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BACKGROUND: Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are the two major antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). OBJECTIVES: To characterize a homogenous AAV cohort and to assess the impact of clinicopathological profiles and ANCA serotypes on clinical presentation and prognosis. Clinical differences in GPA patients according to ANCA serotype and the diagnostic yield for vasculitis of biopsies in different territories were also investigated. RESULTS: This retrospective study (2000-2021) included 152 patients with AAV (77 MPA/75 GPA). MPA patients (96.1% myeloperoxidase [MPO]-ANCA and 2.6% proteinase 3 [PR3]-ANCA) presented more often with weight loss, myalgia, renal involvement, interstitial lung disease (ILD), cutaneous purpura, and peripheral nerve involvement. Patients with GPA (44% PR3-ANCA, 33.3% MPO, and 22.7% negative/atypical ANCA) presented more commonly with ear, nose, and throat and eye/orbital manifestations, more relapses, and higher survival than patients with MPA. GPA was the only independent risk factor for relapse. Poor survival predictors were older age at diagnosis and peripheral nerve involvement. ANCA serotypes differentiated clinical features in a lesser degree than clinical phenotypes. A mean of 1.5 biopsies were performed in 93.4% of patients in different territories. Overall, vasculitis was identified in 80.3% (97.3% in MPA and 61.8% in GPA) of patients. CONCLUSIONS: The identification of GPA presentations associated with MPO-ANCA and awareness of risk factors for relapse and mortality are important to guide proper therapeutic strategies in AAV patients. Biopsies of different affected territories should be pursued in difficult-to-diagnose patients based on their significant diagnostic yield.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Granulomatose com Poliangiite , Poliangiite Microscópica , Humanos , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/tratamento farmacológico , Poliangiite Microscópica/diagnóstico , Poliangiite Microscópica/complicações , Anticorpos Anticitoplasma de Neutrófilos/uso terapêutico , Estudos Retrospectivos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Mieloblastina , RecidivaRESUMO
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.
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Síndrome Antifosfolipídica , Trombose , Gravidez , Feminino , Humanos , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/tratamento farmacológico , Síndrome Antifosfolipídica/induzido quimicamente , Estudos Retrospectivos , Estudos Longitudinais , Trombose/induzido quimicamente , Anticoagulantes/uso terapêuticoRESUMO
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.
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INTRODUCTION: Antibodies to hexokinase 1 (HK1) and kelch-like 12 (KLHL12) have been identified as potential biomarkers in primary biliary cholangitis (PBC), and this study assesses changes of these antibodies over time and if they are associated with clinical outcomes. METHODS: Two hundred fifty-four PBC patients (93.3% female, 51 ± 12.3 years old) were tested for anti-HK1 and anti-KLHL12, antimitochondrial (AMA), anti-gp210, and anti-sp100 antibodies. One hundred sixty-nine patients were tested twice and 49 three times within 4.2 (0.8-10.0) years. Biochemistry and clinical features at diagnosis, response to therapy, events of decompensation, and liver-related death or transplantation were evaluated. RESULTS: Anti-HK1 and anti-KLHL2 were detected in 46.1% and 22.8% patients, respectively. AMA were positive in 93.7%, anti-sp100 in 26.4%, and anti-gp210 in 21.3% of patients. Anti-HK1 and anti-KLHL12 positivity changed over time in 13.3% and 5.5% of patients, respectively. Anti-HK1 or anti-KLHL12 were present in 37.5% of AMA-negative patients, and in 40% of AMA, anti-gp210, and anti-sp100 negative. No significant differences were observed between those with or without HK1 and KLHL12 antibodies, but transplant-free survival and time to liver decompensation were significantly lower in patients anti-HK1 positive (P = 0.039; P = 0.04) and in those anti-sp100 positive (P = 0.01; P = 0.007). No changes in survival and events of liver decompensation were observed according to the positivity of AMA, anti-KLHL12, or anti-gp210 antibodies. DISCUSSION: HK1 and KLHL12 antibodies are present in 40% of PBC patients who are seronegative by the conventional PBC-specific antibodies. The novel antibodies remain rather steady during the course of the disease, and HK1 antibodies are associated with unfavourable outcomes.
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Autoanticorpos/imunologia , Hexoquinase/imunologia , Cirrose Hepática Biliar/imunologia , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Adulto , Antígenos Nucleares/imunologia , Autoantígenos/imunologia , Colagogos e Coleréticos/uso terapêutico , Progressão da Doença , Feminino , Humanos , Imunossupressores/uso terapêutico , Cirrose Hepática Biliar/terapia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/imunologia , Complexo de Proteínas Formadoras de Poros Nucleares/imunologia , Prognóstico , Ácido Ursodesoxicólico/uso terapêuticoRESUMO
BACKGROUND AND AIMS: Recent studies have found an increase in the seroprevalence of hepatitis E virus (HEV) infection in patients with autoimmune hepatitis (AIH). We aimed to assess the prevalence of positive anti-HEV IgM and IgG, and HEV-RNA in a cohort of patients with AIH, to determine the impact of positive HEV serology on patient outcome, and to evaluate the role of hypergammaglobulinemia and positive autoantibodies in the presence of positive anti-HEV serology. METHODS: One hundred and five patients tested for HEV infection between 2014 and 2018 were included in the study: 50 with chronic AIH (more than 1 year on treatment), and 55 with an acute hepatitis (30 patients with acute AIH and 25 with non-AIH). RESULTS: Seroprevalence of HEV was higher in patients with acute AIH (17% vs 10% in patients with chronic AIH and 8% in patients with non-AIH). Patients with acute AIH and positive anti-HEV IgG were older (58 vs 40; P = .006), had higher IgG levels (27 g/dL vs 13 g/dL; P = .03) and antismooth muscle antibodies (ASMA) titres (1:160 vs 1:80; P = .045), and were more likely to have another autoimmune disease (60% vs 16%; P = .03). At the time of HEV testing, anti-HEV IgG positive patients had significantly higher serum IgG levels (17 g/L vs 11 g/L; P = .009), ANA (1:160 vs 1:60; P = .026) and ASMA titres (1:80 vs 1:40; P = .021). CONCLUSION: Seroprevalence of HEV in patients with AIH in Catalonia does not differ from that of the general population. The higher HEV seroprevalence in patients with acute AIH with higher levels of gammaglobulins and high antibody titres suggest the presence of cross-reactivity between HEV and liver antigens.
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Vírus da Hepatite E , Hepatite E , Hepatite Autoimune , Anticorpos Anti-Hepatite , Hepatite E/epidemiologia , Hepatite Autoimune/epidemiologia , Humanos , Imunoglobulina M , Estudos SoroepidemiológicosRESUMO
BACKGROUND: The feminization of medicine has risen dramatically over the past decades. The aim of this article was to compare the advance of women with that of men and determine the differences between hierarchical status and professional recognition achieved by women in medicine. METHODS: A retrospective study was carried out in the Hospital Clinic Barcelona, Spain, of the period from 1996 to 2008. Data relating to temporary and permanent positions, hierarchy and career promotion achieved, specialty, age and the sex of the participants were analysed with the ANOVA test and logistic regression using the generalized estimated equation. RESULTS: After completion of specialist training, fewer women than men doctors obtained permanent positions. The ratios between the proportions of women and men remained 1.2 for permanent non-hierarchal medical positions and below 0.2 for higher hierarchal levels. Fewer women than men with hierarchy and fewer women than men achieved the rank of consultant. Promotion to consultant and senior consultant was lower than that to senior specialist, being higher in specialties with gender parity and in masculinised specialties. On comparing the two genders using a statistical model, the probability of continuous promotion decreased with the year of the application and the age of the applicant, except in women. CONCLUSIONS: Despite the number of women training as specialists having increased to 50%, women remained in temporary positions twofold longer than men. Compared to women, men showed significant representation in hierarchal medical positions, and women showed a lower adjusted probability of internal professional promotion throughout the study period.
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Mobilidade Ocupacional , Emprego , Hospitais Universitários , Médicas/tendências , Direitos da Mulher , Feminino , Identidade de Gênero , Hospitais Universitários/tendências , Humanos , Masculino , Encaminhamento e Consulta , Estudos Retrospectivos , Espanha , Especialização , Recursos HumanosRESUMO
INTRODUCTION: This study assesses the accuracy of neutrophil activation markers, including neutrophil extracellular traps (NETs) and calprotectin, as biomarkers of disease activity in patients with established rheumatoid arthritis (RA). We also analyse the relationship between NETs and various types of therapies as well as their association with autoimmunity. METHODS: Observational cross-sectional study of patients with RA receiving treatment with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (JAK-inhibitors) for at least 3 months. Plasma calprotectin levels were measured using an enzyme-linked immunosorbent assay test kit and NETs by measuring their remnants in plasma (neutrophil elastase-DNA and histone-DNA complexes). We also assessed clinical disease activity, joint ultrasound findings and autoantibody status [reumatoid factor (RF), anti-citrullinated peptide/protein antibodies (ACPAs) and anti-carbamylated protein (anti-CarP)]. Associations between neutrophilic biomarkers and clinical or ultrasound scores were sought using correlation analysis. The discriminatory capacity of both neutrophilic biomarkers to detect ultrasound synovitis was analysed through receiver-operating characteristic (ROC) curves. RESULTS: One hundred fourteen patients were included. Two control groups were included to compare NET levels. The active control group consisted of 15 patients. The second control group consisted of 30 healthy subjects. Plasma NET levels did not correlate with clinical disease status, regardless of the clinic index analysed or the biological therapy administered. No significant correlation was observed between NET remnants and ultrasound synovitis. There was no correlation between plasma NET and autoantibodies. In contrast, plasma calprotectin positively correlated with clinical parameters (swollen joint count [SJC] rho = 0.49; P < 0.001, Clinical Disease Activity Index [CDAI] rho = 0.30; P < 0.001) and ultrasound parameters (rho > 0.50; P < 0.001). Notably, this correlation was stronger than that observed with acute phase reactants. CONCLUSION: While NET formation induced by neutrophils may play a role in RA pathogenesis, our study raises questions about the utility of NET remnants in peripheral circulation as a biomarker for inflammatory activity. In contrast, this study strongly supports the usefulness of calprotectin as a biomarker of inflammatory activity in patients with RA.
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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.
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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.
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OBJECTIVES: To evaluate how determination of antibodies against the Ro52 antigen influences the classification and clinical characterisation of patients with suspected primary Sjögren's syndrome (SS). METHODS: The cohort study included 187 patients who fulfilled at least four of the six 1993 SS classification criteria, including positive autoantibodies (antinuclear antibodies [ANA], rheumatoid factor [RF], anti-Ro/SSA and/or anti-La/SS-B antibodies) as mandatory criterium. Anti-Ro/SSA antibodies were tested by qualitative ELISA using a commercial assay. Anti-Ro52 antibodies were detected by a semiquantitative ELISA. RESULTS: Anti-Ro52 antibodies were found in 70/187 (37%) patients. A significant percentage of patients with anti-Ro/SSA antibodies were negative for anti-Ro52 antibodies (22%), while 13 patients (12%) were negative for anti-Ro/SSA antibodies but positive for anti-Ro52 antibodies, meaning that they fulfilled the 2002 SS criteria while avoiding the need for a salivary biopsy. Higher mean titers of anti-Ro52 antibodies were associated with severe scintigraphic involvement, positive salivary gland biopsy, parotid enlargement, anaemia, leukopenia and RF. A statistical correlation was found between anti-Ro52 titers and age, gammaglobulin levels, RF titers and serum IgA and IgG. Patients with positive anti-Ro/SSA and anti-Ro52 antibodies had a higher frequency of positive salivary gland biopsy, parotid enlargement and positive RF, and higher levels of serum IgG and IgA levels in comparison with patients with positive anti-Ro/SSA but negative anti-Ro52 antibodies. CONCLUSIONS: Anti-Ro52 antibodies were closely associated with the main clinical, histopathological and immunological features of primary SS. Anti-Ro52 autoantibody testing may help to identify a specific subset of SS patients with more aggressive disease, in whom a closer follow-up and earlier, more robust therapeutic management may be necessary.
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Anticorpos Antinucleares/sangue , Ribonucleoproteínas/imunologia , Síndrome de Sjogren/diagnóstico , Biomarcadores/sangue , Biópsia , Distribuição de Qui-Quadrado , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Fator Reumatoide/sangue , Glândulas Salivares/imunologia , Glândulas Salivares/patologia , Síndrome de Sjogren/sangue , Síndrome de Sjogren/classificação , Síndrome de Sjogren/imunologiaRESUMO
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.
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Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica , Humanos , Estudos Longitudinais , Inibidor de Coagulação do Lúpus , Imunoglobulina G , Anticorpos AnticardiolipinaRESUMO
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.
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Síndrome Antifosfolipídica , COVID-19 , Insuficiência Respiratória , Trombose , Idoso , Anticorpos Antifosfolipídeos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , SARS-CoV-2RESUMO
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.
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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.
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Anticorpos Anticardiolipina/sangue , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/imunologia , Autoantígenos/imunologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lúpus Eritematoso Sistêmico/imunologia , Fosfatidilserinas/imunologia , Protrombina/imunologia , Trombofilia/etiologia , beta 2-Glicoproteína I/imunologia , Adulto , Síndrome Antifosfolipídica/sangue , Doenças Autoimunes/sangue , Doenças Autoimunes/imunologia , Biomarcadores , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Inibidor de Coagulação do Lúpus/sangue , Lúpus Eritematoso Sistêmico/sangue , Masculino , Pessoa de Meia-Idade , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/imunologia , Estudos Retrospectivos , Risco , Trombofilia/sangue , Fatores de TempoRESUMO
OBJECTIVE: In patients with antinuclear antibodies (ANA) and undifferentiated features of systemic autoimmune disease, the coexistence of monospecific anti-dense fine speckled 70 (anti-DFS70) antibodies is associated with a lower risk of progression to overt disease. Therefore, they might help in correctly classifying ANA- positive patients and avoiding unnecessary followup diagnostic procedures. The aim of this study was to analyze the economic effect of the introduction of the anti-DFS70 antibody test in a hospital setting. METHODS: A case-control study was performed to detect monospecific anti-DFS70 antibodies in ANA-positive subjects with undifferentiated features (cases, n = 124) and with a defined systemic autoimmune disease (controls, n = 290). Based on current clinical practice, a decision tree was developed to represent the disease course of patients with undifferentiated features in the subsequent 3 years. A budget impact analysis (BIA) was performed to estimate the effect of implementing the screening for anti-DFS70 antibodies in the case group on the total costs. A sensitivity analysis was conducted to calculate the effect of the uncertainty of the input variables on the results. RESULTS: Among the 124 patients in the case group, 5 (4.0%) tested positive for anti-DFS70 antibodies versus 4/290 (1.4%) in the control group (p = not significant). The mean cost per patient under the current clinical practice decreased from 3274 to 3192 in our scenario. The BIA reports cost savings of 10,128. CONCLUSION: The introduction of anti-DFS70 antibody test would avoid unnecessary followup diagnostic procedures and minimize the use of health resources generated by suspicion of a potential systemic autoimmune disease.
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Doenças Autoimunes , Proteínas Adaptadoras de Transdução de Sinal , Anticorpos Antinucleares , Doenças Autoimunes/diagnóstico , Estudos de Casos e Controles , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Fatores de TranscriçãoRESUMO
BACKGROUND: M-type phospholipase A2 receptor (APLA2R) is considered the major antigen involved in the pathogenesis of adult primary membranous nephropathy (MN), which is the leading cause of non-diabetic nephrotic syndrome. Antibodies to this antigen have been proved to be an excellent biomarker of disease activity in primary MN. In fact, preliminary data suggest that the higher the antibody level the more proteinuria, and that a decrease in antibody level precedes the remission of proteinuria, but more solid evidence is needed. METHODS: The present work aims to characterize the predictive value of the level of antibodies against PLA2R as a biomarker of disease course and treatment response in a well-defined cohort of 62 patients from University Hospitals Clinic of Barcelona and Josep Trueta in Girona. The primary outcome was the appearance of a spontaneous complete remission (CR), defined as induction of a CR without the use of immunosuppressive agents. RESULTS: In common with other reports, this work confirms that spontaneous CR is more frequent in patients with low titre of APLA2R at diagnosis, but strikingly, in this cohort we found that spontaneous CR was achieved in patients with APLA2R levels <40 UI/mL. Furthermore, spontaneous CR were less frequently observed in patients with proteinuria >8 g/day. CONCLUSIONS: In conclusion, these findings point out the important role of APLA2R as a tool to predict the disease course and establish personalized therapeutic options at the moment of diagnosis of primary MN. Specifically, patients with low titre of APLA2R (<40 UI/mL) and proteinuria <4/day could obtain benefit of a longer period of follow-up with conservative treatment after diagnosis.
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Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is present worldwide. Autoantibodies, in particular anti-mitochondrial antibodies (AMA) detected by indirect immunofluorescence assays or newer solid phase immunoassays can detect most, but not all individuals with PBC. Detection of antibodies to the anti-nuclear antigens sp100 and gp210 can identify additional PBC patients, but some seronegative patients remain, often resulting in delayed diagnosis and treatment. Antibodies to kelch-like 12 (KLHL12) and hexokinase 1 (HK-1) were recently identified as new biomarkers for PBC and notably identify patients who are negative for conventional autoantibodies. To become globally adopted, it is important to validate these new biomarkers in different geographic areas. In the present study we evaluated the prevalence of anti-KLHL12 (measured by a KLHL12-derived peptide referred to as KL-p) and anti-HK-1 antibodies by ELISA at five sites within Europe and North America and demonstrated the presence of these antibodies in patients with PBC in all geographies.
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Proteínas Adaptadoras de Transdução de Sinal , Autoanticorpos/sangue , Hexoquinase , Cirrose Hepática Biliar/sangue , Peptídeos , Biomarcadores/sangue , Feminino , Humanos , MasculinoRESUMO
OBJECTIVE: It has been hypothesized that monoclonal antibody D8/17 identifies a B lymphocyte antigen with expanded expression in patients with rheumatic fever, childhood onset obsessive-compulsive disorder (OCD), Tourette syndrome (TS) or prepubertal anorexia nervosa (AN). Our purpose was to replicate these studies in a Spanish population and to determine whether D8/17 identifies a subgroup of these patients, focusing especially on OCD subjects. METHOD: D8/17 expression was assessed with double immunofluorescence and flow cytometry using monoclonal immunoglobulin M (IgM) in three groups of patients with diagnoses of OCD (n = 17), TS (n = 5) and prepubertal AN (n = 5), recruited during 2001. RESULTS: In the sample studied the average percentage of B cells expressing D8/17 was 4.8%. The D8/17 positive proportion of B lymphocytes was above 11% in only two out of 17 OCD patients (7.4% of total sample) and in none of the TS or prepubertal AN patients. No statistically significant differences were found in mean percentages of D8/17 between the three groups. CONCLUSIONS: In the sample studied the expression of D8/17 in B cells was very low and the great majority of patients were negative for the D8/17 marker. The molecular characterization of D8/17 would be a major step forward in clarifying its implication for these diseases.
Assuntos
Anticorpos Monoclonais/sangue , Linfócitos B/imunologia , Transtorno Obsessivo-Compulsivo/imunologia , Adolescente , Biomarcadores/sangue , Criança , Feminino , Citometria de Fluxo , Humanos , Imunoglobulina M/sangue , Masculino , Transtorno Obsessivo-Compulsivo/sangueRESUMO
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Assuntos
Humanos , Doença Relacionada a Imunoglobulina G4/imunologia , Hepatite Autoimune/imunologia , Colangite/imunologia , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/diagnóstico , Colangite/tratamento farmacológico , Colangite/diagnósticoRESUMO
BACKGROUND: Secretory phospholipase A2 receptor (PLA2R) is the target antigen of the auto-antibodies produced in most (â¼ 70%) patients with primary membranous nephropathy (pMN). The applicability of anti-PLA2R1 antibody monitoring for the prediction of MN recurrence in kidney transplant recipients still is a matter of debate. METHODS: We sought to characterize the presence and concentration of anti-PLA2R antibodies by enzyme-linked immunosorbent assay (ELISA) in a cohort of 21 patients with pMN before and after transplantation to evaluate whether anti-PLA2R concentrations could predict pMN recurrence. RESULTS: The presence of pMN recurrence was significantly correlated with the existence of a positive ELISA assay at graft biopsy or with high level of anti-PLA2R1 activity before transplantation (P = 0.03). In the receiver operating characteristic analysis, anti-PLA2R levels (cut-off of 45 U/mL) during the pretransplantation period accurately predicted pMN recurrence, with a sensitivity of 85.3%, specificity of 85.1%, negative predictive value of 92%, and an area under the curve of 90.8%. This finding supports the hypothesis that anti-PLA2R cause pMN recurrence in humans and indicates the need to prove in an experimental model. Furthermore, 6 of 7 patients with recurrence were carriers of HLA DQA1* 05:01/05 and DQB1* 02:01, confirming these DQ alleles as those associated with higher anti-PLA2R levels. CONCLUSIONS: This study is the first to demonstrate pretransplantation circulating anti-PLA2R antibodies in a cohort of renal transplant recipients who prospectively developed recurrent disease. Currently, anti-PLA2R levels measured by ELISA may be a rational tool to establish the risk of MN recurrence in renal allograft recipients.