RESUMEN
OBJECTIVE: To assess the effect of the average adjusted global APS score (aGAPSS) over time on recurrence of clinical manifestations in APS patients through a retrospective longitudinal study. MATERIAL AND METHODS: The study included 200 patients with APS. The aGAPSS was calculated for each patient at baseline and on a yearly basis for either up to 6 years (minimum 3 years) or just before the clinical event in patients who experienced clinical recurrence. The mean score per patient was computed. In patients under vitamin K antagonists (VKA) the percentage of time spent within the therapeutic range (TTR) was calculated. Cox regression analysis was performed to determine the cut-off value of the aGAPSS with the strongest association with clinical recurrence. RESULTS: Higher average aGAPSS values were found in patients who experienced clinical recurrence in comparison to patients who did not [8.81 (95% CI 7.53, 10.08) vs 6.38 (95% CI 5.64, 7.12), P = 0.001], patients with thrombotic recurrence compared with patients with obstetric recurrence [9.48 (95% CI 8.14, 10.82) vs 4.25 (95% CI 0.85, 7.65), P = 0.006] and patients with arterial thrombosis compared with patients with venous thrombosis [10.66 (S.D. 5.48) vs 6.63 (S.D. 4.42), P = 0.01]. aGAPSS values >13 points were associated with the highest risk of recurrence in multivariate analysis [HR = 3.25 (95% CI 1.93, 5.45), P < 0.0001]. TTR was not statistically different between patients who had thrombosis recurrence and patients who had not. CONCLUSIONS: Our data support the role of periodic (annual) monitoring of the aGAPSS score in predicting clinical recurrence in patients with APS.
Asunto(s)
Síndrome Antifosfolípido , Trombosis , Embarazo , Femenino , Humanos , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/tratamiento farmacológico , Síndrome Antifosfolípido/inducido químicamente , Estudios Retrospectivos , Estudios Longitudinales , Trombosis/inducido químicamente , Anticoagulantes/uso terapéuticoRESUMEN
OBJECTIVES: Anti-CENP-B (ACA), anti-topoisomerase I (ATA) and anti-RNA polymerase III (RP3) autoantibodies are included in the 2013 SSc-ACR/EULAR classification criteria. The detection of additional autoantibodies is of interest when those are negative. Additionally, we wonder if the IgA isotype might play a role in SSc. The aims of the study were to assess the prevalence of ACA, ATA, RP3, and Ro52 autoantibodies of IgG and IgA isotype and to describe their association with clinical manifestations in a cohort of patients with SSc. METHODS: Samples from 97 patients with SSc fulfilling the 2013 ACR/EULAR classification criteria, and 50 blood donors were included and tested for IgA and IgG isotypes of ACA, ATA, RP3, and Ro52 by FEIA. RESULTS: The prevalence of IgG+IgA isotypes for the same specificity was 62.5%, 82.6%, 80.0%, 36.8%, for ACA, ATA, RP3 and Ro52, respectively. Isolated IgG was present in 35.4%, 13.0%, 20.0% and 42.1% of patients for ACA, ATA, RP3 and Ro52, respectively. Only six patients were isolated IgA for a unique specificity. Clinically, ILD tended to be associated with ATA-IgG and ATA-IgG+IgA, telangiectasias with ACA-IgG+IgA and arthritis with ACA-IgA. Indeed, digital ulcers were more frequent in ATA-IgG patients. CONCLUSIONS: Most of the patients presented ACA, ATA, or RP3 autoantibodies of IgA isotype in addition to IgG. Regarding clinical relevance, Ro52-IgG+IgA and ACA-IgG had a tendency towards sineSSc phenotype, while ACA-IgG+IgA to lcSSc phenotype. Thus, if confirmed, the determination of ACA-IgA could provide a tool to stratify patients according to the cutaneous phenotype.
RESUMEN
Anti-dsDNA, anti-Sm, and anti-ribosomal-P autoantibodies are hallmarks of systemic lupus erythematosus (SLE), being anti-dsDNA and anti-Sm included in 2019-ACR/EULAR SLE-Classification Criteria. Enzyme-linked (ELISA) and chemiluminescence assays (CIA) are widely established in immunology laboratories, but new technologies, such as particle-based multi-analyte technology (PMAT), are nowadays available. The present study aimed to compare the presence of anti-dsDNA and anti-Sm autoantibodies measured by CIA and PMAT and analyze diagnostic and clinical SLE activity performance. Anti-ribosomal-P autoantibodies by PMAT were also included. Consequently, anti-dsDNA and anti-Sm detected by CIA showed substantial agreement with PMAT (Cohen's kappa = 0.662 and 0.671, respectively). Anti-dsDNA autoantibodies measured by PMAT showed a positive correlation with clinical SLEDAI-2K (p < 0.001) and a negative correlation with complement consumption (p < 0.001). Anti-Sm and anti-ribosomal-P autoantibodies showed a positive correlation with SLEDAI-2K (p < 0.001 and p = 0.001, respectively) and a negative correlation with complement consumption (p < 0.001 and p = 0.001, respectively). Finally, anti-Sm autoantibodies were associated with renal involvement (p < 0.05).
RESUMEN
BACKGROUND: M2-type anti-mitochondrial autoantibodies are considered the hallmark of primary biliary cholangitis and are directed mainly against the E2 subunits of the 2-oxo acid dehydrogenase complex enzymes (PDC, BCOADC and OGDC). The aim of this study was to determine whether a Dot-blot that includes these E2 subunits separately could confirm the results of methods with non-separated subunits in patients with low positive or discordant results between techniques. METHODS: Sera of 24 patients with low positive or discordant results and of 10 patients with clear positive results by non-separated subunits methods were analyzed by Dot-blot with separated subunits. RESULTS: Autoantibodies against E2 subunits of PDC, BCOADC or OGDC were detected in all patients, except in one case from the low positive or discordant results group, by Dot-blot with separated subunits. CONCLUSIONS: It would be advisable to use methods that include the three E2 subunits, and a Dot-blot with separated subunits could confirm doubtful cases by non-separated assays.
RESUMEN
Anti-dsDNA autoantibodies quantification and complement levels are widely used to monitor disease activity in systemic lupus erythematosus (SLE). However, better biomarkers are still needed. We hypothesised whether the dsDNA antibody-secreting B-cells could be a complementary biomarker in disease activity and prognosis of SLE patients. Fifty-two SLE patients were enrolled and followed for up to 12 months. Additionally, 39 controls were included. An activity cut-off (comparing active and non-active patients according to clinical SLEDAI-2K) was established for SLE-ELISpot, chemiluminescence and Crithidia luciliae indirect immunofluorescence tests (≥11.24, ≥374.1 and ≥1, respectively). Assays performances together with complement status were compared regarding major organ involvement at the inclusion and flare-up risk prediction after follow-up. SLE-ELISpot showed the best performance in identifying active patients. High SLE-ELISpot results were associated with haematological involvement and, after follow-up, with an increased hazard ratio for disease flare-up (3.4) and especially renal flare (6.5). Additionally, the combination of hypocomplementemia and high SLE-ELISpot results increased those risks up to 5.2 and 32.9, respectively. SLE-ELISpot offers complementary information to anti-dsDNA autoantibodies to evaluate the risk of a flare-up in the following year. In some cases, adding SLE-ELISpot to the current follow-up protocol for SLE patients can improve clinicians' personalised care decisions.
RESUMEN
PURPOSE: To analyze the antiphospholipid antibody (aPL) persistence over time in patients with antiphospholipid syndrome (APS) and its association with clinical recurrence and to identify predictors of aPL persistence over time. PATIENTS AND METHODS: 200 patients with a diagnosis of APS and at least three follow-up aPL determinations were included. Persistent aPL profile was defined as the presence of lupus anticoagulant (LAC) and/or IgG/IgM anticardiolipin (aCL) and/or IgG/IgM anti-ß2 glycoprotein-I (aß2GPI) (> 99th percentile) antibodies in at least 66% of follow-up measurements. Multilevel mixed-effect generalized linear models with logit link were used. RESULTS: 112 (56%) patients maintained persistent aPL profiles over time, while 88 (44%) were transient. Median follow-up time was 172.5 months. Follow-up time did not affect the odds of aPL persistence in multivariate analysis (p = 1.00). Baseline triple aPL positivity [OR 78 (95%CI 16.9-359.7, p < 0.001)] and double aPL positivity [OR = 7.6 (95%CI 3.7-15.7, p < 0.001)] correlated with persistent aPLs over time, while isolated LAC [OR = 0.26 (95% CI 0.08-0.49, p = 0.002)] or isolated IgG/IgM aCL [OR = 0.20 (95% CI 0.11-0.59, p = 0.004)] positivity, were predictors of transient aPL profile. Patients with persistent aPLs had higher rate of clinical recurrence in comparison to patients with transient aPLs [OR = 2.48 (95%CI 1.34-4.58, p = 0.003)]. CONCLUSIONS: More than half of patients with baseline medium-high titer aPL positivity had persistent positive aPLs over time. Patients with persistent aPLs were more prone to present recurrence of clinical manifestations. Multiple aPL positivity increased the odds of a persistent aPL profile over time, while isolated LAC and aCL positivity decreased it.
Asunto(s)
Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido , Humanos , Estudios Longitudinales , Inhibidor de Coagulación del Lupus , Inmunoglobulina G , Anticuerpos AnticardiolipinaRESUMEN
Objective: Patients with COVID-19 presented with an elevated prevalence of antiphospholipid antibodies (aPL) but the relationship with thrombosis is controversial. We analysed the persistence of aPL and their association with the clinical outcomes during hospitalisation in a cohort of COVID-19 patients. Patients and Methods: We conducted a prospective study including consecutive hospitalised patients with COVID-19 from Hospital Clínic of Barcelona between March 28th and April 22nd, 2020. Clinical outcomes during hospitalisation were thrombosis, intensive care unit (ICU) admission, and severe ventilatory failure. We determined both criteria and non-criteria aPL. Of note, in those patients with a positive result in the first determination, a second sample separated by at least 12 weeks was drawn to test the persistence of aPL. Results: One hundred and fifty-eight patients (59.5% men) with a mean age of 61.4 ± 14.9 years old were included. Thrombosis was present in 28 (17.7%) patients, severe respiratory failure in 47 (30.5%), and 30 (18.9%) patients were admitted to ICU. Sixteen (28.6%) patients were positive for the criteria aPL at both determinations and only two (3.6%) of them suffered from thrombosis during hospitalisations (both had aCL IgG). However, they presented with low titers of aCL. Of note, aPL were not related to thrombosis, ICU admission or severe respiratory failure. Conclusion: Although aPL were prevalent in our cohort of hospitalised COVID-19 patients and they were persistent in half of tested patients, most determinations were at low titers and they were not related to worse clinical outcomes.
Asunto(s)
Síndrome Antifosfolípido , COVID-19 , Insuficiencia Respiratoria , Trombosis , Anciano , Anticuerpos Antifosfolípidos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , SARS-CoV-2RESUMEN
Autoantibody detection is the cornerstone of autoimmune liver diseases (AILD) diagnosis. Standardisation of working algorithms among autoimmunity laboratories, as well as being aware of the sensitivity and specificity of various commercial techniques in daily practice, are still necessary. The aim of this nationwide study is to report the results of the 2020 Autoimmunity Workshop organised by the Autoimmunity Group of the Spanish Society of Immunology and to provide useful information to clinicians and laboratory specialists to improve the management of autoantibody detection in AILD diagnoses. Serum samples from 17 patients with liver diseases were provided by the organisers of the 2020 Autoimmunity Workshop and were subsequently analysed by the 40 participating laboratories. Each laboratory used different techniques for the detection of autoantibodies in each patients' serum sample, according to their working algorithm. Thus, almost 680 total complete patient reports were obtained, and the number of results from different autoantibody detection techniques was >3000. Up to eight different working algorithms were employed, including indirect immunofluorescence assays (IFA) and antigen-specific techniques (AgST). The IFA of HEp-2 cells was more sensitive than IFA of rat triple tissue for the study of anti-nuclear autoantibodies (ANA) associated with AILD. The IFA of a human neutrophil study for the analysis of anti-neutrophil cytoplasmic autoantibodies was not carried out systemically in all patients, or by all laboratories. AgSTs were the most sensitive methods for the detection of anti-smooth muscle/F-actin, soluble liver antigen, liver cytosol-1, M2-mitochondrial autoantibodies, and ANA associated with primary biliary cholangitis. The main differences in AMA detection were due to patients with autoantibodies against the non-dominant epitope of pyruvate dehydrogenase complex. Given that they are complementary, IFA and AgST should be performed in parallel. If there is high suspicion of AILD, AgST should always be performed.
RESUMEN
OBJECTIVE: To evaluate the incidence and characteristics of SARS-CoV-2 infection among patients with systemic lupus erythematosus (SLE) and to compare it to that described in the general population. METHODS: For 5 weeks, we carried out a cross-sectional study consisting of telephone interviews of SLE patients. We collected epidemiological data, symptoms suggesting COVID-19, results of nasopharyngeal swabs, and ongoing treatments. In those patients who required hospital admission, clinical, radiological, and laboratory features, and outcome were investigated. RESULTS: Four hundred patients with SLE completed the survey. Overall, 4 (1.00%, 95%CI 0.02-1.98) patients were classified as confirmed cases of COVID-19 and 26 (6.51%, 95%CI 4.08-8.94) as possible clinical cases. The incidence of confirmed cases in our series was similar to that of the Catalan population (1.00% versus 0.63%; p = 0.456), whereas the incidence of possible cases was higher in our series (6.51% versus 1.29%; p < 0.005). The only difference between SLE patients with confirmed and possible COVID-19 and those without was the percentage of patients who have had contact with a confirmed or possible case of COVID-19 (26.7% versus 9.2%; p = 0.003) CONCLUSIONS: The incidence of COVID-19 in SLE patients with inactive disease is low and, in our series, all cases with confirmed infection recovered. Key Points ⢠In a cohort of SLE patients with stable and clinical inactive disease, the incidence of COVID-19 is low. ⢠All SLE patients with confirmed SARS-CoV-2 infection recovered.
Asunto(s)
COVID-19 , Lupus Eritematoso Sistémico , Estudios Transversales , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/epidemiología , SARS-CoV-2 , España/epidemiologíaRESUMEN
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.
Asunto(s)
Anticuerpos Anticardiolipina/sangre , Anticuerpos Antifosfolípidos/sangre , Síndrome Antifosfolípido/inmunología , Autoantígenos/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Lupus Eritematoso Sistémico/inmunología , Fosfatidilserinas/inmunología , Protrombina/inmunología , Trombofilia/etiología , beta 2 Glicoproteína I/inmunología , Adulto , Síndrome Antifosfolípido/sangre , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/inmunología , Biomarcadores , Femenino , Humanos , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Inhibidor de Coagulación del Lupus/sangre , Lupus Eritematoso Sistémico/sangre , Masculino , Persona de Mediana Edad , Embarazo , Complicaciones del Embarazo/sangre , Complicaciones del Embarazo/inmunología , Estudios Retrospectivos , Riesgo , Trombofilia/sangre , Factores de TiempoRESUMEN
No disponible