RESUMEN
Patients with COVID-19 may develop a hypercoagulable state due to tissue and endothelial injury, produced by an unbalanced immune response. Therefore, an increased number of thromboembolic events has been reported in these patients. The aim of this study is to investigate the presence of antiphospholipid antibodies (aPL) in COVID-19 patients, their role in the development of thrombosis and their relationship with the severity of the disease. In this retrospective study, serum samples from 159 COVID-19 patients and 80 healthy donors were analysed for the presence of aPL. A total of 29 patients (18.2%) and 14 healthy donors (17.5%) were positive for aPL. Nineteen COVID-19 patients (12%) but no healthy donor presented a positive percentage of the IgA isotype aPL. IgA anti-ß2-glycoprotein I antibodies (anti-ß2GPI) were the most frequent type (6.3%) in patients but was not detected in any healthy donor. The positivity of this antibody was found to be significantly elevated in patients with thromboembolic events (25% vs. 5%, p = 0.029); in fact, patients with positive IgA anti-ß2GPI had an incidence of thrombosis over six times higher than those who had normal antibody concentrations [OR (CI 95%) of 6.67 (1.5-30.2), p = 0.014]. Additionally, patients with moderate-severe disease presented a higher aPL positivity than patients with mild disease according to the Brescia (p = 0.029) and CURB-65 (p = 0.011) severity scales. A multivariate analysis showed that positivity for IgA anti-ß2GPI is significantly associated with disease severity measured by CURB-65 [OR (CI 95%) 17.8 (1.7-187), p = 0.0016]. In conclusion, COVID-19 patients have a significantly higher positive percentage of the IgA isotype aPL than healthy donors. IgA anti-ß2GPI antibodies were the most frequently detected aPL in COVID-19 patients and were associated with thrombosis and severe COVID-19 and are thus proposed as a possible marker to identify high-risk patients.
Asunto(s)
Anticuerpos Antifosfolípidos , Biomarcadores , COVID-19 , Inmunoglobulina A , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Trombosis , beta 2 Glicoproteína I , Humanos , COVID-19/inmunología , COVID-19/complicaciones , COVID-19/sangre , Masculino , beta 2 Glicoproteína I/inmunología , Femenino , Inmunoglobulina A/sangre , Persona de Mediana Edad , Trombosis/inmunología , Estudios Retrospectivos , Anticuerpos Antifosfolípidos/sangre , Adulto , Anciano , Biomarcadores/sangre , SARS-CoV-2/inmunología , Anciano de 80 o más AñosRESUMEN
Antiphospholipid syndrome (APS) is a systemic autoimmune syndrome characterized by arterial or venous thrombosis, pregnancy complications and thrombocytopenia. The aim of this study is to investigate the association between APS and atrial fibrillation (AF) among patients in Peking University People's Hospital. A single center retrospective study was conducted. Cases were hospitalized patients diagnosed with AF by a cardiologist while the control group patients did not exhibit cardiac diseases. The results of the study revealed that in multivariable logistic regression, APS, anticardiolipin antibody (aCL) positivity and anti-beta-2-glycoprotein antibody (anti-ß2GPI) positivity are independent risk factors of AF. APS, aCL positivity and anti-ß 2GPI positivity are statistically different between AF patients and non-AF patients. Forthcoming studies are needed to clarify the potential link between APS and AF.
Asunto(s)
Síndrome Antifosfolípido , Fibrilación Atrial , Humanos , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/inmunología , Estudios Retrospectivos , Femenino , Fibrilación Atrial/epidemiología , Fibrilación Atrial/etiología , Masculino , Persona de Mediana Edad , Estudios de Casos y Controles , Factores de Riesgo , Anticuerpos Anticardiolipina/sangre , Adulto , Anciano , beta 2 Glicoproteína I/inmunología , China/epidemiologíaRESUMEN
Objective To observe the expression of anti-ß2 glycoprotein I (ß2GPI) autoantibody in connective tissue diseases and its relationship with the degree of inflammation and immune function. Methods Patients with broad connective tissue diseases including connective tissue disease (CTD), rheumatoid arthritis (RA), Sjogren's syndrome (SS), and systemic lupus erythematosus (SLE) were observed. ß2GPI was quantified by chemiluminescence, ESR was measured by Weil's method, and C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated polypeptide (CCP) antibody were measured by automatic biochemical analyzer. Results ß2GPI and their subtypes were significantly higher in RA patients compared with CTD, SS, and SLE patients. CRP was positively associated with anti-ß2GPI antibody and anti-ß2GPI antibody IgM in patients with connective tissue disease. ESR was positively associated with anti-ß2GPI antibody. Anti-ß2GPI antibody and anti-ß2GPI antibody IgM were elevated in the abnormal CRP group compared with the normal CRP group. Compared with the ESR normal group, anti-ß2GPI antibody and anti-ß2GPI antibody IgG were elevated in the ESR abnormal group. Anti-ß2GPI antibody was positively correlated with ESR and anti-CCP antibody in RA patients. Anti-ß2GPI antibody IgG was positively correlated with RF. Conclusion ß2GPI can be used as a predictor of the degree of inflammation and assessment of immune disorders in CTD.
Asunto(s)
Autoanticuerpos , Enfermedades del Tejido Conjuntivo , Inflamación , beta 2 Glicoproteína I , Humanos , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , beta 2 Glicoproteína I/inmunología , Enfermedades del Tejido Conjuntivo/inmunología , Enfermedades del Tejido Conjuntivo/sangre , Femenino , Masculino , Persona de Mediana Edad , Adulto , Inflamación/inmunología , Inflamación/sangre , Proteína C-Reactiva/análisis , Proteína C-Reactiva/inmunología , Factor Reumatoide/sangre , Factor Reumatoide/inmunología , Anciano , Síndrome de Sjögren/inmunología , Síndrome de Sjögren/sangre , Adulto Joven , Artritis Reumatoide/inmunología , Artritis Reumatoide/sangreRESUMEN
Beta 2 glycoprotein I (ß2GPI) is the major autoantigen in the antiphospholipid syndrome, an autoimmune disorder characterized by thrombotic and obstetric complications. The autoantibodies that target beta 2 glycoprotein I are pathogenic and contribute to disease pathogenesis. The ß2GPI molecule is composed of 5 domains that are numbered 1 through to 5. Autoantibodies bind mainly to domain 1 whereas the majority of the biological functions of the ß2GPI molecule in diverse processes such as apoptotic cell clearance, complement regulation, lipopolysaccharide clearance and anticoagulation have been localised to domain 5 and its unique biochemistry, reviewed in this article. The role of purified domain 5 peptide as a potential therapeutic agent in APS and ischemia reperfusion injury is discussed.
Asunto(s)
Síndrome Antifosfolípido , Autoanticuerpos , beta 2 Glicoproteína I , Humanos , beta 2 Glicoproteína I/inmunología , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/tratamiento farmacológico , Autoanticuerpos/inmunología , Dominios Proteicos , Animales , Autoantígenos/inmunología , Daño por Reperfusión/inmunologíaRESUMEN
The relationship between antiphospholipid syndrome (APS) and acute viral infection, such as SARS-CoV-2, is unclear. This study aims to assess symptoms, antiphospholipid antibody (aPL) fluctuations, and complication risks in APS patients infected with SARS-CoV-2. APS patients from Peking Union Medical College Hospital during the COVID-19 outbreak (October-December 2022) were included. Age- and gender-matched APS patients without infection served as controls. Data on demographics, symptoms, treatments, and serum aPL levels were analyzed. Of 234 APS patients, 107 (45.7%) were infected with SARS-CoV-2. Typical symptoms included high fever (81.3%), cough/expectoration (70.1%), and pharyngalgia (52.3%). Age- and gender-based matching selected 97 patients in either infected or uninfected group. After infection, anti-ß-2-glycoprotein I-IgG (aß2GP1-IgG) increased from 4.14 to 4.18 AU/ml, aß2GP1-IgM decreased from 9.85 to 7.38 AU/ml, and anticardiolipin-IgA (aCL-IgA) significantly increased with a median remaining at 2.50 APLU/ml. Lupus anticoagulants and other aPLs remained stable. Arterial thrombosis incidence increased from 18 (18.6%) to 21 (21.6%), while venous thrombosis incidence did not change. Additionally, 7 (6.5%) patients presented either new-onset or worsening thrombocytopenia, characterized by a significant decline in platelet count (no less than 10 × 109/L) within two weeks of SARS-CoV-2 infection, all of which recovered within 2 weeks. Acute SARS-CoV-2 infection may induce or worsen thrombocytopenia but does not substantially increase thrombotic events in APS. The process of SARS-CoV-2 infection was related to mild titer fluctuation of aß2GP1-IgG, aß2GP1-IgM and aCL-IgA in APS patients, necessitating careful monitoring and management.
Asunto(s)
Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/inmunología , Masculino , Femenino , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/sangre , Adulto , Persona de Mediana Edad , Anticuerpos Antifosfolípidos/sangre , SARS-CoV-2/inmunología , China/epidemiología , Anticuerpos Anticardiolipina/sangre , beta 2 Glicoproteína I/inmunología , Inmunoglobulina G/sangre , AncianoRESUMEN
BACKGROUND: Improving harmonization of the clinical interpretation of anticardiolipin (aCL) and anti-ß2-glycoprotein I (aß2GPI) antibodies immunoglobulin G (IgG)/immunoglobulin M (IgM) in the diagnosis of antiphospholipid syndrome (APS) is desirable. Likelihood ratios (LRs) with corresponding test-result intervals can identify the power of a test to discriminate between a diseased and nondiseased patient and may be useful for the semiquantitative interpretation of aCL/aß2GPI results. OBJECTIVES: To determine moderate and high thresholds for aCL and aß2GPI IgG/IgM measured with chemiluminescent immunoassay, enzyme-linked immunosorbent assay, fluorescence enzyme immunoassay, and multiplex flow immunoassay. METHODS: aCL and aß2GPI antibodies IgG/IgM were determined with 4 solid-phase systems in a case-control study population including 381 APS patients and 727 controls. Interval-specific LRs (IS-LR) were calculated for ranges determined by prespecified specificity and sensitivity levels. Three methods were used for determining thresholds that separated low, moderate, and high positive antibody levels. Interassay agreement was checked with Cohen's kappa statistics. RESULTS: Assay- and antibody-specific thresholds demonstrated increasing IS-LR, reflecting different clinical significance for low, moderate, and high levels, especially for IgG aCL and aß2GPI and in thrombotic APS. IS-LRs per antibody and unit range were comparable across solid-phase platforms resulting in enhanced harmonization of result interpretation. Agreement between assays for identifying high levels was improved by semiquantitative interpretation compared with that by quantitative reporting. CONCLUSION: aCL and aß2GPI IgG/IgM moderate and high thresholds were determined for 4 analytical platforms. Thresholds improve harmonized interpretation of aCL/aß2GPI levels across platforms. The proposed thresholds should be verified in an independent case-control study to check interlaboratory transferability.
Asunto(s)
Anticuerpos Anticardiolipina , Síndrome Antifosfolípido , Inmunoglobulina G , Inhibidor de Coagulación del Lupus , beta 2 Glicoproteína I , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/inmunología , Humanos , Anticuerpos Anticardiolipina/sangre , beta 2 Glicoproteína I/inmunología , Inhibidor de Coagulación del Lupus/sangre , Estudios de Casos y Controles , Inmunoglobulina G/sangre , Femenino , Masculino , Anticuerpos Antifosfolípidos/sangre , Funciones de Verosimilitud , Inmunoglobulina M/sangre , Valor Predictivo de las Pruebas , Ensayo de Inmunoadsorción Enzimática/normas , Ensayo de Inmunoadsorción Enzimática/métodos , Persona de Mediana Edad , Adulto , Reproducibilidad de los Resultados , Biomarcadores/sangre , Mediciones LuminiscentesRESUMEN
OBJECTIVES: To evaluate the effectiveness of the 2023 ACR/EULAR criteria for antiphospholipid syndrome (APS) in a Chinese cohort, and compare them with the Sapporo and revised Sapporo criteria. METHODS: A cohort comprising 436 patients diagnosed with APS and 514 control subjects was enrolled, including 83 with seronegative APS and 86 classified as antiphospholipid antibody (aPL) carriers. We assessed IgG and IgM anticardiolipin antibodies (aCL) and anti-ß2-glycoprotein I (aß2GPI) antibodies using ELISA, along with a systematic collection of lupus anticoagulant data. Subsequently, we compared the sensitivity and specificity across the three classification criteria. RESULTS: The 2023 ACR/EULAR criteria exhibited improved specificity at 98 %, surpassing the revised Sapporo (90 %) and original Sapporo (91 %) criteria. However, this came with decreased sensitivity at 82 %, in contrast to higher sensitivities in the revised Sapporo (98 %) and Sapporo (91 %) criteria. Examining individual components sheds light on the scoring system's rationale within the new criteria. The inclusion of microvascular thrombosis, cardiac valve disease, and thrombocytopenia improved the identification of nine patients previously classified as "probable APS". Insufficient scoring in 78 previously diagnosed APS individuals was linked to traditional risk factor evaluations for thrombotic events, the emphasis on determining whether obstetric events are linked to severe preeclampsia (PEC) or placental insufficiency (PI), and the lower scores assigned to IgM aCL and/or aß2GPI antibody. Seronegative APS remained a challenge, as non-criteria aPL and other methods were not included. CONCLUSIONS: The new criteria presented notable advancements in specificity. This study provides detailed insights into the strengths and possible challenges of the 2023 ACR/EULAR criteria, enhancing our understanding of their impact on clinical practice.
Asunto(s)
Anticuerpos Anticardiolipina , Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido , beta 2 Glicoproteína I , Humanos , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/sangre , Femenino , Masculino , Adulto , Persona de Mediana Edad , Anticuerpos Antifosfolípidos/sangre , Anticuerpos Antifosfolípidos/inmunología , beta 2 Glicoproteína I/inmunología , Anticuerpos Anticardiolipina/sangre , China/epidemiología , Embarazo , Estudios de Cohortes , Inhibidor de Coagulación del Lupus/sangre , Sensibilidad y Especificidad , Inmunoglobulina M/sangre , Inmunoglobulina M/inmunología , Pueblo Asiatico , Pueblos del Este de AsiaRESUMEN
Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by arterial and venous thrombosis, and obstetric complications in the presence of antiphospholipid antibodies (aPL), including lupus anticoagulant, anticardiolipin and anti-ß2-glycoprotein I antibodies. APS manifests as single, often as recurrent events, and rarely as a catastrophic condition. Most studies of APS pathogenesis to date have focused on the prothrombotic role of aPL, while innate immune responses such as monocyte, complement and neutrophil activation have been also recognized as part of the thrombo-inflammatory cascade in APS. While the presence of autoreactive T cells against ß2-glycoprotein I has been long known, less data are available on their pathogenetic role in APS. In this review, we summarize current knowledge on the involvement of T cells in APS pathophysiology, alterations of T cell subsets in peripheral blood, and clinical associations. We also highlight potential therapeutic opportunities by targeting T helper-B cell interactions in these patients.
Asunto(s)
Síndrome Antifosfolípido , Humanos , Síndrome Antifosfolípido/inmunología , Linfocitos T/inmunología , Anticuerpos Antifosfolípidos/inmunología , beta 2 Glicoproteína I/inmunología , Subgrupos de Linfocitos T/inmunologíaRESUMEN
Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombotic manifestations and/or obstetric complications in patients with persistently positive antiphospholipid antibodies (aPL). aPL are a heterogeneous group of autoantibodies, but only lupus anticoagulant, anticardiolipin (aCL), and antibeta2-glycoprotein I antibodies (aß2GPI) IgG or IgM are included as laboratory classification criteria. Seronegative APS patients are usually defined as patients with the clinical symptoms of APS but who test negative for aPL. The negativity to classic aPL criteria does not exclude the presence of other aPL. Several noncriteria aPL have been identified. Some noncriteria aPL are well studied, such as IgA aCL and aß2GPI, the antiphosphatidylserine-prothrombin (aPS/PT) antibodies, and the antibodies against the domain I of beta2-glycoprotein I (aDI), both latter groups receiving more attention for their role in thrombotic events and pregnancy complications. Other noncriteria aPL that have been studied are antibodies against annexin V, prothrombin, phosphatidylethanolamine, phosphatidic acid, phosphatidylserine, phosphatidylinositol, vimentin-cardiolipin complex, anti-protein S/protein C. Measurement of some of these noncriteria aPL (aPS/PT, aDI) is useful in the laboratory work-out of APS in specific situations. We have to differentiate between patients who are positive for noncriteria aPL only, and patients who have both criteria and noncriteria aPL to enable us to study their role in the diagnosis or risk stratification of APS. The research on noncriteria aPL is continually developing as the clinical relevance of these antibodies is not yet fully clarified.
Asunto(s)
Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido , Humanos , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/sangre , Anticuerpos Antifosfolípidos/sangre , Anticuerpos Antifosfolípidos/inmunología , Femenino , Embarazo , Trombosis/etiología , Trombosis/inmunología , Trombosis/sangre , Trombosis/diagnóstico , beta 2 Glicoproteína I/inmunología , Autoanticuerpos/sangre , Autoanticuerpos/inmunologíaRESUMEN
BACKGROUND: The clinical relevance of different antiphospholipid antibody (aPL) profiles, including low level anticardiolipin (aCL) and anti-ß2-glycoprotein-I (aß2GPI) antibodies, is ill-defined in the pediatric population. Our purpose is to describe the demographic, clinical, and laboratory characteristics of aPL positive pediatric patients based on different aPL profiles. FINDINGS: In this single center retrospective cohort study, based on the screening of our pediatric (age ≤ 18) rheumatology electronic medical records (2016-2022), we identified patients who had at least one "positive" aPL (lupus anticoagulant [LA], aCL IgG/M, or aß2GPI IgG/M) result. Patients were grouped into high- (LA positive and/or aCL/aß2GPI IgG/M > 40U [ELISA]) and low-risk (LA negative and aCL/aß2GPI IgG/M 20-39U) aPL profiles; those with persistently positive aPL were descriptively analyzed for demographic and clinical characteristics. Of 57 included patients, 34 (59%) had initial high- and 23 (40%) had initial low-risk profiles. Based on subsequent aPL results available in 42/57 (74%) patients, 25/27 (93%) in the high-, and 7/15 (47%) in the low-risk groups remained still positive. Of these 32 patients with persistently positive aPL, moderate-to-large vessel or microvascular thrombosis occurred in nine (28%) patients with high-risk and in none with low-risk aPL profiles; non-thrombotic aPL-related manifestations were reported in 15 (47%) patients with persistent aPL positivity. CONCLUSION: An initial high-risk aPL profile was persistent in approximately 90% of our cohort, a third of whom had thrombosis, and half had non-thrombotic aPL manifestations. Our results underscore the need for a large-scale effort to better characterize aPL-related manifestations in pediatric patients with persistent high-risk aPL-profiles.
Asunto(s)
Anticuerpos Anticardiolipina , Anticuerpos Antifosfolípidos , beta 2 Glicoproteína I , Humanos , Femenino , Masculino , Niño , Estudios Retrospectivos , Anticuerpos Antifosfolípidos/sangre , Anticuerpos Antifosfolípidos/inmunología , Adolescente , beta 2 Glicoproteína I/inmunología , Anticuerpos Anticardiolipina/sangre , Anticuerpos Anticardiolipina/inmunología , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/complicaciones , Preescolar , Inhibidor de Coagulación del Lupus/sangre , Inhibidor de Coagulación del Lupus/inmunología , Enfermedades Reumáticas/inmunología , Enfermedades Reumáticas/sangre , Trombosis/etiología , Trombosis/inmunología , Relevancia ClínicaRESUMEN
OBJECTIVE: This article aims to evaluate the magnitude of adverse pregnancy outcomes (APOs) risks associated with different antiphospholipid antibody (aPL) profiles in women with systemic lupus erythematosus (SLE). METHODS: Multiple databases were investigated to identify articles that explored the relationship between aPLs and APOs in SLE patients. A random effects model was used for calculating pooled odds ratios (OR). Stata version 15.0 was utilized to conduct the meta-analysis. RESULTS: There were 5234 patients involved in 30 studies. Overall aPL was linked to an increased incidence of any kind of APOs, fetal loss, and preterm birth. Any kind of APOs and preterm delivery were more common in patients with lupus anticoagulant (LA) positive. Anticardiolipin antibody (aCL) was associated with an increased risk of any kind of APOs and fetal loss. The association between aCL-IgM and fetal loss was also significant. Patients with anti-beta2-glycoprotein1 antibody (antiß2GP1) positivity had an increased risk of fetal loss. CONCLUSIONS: Both LA and aCL were risk factors of APOs in patients with SLE. Not only ACL, particularly aCL-IgM, but antiß2GP1 were associated with an increased risk of fetal loss, while LA appeared to indicate the risk of preterm birth.PROSPERO (CRD42023388122).
Asunto(s)
Anticuerpos Antifosfolípidos , Lupus Eritematoso Sistémico , Complicaciones del Embarazo , Resultado del Embarazo , Humanos , Embarazo , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/complicaciones , Femenino , Anticuerpos Antifosfolípidos/sangre , Anticuerpos Antifosfolípidos/inmunología , Complicaciones del Embarazo/inmunología , Complicaciones del Embarazo/epidemiología , Anticuerpos Anticardiolipina/sangre , Anticuerpos Anticardiolipina/inmunología , Inhibidor de Coagulación del Lupus/sangre , Inhibidor de Coagulación del Lupus/inmunología , Factores de Riesgo , Riesgo , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/inmunología , beta 2 Glicoproteína I/inmunologíaAsunto(s)
Anticuerpos Anticardiolipina , Inmunoglobulina A , beta 2 Glicoproteína I , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Anticardiolipina/sangre , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/diagnóstico , beta 2 Glicoproteína I/inmunología , Relevancia Clínica , Inmunoglobulina A/sangre , Inmunoglobulina A/inmunología , Isotipos de Inmunoglobulinas/sangre , Isotipos de Inmunoglobulinas/inmunologíaRESUMEN
In antiphospholipid syndrome (APS), the risk of clinical manifestations increases with higher titers of antiphospholipid antibodies (aPL). Despite the adoption of aPL titers in the classification approach to aPL-positive subjects, the value of longitudinal monitoring of those titers in the follow-up is still debated, being well studied only in systemic lupus erythematosus (SLE). The literature suggests that the rate of aPL positivity decreases during follow-up in primary APS, estimating that seroconversion occurs in between 8.9 and 59% of patients over time. Negativisation of aPL occurs more frequently in asymptomatic aPL carriers than in patients with full-blown APS as well as in subjects with single aPL positivity or low aPL antibody titers. In patients with SLE, aPL typically behave fluctuating from positive to negative and back again in the course of follow-up. The few studies assessing the longitudinal course of aPL positivity with no associated systemic connective tissue disease reported a progressive decrement of aPL titers over time, in particular of antibodies against ß2 glycoprotein I (antiß2GPI) and cardiolipin (aCL) of IgG isotype. After a thrombotic event, aPL titers tend to decrease, as emerged from cohorts of both primary and secondary APS. Hydroxychloroquine has been identified as the most effective pharmacological agent to reduce aPL titers, with multiple studies demonstrating a parallel reduction in thrombosis rate. This review addresses available evidence on the significance of aPL titer fluctuation from clinical, therapeutic and pathogenic perspectives.
Asunto(s)
Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido , Humanos , Anticuerpos Antifosfolípidos/sangre , Anticuerpos Antifosfolípidos/inmunología , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/diagnóstico , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , beta 2 Glicoproteína I/inmunología , Trombosis/inmunología , Trombosis/sangre , Trombosis/etiología , Relevancia ClínicaRESUMEN
OBJECTIVE: The aim of this research was to determine the frequency of antiphospholipid antibodies (aPL) in patients with COVID-19. METHODS: The frequency and titers of anticardiolipin antibodies (aCL) and anti-ß2 glycoprotein I antibodies (aß2GPI) were determined in sera of adult patients hospitalized with COVID-19. Immunoglobulin (Ig)G, IgA, IgM aCL, and aß2GPI were measured using enzyme-linked immunosorbent assay. RESULTS: Eighty-three patients were included in the study. The mean age of patients was 62 ± 13.9 years, ranging from 23 to 86 years. Stratification according to severity of infection divided patients in 2 groups: 45 patients with moderate infection and 38 patients with critical or severe infection. Out of the 83 patients suffering from COVID-19, aPL (aCL or aß2GPI) were detected in 24 patients (28.9%). IgG, IgA and IgM aß2GPI were positive in 2.4%, 16.9% and 8.4%, respectively. IgG, IgA and IgM aCL showed positivity in 7.2%, 0%, and 4.8%, respectively. The frequency of aPL was 36.8% in patients with critical/severe infection and 22.2% in patients with moderate infection. In critical/severe patients, the frequency of aß2GPI was significantly higher than aCL (34.2% vs 13.2%, P = .03) and aß2GPI-IgA were significantly more frequent than aß2GPI-IgG (21.1% vs 2.6%, P = .028). CONCLUSION: In this cross-sectional study, aPL and particularly aß2GPI-IgA were common in patients with COVID-19.
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COVID-19 , Inmunoglobulina A , SARS-CoV-2 , beta 2 Glicoproteína I , Humanos , COVID-19/inmunología , COVID-19/sangre , Persona de Mediana Edad , Masculino , Femenino , Adulto , Anciano , Inmunoglobulina A/sangre , beta 2 Glicoproteína I/inmunología , Anciano de 80 o más Años , SARS-CoV-2/inmunología , Adulto Joven , Anticuerpos Antifosfolípidos/sangre , Anticuerpos Anticardiolipina/sangre , Inmunoglobulina M/sangre , Inmunoglobulina M/inmunología , Ensayo de Inmunoadsorción EnzimáticaRESUMEN
BACKGROUND: The acquired thrombotic risk factor known as lupus anticoagulant (LA) interferes with laboratory clotting assays and can be caused by autoantibodies against ß2-glycoprotein I (ß2GPI) and prothrombin. LA is associated with activated protein C (APC) resistance, which might contribute to thrombotic risk in patients with antiphospholipid syndrome. How antibodies against ß2GPI and prothrombin cause APC resistance is currently unclear. OBJECTIVES: To investigate how anti-ß2GPI and antiphosphatidylserine/prothrombin (PS/PT) antibodies induce APC resistance. METHODS: The effects of anti-ß2GPI and anti-PS/PT antibodies on APC resistance were studied in plasma (of patients with antiphospholipid syndrome) and with purified coagulation factors and antibodies. RESULTS: APC resistance was observed in LA-positive patients with anti-ß2GPI or anti-PS/PT antibodies and in normal plasma spiked with monoclonal anti-ß2GPI or anti-PS/PT antibodies with LA activity. Analysis of factor (F)V cleavage patterns after APC incubation indicated that anti-ß2GPI antibodies attenuated APC-mediated FV cleavage at R506 and R306. APC-mediated cleavage at R506 is required for FV cofactor activity during inactivation of FVIIIa. Assays with purified coagulation factors confirmed that anti-ß2GPI antibodies interfered with the cofactor function of FV during FVIIIa inactivation but not with FVa inactivation. Anti-PS/PT antibodies attenuated APC-mediated FVa and FVIIIa inactivation. Analysis of FV(a) cleavage patterns after APC incubation indicated that anti-PS/PT antibodies interfere with APC-mediated cleavage of FV at positions R506 and R306. CONCLUSION: Anti-ß2GPI antibodies with LA activity contribute to a procoagulant state by causing APC resistance via interference with the cofactor function of FV during FVIIIa inactivation. LA-causing anti-PS/PT antibodies interfere with the anticoagulant function of APC by preventing FV(a) cleavage.
Asunto(s)
Resistencia a la Proteína C Activada , Síndrome Antifosfolípido , Autoanticuerpos , Factor V , Trombosis , Humanos , beta 2 Glicoproteína I/inmunología , Factor V/metabolismo , Inhibidor de Coagulación del Lupus , Fosfatidilserinas/inmunología , Proteína C/metabolismo , Protrombina/inmunologíaRESUMEN
Antiphospholipid syndrome (APS) is an autoimmune disease characterized by venous, arterial, or small-vessel thrombosis and/or pregnancy-related morbidity, associated with persistent positivity of antiphospholipid antibodies (aPL). Pregnancy-related morbidity in APS patients is characterized by unexplained fetal deaths, premature birth of morphologically normal newborns, and/or consecutive pregnancy losses before the 10th week of gestation. Beta 2-glycoprotein 1 (ß2GP1) is the main antigen recognized by aPL and plays an essential role in the pathogenesis of APS. Antibodies against ß2GP1 (aß2GP1) are involved in damage-generating mechanisms in APS due to their interaction with trophoblasts, decidua, and endothelial cells. aß2GP1 might be used as a prognostic tool for obstetric risk stratification and ß2GP1 could be a target for molecular-targeted treatment to prevent pregnancy morbidity in APS. This review describes these aspects of aß2GP1, including effects on different cellular targets, its association with the severity of obstetric manifestations and the potential of ß2GP1-targeted therapies for APS.
Asunto(s)
Síndrome Antifosfolípido/inmunología , Autoanticuerpos/inmunología , Complicaciones del Embarazo/inmunología , beta 2 Glicoproteína I/inmunología , Femenino , Humanos , EmbarazoRESUMEN
OBJECTIVE: We aimed to analyse the prevalence of non-criteria anti-phospholipid (aPL) antibodies and their role in the diagnosis, treatment and prognosis in a cohort of patients with clinical features consistent with a diagnosis of antiphospholipid syndrome (APS), but persistently negative for criteria aPL - anti-cardiolipin antibodies (aCL), anti-ß2-glycoprotein I antibodies (aß2-GPI) and lupus anticoagulant (LA) - named seronegative APS (SN-APS). METHODS: Sera from SN-APS patients were tested for aCL by TLC-immunostaining, anti-vimentin/cardiolipin (aVim/CL) and anti-phosphatidylserine/prothrombin (anti-PS/PT) by ELISA. Control groups of our study were APS patients and healthy controls. RESULTS: We enrolled 114 consecutive SN-APS patients, 69 (60.5%) resulted positive for at least one non-criteria test in two occasions 12 weeks apart. Among the persistently positive patients to these tests, 97% resulted positive for aCL by TLC-immunostaining, 52.3% for aVim/CL and 17.4% for aPS/PT. SN-APS patients with double positivity (aCL by TLC-immunostaining and aVim/CL) showed a likelihood positive ratio of 8 to present mixed thrombotic and obstetrical features. Among SN-APS patients tested positive, after the therapeutic changes, three cases of recurrent thrombosis were observed [median follow-up 41 months (IQR 39.5)]. Twenty pregnancies were recorded in 17 SN-APS patients after the detection of unconventional aPL and 12 of them (60%) experienced a good outcome under conventional treatment for APS. CONCLUSIONS: This is the largest monocentric study demonstrating that aCL tested by TLC-immunostaining and aVim/CL can detect aPL positivity in SN-APS. It may encourage clinicians to monitor and provide adequate targeted therapy, which improve SN-APS prognosis.
Asunto(s)
Anticuerpos Antifosfolípidos/sangre , Síndrome Antifosfolípido/diagnóstico , Adulto , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/inmunología , Cardiolipinas/inmunología , Estudios de Casos y Controles , Cromatografía en Capa Delgada , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fosfatidilserinas/inmunología , Pronóstico , Protrombina/inmunología , Vimentina/inmunología , beta 2 Glicoproteína I/inmunologíaRESUMEN
OBJECTIVE: Anti-ß-2 glycoprotein I (anti-ß2GPI) antibodies, defined as primary pathogenic antibody in antiphospholipid syndrome (APS). It has been reported that IgG Fc N-glycosylation affects IgG effector, we aim to investigate the association of Fc glycosylation profiles of purified anti-ß2GP1 IgG with clinical features of APS. METHODS: We purify anti-ß2GPI IgG and total IgG from 82 APS patients including nine catastrophic antiphospholipid syndrome (CAPS) patients, as well as total IgG from 103 healthy controls to quantitatively analyse all detectable Fc N-glycanforms of all IgG subclasses with Multiple Reaction Monitoring (MRM) method based on UPLC-ESI-QqQ mass spectrometry. RESULTS: Both purified anti-ß2GPI IgG and APS total IgG showed altered N-glycan profiles when compared with healthy control (HC) IgG. Anti-ß2GPI IgG presented with lower galactosylation, increased bisection and core fucosylation compared with APS total IgG and HC IgG. We found higher galactosylation of aß2GPI IgG2 in thrombotic APS compared with the obstetric APS, and lower galactosylation of aß2GPI IgG2 associated with late pregnancy morbidity. Moreover, low galactosylation of all anti-ß2GPI IgG subclasses, increased bisection and core fucosylation of anti-ß2GPI IgG1/2 were strongly associated with CAPS and triple positivity of antiphospholipid antibodies (aPLs). CONCLUSION: We comprehensively characterize the N-Glycans landscape of both anti-ß2GP1 and total IgG in APS. Altered N-glycan profiles of anti-ß2GPI IgG enables enabled the antibodies with proinflammatory properties. Furthermore, we associated levels of IgG Fc-glycosylation with clinical features antiphospholipid syndrome. These findings could increase our understanding of anti-ß2GPI antibody mediated mechanisms in APS and be used to develop diagnostics and new target treatments.
Asunto(s)
Anticuerpos Antifosfolípidos/inmunología , Síndrome Antifosfolípido/inmunología , Inmunoglobulina G/inmunología , Complicaciones del Embarazo/inmunología , Trombosis/inmunología , beta 2 Glicoproteína I/inmunología , Femenino , Humanos , EmbarazoRESUMEN
Antibodies to phospholipids (aPL) and associated proteins are a hallmark in the diagnosis of anti-phospholipid syndrome (APS). Those included in the classification criteria are the lupus anticoagulant (LA) and the IgG and IgM isotypes of anticardiolipin (aCL) and anti-beta-2 glycoprotein I (ß2GPI) antibodies. Non-classification criteria markers such as autoantibodies that recognize the phosphatidylserine/prothrombin (aPS/PT) complex have been proposed as biomarkers for APS. Studies of aPS/PT antibodies have shown a strong correlation to clinical manifestations and LA. We aimed to study the value and the persistence of aPS/PT IgG and IgM antibodies in a cohort of consecutive patients with clinical suspicion of APS and their utility as thrombotic risk markers. Our study, with 103 patients, demonstrates that persistently positive results for aPS/PT IgG antibodies were significantly associated with APS classification, thrombosis, triple aPL positivity, LA positive result, and the Global APS Score (GAPSS) > than 9 points (p < 0.01, for each condition). On the other hand, no association was seen with pregnancy morbidity (p = 0.56) and SLE (p = 0.07). Persistence of aPS/PT antibodies, defined according to the current laboratory classification criteria, likely improves the diagnosis and clinical assessment of patients with APS.