RESUMO
Systemic lupus erythematosus and rheumatoid arthritis are autoimmune diseases characterised by B-cell hyperactivation and production of autoantibodies (AutoAbs) against various self-antigens, including extractable nuclear antigens and citrullinated peptides. Therefore, B lymphocytes and antibody-secreting cells are considered relevant targets for therapies. However, isolation and characterisation of auto-reactive specific B lymphocytes are limited, primarily due to technical issues. In this work, we purified extractable nuclear antigen-specific and citrullinated peptide-specific auto-reactive B lymphocytes by magnetic selection with ENA- and citrullinated peptide-bound immunobeads. We obtained blood auto-reactive B lymphocytes from most patients. Their nature was primarily naïve B cells, some of them in an active status, with low levels of somatic hypermutations in the immunoglobulin heavy-chain variable regions. Their presence correlated with serum levels of autoAb. Auto-reactive B lymphocytes were able to differentiate into auto-reactive antibody-secreting cells under conditions of stimulation. In addition, based on the presence of circulating auto-reactive B cells and/or antibody-secreting cells, four different profiles were described in lupus patients. Thus, tracking auto-reactive B cells and/or antibody-secreting cells in patient blood could represent a biomarker for deciding whether to use therapies blocking either B cells, plasma cells or both, as well as a new tool for monitoring minimal residual autoimmune disease in patients.
Assuntos
Antígenos Nucleares/metabolismo , Artrite Reumatoide/imunologia , Linfócitos B/imunologia , Separação Imunomagnética/métodos , Lúpus Eritematoso Sistêmico/imunologia , Adolescente , Adulto , Idoso , Autoantígenos/imunologia , Biomarcadores , Células Cultivadas , Citrulinação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ligação Proteica , Adulto JovemRESUMO
BACKGROUND/OBJECTIVE: Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis that often results in frequent hospitalizations. We investigated the characteristics and predictors of 30-day hospital readmissions in GPA. METHODS: We performed a cross-sectional analysis using the 2014 National Readmission Database. We included nonelective admissions with a primary or secondary diagnosis of GPA. We compared characteristics between readmissions and nonreadmissions. Independent predictors for readmissions were studied using mixed-effects multivariable logistic regression. RESULTS: We evaluated a total of 9749 hospital admissions with GPA, among which there were 2173 readmissions (22.3%) within 30 days of discharge. The top 5 primary reasons for readmissions were GPA, sepsis, pneumonia, acute respiratory failure, and acute kidney injury. Granulomatosis with polyangiitis readmissions were associated with higher length of stay (8.0 vs 7.2 days; p = 0.019) and less discharge home (50% vs 63%, p < 0.001). Independent predictors for readmissions were younger age (odds ratio [OR], 0.99; p = 0.013), no private insurance (OR, 0.50; p < 0.001), higher Charlson Comorbidity Index (OR, 1.12; p = 0.039), congestive heart failure (OR, 1.71; p = 0.001), acute kidney injury (OR, 1.39; p = 0.005), and discharge to home health care (OR, 1.29; p = 0.039). CONCLUSIONS: We found a significant burden of 30-day readmissions among GPA populations. Clinicians should be vigilant regarding patients with high risk of readmissions, including those with younger age, public insurance, higher comorbidity burden, cardiac and renal complications, and unfavorable discharge dispositions.
Assuntos
Granulomatose com Poliangiite , Readmissão do Paciente , Estudos Transversais , Bases de Dados Factuais , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/epidemiologia , Granulomatose com Poliangiite/terapia , Hospitais , Humanos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologiaRESUMO
Disturbances of plasma cell homeostasis and auto-antibody production are hallmarks of systemic lupus erythematosus. The aim of this study was to explore the presence of circulating anti-ENA and anti-dsDNA antibody-secreting cells, to determine their dependence on plasma cell-niche cytokines and to analyze their clinical value. The study was performed in SLE patients with serum anti-ENA and/or anti-dsDNA antibodies (n = 57). Enriched B-cell fractions and sorted antibody-secreting cells (CD19low CD38high ) were obtained from blood. dsDNA- and ENA-specific antibody-secreting cells were identified as cells capable of active auto-antibody production in culture. The addition of a combination of IL-6, IL-21, BAFF, APRIL, and CXCL12 to the cultures significantly augmented auto-antibody production and antibody-secreting cell proliferation, whereas it diminished apoptosis. The effect on auto-antibody production was dependent on STAT-3 activation as it was abrogated in the presence of the JAK/STAT-3 pathway inhibitors ruxolitinib and stattic. Among patients with serum anti-dsDNA antibodies, the detection of circulating anti-dsDNA-antibody-secreting cells was associated with higher disease activity markers. In conclusion, auto-antibody production in response to plasma cell-niche cytokines that are usually at high levels in SLE patients is dependent on JAK/STAT-3 activation. Thus, patients with circulating anti-dsDNA antibody-secreting cells and active disease could potentially benefit from therapies targeting the JAK/STAT3 pathway.
Assuntos
Anticorpos Antinucleares/sangue , Células Produtoras de Anticorpos/imunologia , DNA/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Fator de Transcrição STAT3/metabolismo , Adolescente , Adulto , Idoso , Anticorpos Antinucleares/imunologia , Células Produtoras de Anticorpos/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Fator Ativador de Células B/farmacologia , Proliferação de Células , Quimiocina CXCL2/farmacologia , Óxidos S-Cíclicos/farmacologia , DNA/sangue , Feminino , Humanos , Interleucina-6/farmacologia , Interleucinas/farmacologia , Lúpus Eritematoso Sistêmico/sangue , Masculino , Pessoa de Meia-Idade , Nitrilas , Pirazóis/farmacologia , Pirimidinas , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/farmacologia , Adulto JovemAssuntos
Teste de Degranulação de Basófilos/métodos , Dessensibilização Imunológica/métodos , Hipersensibilidade a Drogas/prevenção & controle , Imunoconjugados/efeitos adversos , Adulto , Brentuximab Vedotin , Feminino , Doença de Hodgkin/tratamento farmacológico , Humanos , Imunoconjugados/imunologia , Masculino , Pessoa de Meia-IdadeAssuntos
Infecções Comunitárias Adquiridas/diagnóstico , Eosinófilos/imunologia , Doenças Pulmonares Intersticiais/diagnóstico , Neutrófilos/imunologia , Pneumonia/diagnóstico , Treonina-tRNA Ligase/imunologia , Adulto , Alanina Transaminase/sangue , Autoanticorpos/sangue , Proteína C-Reativa/metabolismo , Ciclofosfamida/administração & dosagem , Diagnóstico Diferencial , Humanos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/imunologia , Masculino , Metilprednisolona/administração & dosagem , Radiografia Torácica , SíndromeRESUMO
Rheumatoid arthritis (RA) prevalence is believed to be around 1% worldwide, although it varies considerably among different populations. The aim of EPISER2016 study was to estimate the prevalence of RA in the general adult population in Spain. We designed a population-based cross-sectional study. A national survey was conducted between November 2016 and October 2017 involving a probabilistic sample from the general population aged 20 years or older. Subjects were randomly selected for phone screening using a computer-assisted telephone interviewer system. Positive RA screening results were evaluated by a rheumatologist. Cases fulfilled the 1987 ACR and/or the 2010 ACR/EULAR criteria; previous diagnosis established by a rheumatologist and clearly identified in medical records were also accepted regardless of the criteria used. Prevalence estimates with 95% CI were calculated taking into account the design of the sample (weighting based on age, sex, and geographic origin using as a reference the distribution of the population in Spain). 4916 subjects participated in the study and 39 RA cases were confirmed. RA estimated prevalence was 0.82% (95% CI 0.59-1.15). Mean age of RA cases was 60.48 (14.85) years, they were more frequently women (61.5%), from urban areas (74.4%), non-smokers (43.6%), and with a high body mass index (53.8% with overweight). Extrapolating to the population in Spain (approximately 37 million are ≥ 20 years old), it was estimated that there were between 220,000 and 430,000 people aged 20 years or older with RA. No undiagnosed cases were detected, which could be related to the establishment of early arthritis clinics around the country, increasing the rates of diagnosis during early phases of RA.
Assuntos
Artrite Reumatoide/epidemiologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Distribuição por Sexo , Fatores Sexuais , Espanha/epidemiologia , Adulto JovemRESUMO
Objectives: To investigate the incidence of COVID-19 in a cohort of adult and paediatric patients with rheumatic diseases receiving targeted biologic and synthetic disease modifying anti-rheumatic drugs (tDMARDs) and to explore the possible effect of these treatments in the clinical expression of COVID-19. Methods: A cross-sectional study comprising of a telephone survey and electronic health records review was performed including all adult and paediatric patients with rheumatic diseases treated with tDMARDs in a large rheumatology tertiary centre in Barcelona, Spain. Demographics, disease activity, COVID-19 related symptoms and contact history data were obtained from the start of the 2020 pandemic. Cumulative incidence of confirmed cases (SARS-CoV-2 positive PCR test) was compared to the population estimates for the same city districts from a governmental COVID-19 health database. Suspected cases were defined following WHO criteria and compared to those without compatible symptoms. Results: 959 patients with rheumatic diseases treated with tDMARDs were included. We identified 11 confirmed SARS-CoV-2 positive cases in the adult cohort and no confirmed positive cases in the paediatric cohort. COVID-19 incidence rates of the rheumatic patient cohort were very similar to that of the general population [(0.48% (95% CI 0.09 to 0.87%)] and [0.58% (95% CI 0.56 to 0.60%)], respectively. We found significant differences in tDMARDs proportions between the suspected and non-suspected cases (p=0.002). Conclusion: Adult and paediatric patients with rheumatic diseases on tDMARDs do not seem to present a higher risk of COVID-19 or a more severe disease outcome when compared to general population.