of entorhinal MD on serial DTI was accelerated in MAPT mutation carriers compared with noncarriers. Entorhinal WM diffusion abnormalities precede the symptom onset and track with disease progression in MAPT mutation carriers. Our cross-sectional and longitudinal data showed a potential clinical utility for DTI to track neurodegenerative disease progression for MAPT mutation carriers in clinical trials.
| S-EPMC6858933 | biostudies-literature
Project description:BackgroundAntiphospholipid syndrome (APS) is associated with a high incidence of thrombotic events, either arterial thrombosis or venous thrombosis. However, APS-related non-thrombotic venous stenosis is rarely reported.Case presentationThis study described two cases of young women with APS-related internal jugular vein stenosis (IJVS) and reviewed current literature on this issue, including clinical features, diagnosis, and treatment.ConclusionsIJVS is a rather rare complication of APS. Two cases were reported for the first time that high titer of antiphospholipid antibodies (aPL) might mediate direct vessel wall damage and further induce venous stenosis despite long-term standardized anticoagulation to prevent thrombus formation. Therefore, dynamic monitoring of autoantibodies and concomitant use of anticoagulants and corticosteroids may be necessary to the management of APS and its complications.
| S-EPMC7789703 | biostudies-literature
Project description:IntroductionCitrullinemia Type 1 (CTLN1) is an autosomal recessive disorder caused by variants in the ASS1 gene. This study intends to clarify the etiology of false positives in newborn screening for citrullinemia.MethodNewborns who had elevated dried-blood spot citrulline levels were enrolled, and medical records were reviewed retrospectively. Common ASS1 variants were screened using high-resolution melting analysis.ResultBetween 2011 and 2021, 130 newborns received confirmatory testing for citrullinemia, 4 were found to be patients for CTLN1; 11 were patients with citrin deficiency; and 49 newborns were confirmed to be carrying one pathogenic ASS1 variant. The incidence of CTLN1 was 1 in 188,380 (95% confidence interval: 1 in 73,258 to 1 in 484,416). All ASS1 variants studied in this cohort were located in exons 11 to 15, which encode the tetrameric interface regions of the ASS1 protein. Among 10 ASS1 carriers with elevated citrulline levels and complete sequence data, four (40%) revealed additional non-benign ASS1 variants; in contrast, only 2 of the 26 controls (7.7%), with normal citrulline levels, had additional ASS1 variants.ConclusionHeterozygote ASS1 variants may lead to a mild elevation of blood citrulline levels: about 2-6 times the population mean. Molecular testing and family studies remain critical for precise diagnosis, genetic counseling, and management.
| S-EPMC9482393 | biostudies-literature
Project description:Antiphospholipid syndrome (APS) is a multisystem disorder characterized by thrombosis and/or recurrent fetal loss. This clinical phenotype heterogeneity may result in differences in response to treatment and prognosis. In this study, we aimed to identify primary thrombotic APS (TAPS) from primary obstetric APS (OAPS) using urine proteomics as a non-invasive method. Only patients with primary APS were enrolled in this study from 2016 to 2018 at a single clinical center in Shanghai. Urine samples from 15 patients with TAPS, 9 patients with OAPS, and 15 healthy controls (HCs) were collected and analyzed using isobaric tags for relative and absolute quantification (iTRAQ) labeling combined with liquid chromatography-tandem mass spectrometry analysis to identify differentially expressed proteins. Cluster analysis of urine proteomics identified differentiated proteins among the TAPS, OAPS, and HC groups. Urinary proteins were enriched in cytokine and cytokine receptor pathways. Representative secreted cytokines screened out (fold change >1.20, or <0.83, p<0.05) in these differentiated proteins were measured by enzyme-linked immunosorbent assay in a validation cohort. The results showed that the levels of C-X-C motif chemokine ligand 12 (CXCL12) were higher in the urine of patients with TAPS than in those with OAPS (p=0.035), while the levels of platelet-derived growth factor subunit B (PDGFB) were lower in patients with TAPS than in those with OAPS (p=0.041). In addition, correlation analysis showed that CXCL12 levels were positively correlated with immunoglobulin G anti-β2-glycoprotein I antibody (r=0.617, p=0.016). Our results demonstrated that urinary CXCL12 and PDGFB might serve as potential non-invasive markers to differentiate primary TAPS from primary OAPS.
| S-EPMC8416615 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19) asymptomatic cases are hard to identify, impeding transmissibility estimation. The value of COVID-19 transmissibility is worth further elucidation for key assumptions in further modelling studies. Through a population-based surveillance network, we collected data on 1342 confirmed cases with a 90-days follow-up for all asymptomatic cases. An age-stratified compartmental model containing contact information was built to estimate the transmissibility of symptomatic and asymptomatic COVID-19 cases. The difference in transmissibility of a symptomatic and asymptomatic case depended on age and was most distinct for the middle-age groups. The asymptomatic cases had a 66.7% lower transmissibility rate than symptomatic cases, and 74.1% (95% CI 65.9-80.7) of all asymptomatic cases were missed in detection. The average proportion of asymptomatic cases was 28.2% (95% CI 23.0-34.6). Simulation demonstrated that the burden of asymptomatic transmission increased as the epidemic continued and could potentially dominate total transmission. The transmissibility of asymptomatic COVID-19 cases is high and asymptomatic COVID-19 cases play a significant role in outbreaks.
| S-EPMC9588416 | biostudies-literature
Project description:The pandemic of coronavirus disease 2019 (COVID-19) has emerged as a major public health challenge worldwide. A comprehensive understanding of clinical characteristics and immune responses in asymptomatic carriers and symptomatic patients with COVID-19 is of great significance to the countermeasures of patients with COVID-19. Herein, we described the clinical information and laboratory findings of 43 individuals from Hunan Province, China, including 13 asymptomatic carriers and 10 symptomatic patients with COVID-19, as well as 20 healthy controls in the period from 25 January to 18 May 2020. The serum samples of these individuals were analyzed to measure the cytokine responses, receptor-binding domain (RBD), and nucleocapsid (N) protein-specific antibody titers, as well as SARS-CoV-2 neutralizing antibodies (nAbs). For cytokines, significantly higher Th1 cytokines including IL-2, IL-8, IL-12p70, IFN-γ, and TNF-α, as well as Th2 cytokines including IL-10 and IL-13 were observed in symptomatic patients compared with asymptomatic carriers. Compared with symptomatic patients, higher N-specific IgG4/IgG1 ratio and RBD-specific/N-specific IgG1 ratio were observed in asymptomatic carriers. Comparable nAbs were detected in both asymptomatic carriers and symptomatic patients with COVID-19. In the symptomatic group, nAbs in patients with underlying diseases were weaker than those of patients without underlying diseases. Our retrospective study will enrich and verify the clinical characteristics and serology diversities in asymptomatic carriers and symptomatic patients with COVID-19.
| S-EPMC9171238 | biostudies-literature
Project description:BackgroundHepatitis B virus (HBV) is a small DNA-containing virus with 4 genes, C, S, X and P. The S gene codes for the surface antigen (HBsAg), which contains the "a" determinant, the main region for induction of a protective humoral immune response. To compare the genotype and sequence of the "a" determinant between strains isolated from asymptomatic and symptomatic Mexican HBV carriers.Results21 asymptomatic (blood donors) and 12 symptomatic (with clinical signs and with >1 year lamivudine treatment) HBV carriers were studied; all patients were positive for the HBsAg in serum. Viral load, genotypes, and subtypes were determined in plasma. A fragment of the S gene including the "a" determinant was PCR amplified and sequenced to determine genotype, subtype and to identify mutations. Mean viral load was 0.7965 x 104 copies/ml in asymptomatic carriers and 2.73 x 106 copies/ml in symptomatic patients. Genotypes H, C, and F were identified in asymptomatic individuals; whereas H was dominant in symptomatic patients. A fragment of 279 bp containing the "a" determinant was amplified from all 33 carriers and sequences aligned with S gene sequences in the GenBank. Mutations identified were Y100N, T126I, Q129H and N146K in the asymptomatic group, and F93I and A128V in the symptomatic group.ConclusionDifferences in genotype and in mutations in the "a" determinant were found between strains from asymptomatic and symptomatic HBV Mexican carriers.
| S-EPMC1781063 | biostudies-literature
Project description:ObjectiveTo analyse the clinical and laboratory features of patients with thrombotic microangiopathic haemolytic anaemia (TMHA) associated with antiphospholipid antibodies (aPL).MethodsA computer assisted (PubMed) search of the literature was performed to identify all cases of TMHA associated with aPL from 1983 to December 2002.Results46 patients (36 female) with a mean (SD) age at presentation of TMHA of 34 (15) years were reviewed. Twenty eight (61%) patients had primary antiphospholipid syndrome (APS). TMHA was the first clinical manifestation of APS in 26 (57%) patients. The clinical presentations were haemolytic-uraemic syndrome (26%), catastrophic APS (23%), acute renal failure (15%), malignant hypertension (13%), thrombotic thrombocytopenic purpura (13%), and HELLP (haemolysis, elevated liver enzymes, and low platelet count in association with eclampsia) syndrome (4%). Lupus anticoagulant was detected in 86% of the episodes of TMHA, and positive anticardiolipin antibodies titres in 89%. Steroids were the most common treatment (69% of episodes), followed by plasma exchange (PE) (62%), anticoagulant or antithrombotic agents (48%), immunosuppressive agents (29%), and immunoglobulins (12%). Recovery occurred in only 10/29 (34%) episodes treated with steroids, and in 19/27 (70%) episodes treated with PE. Death occurred in 10/46 (22%) patients.ConclusionsThe results emphasise the need for systematic screening for aPL in all patients with clinical and laboratory features of TMHA. The existence of TMHA in association with an APS forces one to rule out the presence of the catastrophic variant of this syndrome. PE is indicated as a first line of treatment for all patients with TMHA associated with aPL.
| S-EPMC1755024 | biostudies-literature
Project description:Loss-of-function mutations in the progranulin gene (GRN) are one of the major causes of familial frontotemporal lobar degeneration. Our objective was to determine the rates and trajectories of lobar cortical atrophy from longitudinal structural magnetic resonance imaging in both asymptomatic and symptomatic GRN mutation carriers. Individuals in this study were from the ADRC and LEFFTDS studies at the Mayo Clinic. We identified 13 GRN mutation carriers (8 asymptomatic, 5 symptomatic) and noncarriers (n = 10) who had at least 2 serial T1-weighted structural magnetic resonance images and were followed annually with a median of 3 years (range 1.0-9.8 years). Longitudinal changes in lobar cortical volume were analyzed using the tensor-based morphometry with symmetric normalization (TBM-SyN) algorithm. Linear mixed-effect models were used to model cortical volume change over time among 3 groups. The annual rates of frontal (p < 0.05) and parietal (p < 0.01) lobe cortical atrophy were higher in asymptomatic GRN mutation carriers than noncarriers. The symptomatic GRN mutation carriers also had increased rates of atrophy in the frontal (p < 0.01) and parietal lobe (p < 0.01) cortices than noncarriers. In addition, greater rates of cortical atrophy were observed in the temporal lobe cortices of symptomatic GRN mutation carriers than noncarriers (p < 0.001). We found that a decline in frontal and parietal lobar cortical volume occurs in asymptomatic GRN mutation carriers and continues in the symptomatic GRN mutation carriers, whereas an increased rate of temporal lobe cortical atrophy is observed only in symptomatic GRN mutation carriers. This sequential pattern of cortical involvement in GRN mutation carriers has important implications for using imaging biomarkers of neurodegeneration as an outcome measure in potential treatment trials involving GRN mutation carriers.
| S-EPMC7767622 | biostudies-literature