Confirmation of antiphospholipid antibody positivity: a year's results in a cohort of 113 patients

Objective: To evaluate the confirmation rate of antiphospholipid antibodies (aPL), to analyze their behaviour at confirmation time, and to study the clinical value of their confirmation. Methods: Blood samples from 380 subjects, enrolled in this study from June 1, 2007 to May 31, 2008, were tested for anti-cardiolipin (aCL) and anti-beta2glycoprotein (aβ2GPI) antibodies using an ELISA method and for Lupus anticoagulant (LA) using a series of clotting tests. The samples of the 113 subjects resulting positive at the first testing time were assayed again to confirm antiphospholipid positivity. Results: aPL positivity was confirmed in 67 out of the 113 subjects (59.3%). Medium-high antibody levels of all, except IgM aCL, aPL/ELISA had a significantly higher confirmation rate with respect to that in subjects with low levels. The confirmation rate in the category I antibody patients (multiple positivity) was higher than that in the category II antibody subjects (single positivity). LA positivity was confirmed only when it was associated to other aPL. The cut-off of 40 GPL produced a confirmation rate equal to that resulting from a 99th percentile cut-off. Confirmation of aPL positivity made it possible for us to confirm the diagnosis of antiphospholipid syndrome (APS) in 8 out of the 113 subjects originally resulting positive (7,1%). APS clinical features were vascular thrombosis in 4 of these and pregnancy morbidity in the other 4. Conclusions: Our data emphasize aPL positivity confirmation selectivity, and medium-high antibody levels and category I antibodies (multiple positivity) had the best confirmation rates

Global wood anatomical perspective on the onset of the Late Antique Little Ice Age (LALIA) in the mid-6th century CE

Linked to major volcanic eruptions around 536 and 540 CE, the onset of the Late Antique Little Ice Age has been described as the coldest period of the past two millennia. The exact timing and spatial extent of this exceptional cold phase are, however, still under debate because of the limited resolution and geographical distribution of the available proxy archives. Here, we use 106 wood anatomical thin sections from 23 forest sites and 20 tree species in both hemispheres to search for cell-level fingerprints of ephemeral summer cooling between 530 and 550 CE. After cross-dating and double-staining, we identified 89 Blue Rings (lack of cell wall lignification), nine Frost Rings (cell deformation and collapse), and 93 Light Rings (reduced cell wall thickening) in the Northern Hemisphere. Our network reveals evidence for the strongest temperature depression between mid-July and early-August 536 CE across North America and Eurasia, whereas more localised cold spells occurred in the summers of 532, 540–43, and 548 CE. The lack of anatomical signatures in the austral trees suggests limited incursion of stratospheric volcanic aerosol into the Southern Hemisphere extra-tropics, that any forcing was mitigated by atmosphere-ocean dynamical responses and/or concentrated outside the growing season, or a combination of factors. Our findings demonstrate the advantage of wood anatomical investigations over traditional dendrochronological measurements, provide a benchmark for Earth system models, support cross-disciplinary studies into the entanglements of climate and history, and question the relevance of global climate averages. © 2022 Science China PressFritz & Elisabeth Schweingruber FoundationNational Science Foundation, NSF, (1203749, 1902625, 2002454, 2112314, 2124885, RSF 18-14-00072P, RSF 21-14-00330)Engineering Research Centers, ERCEuropean Research Council, ERC, (AdG 882727, CZ.02.1.01/0.0/0.0/16_019/0000797)Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, SNF, (CRSII5 183571)Fondo Nacional de Desarrollo Científico y Tecnológico, FONDECYT, (1201411, 1221307)Vetenskapsrådet, VR, (2018-01272)Universität BielefeldRussian Science Foundation, RSF, (RSF 21-17-00006)Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias, FONDAP, (15110009, BASAL FB210018)Neurosciences Foundation, NSFAgencia Nacional de Investigación y Desarrollo, ANIDFunding text 1: Ulf Büntgen and Jan Esper received funding from the ERC Advanced Project MONOSTAR (AdG 882727). Ulf Büntgen, Jan Esper, and Mirek Trnka received funding from SustES: adaptation strategies for sustainable ecosystem services and food security under adverse environmental conditions (CZ.02.1.01/0.0/0.0/16_019/0000797). Ulf Büntgen, Jan Esper, and Clive Oppenheimer discussed many aspects of this study at the Center for Interdisciplinary Research (ZiF) at the University of Bielefeld, Germany. Alan Crivellaro received funding from the Fritz & Elisabeth Schweingruber Foundation. Duncan A. Christie and Carlos Le Quesne received funding from the ANID (FONDECYT 1201411, 1221307, FONDAP 15110009, BASAL FB210018). Olga V. Churakova (Sidorova) received funding from the Russian Science Foundation grant (RSF 21-17-00006). Rosanne D'Arrigo received funding from NSF Arctic Social Science 2112314 and NSF Arctic Natural Science 2124885, as well as the NSF P2C2 (Paleo Perspectives on Climatic Change) program (various grants). Rashit M. Hantemirov received funding from the Russian Science Foundation grant (RSF 21-14-00330). Alexander V. Kirdyanov received funding from the Russian Science Foundation grant (RSF 18-14-00072P). Fredrik C. Ljungqvist was supported by the Swedish Research Council (2018-01272). Patrick Fonti and Markus Stoffel received funding from the Swiss National Science Foundation through the SNSF Sinergia CALDERA project (CRSII5 183571). Matthew Salzer and Malcolm K. Hughes received funding from the National Science Foundation's P2C2 Program (1902625 and 1203749) and from the Malcolm H. Wiener Foundation. Greg Wiles was funded through NSF P2C2 Program (2002454). Ulf Büntgen designed the study and wrote the first draft of this manuscript with input from Jan Esper, Paul J. Krusic, and Clive Oppenheimer. Samples were processed and analysed by Alma Piermattei and Alan Crivellaro. All authors provided data and/or contributed to discussion and improving the article.Funding text 2: Ulf Büntgen and Jan Esper received funding from the ERC Advanced Project MONOSTAR (AdG 882727). Ulf Büntgen, Jan Esper, and Mirek Trnka received funding from SustES : adaptation strategies for sustainable ecosystem services and food security under adverse environmental conditions (CZ.02.1.01/0.0/0.0/16_019/0000797). Ulf Büntgen, Jan Esper, and Clive Oppenheimer discussed many aspects of this study at the Center for Interdisciplinary Research (ZiF) at the University of Bielefeld, Germany. Alan Crivellaro received funding from the Fritz & Elisabeth Schweingruber Foundation . Duncan A. Christie and Carlos Le Quesne received funding from the ANID ( FONDECYT 1201411 , 1221307, FONDAP 15110009 , BASAL FB210018). Olga V. Churakova (Sidorova) received funding from the Russian Science Foundation grant ( RSF 21-17-00006 ). Rosanne D’Arrigo received funding from NSF Arctic Social Science 2112314 and NSF Arctic Natural Science 2124885 , as well as the NSF P2C2 (Paleo Perspectives on Climatic Change) program (various grants). Rashit M. Hantemirov received funding from the Russian Science Foundation grant (RSF 21-14-00330). Alexander V. Kirdyanov received funding from the Russian Science Foundation grant (RSF 18-14-00072P). Fredrik C. Ljungqvist was supported by the Swedish Research Council (2018-01272). Patrick Fonti and Markus Stoffel received funding from the Swiss National Science Foundation through the SNSF Sinergia CALDERA project (CRSII5 183571). Matthew Salzer and Malcolm K. Hughes received funding from the National Science Foundation’s P2C2 Program (1902625 and 1203749) and from the Malcolm H. Wiener Foundation . Greg Wiles was funded through NSF P2C2 Program (2002454)

Clinical value of antibodies to lysobisphosphatidic acid in patients with primary antiphospholipid sindrome

To assess the clinical value of anti-lysobisphosphatidic acid (anti-LBPA) antibodies in patients with primary antiphospholipid syndrome (APS), the sera of 140 primary APS patients were tested and compared with those of 70 control subjects affected with rheumatic systemic diseases (n. 24) or autoimmune thyroiditis (n. 46). Anti-LBPA anticardiolipin (aCL) and anti-β2 Glycoprotein I (anti-β2GPI) antibodies were determined using a “home made” ELISA method. Lupus anticoagulant (LA) was assessed using a series of clotting tests in accordance with the literature. IgG anti-LBPA was significantly prevalent in primary APS (p=0.000) with a sensitivity of 58.6% and a specificity of 92.9%. IgM anti-LBPA showed a significant frequency in primary APS (p=0.000) with a sensitivity of 28.6% and a specificity of 97.1%. Anti-LBPA’s sensitivity and specificity for APS were lower or equal to those of aCL and anti-β2GPI. The prevalence of anti-LBPA in the different clinical and laboratory subsets of APS was lower than those of aCL and anti- β2GPI. It is interesting to observe that both IgG and IgM anti-LBPA were never found alone. The comparison between anti-LBPA and LA showed that the former had a higher sensitivity but a lower specificity. In conclusion, in view of our results anti-LBPA cannot at present be considered a further tool to be utilized to diagnose APS and to differentiate the different clinical and laboratory subsets of this disease

Clinical value of antibodies to lysobisphosphatidic acid in patients with primary antiphospholipid syndrome.

To assess the clinical value of anti-lysobisphosphatidic acid (anti-LBPA) antibodies in patients with primary antiphospholipid syndrome (APS), the sera of 140 primary APS patients were tested and compared with those of 70 control subjects affected with rheumatic systemic diseases (n. 24) or autoimmune thyroiditis (n. 46). Anti-LBPA anticardiolipin (aCL) and anti-β2 Glycoprotein I (anti-β2GPI) antibodies were determined using a "home made" ELISA method. Lupus anticoagulant (LA) was assessed using a series of clotting tests in accordance with the literature. IgG anti-LBPA was significantly prevalent in primary APS (p=0.000) with a sensitivity of 58.6% and a specificity of 92.9%. IgM anti-LBPA showed a significant frequency in primary APS (p=0.000) with a sensitivity of 28.6% and a specificity of 97.1%. Anti-LBPA's sensitivity and specificity for APS were lower or equal to those of aCL and anti-β2GPI. The prevalence of anti-LBPA in the different clinical and laboratory subsets of APS was lower than those of aCL and anti- β2GPI. It is interesting to observe that both IgG and IgM anti-LBPA were never found alone. The comparison between anti-LBPA and LA showed that the former had a higher sensitivity but a lower specificity. In conclusion, in view of our results anti-LBPA cannot at present be considered a further tool to be utilized to diagnose APS and to differentiate the different clinical and laboratory subsets of this disease

Clinical value of antibodies to lysobisphosphatidic acid in patients with primary antiphospholipid syndrome.

To assess the clinical value of anti-lysobisphosphatidic acid (anti-LBPA) antibodies in patients with primary antiphospholipid syndrome (APS), the sera of 140 primary APS patients were tested and compared with those of 70 control subjects affected with rheumatic systemic diseases (n. 24) or autoimmune thyroiditis (n. 46). Anti-LBPA anticardiolipin (aCL) and anti-beta2 Glycoprotein I (anti-beta2GPI) antibodies were determined using a "home made" ELISA method. Lupus anticoagulant (LA) was assessed using a series of clotting tests in accordance with the literature. IgG anti-LBPA was significantly prevalent in primary APS (p=0.000) with a sensitivity of 58.6% and a specificity of 92.9%. IgM anti-LBPA showed a significant frequency in primary APS (p=0.000) with a sensitivity of 28.6% and a specificity of 97.1%. Anti-LBPA's sensitivity and specificity for APS were lower or equal to those of aCL and anti-beta2GPI. The prevalence of anti-LBPA in the different clinical and laboratory subsets of APS was lower than those of aCL and anti-beta2GPI. It is interesting to observe that both IgG and IgM anti-LBPA were never found alone. The comparison between anti-LBPA and LA showed that the former had a higher sensitivity but a lower specificity. In conclusion, in view of our results anti-LBPA cannot at present be considered a further tool to be utilized to diagnose APS and to differentiate the different clinical and laboratory subsets of this diseas

The clinical significance of autoantibodies directed against prothrombin in primary antiphospholipid syndrome.

Abstract BACKGROUND:To evaluate the clinical significance of IgG/IgM antibodies directed against prothrombin (PT) in a homogeneous cohort of patients with primary APS (PAPS). METHODS:IgG/IgM anti-prothrombin (aPT) antibodies were measured using a commercial ELISA kit in 158 PAPS patients and in 214 control subjects (100 healthy blood donors and 114 patients with autoimmune diseases). RESULTS:IgG/IgM aPT antibodies were significantly associated with PAPS (OR, 95% CI: 52.0, 7.0-385.5; 9.8, 1.2-80.8, respectively). They were found to have a high specificity (IgG 99.50%, IgM 99.54%) but a low sensitivity (IgG 19.60%, IgM 3.80%) for PAPS. IgG aPT antibodies were significantly higher in the PAPS patients with thrombosis (OR, 95% CI: 69.2, 9.2-519.1) as well as in those with pregnancy morbidity alone (OR, 95% CI: 20.5, 2.4-174.5). The prevalence of IgG aPT was not significantly different in the thrombotic and obstetric patients, and the presence of IgM aPT antibodies was significant only in patients with thrombosis (OR, 95% CI: 2.6, 1.6-110.8). CONCLUSIONS:The study's findings confirm that IgG/IgM aPT antibodies are significantly associated with PAPS and indicate that IgG aPT antibodies are associated with clinical subsets of the disease. For the time being, however, the lower sensitivity of IgG/IgM antibodies with respect to conventional aPL antibodies precludes their inclusion in the recommendations for the diagnosis of PAP

Antiphosphatidylserine/prothrombin antibodies in primary antiphospholipid syndrome.

Antiprothrombin (aPT) antibodies may be detected by an enzyme-linked immunosorbent assay (ELISA) using a purified antigen or a phosphatidylserine/prothrombin complex (aPS/PT). IgG/IgM antibodies directed against aPS/PT were assessed in 158 patients with primary antiphospholipid syndrome (PAPS). They were detected in 80/158 (50.6%) PAPS patients; IgG alone was positive in 12 (7.6%), IgM alone in 36 (22.8%), and both IgG and IgM isotypes in 32 (20.2%) PAPS patients. IgG and IgM aPS/PT were significantly associated with both vascular thrombosis and pregnancy morbidity. IgG aPS/PT was significantly associated with venous thrombosis ( p = 0.023), whilst IgG and IgM aPS/PT were associated with arterial thrombosis ( p &lt; 0.001 and p &lt; 0.001, respectively). Logistic regression analysis showed that IgM and IgG aPS/PT were independent risk factors for thrombosis (odds ratio (OR) 3.5 [95% confidence interval (CI) 1.6–7.9] and OR 4.1 [95% CI 1.4–11.7], respectively) and IgM aPS/PT was an independent risk factor for arterial thrombosis (OR 2.7 [95% CI 1.1–6.7]). In conclusion, these findings indicate that aPS/PT are clinically relevant in PAPS. </jats:p