RESUMO
INTRODUCTION: Vaccination represents a cornerstone in mastering the COVID-19 pandemic. Data on immunogenicity and safety of messenger RNA (mRNA) vaccines in patients with autoimmune inflammatory rheumatic diseases (AIIRD) are limited. METHODS: A multicentre observational study evaluated the immunogenicity and safety of the two-dose regimen BNT162b2 mRNA vaccine in adult patients with AIIRD (n=686) compared with the general population (n=121). Serum IgG antibody levels against SARS-CoV-2 spike S1/S2 proteins were measured 2-6 weeks after the second vaccine dose. Seropositivity was defined as IgG ≥15 binding antibody units (BAU)/mL. Vaccination efficacy, safety, and disease activity were assessed within 6 weeks after the second vaccine dose. RESULTS: Following vaccination, the seropositivity rate and S1/S2 IgG levels were significantly lower among patients with AIIRD versus controls (86% (n=590) vs 100%, p<0.0001 and 132.9±91.7 vs 218.6±82.06 BAU/mL, p<0.0001, respectively). Risk factors for reduced immunogenicity included older age and treatment with glucocorticoids, rituximab, mycophenolate mofetil (MMF), and abatacept. Rituximab was the main cause of a seronegative response (39% seropositivity). There were no postvaccination symptomatic cases of COVID-19 among patients with AIIRD and one mild case in the control group. Major adverse events in patients with AIIRD included death (n=2) several weeks after the second vaccine dose, non-disseminated herpes zoster (n=6), uveitis (n=2), and pericarditis (n=1). Postvaccination disease activity remained stable in the majority of patients. CONCLUSION: mRNA BNTb262 vaccine was immunogenic in the majority of patients with AIIRD, with an acceptable safety profile. Treatment with glucocorticoids, rituximab, MMF, and abatacept was associated with a significantly reduced BNT162b2-induced immunogenicity.
Assuntos
Doenças Autoimunes/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Hospedeiro Imunocomprometido/imunologia , Imunogenicidade da Vacina/imunologia , Doenças Reumáticas/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Doenças Autoimunes/tratamento farmacológico , Vacina BNT162 , Vacinas contra COVID-19/efeitos adversos , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doenças Reumáticas/tratamento farmacológico , SARS-CoV-2 , Adulto JovemRESUMO
OBJECTIVES: We aimed to assess the immunogenicity and safety of vaccination against seasonal influenza in psoriatic arthritis (PsA) and psoriasis (Pso) patients. METHODS: Patients with PsA or Pso and healthy controls were vaccinated with the Sanofi Pasteur vaccine recommended by the WHO in 2012. Clinical and laboratory assessments were performed on the day of the vaccination and 4-6 weeks later. The immunogenicity of the vaccine was evaluated by haemagglutination inhibition assay. RESULTS: The study included 63 consecutive PsA patients and 4 Pso patients (mean age 50.1, 37 females, 30 males, 55.2% treated with tumour necrosis factor alpha blockers [TNF-α], 31.3% on disease-modifying anti-rheumatic drugs [DMARDs]) and 30 healthy controls. The geometric mean titers increased significantly in all participants for each of the subtypes tested. A substantial and similar proportion of patients in both groups responded to the vaccine. The response rate was not affected by parameters such as age, gender, disease activity or the use of TNF-α blockers or DMARDs. There were no significant changes in the patients' 68 tender and 66 swollen joint counts, dactylitis, PASI, global evaluation of the patient and physician and ESR, while there was a rise in CRP levels. CONCLUSIONS: Vaccination against seasonal influenza is safe and induces an appropriate response in patients with PsA, similar to healthy controls.
Assuntos
Artrite Psoriásica/imunologia , Imunização , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza B/imunologia , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Psoríase/imunologia , Estações do Ano , Adulto , Anticorpos Antivirais/sangue , Artrite Psoriásica/sangue , Artrite Psoriásica/diagnóstico , Estudos de Casos e Controles , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/imunologia , Influenza Humana/sangue , Influenza Humana/diagnóstico , Influenza Humana/imunologia , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Psoríase/sangue , Psoríase/diagnóstico , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Memory impairment is prevalent in systemic lupus erythematosus (SLE); however, the pathogenesis is unknown. METHODS: We studied 12 patients with SLE without clinically overt neuropsychiatric manifestations and 11 matched healthy controls, aiming to characterize neural correlates of memory impairment, using structural and functional magnetic resonance imaging (MRI). The paradigm consisted of three encoding and free-recall cycles, allowing characterization of dynamics along consecutive retrieval attempts. RESULTS: During learning, patients with SLE and healthy controls showed brain activity changes in two principal networks, the default mode network (DMN) and the task-positive network (TPN). Patients with SLE demonstrated significantly less deactivation in the DMN and greater activation in the TPN, reflecting greater recruitment of both networks. The anterior medial prefrontal cortex (amPFC) of the DMN emerged as the only region where brain activity dynamics were altered both over the learning process (p < 0.006), and within free-recall period attempts (p < 0.034). Patients showed significant positive correlations between learning efficiency and hippocampal activity, and greater hippocampal functional connectivity, with pronounced connectivity to DMN structures. CONCLUSIONS: Increased brain activation in patients with SLE during learning may reflect compensatory mechanisms to overcome memory impairment. Our findings localize this impairment to the amPFC, consistent with the behavioral pattern seen in SLE. Altered networking of the hippocampal subsystem of the DMN is consistent with hippocampal neuronal damage seen in SLE, and may reflect compensatory cortical reorganization to cope with dysfunction in these regions pivotal to mnemonic functions.
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Lúpus Eritematoso Sistêmico/fisiopatologia , Imageamento por Ressonância Magnética , Transtornos da Memória/fisiopatologia , Rememoração Mental/fisiologia , Adulto , Mapeamento Encefálico , Estudos de Casos e Controles , Feminino , Hipocampo/metabolismo , Humanos , Aprendizagem/fisiologia , Transtornos da Memória/etiologia , Pessoa de Meia-Idade , Vias Neurais/fisiologia , Neurônios/patologia , Córtex Pré-Frontal/metabolismo , Adulto JovemRESUMO
OBJECTIVES: To assess the efficacy and safety of the influenza virus vaccine in systemic sclerosis (SSc) patients compared to healthy controls. METHODS: Twenty-six SSc patients and 16 healthy controls were vaccinated with a trivalent influenza subunit vaccine (H1N1 A/Brisbane/59/2007(TGA 2008/81B) (H1N1), H3N2 A/Uruguay/716/2007 (A/Brisbane/10/2007-like, NIBSC8/124) (H3N2) and B B/Brisbane/60/2008 (TGA 2009/82/B) (B)). The subjects were evaluated on the day of vaccination and 6 weeks later. Disease activity was assessed by the Rodnan score, number of ulcers, number of tender and swollen joints, the presence of dyspnea, cough, dyspepsia and dysphagia, and patient (PDAI) and physician (PHDAI) disease activity evaluation by the visual activity score (VAS), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level. The humoral response was evaluated by haemagglutination inhibition (HI). RESULTS: At baseline, 62%, 15% and 88% of the SSc patients had protective levels against H1N1, H3N2 and B, respectively, versus 56%, 62% and 87% for controls. Six weeks later, the proportion of responders to H1N1 was significantly higher in the SSc patients (73%) compared to controls (37.5%) (p=0.0225). The proportion of responders to H3N2 and B was similar in both groups, and both had a significant increase in geometric mean titers for each antigen. A lower response to H1N1 was associated with interstitial lung disease, while patients on combination calcium channel blockers and iloprost therapy showed significantly better response to H1N1 and B antigens. Most underlying disease activity parameters remained unchanged. CONCLUSIONS: The influenza virus vaccine was safe and generated a satisfactory humoral response in SSc patients.
Assuntos
Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza B/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Escleroderma Sistêmico/complicações , Adulto , Anticorpos Antivirais/sangue , Estudos de Casos e Controles , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Imunidade Humoral/efeitos dos fármacos , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/efeitos adversos , Influenza Humana/complicações , Influenza Humana/imunologia , Influenza Humana/virologia , Israel , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/imunologia , Fatores de Tempo , Resultado do Tratamento , VacinaçãoRESUMO
OBJECTIVES: To assess the effect of vaccination against streptococcus pneumoniae on the generation of autoantibodies in patients with SLE. MATERIALS AND METHODS: Twenty-four consecutive patients with SLE were vaccinated against streptococcus pneumoniae. Assessment was performed the day of vaccination and 2 months later and included evaluation of disease activity using the SLEDAI, serum levels of ESR, CRP, C3 and C4. The sera of the patients were tested by ELISA for anti-dsDNA, anticardiolipin (IgG and IgM), anti-Sm, anti-nRNP, anti-Ro/SSA, and anti-La/SSB. RESULTS: The mean age at enrollment into the study was 39, mean disease duration 6.9 years. The SLEDAI score (mean +/- SD) was 4.41 +/- 2.92 at the time of vaccination and 4.47 +/- 3.11, 2 months apart. At the time of vaccination, 10 patients had anti-dsDNA, 2 patients had anti-Sm, 5 had anti-nRNP, and 9 had anti-Ro/SSA, 4 had anti-La/SSB, 4 had anticardiolipin IgG and IgM. Two months after vaccination, no change was observed in the proportion of patients with anti-Sm, anti-dsDNA, anti-RNP, anti-Ro/SSA and anticardiolipin IgM. A single patient developed anticardiolipin IgG and another one turned anti-RNP negative. CONCLUSIONS: Vaccination against streptococcus pneumoniae did not trigger the generation of autoantibodies and confirms the clinical safety of this vaccine in SLE patients.
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Anticorpos Antibacterianos/biossíntese , Autoanticorpos/biossíntese , Lúpus Eritematoso Sistêmico/imunologia , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/imunologia , Adulto , Anticorpos Antibacterianos/sangue , Autoanticorpos/sangue , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologiaRESUMO
OBJECTIVE: The longterm use of tumor necrosis factor (TNF)-α blockers is limited by the formation of neutralizing antibodies. To the best of our knowledge, immunogenicity in psoriatic arthritis (PsA) has not been investigated in depth. Our objective was to evaluate the prevalence and significance of TNF-α blocker immunogenicity in PsA. METHODS: Consecutive patients with PsA treated with either infliximab (IFX), adalimumab (ADA), or etanercept (ETN) > 3 months participated in our cross-sectional study. Their demographic and clinical characteristics, skin and joint disease activity, and records of use of methotrexate (MTX) and other medications were collected. Drug levels (ELISA) and antidrug antibodies (ADAb; Bridging ELISA) were evaluated before the next injection or infusion. RESULTS: A total of 93 patients with PsA were recruited (48 receiving ADA, 24 IFX, and 21 ETN), with a mean age of 53 years (range 21-83 yrs), composed of 53% women. One-fourth of the patients were concomitantly treated with MTX. Altogether, 77% of the patients demonstrated therapeutic drug levels. High levels of ADAb were found in 29% of patients taking ADA, 21% taking IFX, and 0% taking ETN. ADAb significantly correlated with lower drug levels, higher 28-joint Disease Activity Scores, and higher global assessments. MTX use correlated significantly with a lower prevalence of ADAb. CONCLUSION: Significant levels of ADAb were present in up to 29% of patients with PsA treated with ADA or IFX. ADAb clearly correlated with low therapeutic drug levels and higher disease activity variables. The use of MTX significantly decreased ADAb prevalence, and its use should be strongly considered in combination with TNF-α blocker antibodies in patients with PsA.
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Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Antirreumáticos/imunologia , Artrite Psoriásica/imunologia , Imunoglobulina G/imunologia , Receptores do Fator de Necrose Tumoral/imunologia , Adalimumab , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Estudos Transversais , Etanercepte , Feminino , Humanos , Imunoglobulina G/uso terapêutico , Infliximab , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Receptores do Fator de Necrose Tumoral/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto JovemRESUMO
BACKGROUND: Statins (3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors) exert favorable effects on lipoprotein metabolism, but appeared to possess anti-inflammatory properties among others, as suggested by their ability to inhibit collagen-induced arthritis in mice. Their activity in fibroblast-like synovial cells (FLS) has not yet been studied. OBJECTIVES: To evaluate the effect of varying doses of simvastatin on apoptosis of FLS. METHODS: Synovial tissue, obtained during total knee replacement due to osteoarthritis, was cut into small pieces and cultured in Petri dishes with test materials, as previously described. FLS were incubated for 48 hours with 1 mumol/ml, 5 mumol/ ml, 15 mumol/ml and 50 mumol/ml of simvastatin. Following incubation, apoptosis was analyzed by two-dimensional flow cytometry (FACS) using annexin V/PI staining according to the manufacturer's instructions. RESULTS: Different concentrations of simvastatin induced apoptosis of FLS. The level proportion of apoptotic cells of resting or activated with lipopolysaccharide (LPS; 3 mug/ml) FLS, not treated with simvastatin, was 21%. At 48 hours, the rate of apoptosis of activated fibroblasts, incubated with 1 mumol/ml, 5 mumol/ml, 15 and 50 mumol/ml was 22%, 32%, 48% and 41% respectively. Synovial cell viability evaluated by tetrazolium salt XXT was unaffected by the simvastatin concentration used. CONCLUSION: Varying concentrations of simvastatin induce apoptosis of activated fibroblast-like synoviocytes, suggesting another possible mechanism of anti-inflammatory effects of statins in inflammatory conditions.