Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 94
Filtrar
1.
Lupus ; 32(5): 675-679, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36952594

RESUMO

INTRODUCTION: Over 95% of healthy subjects develop anti-COVID IgG antibodies after receiving two doses of BNT162b2 COVID-19 vaccine. In comparison, 20%-30% of SLE patients do not seroconvert following 1-2 doses of COVID vaccines, potentially due to immunosuppression. The aim of this study was to assess immunogenicity and safety of BNT vaccine in SLE patients treated with Belimumab and especially the yield of a booster third dose in this population. METHODS: SLE patients treated with Belimumab in the Sheba Medical Center, Israel, were included in this study. All were recommended to receive the BNT vaccine according to national guidelines; and were advised to perform serologic tests after receiving second and third doses. Clinical data included demographics, SLE treatments, adverse effects to vaccines and SLEDAI scores performed 2 weeks before vaccinations and 6-12 weeks after receiving the second or third dose of the vaccine. RESULTS: Our cohort included 17 patients, 14 (82.35%) females, median age 50 ± 14.2 years, and disease duration 12 ± 10.57 years. Belimumab therapy was given for a mean of 6 ± 2.5 years. Of them, 15/17 patients received 3-doses of BNT vaccine. Serologic assessment was performed for 10 patients, 7/10(70%) became seropositive following the second dose, while 2/3 patients seroconverted only after the third dose. Vaccinations were well tolerated with minimal adverse events and no disease flares. SLEDAI scores before and after vaccinations were 4 ± 3.8 and 4 ± 2.7 (p = 0.69), respectively. CONCLUSIONS: Immunization with the BNT vaccine is efficacious and safe for SLE patients treated with Belimumab. Following the third dose of vaccine, immunogenicity among SLE patients mounted to 90%, thereby approximating the general healthy population. No SLE disease flares and/or significant adverse events were noted in our cohort. Assessment of seroconversion and consideration of subsequent boosters of COVID-vaccine should be considered in this group of patients.


Assuntos
COVID-19 , Lúpus Eritematoso Sistêmico , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Masculino , Vacinas contra COVID-19 , Vacina BNT162 , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Resultado do Tratamento , Anticorpos Antivirais
2.
Isr Med Assoc J ; 23(6): 350-352, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34155847

RESUMO

BACKGROUND: Granulomatosis with polyangiitis (GPA) is a rare small vessel vasculitis. It usually involves the respiratory tract and kidney. Rarely, tumor-resembling inflammatory changes ensue. OBJECTIVES: To report three unique cases of GPA presenting with tumor-like lesions in various organs. METHODS: We presented three cases of GPA. Case 1 presented with typical upper respiratory symptoms of GPA and a mediastinal mass. Case 2 presented with low back pain, a large retroperitoneal mass, and nodular skin lesions. Case 3 presented with epigastric pain and a paravertebral inflammatory mass. RESULTS: The patients were treated successfully with rituximab. CONCLUSIONS: Clinicians should be aware of this presentation of granulomatosis with polyangiitis, which is known as Tumefaction Wegener's granulomatosis.


Assuntos
Granulomatose com Poliangiite , Neoplasias Renais/diagnóstico , Neoplasias do Mediastino/diagnóstico , Neoplasias Retroperitoneais/diagnóstico , Rituximab/administração & dosagem , Adulto , Anticorpos Anticitoplasma de Neutrófilos/sangue , Biomarcadores/sangue , Biópsia/métodos , Diagnóstico Diferencial , Feminino , Granuloma/patologia , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/tratamento farmacológico , Granulomatose com Poliangiite/patologia , Granulomatose com Poliangiite/fisiopatologia , Humanos , Imunossupressores/administração & dosagem , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Mieloblastina/imunologia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
3.
Eur J Clin Invest ; 50(9): e13268, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32478417

RESUMO

BACKGROUND: Mood disorders, such as anxiety and depression, are extremely prevalent among patients with rheumatoid arthritis (RA). In this study, we assessed the impact of treatment with tocilizumab (TCZ), an IL-6 antagonist, upon anxiety and depressive symptoms in a cohort of RA patients. MATERIALS AND METHODS: Study participants were adults diagnosed with RA who received a weekly subcutaneous injection of tocilizumab for 24 weeks. We used the Hamilton Depression (HDRS) and Anxiety (HAMA) scores in order to assess the severity of depression and anxiety, respectively. RA disease activity indices and depression and anxiety levels were assessed at baseline, 4 weeks and study completion. RESULTS: Ultimately, 91 patients were included in the study. The mean age was 54 years, and the majority were female (79%). The mean score in all disease activity indices as well as depression and anxiety levels decreased dramatically from baseline to study completion. Sixty patients (66%) demonstrated a significant decrease in anxiety and/or depression levels. When logistic regression was performed, an HDRS score indicative of depression at study baseline demonstrated an independent association with a significant psychiatric response whilst older age and increased baseline weight were negatively associated. HAMA and HDRA scores correlated with the following RA disease activity parameters, respectively; HAQ-DI (r = .4, .42), DAS28 (r = .29, .32) and CDAI (0.28 and 0.33), all of them were statistically significant (P < .01). CONCLUSIONS: This study has demonstrated a favourable impact of TCZ therapy on parameters reflecting depression and anxiety severity in patients with RA.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Ansiedade/psicologia , Artrite Reumatoide/tratamento farmacológico , Depressão/psicologia , Adulto , Fatores Etários , Idoso , Artrite Reumatoide/fisiopatologia , Artrite Reumatoide/psicologia , Peso Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento
4.
Isr Med Assoc J ; 22(9): 557-563, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33236554

RESUMO

BACKGROUND: Tocilizumab is an interleukin 6 (IL-6) receptor antagonist used treat moderate to severe active rheumatoid arthritis (RA). Both intravenous (IV) and subcutaneous (SC) routes are approved for the treatment of adults with RA. OBJECTIVES: To evaluate SC tocilizumab in a real-life clinical setting. METHODS: Our study was a multi-center, open-label, single-arm study. Participants were adults with a diagnosis of active RA, previously treated with disease-modifying antirheumatic drugs (DMARDs), with or without biologic agents. Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy or in combination with methotrexate or DMARDs for 24 weeks. Efficacy, safety, and immunogenicity were assessed. RESULTS: Treatment of 100 patients over 24 weeks resulted in improvement in all efficacy parameters assessed: Clinical Disease Activity Index, Disease Activity Score using 28 joint counts and erythrocyte sedimentation rate, American College of Rheumatology response scores, Simplified Disease Activity Index, tender and swollen joint counts, and patient-reported outcomes including fatigue, global assessment of disease activity, pain, and Health Assessment Quality of Life Disease Index. Improvement was achieved as early as the second week of treatment. There were 473 adverse events (AEs)/100 patient-years (PY) and 16.66 serious AEs/100 PY. The most common AEs were neutropenia (12%), leukopenia (11%), and increased hepatic enzymes (11%). Of a total of 42 PY, the rates of serious infections and AEs leading to discontinuation were 4.8, and 11.9 events/100 PY, respectively. CONCLUSIONS: The safety, tolerability, and efficacy profile of tocilizumab SC were comparable to those reported in other studies evaluating the IV and SC routes of administration.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Injeções Subcutâneas , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente
5.
Clin Exp Rheumatol ; 36(2): 228-232, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29185966

RESUMO

OBJECTIVES: To evaluate the prevalence of immunogenicity of TNF-α blockers in axial spondyloarthritis (SpA) patients and to assess the effect of immunogenicity on drug levels and clinical response. METHPDS: Patients with axial SpA treated with either infliximab (INF), adalimumab (ADA) or etanercept (ETN) were recruited to our observational cross-sectional study. Demographic and clinical data were collected and disease activity scores were assessed. Drug trough levels and anti-drug antibodies were measured in serum samples and collected before the next administration. RESULTS: Thirty-nine patients with axial SpA with a mean age of 46.3±12.7 (10 women) were recruited to the study (14 receiving INF, 16 ADA and 9 ETN). Patients' mean therapy duration was 50.6 months (±46.4) and 6 (15%) of them were using MTX concomitantly with the TNF-α blockers. Anti-drug antibodies were found in 6 (15%) patients (4 with INF and 2 with ADA), all of which had undetectable drug level. No anti-drug antibodies were detected in patients treated with ETN. Immunogenicity was associated with higher BASDAI (Bath Ankylosing Spondylitis Disease Index), ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score) and ASDAS-ESR. CONCLUSIONS: Axial SpA patients failure to respond to TNF-α blockers may be at least partially related to immunogenicity. Measurement of anti-drug antibodies and drug levels in these patients may assist in determining further treatment strategies.


Assuntos
Adalimumab/imunologia , Anticorpos/sangue , Etanercepte/imunologia , Infliximab/imunologia , Espondilartrite/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
6.
Clin Exp Rheumatol ; 36(1): 121-126, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28770702

RESUMO

OBJECTIVES: Autoantibodies to the dense fine speckled 70 (DFS70) antigen are common among antinuclear antibodies (ANA) positive healthy individuals (HI). We assessed the prevalence of anti-DFS70 antibodies in patients with and without ANA-associated rheumatic diseases (AARDs) by two methods: chemiluminescent immunoassay (CIA) and an indirect immunofluorescence (IIF) assay based on immunoadsorption for DFS70. METHODS: Fifty-one ANA-positive sera samples from patients with confirmed clinical diagnosis of AARD, 92 samples from HI and 85 samples submitted to a reference laboratory for routine ANA testing were evaluated for the presence of anti-DFS70 antibodies. The samples were evaluated by QUANTA Flash DFS70 CIA using BIO-FLASH instrument and by NOVA Lite selected HEp-2 kit on NOVA View - an automated IIF system. Sera with DFS positive pattern were pre-absorbed with highly purified human DFS70 antigen, and then tested again. RESULTS: Twenty-four samples (10.5%) tested by QUANTA Flash DFS70 CIA were positive for anti-DFS70 antibodies. The prevalence of monospecific anti-DFS70 antibodies was significantly higher in healthy subjects than in patients with AARDs (10.9% vs. 1.9%, p=0.02). The frequency of anti-DFS70 antibodies in samples submitted for routine ANA testing was 15.2%. A very good agreement was found between CIA and the DFS pattern identified by the automated HEp-2 IIF (kappa=0.97). In 80% of the samples obtained from patients without AARDs, immunoadsorption effectively inhibited the anti-DFS70 antibodies. CONCLUSIONS: The data confirm that mono-specific anti-DFS70 antibodies are a strong discriminator between ANA positive HI and AARD patients, and their evaluation should be included in ANA testing algorithms.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/imunologia , Anticorpos Antinucleares/sangue , Autoimunidade , Doenças Reumáticas/imunologia , Fatores de Transcrição/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Imunoensaio , Técnicas de Imunoadsorção , Medições Luminescentes , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Doenças Reumáticas/sangue , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/epidemiologia , Estudos Soroepidemiológicos
7.
Isr Med Assoc J ; 20(4): 239-244, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29629732

RESUMO

BACKGROUND: Chronic fatigue is common among patients with rheumatoid arthritis (RA), affecting quality of life. Osteoporosis is a prevalent co-morbidity in RA patients. OBJECTIVES: To assess the effect of long-term treatment with tocilizumab on fatigue and bone mineral density (BMD) in RA patients with inadequate response to synthetic or biologic disease-modifying anti-rheumatic drugs. METHODS: In this multicenter, open-label, non-controlled, single-arm study, patients ≥ 18 years of age received intravenous tocilizumab 8 mg/kg every 4 weeks for 96 weeks. The primary outcome was the change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to weeks 24, 48, 72, and 96. BMD was assessed before and 96 weeks after treatment. RESULTS: The study comprised 145 patients (mean age 53.4 ± 13.4 years, 83.4% women). Of these, 88 (60.7%) completed the 2 year treatment period. The mean FACIT-Fatigue score improved consistently starting from week 4 and showed a statistically significant increase of 5.0 ± 9.7, 6.8 ± 10.5, 7.3 ± 10.9, and 7.3 ± 10.4 from baseline to weeks 24, 48, 72, and 96, respectively (P < 0.0001). Mean BMD of femoral neck and total spine remained stable. Disease activity, acute phase reactants, and composite efficacy measures decreased during the study, while hemoglobin levels increased. Adverse events and serious adverse events were as expected for the known and previously described data. CONCLUSIONS: Tocilizumab therapy for 2 years significantly and clinically decreased fatigue. BMD remained stable and no new safety issue was reported.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Densidade Óssea/efeitos dos fármacos , Fadiga/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/fisiopatologia , Doença Crônica , Fadiga/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
8.
Isr Med Assoc J ; 19(1): 44-48, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28457114

RESUMO

BACKGROUND: Anti-BLyS treatment with the human belimumab monoclonal antibody was shown to be a safe and effective therapeutic modality in lupus patients with active disease (i.e., without significant neurological/renal involvement) despite standard treatment. OBJECTIVES: To evaluate the "real-life" safety and efficacy of belimumab added to standard therapy in patents with active lupus in five Israeli medical centers. METHODS: We conducted a retrospective open-labeled study of 36 lupus patients who received belimumab monthly for at least 1 year in addition to standard treatment. Laboratory tests (C3/C4, anti dsDNA autoantibodies, chemistry, urinalysis and complete blood count) were done every 3-4 months. Adverse events were obtained from patients' medical records. Efficacy assessment by the treating physicians was defined as excellent, good/partial, or no response. RESULTS: The study group comprised 36 lupus patients (8 males, 28 females) with a mean age of 41.6 } 12.2 years. Belimumab was given for a mean period of 2.3 } 1.7 years (range 1-7). None of the patients discontinued belimumab due to adverse events. Four patients (11.1%) had an infection related to belimumab. Only 5 patients (13.9%) stopped taking belimumab due to lack of efficacy. The response was excellent in 25 patients (69.5%) and good/partial in the other 6 (16.6%). Concomitantly, serological response (reduction of C3/C4 and anti-dsDNA autoantibodies) was also observed. Moreover, following belimumab treatment, there was a significant reduction in the usage of corticosteroids (from 100% to 27.7%) and immunosuppressive agents (from 83.3% to 8.3%). CONCLUSIONS: Belimumab, in addition to standard therapy, is a safe and effective treatment for active lupus patients.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Autoanticorpos/sangue , Complemento C3/análise , Complemento C4/análise , DNA/imunologia , Feminino , Humanos , Israel/epidemiologia , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Infecções Oportunistas/epidemiologia , Estudos Retrospectivos
9.
Immunology ; 146(3): 401-10, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26227667

RESUMO

In the course of investigating anti-DNA autoantibodies, we examined IgM and IgG antibodies to poly-G and other oligonucleotides in the sera of healthy persons and those diagnosed with systemic lupus erythematosus (SLE), scleroderma (SSc), or pemphigus vulgaris (PV); we used an antigen microarray and informatic analysis. We now report that all of the 135 humans studied, irrespective of health or autoimmune disease, manifested relatively high amounts of IgG antibodies binding to the 20-mer G oligonucleotide (G20); no participants entirely lacked this reactivity. IgG antibodies to homo-nucleotides A20, C20 or T20 were present only in the sera of SLE patients who were positive for antibodies to dsDNA. The prevalence of anti-G20 antibodies led us to survey human, mouse and Drosophila melanogaster (fruit fly) genomes for runs of T20 and G20 or more: runs of T20 appear > 170,000 times compared with only 93 runs of G20 or more in the human genome; of these runs, 40 were close to brain-associated genes. Mouse and fruit fly genomes showed significantly lower T20/G20 ratios than did human genomes. Moreover, sera from both healthy and SLE mice contained relatively little or no anti-G20 antibodies; so natural anti-G20 antibodies appear to be characteristic of humans. These unexpected observations invite investigation of the immune functions of anti-G20 antibodies in human health and disease and of runs of G20 in the human genome.


Assuntos
Autoanticorpos/sangue , Autoantígenos/genética , Autoantígenos/imunologia , Poli G/genética , Poli G/imunologia , Animais , Anticorpos Antinucleares/sangue , Estudos de Casos e Controles , Ilhas de CpG , Drosophila melanogaster/genética , Feminino , Genoma Humano , Genoma de Inseto , Humanos , Imunidade Inata , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NZB , Pênfigo/genética , Pênfigo/imunologia , Poli T/genética , Poli T/imunologia , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/imunologia , Especificidade da Espécie
10.
Immunology ; 141(2): 276-85, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24164500

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disease that can attack many different body organs; the triggering event is unknown. SLE has been associated with more than 100 different autoantibody reactivities - anti-dsDNA is prominent. Nevertheless, autoantibodies to dsDNA occur in only two-thirds of SLE patients. We previously reported the use of an antigen microarray to characterize SLE serology. We now report the results of an expanded study of serology in SLE patients and scleroderma (SSc) patients compared with healthy controls. The analysis validated and extended previous findings: two-thirds of SLE patients reacted to a large spectrum of self-molecules that overlapped with their reactivity to dsDNA; moreover, some SLE patients manifested a deficiency of natural IgM autoantibodies. Most significant was the finding that many SLE patients who were negative for autoantibodies to dsDNA manifested abnormal antibody responses to Epstein-Barr virus (EBV): these subjects made IgG antibodies to EBV antigens to which healthy subjects did not respond or they failed to make antibodies to EBV antigens to which healthy subjects did respond. This observation suggests that SLE may be associated with a defective immune response to EBV. The SSc patients shared many of these serological abnormalities with SLE patients, but differed from them in increased IgG autoantibodies to topoisomerase and centromere B; 84% of SLE patients and 58% of SSc patients could be detected by their abnormal antibodies to EBV. Hence an aberrant immune response to a ubiquitous viral infection such as EBV might set the stage for an autoimmune disease.


Assuntos
Anticorpos Antinucleares/sangue , Anticorpos Antivirais/sangue , Herpesvirus Humano 4/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Escleroderma Sistêmico/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue
11.
Harefuah ; 152(12): 742-7, 751, 750, 2013 Dec.
Artigo em Hebraico | MEDLINE | ID: mdl-24483001

RESUMO

Over the past years, considerable progress has been made in understanding the pathogenesis of the fibromyatgia syndrome and the evidence based approach to the diagnosis and management has been significantty extended. The purpose of the current project is to develop practicat and evidence based guidetine recommendations for the Israeli health care system. A panet of physicians with clinical and research experience in the fibromyalgia field was convened under the auspices of the Israeli Rheumatology Association. A systematic review was performed on the current literature regarding the diagnosis and treatment of fibromyalgia. Using an interactive discussion procedure, recommendations were reached and expert opinion was introduced where evidence was considered incomplete. The panel recommendations underline the importance of concomitant and integrated medical therapy, such as serotonin and noradrenaline reuptake inhibitor (SNRI) anti-depressants or gamma-aminobutyric acid (GABA) related anti-epileptics, with regular aerobic physical exercise.


Assuntos
Atenção à Saúde/métodos , Medicina Baseada em Evidências , Fibromialgia/terapia , Terapia por Exercício , Fibromialgia/diagnóstico , Humanos , Israel
12.
Acta Obstet Gynecol Scand ; 90(12): 1428-33, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21729009

RESUMO

OBJECTIVE: To investigate whether in patients with antiphospholipid syndrome (APS), high positive antibody titers are associated with adverse pregnancy outcome. DESIGN: A retrospective cohort study of prospectively collected data. SETTING: Sheba Medical Center, Israel, a tertiary referral center. POPULATION SAMPLE: Pregnant women with APS. METHODS: Anticardiolipin, a-ß2-glycoprotein I antibodies, and lupus anticoagulant were measured before pregnancy. Women were divided into those with antibody titers >four times the upper limit of normal (high positive titer, HPT group), and the rest, into the positive titer (PT) group. All women were treated with daily enoxaparin and aspirin. MAIN OUTCOME MEASURES: Composite adverse fetal/neonatal outcome, defined as one or more of the following: fetal/neonatal loss, preterm birth ≤ 32 weeks, and birthweight below than 10th percentile. Composite adverse fetal/neonatal outcome was compared between the HPT and PT groups. Maternal adverse outcomes were also compared. RESULTS: 51 women with APS were followed during 55 pregnancies, 20 in the HPT and 35 in the PT groups. The two groups were similar with regard to previous obstetric and clinical characteristics. Among HPT women, only 7/20 (35%) pregnancies culminated in appropriately grown, live-born infants >32 weeks' gestation, compared with 27/35 (77%) PT pregnancies. The risk of adverse fetal/neonatal outcome was 5.7 times higher (95%CI 1.9-17.7) for HPT than for PT women. CONCLUSIONS: Pregnant women with APS and high positive antiphospholipid antibody titers are a unique and extremely high risk group for adverse fetal/neonatal outcome. Stricter surveillance and possibly additional therapy options should be explored for this patient population.


Assuntos
Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/sangue , Complicações na Gravidez/sangue , Resultado da Gravidez , Aborto Espontâneo/etiologia , Adulto , Anticorpos Anticardiolipina/sangue , Síndrome Antifosfolipídica/complicações , Estudos de Coortes , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Inibidor de Coagulação do Lúpus/sangue , Gravidez , Complicações na Gravidez/imunologia , Nascimento Prematuro/etiologia , Estudos Retrospectivos , Risco , beta 2-Glicoproteína I/imunologia
13.
Rheumatol Int ; 31(1): 39-43, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19882341

RESUMO

Familial Mediterranean fever (FMF) is a hereditary disease, characterized by recurrent episodes of fever and polyserositis. Heart rate variability (HRV) is a powerful, simple and reliable technique to evaluate autonomic nervous system function. Previous studies of physiologic parameters during tilt-test have suggested that patients with FMF have abnormal cardiovascular reactivity and occult dysautonomia. Prompted by these findings, the present study sought to evaluate HRV in patients with FMF, at rest and in the standing position. The study sample included 34 patients with FMF and 34 sex- and age-matched control subjects. All underwent electrocardiography according to strict criteria. HRV parameters were computed with custom-made software. There was no significant difference in HRV parameters, in either the supine or standing position, between the FMF and control groups. In both groups, the upright position was associated with a significant decrease, when compared with the supine position, in maximal RR interval, minimal RR, average RR, root square of successive differences in RR interval, number of intervals differing by >50 ms from preceding interval (NN50), NN50 divided by total number of intervals (pNN50) and high-frequency components as well as a significant increase in average heart rate, very low frequency or low-frequency components, low-frequency/high-frequency components ratio and total power. In conclusion, patients with FMF who are continuously treated with low-dose colchicine have not developed amyloidosis and have normal HRV parameters in the supine and upright position. Further investigation of occult dysautonomia in FMF is needed.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Febre Familiar do Mediterrâneo/fisiopatologia , Frequência Cardíaca/fisiologia , Eletrocardiografia , Feminino , Humanos , Masculino
14.
Vaccines (Basel) ; 9(5)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33946748

RESUMO

BACKGROUND: Infectious diseases and vaccines can occasionally cause new-onset or flare of immune-mediated diseases (IMDs). The adjuvanticity of the available SARS-CoV-2 vaccines is based on either TLR-7/8 or TLR-9 agonism, which is distinct from previous vaccines and is a common pathogenic mechanism in IMDs. METHODS: We evaluated IMD flares or new disease onset within 28-days of SARS-CoV-2 vaccination at five large tertiary centres in countries with early vaccination adoption, three in Israel, one in UK, and one in USA. We assessed the pattern of disease expression in terms of autoimmune, autoinflammatory, or mixed disease phenotype and organ system affected. We also evaluated outcomes. FINDINGS: 27 cases included 17 flares and 10 new onset IMDs. 23/27 received the BNT - 162b2 vaccine, 2/27 the mRNA-1273 and 2/27 the ChAdOx1 vaccines. The mean age was 54.4 ± 19.2 years and 55% of cases were female. Among the 27 cases, 21 (78%) had at least one underlying autoimmune/rheumatic disease prior the vaccination. Among those patients with a flare or activation, four episodes occurred after receiving the second-dose and in one patient they occurred both after the first and the second-dose. In those patients with a new onset disease, two occurred after the second-dose and in one patient occurred both after the first (new onset) and second-dose (flare). For either dose, IMDs occurred on average 4 days later. Of the cases, 20/27 (75%) were mild to moderate in severity. Over 80% of cases had excellent resolution of inflammatory features, mostly with the use of corticosteroid therapy. Other immune-mediated conditions included idiopathic pericarditis (n = 2), neurosarcoidosis with small fiber neuropathy (n = 1), demyelination (n = 1), and myasthenia gravis (n = 2). In 22 cases (81.5%), the insurgence of Adverse event following immunization (AEFI)/IMD could not be explained based on the drug received by the patient. In 23 cases (85.2%), AEFI development could not be explained based on the underlying disease/co-morbidities. Only in one case (3.7%), the timing window of the insurgence of the side effect was considered not compatible with the time from vaccine to flare. INTERPRETATION: Despite the high population exposure in the regions served by these centers, IMDs flares or onset temporally-associated with SARS-CoV-2 vaccination appear rare. Most are moderate in severity and responsive to therapy although some severe flares occurred. FUNDING: none.

15.
Immunology ; 130(3): 337-43, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20201986

RESUMO

SUMMARY: Patients with systemic lupus erythematosus (SLE) produce antibodies to many different self-antigens. Here, we investigated antibodies in SLE sera using an antigen microarray containing many hundreds of antigens, mostly self-antigens. The aim was to detect sets of antibody reactivities characteristic of SLE patients in each of various clinical states--SLE patients with acute lupus nephritis, SLE patients in renal remission, and SLE patients who had never had renal involvement. The analysis produced two novel findings: (i) an SLE antibody profile persists independently of disease activity and despite long-term clinical remission, and (ii) this SLE antibody profile includes increases in four specific immunoglobulin G (IgG) reactivities to double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), Epstein-Barr virus (EBV) and hyaluronic acid; the profile also includes decreases in specific IgM reactivities to myeloperoxidase (MPO), CD99, collagen III, insulin-like growth factor binding protein 1 (IGFBP1) and cardiolipin. The reactivities together showed high sensitivity (> 93%) and high specificity for SLE (> 88%). A healthy control subject who had the SLE antibody profile was later found to develop clinical SLE. The present study did not detect antibody reactivities that differentiated among the various subgroups of SLE subjects with statistical significance. Thus, SLE is characterized by an enduring antibody profile irrespective of clinical state. The association of SLE with decreased IgM natural autoantibodies suggests that these autoantibodies might enhance resistance to SLE.


Assuntos
Autoanticorpos/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Análise Serial de Proteínas , Antígeno 12E7 , Adulto , Anticorpos Anticardiolipina/imunologia , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Antígenos CD/imunologia , Autoanticorpos/sangue , Moléculas de Adesão Celular/imunologia , Colágeno Tipo III/imunologia , Regulação para Baixo/imunologia , Feminino , Herpesvirus Humano 4/imunologia , Humanos , Ácido Hialurônico/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/imunologia , Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/imunologia , Masculino , Pessoa de Meia-Idade , Peroxidase/imunologia , Sensibilidade e Especificidade , Regulação para Cima/imunologia
16.
Harefuah ; 149(12): 798-802, 810, 2010 Dec.
Artigo em Hebraico | MEDLINE | ID: mdl-21916105

RESUMO

Takayasu's arteritis (TA) is a chronic inflammatory disease, nvolving large blood vessels, such as the aorta and its major branches and the pulmonary arteries. TA is more prevalent in Asia, affecting young adults. This review strives to increase awareness of TA clinical presentation, new diagnostic tools and modern therapeutic options.


Assuntos
Aorta/fisiopatologia , Artéria Pulmonar/fisiopatologia , Arterite de Takayasu/terapia , Ásia/epidemiologia , Humanos , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/epidemiologia , Adulto Jovem
17.
Isr Med Assoc J ; 11(9): 558-63, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19960852

RESUMO

Inflammatory bowel disease, a collective term for ulcerative colitis and Crohn's disease, is a chronic, immune-mediated disease of the gastrointestinal tract that develops in genetically susceptible individuals. The role of infection in the development of inflammatory bowel disease is underscored by various clinical observations, such as the delayed age of onset, suggesting that childhood exposure to pathogens is essential, and the clinical improvement that follows decreasing bacterial intestinal load. Over the years, many a pathogen has been linked to the development and exacerbation of inflammatory bowel disease, notably; Mycobacterium paratuberculosis, Escherichia coli, Listeria monocytogenes and Chlamydia as well as viruses such as measles, mumps, rubella, Epstein-Barr virus and cytomegalovirus. Presently, leading theories of disease pathogenesis suggest loss of immune tolerance to normal commensal bacteria coupled with excessive exposure to bacterial antigenic products. This review describes the most commonly implicated pathogens in the causation of IBD and presents the evidence supporting their pathogenic role as well as data that offset their importance.


Assuntos
Infecções/complicações , Infecções/imunologia , Doenças Inflamatórias Intestinais/etiologia , Doenças Inflamatórias Intestinais/microbiologia , Adulto , Animais , Criança , Modelos Animais de Doenças , Predisposição Genética para Doença , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/fisiopatologia , Doenças Inflamatórias Intestinais/prevenção & controle , Prevalência , Ratos , Ratos Transgênicos
18.
Isr Med Assoc J ; 11(7): 403-6, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19911490

RESUMO

BACKGROUND: Anti-ribosomal-P antibodies have been associated with central nervous system manifestations of systemic lupus erythematosus. However, inconsistencies in their prevalence and clinical correlations have become an obstacle to their use as a diagnostic marker of the disease. This lack of consistency might stem from several factors, such as the lag period between clinical manifestations and the time blood was drawn; or the different methods used for antibodies detection. OBJECTIVES: To evaluate three different enzyme-linked immunosorbent assay tests for the detection of anti-Rib-P Abs in patients with SLE and in normal controls. METHODS: Sera from 50 SLE outpatients and 50 healthy subjects were tested with three ELISA kits: Kit-1, using synthetic peptide comprising the 22 C-terminal aminoacids; Kit-2, using native human ribosomal proteins (P0, P1, P2); and Kit-3, which is coated with affinity-purified human ribosomal proteins. ELISA studies were performed according to the manufacturers' instructions. RESULTS: The prevalence of anti-Rib-P Abs in SLE patients and controls was 30% vs. 0%, 17% vs. 21%, and 30% vs. 14% in kits 1-3 respectively. Anti-Rib-P Abs detected by Kit-1 correlated with the SLEDAI score (SLE Disease Activity Index). No correlation between prior CNS manifestations and anti-Rib-P Abs was observed. CONCLUSIONS: A significant difference was documented between the ELISA kits used for the detection of anti-Rib-P Abs. A correlation was found between these antibodies (evaluated by Kit-1) and concurrent SLEDAI scores, in contrast to the lack of correlation with previous CNS manifestations. This supports the notion of "active serology" that is evaluated at the same time manifestations are present, as well as the need for standardization of laboratory assays in the future which will enable a better assessment of anti-Rib-P Abs presence and clinical significance.


Assuntos
Ensaio de Imunoadsorção Enzimática/métodos , Lúpus Eritematoso Sistêmico/imunologia , Proteínas Ribossômicas/imunologia , Adulto , Autoanticorpos/análise , Feminino , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/imunologia , Proteínas Serina-Treonina Quinases/imunologia , Estudos Soroepidemiológicos
19.
Autoimmun Rev ; 18(6): 627-631, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30959216

RESUMO

BACKGROUND: Approximately 5% of idiopathic recurrent pericarditis (IRP) patients are refractory or intolerant to NSAIDs, Colchicine and corticosteroids. The empiric treatment approach for these patients includes immunosuppression with Azathioprine (AZA) or immunomodulation with intravenous human immunoglobulin (IVIG). We assessed the efficacy and safety of long-term Anakinra treatment in refractory IRP patients after failure of prior immunosuppressive therapy and/or failure of IVIG. METHODS: Clinical data of seven IRP patients were retrospectively analyzed. Treatment efficacy was determined by decrease of IRP recurrence and by the ability to withdraw or taper corticosteroids without a relapse. Safety was assessed by the occurrence of adverse events. RESULTS: 7 IRP patients (4 male, median age 41) with a median disease duration of 4 years (range: 1.25-9 years) were treated with Anakinra (median treatment duration: 20 months). All patients were resistant or intolerant to NSAIDs, Prednisone, Colchicine and at least one immunosuppressive or immunomodulatory drug such as AZA, Methotrexate, Plaquenil, or IVIG. The median number of recurrences before Anakinra was 6 (range: 4-7) and all patients were corticosteroid-dependent and had steroid-related side effects. After initiation of Anakinra, none of the patients had IRP relapse. Prednisone was tapered down to 5 mg/day or less in all patients. Four patients discontinued prednisone altogether. No significant adverse effects have occurred as a result of Anakinra treatment and all patients continued treatment after the study period. CONCLUSION: Long-term Anakinra is a rapid-acting, efficient and safe steroid sparing agent even for patients with IRP refractory to previous immunosuppressive and/or immunomodulatory agents.


Assuntos
Antirreumáticos/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Pericardite/tratamento farmacológico , Adulto , Feminino , Humanos , Masculino , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA