Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 175
Filtrar
3.
Artigo em Inglês | MEDLINE | ID: mdl-34501738

RESUMO

BACKGROUND: Tocilizumab is an anti-IL-6 therapy widely adopted in the management of the so-called "cytokine storm" related to SARS-CoV-2 virus infection, but its effectiveness, use in relation to concomitant corticosteroid therapy and safety were unproven despite widespread use in numerous studies, mostly open label at the start of the pandemic. METHODS: We performed a systematic review and meta-analysis of case-control studies utilising tocilizumab in COVID-19 on different databases (PubMed/MEDLINE/Scopus) and preprint servers (medRxiv and SSRN) from inception until 20 July 2020 (PROSPERO CRD42020195690). Subgroup analyses and meta-regressions were performed. The impact of tocilizumab and concomitant corticosteroid therapy or tocilizumab alone versus standard of care (SOC) on the death rate, need for mechanical ventilation, ICU admission and bacterial infections were assessed. RESULTS: Thirty-nine studies with 15,531 patients (3657 cases versus 11,874 controls) were identified. Unadjusted estimates (n = 28) failed to demonstrate a protective effect of tocilizumab on survival (OR 0.74 ([95%CI 0.55-1.01], p = 0.057), mechanical ventilation prevention (OR 2.21 [95%CI 0.53-9.23], p = 0.277) or prevention of ICU admission (OR 3.79 [95%CI 0.38-37.34], p = 0.254). Considering studies with adjusted, estimated, tocilizumab use was associated with mortality rate reduction (HR 0.50 ([95%CI 0.38-0.64], p < 0.001) and prevention of ICU admission (OR 0.16 ([95%CI 0.06-0.43], p < 0.001). Tocilizumab with concomitant steroid use versus SOC was protective with an OR of 0.49 ([95%CI 0.36-0.65], p < 0.05) as was tocilizumab alone versus SOC with an OR of 0.59 ([95%CI 0.34-1.00], p < 0.001). Risk of infection increased (2.36 [95%CI 1.001-5.54], p = 0.050; based on unadjusted estimates). CONCLUSION: Despite the heterogeneity of included studies and large number of preprint articles, our findings from the first eight of the pandemic in over 15,000 COVID-19 cases suggested an incremental efficacy of tocilizumab in severe COVID-19 that were confirmed by subsequent meta-analyses of large randomized trials of tocilizumab. This suggests that analysis of case-control studies and pre-print server data in the early stages of a pandemic appeared robust for supporting incremental benefits and lack of major therapeutic toxicity of tocilizumab for severe COVID-19.


Assuntos
COVID-19 , Pandemias , Anticorpos Monoclonais Humanizados , COVID-19/tratamento farmacológico , Humanos , SARS-CoV-2 , Padrão de Cuidado , Resultado do Tratamento
4.
Artigo em Inglês | MEDLINE | ID: mdl-34373900

RESUMO

OBJECTIVE: The risk of amyloidosis during the course of ankylosing spondylitis (AS) is yet to be firmly established. We aimed to evaluate the risk, predictors, and prognostic outcomes of amyloidosis among patients with AS. METHODS: A population-based cohort study was conducted comparing AS patients (n = 5,911) with age-, sex- and ethnicity-matched control subjects (n = 29 007) with regard to incident cases of amyloidosis. Hazard ratios (HRs) and odds ratios (ORs) were estimated by Cox regression and logistic regression analyses, respectively. RESULTS: The incidence rate of amyloidosis was 2.15 (95% CI, 1.09-2.82) and 0.35 (95% CI, 0.16-0.66) per 10 000 person-years among patients with AS and controls, respectively. The risk of incident amyloidosis was >6-folds higher among patients with AS relative to control subjects (adjusted HR, 6.16; 95% CI, 2.43-15.62; p< 0.001). A higher comorbidity burden (OR, 1.36; 95% CI, 1.08-1.73; p= 0.010) was found to predict an increased susceptibility to amyloidosis in AS patients. Compared with other patients with AS, those with AS and comorbid amyloidosis had a 14-fold increased risk of end-stage renal disease necessitating dialysis (adjusted HR, 14.7; 95% CI, 2.0-107.2; p= 0.008), but comparable risk of all-cause mortality (adjusted HR, 2.16; 95% CI, 0.69-6.71; p= 0.174). CONCLUSIONS: Patients with AS are at an increased risk of amyloidosis. AS-associated amyloidosis is associated with an elevated risk of dialysis dependence. Awareness of the burden and consequences of this complication may be of help for rheumatologists managing patients with AS.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34437772

RESUMO

We thank Li et al for their commentary on our recently published paper "Mortality in Ankylosing Spondylitis According to Treatment: A Nationwide Retrospective Cohort Study of 5900 Patients from Israel" (1). Their major concern was regarding the findings which demonstrated no excess mortality in ankylosing-spondylitis (AS) patients treated with TNF-inhibitors (TNFi).

6.
Artigo em Inglês | MEDLINE | ID: mdl-34300046

RESUMO

BACKGROUND: The association between giant cell arteritis (GCA) and malignancies had been widely investigated with studies reporting conflicting results. Therefore, in this study, we aimed to investigate this association using a large nationwide electronic database. METHODS: This study was designed as a retrospective cohort study including GCA patients first diagnosed between 2002-2017 and age, sex and enrollment time-matched controls. Follow-up began at the date of first GCA-diagnosis and continued until first diagnosis of malignancy, death or end of study follow-up. RESULTS: The study enrolled 7213 GCA patients and 32,987 age- and sex-matched controls. The mean age of GCA diagnosis was 72.3 (SD 9.9) years and 69.1% were women. During the follow-up period, 659 (9.1%) of GCA patients were diagnosed with solid malignancies and 144 (2.0%) were diagnosed with hematologic malignancies. In cox-multivariate-analysis the risk of solid- malignancies (HR = 1.12 [95%CI: 1.02-1.22]), specifically renal neoplasms (HR = 1.60 [95%CI: 1.15-2.23]) and sarcomas (HR = 2.14 [95%CI: 1.41-3.24]), and the risk of hematologic malignancies (HR = 2.02 [95%CI: 1.66-2.47]), specifically acute leukemias (HR = 1.81 [95%CI: 1.06-3.07]), chronic leukemias (HR = 1.82 [95%CI: 1.19-2.77]), Hodgkin's lymphomas (HR = 2.42 [95%CI: 1.12-5.20]), non-Hodgkin's-lymphomas (HR = 1.66: [95%CI 1.21-2.29]) and multiple myeloma(HR = 2.40 [95%CI: 1.63-3.53]) were significantly increased in GCA patients compared to controls. Older age at GCA-diagnosis (HR = 1.36 [95%CI: 1.25-1.47]), male-gender (HR = 1.46 [95%CI: 1.24-1.72]), smoking (HR = 1.25 [95%CI: 1.04-1.51]) and medium-high socioeconomic status (HR = 1.27 [95%CI: 1.07-1.50]) were independently associated with solid malignancy while age (HR = 1.47 [95%CI: 1.22-1.77]) and male-gender (HR = 1.61 [95%CI: 1.14-2.29]) alone were independently associated with hematologic- malignancies. CONCLUSION: our study demonstrated higher incidence of hematologic and solid malignancies in GCA patients. Specifically, leukemia, lymphoma, multiple myeloma, kidney malignancies, and sarcomas. Age and male gender were independent risk factors for hematological malignancies among GCA patients, while for solid malignancies, smoking and SES were risk factors as well.


Assuntos
Arterite de Células Gigantes , Neoplasias Hematológicas , Idoso , Feminino , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/epidemiologia , Neoplasias Hematológicas/epidemiologia , Humanos , Incidência , Masculino , Estudos Retrospectivos , Fatores de Risco
7.
Artigo em Inglês | MEDLINE | ID: mdl-34069883

RESUMO

Fever of unknown origin (FUO) poses a diagnostic challenge, and 18-fluorodexoyglucose positron emission tomography with computed tomography (18FDG-PET/CT) may identify the source. We aimed to evaluate the diagnostic yield of 18FDG-PET/CT in the work-up of FUO. The records of patients admitted to Sheba Medical Center between January 2013 and January 2018 who underwent 18FDG-PET/CT for the evaluation of FUO were reviewed. Following examination of available medical test results, 18FDG-PET/CT findings were assessed to determine whether lesions identified proved diagnostic. Of 225 patients who underwent 18FDG-PET/CT for FUO work-up, 128 (57%) met inclusion criteria. Eighty (62.5%) were males; mean age was 59 ± 20.3 (range: 18-93). A final diagnosis was made in 95 (74%) patients. Of the 128 18FDG-PET/CT tests conducted for the workup of FUO, 61 (48%) were true positive, 26 (20%) false positive, 26 (20%) true negative, and 15 (12%) false negative. In a multivariate analysis, weight loss and anemia were independently associated with having a contributary results of 18FDG-PET/CT. The test yielded a sensitivity of 70%, specificity of 37%, positive predictive value of 70%, and negative predictive value of 37%. 18FDG-PET/CT is a valuable tool in the diagnostic workup of FUO. It proved effective in diagnosing almost half the patients, especially in those with anemia and weight loss.


Assuntos
Febre de Causa Desconhecida , Fluordesoxiglucose F18 , Adulto , Idoso , Febre de Causa Desconhecida/diagnóstico por imagem , Febre de Causa Desconhecida/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos
8.
Isr Med Assoc J ; 23(6): 373-375, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34155851

RESUMO

BACKGROUND: Surgical interventions in patients with systemic sclerosis (SSc), in particular plastic procedures, might cause undesired consequences. Notably, liposuction seems to possess greater risk as adipose tissue has been shown to play an important role in treating wounds and ulcers in patients with SSc. While anticentromere antibodies were found to be correlated with vasculopathy in SSc, patients with SSc and anticentromere antibodies might be more vulnerable to surgical wound complications following liposuction. A 46-year-old female patient, who had been diagnosed with SSc at the age of 31 years, had antinuclear as well as anticentromere antibodies. She underwent abdominoplasty with liposuction and developed severe skin necrosis of the abdomen following the procedure and at the site of liposuction. The correlation with anticentromere and the role of liposuction in skin necrosis in SSc are presented.


Assuntos
Abdominoplastia , Tecido Adiposo/imunologia , Obesidade Abdominal/cirurgia , Escleroderma Sistêmico , Pele/patologia , Deiscência da Ferida Operatória , Abdominoplastia/efeitos adversos , Abdominoplastia/métodos , Anticorpos Antinucleares/sangue , Cicatriz/diagnóstico , Cicatriz/etiologia , Contraindicações de Procedimentos , Feminino , Humanos , Lipectomia/efeitos adversos , Lipectomia/métodos , Pessoa de Meia-Idade , Necrose/etiologia , Necrose/imunologia , Necrose/cirurgia , Obesidade Abdominal/complicações , Obesidade Abdominal/diagnóstico , Reoperação/efeitos adversos , Reoperação/métodos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/cirurgia , Cirurgia Plástica/efeitos adversos , Cirurgia Plástica/métodos , Deiscência da Ferida Operatória/diagnóstico , Deiscência da Ferida Operatória/etiologia , Deiscência da Ferida Operatória/cirurgia , Resultado do Tratamento
9.
Artigo em Inglês | MEDLINE | ID: mdl-33973404

RESUMO

OBJECTIVES: In this large population-based study we aimed to assess:(1)mortality in ankylosing-spondylitis(AS) patients compared to the general population.Considering demographics,comorbidities and treatment.(2)factors associated with mortality within AS patients. METHODS: This study was designed as a retrospective-cohort study utilizing the electronic-database of the largest health maintenance organization in Israel.All AS patients diagnosed between 2002-2018 were included.Controls were matched by age,gender,clinic, and enrollment-time.Follow-up continued until death or end of study. RESULTS: The study comprised 5,930 AS patients and 29,018 matched controls that were followed-up for a median period of 7.5 years.There were 667 deaths within the AS cohort and 2,919 deaths within controls,the mean age-at-death was 76.9 years and 77.1 years respectively(p=0.74). 3,249(55.8%) of AS patients were treated only with non-steroidal-anti-inflammtory-drugs(NSAIDs), 1,760(30.2%) were treated with tumor-necrosis-factor-α-inhibitors(TNFi),and 1,687(29.0%) with disease-modifying-antirheumatic-drugs(DMARDs).Mortality rates were increased among AS patients compared to controls with an age-and-sex-adjusted HR of 1.19(95%CI1.10-1.30).The association was significant for men(HR=1.15,95%CI 1.04-1.27) and women(HR=1.32,95%CI 1.13-1.54), and after adjusting for background comorbidities (HR=1.14,95%CI 1.05-1.24).AS patients treated with TNFi or with a combination of TNFi and DMARDs did not have significant difference in mortality rates compared to controls(HR=0.67,95%CI 0.38-1.18;HR=0.93,95%CI 0.69-1.25;respectively).Age,male-gender,mean C-reactive-protein(CRP) levels and general comorbidities were predictors of mortality within the AS cohort. CONCLUSION: AS patients had increased mortality risk compared to the general population after adjusting for age, sex, and baseline comorbidities.AS patients treated with TNFi did not demonstrate excess mortality compared to matched controls.Within the AS cohort age, male-gender, background comorbidities, and higher CRP levels were identified as risk factors for mortality.

10.
Front Immunol ; 12: 635018, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936047

RESUMO

Objective: Bacterial and viral infectious triggers are linked to spondyloarthritis (SpA) including psoriatic arthritis (PsA) development, likely via dendritic cell activation. We investigated spinal entheseal plasmacytoid dendritic cells (pDCs) toll-like receptor (TLR)-7 and 9 activation and therapeutic modulation, including JAK inhibition. We also investigated if COVID-19 infection, a potent TLR-7 stimulator triggered PsA flares. Methods: Normal entheseal pDCs were characterized and stimulated with imiquimod and CpG oligodeoxynucleotides (ODN) to evaluate TNF and IFNα production. NanoString gene expression assay of total pDCs RNA was performed pre- and post- ODN stimulation. Pharmacological inhibition of induced IFNα protein was performed with Tofacitinib and PDE4 inhibition. The impact of SARS-CoV2 viral infection on PsA flares was evaluated. Results: CD45+HLA-DR+CD123+CD303+CD11c- entheseal pDCs were more numerous than blood pDCs (1.9 ± 0.8% vs 0.2 ± 0.07% of CD45+ cells, p=0.008) and showed inducible IFNα and TNF protein following ODN/imiquimod stimulation and were the sole entheseal IFNα producers. NanoString data identified 11 significantly upregulated differentially expressed genes (DEGs) including TNF in stimulated pDCs. Canonical pathway analysis revealed activation of dendritic cell maturation, NF-κB signaling, toll-like receptor signaling and JAK/STAT signaling pathways following ODN stimulation. Both tofacitinib and PDE4i strongly attenuated ODN induced IFNα. DAPSA scores elevations occurred in 18 PsA cases with SARS-CoV2 infection (9.7 ± 4 pre-infection and 35.3 ± 7.5 during infection). Conclusion: Entheseal pDCs link microbes to TNF/IFNα production. SARS-CoV-2 infection is associated with PsA Flares and JAK inhibition suppressed activated entheseal plasmacytoid dendritic Type-1 interferon responses as pointers towards a novel mechanism of PsA and SpA-related arthropathy.


Assuntos
Artrite Psoriásica/complicações , COVID-19/complicações , Células Dendríticas/metabolismo , Interferon-alfa/metabolismo , Janus Quinases/antagonistas & inibidores , Adjuvantes Imunológicos/farmacologia , Adulto , Idoso , COVID-19/genética , COVID-19/metabolismo , Biologia Computacional , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Células Dendríticas/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Humanos , Imiquimode/farmacologia , Janus Quinases/metabolismo , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Oligonucleotídeos/farmacologia , Inibidores da Fosfodiesterase 4/farmacologia , Piperidinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Receptor 7 Toll-Like/metabolismo , Receptor Toll-Like 9/metabolismo , Transcriptoma , Fator de Necrose Tumoral alfa/metabolismo
11.
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.

12.
Front Immunol ; 12: 614255, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815371

RESUMO

The term spondyloarthritis pertains to both axial and peripheral arthritis including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), which is strongly linked to psoriasis and also the arthritis associated with inflammatory bowel disease. The argument supporting the role for IL-23 across the spectrum of SpA comes from 4 sources. First, genome wide associated studies (GWAS) have shown that all the aforementioned disorders exhibit IL-23R pathway SNPs, whereas HLA-B27 is not linked to all of these diseases-hence the IL-23 pathway represents the common genetic denominator. Secondly, experimental animal models have demonstrated a pivotal role for the IL-23/IL-17 axis in SpA related arthropathy that initially manifests as enthesitis, but also synovitis and axial inflammation and also associated aortic root and cutaneous inflammation. Thirdly, the emergent immunology of the human enthesis also supports the presence of IL-23 producing myeloid cells, not just at the enthesis but in other SpA associated sites including skin and gut. Finally, drugs that target the IL-23 pathway show excellent efficacy for skin disease, efficacy for IBD and also in peripheral arthropathy associated with SpA. The apparent failure of IL-23 blockade in the AS which is effectively a spinal polyenthesitis but evidence for efficacy of IL-23 inhibition for peripheral enthesitis in PsA and preliminary suggestions for benefit in axial PsA, raises many questions. Key amongst these is whether spinal inflammation may exhibit entheseal IL-17A production independent of IL-23 but peripheral enthesitis is largely dependent on IL-23 driven IL-17 production. Furthermore, IL-23 blocking strategies in animal models may prevent experimental SpA evolution but not prevent established disease, perhaps pointing towards a role for IL-23 in innate immune disease initiation whereas persistent disease is dependent on memory T-cell responses that drive IL-17A production independently of IL-23, but this needs further study. Furthermore, IL-12/23 posology in inflammatory bowel disease is substantially higher than that used in AS trials which merits consideration. Therefore, the IL-23 pathway is centrally involved in the SpA concept but the nuances and intricacies in axial inflammation that suggest non-response to IL-23 antagonism await formal definition. The absence of comparative immunology between the different skeletal sites renders explanations purely hypothetical at this juncture.


Assuntos
Suscetibilidade a Doenças , Interleucina-23/antagonistas & inibidores , Interleucina-23/metabolismo , Espondilite Anquilosante/etiologia , Espondilite Anquilosante/metabolismo , Animais , Biomarcadores , Diagnóstico Diferencial , Gerenciamento Clínico , Predisposição Genética para Doença , Humanos , Interleucina-17/metabolismo , Terapia de Alvo Molecular , Transdução de Sinais , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/tratamento farmacológico , Resultado do Tratamento
13.
Artigo em Inglês | MEDLINE | ID: mdl-33920065

RESUMO

Polymyositis (PM) and dermatomyositis (DM) are autoimmune-mediated multisystemic myopathies, characterized mainly by proximal muscle weakness. A connection between epilepsy and PM/DM has not been reported previously. Our study aim is to evaluate this association. A case-control study was conducted, enrolling a total of 12,278 patients with 2085 cases (17.0%) and 10,193 subjects in the control group (83.0%). Student's t-test was used to evaluate continuous variables, while the chi-square test was applied for the distribution of categorical variables. Log-rank test, Kaplan-Meier curves and multivariate Cox proportional hazards method were performed for the analysis regarding survival. Of the studied 2085 cases, 1475 subjects (70.7%) were diagnosed with DM, and 610 patients (29.3%) with PM. Participants enrolled as cases had a significantly higher rate of epilepsy (n = 48 [2.3%]) as compared to controls (n = 141 [1.4%], p < 0.0005). Using multivariable logistic regression analysis, PM was found only to be significantly associated with epilepsy (OR 2.2 [95%CI 1.36 to 3.55], p = 0.0014), whereas a non-significant positive trend was noted in DM (OR 1.51 [95%CI 0.99 to 2.30], p = 0.0547). Our data suggest that PM is associated with a higher rate of epilepsy compared to controls. Physicians should be aware of this comorbidity in patients with immune-mediated myopathies.


Assuntos
Dermatomiosite , Epilepsia , Polimiosite , Estudos de Casos e Controles , Comorbidade , Estudos Transversais , Dermatomiosite/epidemiologia , Epilepsia/epidemiologia , Humanos , Polimiosite/epidemiologia
14.
J Autoimmun ; 120: 102631, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33799099

RESUMO

IMPORTANCE AND OBJECTIVES: There is unmet medical need to understand the pathogenic mechanism of the panoply of clinical manifestations associated with silicone breast implants (SBIs) such as severe fatigue, widespread pain, palpitations, dry mouth and eyes, depression, hearing loss etc. We aimed to determine whether autoantibodies against the autonomic nervous system receptors can explain the enigmatic and subjective clinical manifestation reported by women with SBIs. RESULTS: Circulating level of autoantibodies against G protein-coupled receptors (GPCRs) of the autonomic nervous system (adrenergic, muscarinic, endothelin and angiotensin receptors) have been evaluated in symptomatic women with SBIs using an ELISA method. These women with SBIs addressed our clinic due to various subjective and autonomic-related manifestations such as chronic severe fatigue, cognitive impairment, widespread pain, memory loss, sleep disorders, palpitations, depression, hearing abnormalities etc. We report for the first time, a significant reduction in the sera level of anti-ß1 adrenergic receptor (p < 0.001), anti-angiotensin II type 1 receptor (p < 0.001) and anti-endothelin receptor type A (p = 0.001) autoantibodies in women with SBIs (n = 93) as compared with aged matched healthy women (n = 36). Importantly, anti-ß1 adrenergic receptor autoantibody was found to significantly correlate with autonomic-related manifestations such as: sleep disorders and depression in women with SBIs. CONCLUSIONS: Chronic immune stimulation by silicone material may lead to an autoimmune dysautonomia in a subgroup of potentially genetically susceptible women with SBIs. The appearance of autoantibodies against GPCRs of the autonomic nervous system serve as an explanation for the subjective autonomic-related manifestations reported in women with SBIs.

15.
Front Immunol ; 12: 610019, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679746

RESUMO

Objectives: We theorized that myelodysplastic syndrome (MDS) with somatic mutations and karyotype abnormalities are associated with autoinflammation, and that the presence of autoinflammatory disease affected prognosis in MDS. Methods: One hundred thirty-four MDS patients were assessed for the prevalence of autoinflammatory complications and its link with karyotypes and somatic mutation status. Autoinflammatory complications were described either as well-defined autoinflammatory diseases (AD) or undifferentiated "autoinflammatory disease" (UAD) (defined as CRP over 10.0 mg/L on five consecutive occasions, taken at separate times and not explained by infection). Several patient characteristics including demographic, clinical, laboratory, cytogenetics charts, and outcomes, were compared between different groups. Results: Sixty-two (46.3%) patients had an autoinflammatory complication manifesting as arthralgia (43.5% vs. 23.6%, p = 0.0146), arthritis (30.6% vs. 15.3%, p = 0.0340), skin rash (27.4% vs. 12.5%, p = 0.0301), pleuritis (14.5% vs. 4.2%, p = 0.0371) and unexplained fever (27.4% vs. 0%, p < 0.0001). AD were found in 7.4% of MDS patients (with polymyalgia rheumatic being the most frequently one). Classical autoimmune diseases were found only in 4 MDS patients (3.0%). Transcription factor pathway mutations (RUNX1, BCOR, WTI, TP53) (OR 2.20 [95%CI 1.02-4.75], p = 0.0451) and abnormal karyotypes (OR 2.76 [95%CI 1.22-6.26], p = 0.0153) were associated with autoinflammatory complications. Acute leukaemic transformation was more frequent in MDS patients with autoinflammatory features than those without (27.4% vs. 9.7%, p = 0.0080). Conclusions: Autoinflammatory complications are common in MDS. Somatic mutations of transcription factor pathways and abnormal karyotypes are associated with greater risk of autoinflammatory complications, which are themselves linked to malignant transformation and a worse prognosis.


Assuntos
Predisposição Genética para Doença , Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/etiologia , Mutação , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Autoanticorpos/imunologia , Autoimunidade/genética , Criança , Aberrações Cromossômicas , Feminino , Estudos de Associação Genética , Humanos , Cariótipo , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Fatores de Risco , Adulto Jovem
17.
Lancet Rheumatol ; 3(3): e224-e233, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33521655

RESUMO

COVID-19 has been occasionally linked to histologically confirmed cutaneous vasculitis and a Kawasaki-like vasculitis, with these entities generally having minimal or no lung involvement and a good prognosis. Unlike these vasculitis types, patients with severe COVID-19 pneumonia can develop cutaneous vasculitis-like lesions and systemic arterial and venous thromboemboli, including cryptogenic strokes and other vasculopathy features. Proposed underlying mechanisms for these severe manifestations have encompassed immune dysregulation, including an anti-phospholipid syndrome-like state, complement activation, viral dissemination with direct systemic endothelial infection, viral RNAaemia with immunothrombosis, clotting pathway activation mediated by hypoxaemia, and immobility. In this Viewpoint, we highlight how imaging and post-mortem findings from patients with COVID-19 indicate a novel thrombosis in the pulmonary venous territory distal to the alveolar capillary bed, a territory that normally acts as a clot filtration system, which might represent an unappreciated nidus for systemic microembolism. Additionally, we suggest that this mechanism represents a novel vasculitis mimic related to COVID-19 that might lead to cryptogenic strokes across multivessel territories, acute kidney injury with haematuria, a skin vasculitis mimic, intestinal ischaemia, and other organ ischaemic manifestations. This finding is supported by pathological reports of extensive pulmonary venular thrombosis and peripheral organ thrombosis with pauci-immune cellular infiltrates. Therefore, severe COVID-19 pneumonia with extensive pulmonary intravascular coagulopathy might help to explain the numerous systemic complications of COVID-19, in which the demonstration of direct organ infection has not adequately explained the pathology.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33590869

RESUMO

OBJECTIVE: To assess the association between familial Mediterranean fever and asthma. METHODS: This study was designed as a cross-sectional study. All patients diagnosed with familial Mediterranean fever between January 1, 2000, to December 31, 2016, who were prescribed colchicine were included in the study. Controls were matched by sex, date of birth, residential socioeconomic status, and country of birth. Logistic regression models were used to determine the odds ratio for asthma in familial Mediterranean fever patients and controls. RESULTS: A total of 7,098 familial Mediterranean fever patients who were prescribed colchicine were identified. Of them, 3,547 (50%) were females, 3,632 (51%) were of low residential socioeconomic status and 6,160 (87%) were born in Israel. Their median age at the end of follow-up was 37 years (23-54). In an unadjusted logistic regression, familial Mediterranean fever was associated with asthma (OR = 1.33, 95%CI 1.17-1.51; p < 0.001). The association persisted after adjusting for sex, socioeconomic status, and country of birth (OR = 1.33, 95%CI 1.18-1.52; p < 0.001). CONCLUSIONS: Familial Mediterranean fever is positively associated with asthma. Further research is required to validate our results and explore possible explanations of this association. These findings cast doubt on previous studies implying familial Mediterranean fever to be a protective factor from asthma.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33568039

RESUMO

Bisphenol A (BPA) is a monomer that is widely used in the manufacture of polycarbonate plastics including storage plastics and baby bottles, and is considered one of the most widely used synthetic compounds in the manufacturing industry. Exposure to BPA mainly occurs after oral ingestion and results from leaks into food and water from plastic containers and according to epidemiological data exposure is widespread and estimated to occur in 90% of individuals. BPA exertspleiotropiceffects and demonstrates estrogen like effects, thus considered an endocrine disrupting chemical. Growing body of evidence highlight the role of BPA in modulating immune responses and signaling pathways resulting in a proinflammatory response by enhancing the differential polarization of immune cells and cytokine production profile to one that is consistent with proinflammation. Indeed, epidemiological studies have uncovered associations between several autoimmune diseases and BPA exposure. Data from animal models provided consistent evidence highlighting the role of BPA in the pathogenesis, exacerbation and perpetuation of various autoimmune phenomena including neuroinflammation in the context of multiple sclerosis, colitis in inflammatory bowel disease, nephritis in systemic lupus erythematosus, and insulitis in type 1 diabetes mellitus. Given the wide spread of BPA use and its effects in immune systemdysregulation, a call for careful assessment of patients' risks and for public health measures are needed to limit exposure and subsequent deleterious effects. The purpose of this paper is to explore the autoimmune triggering mechanisms and present the current literature supporting the role of BPA in the pathogenesis of autoimmune diseases.

20.
Cells ; 10(2)2021 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-33562025

RESUMO

OBJECTIVE: The spondylarthritides (SpA) are intimately linked to new bone formation and IL-17A and TNF pathways. We investigated spinal soft tissue and bone mesenchymal stem cell (MSC) responses to IL-17A and TNF, including their osteogenesis, adipogenesis, and stromal supportive function and ability to support lymphocyte recruitment. METHODS: Normal spinal peri-entheseal bone (PEB) and entheseal soft tissue (EST) were characterized for MSCs by immunophenotypic, osteogenic, chondrogenic, and adipogenic differentiation criteria. Functional and gene transcriptomic analysis was carried out on undifferentiated, adipo- differentiated, and osteo-differentiated MSCs. The enthesis C-C Motif Chemokine Ligand 20-C-C Motif Chemokine Receptor 6 (CCL20-CCR6) axis was investigated at transcript and protein levels to ascertain whether entheseal MSCs influence local immune cell populations. RESULTS: Cultured MSCs from both PEB and EST displayed a tri-lineage differentiation ability. EST MSCs exhibited 4.9-fold greater adipogenesis (p < 0.001) and a 3-fold lower osteogenic capacity (p < 0.05). IL-17A induced greater osteogenesis in PEB MSCs compared to EST MSCs. IL-17A suppressed adipogenic differentiation, with a significant decrease in fatty acid-binding protein 4 (FABP4), peroxisome proliferator-activated receptor gamma (PPARγ), Cell Death Inducing DFFA Like Effector C (CIDEC), and Perilipin-1 (PLIN1). IL-17A significantly increased the CCL20 transcript (p < 0.01) and protein expression (p < 0.001) in MSCs supporting a role in type 17 lymphocyte recruitment. CONCLUSIONS: Normal spinal enthesis harbors resident MSCs with different in vitro functionalities in bone and soft tissue, especially in response to IL-17A, which enhanced osteogenesis and CCL20 production and reduced adipogenesis compared to unstimulated MSCs. This MSC-stromal-enthesis immune system may be a hitherto unappreciated mechanism of "fine tuning" tissue repair responses at the enthesis in health and could be relevant for SpA understanding.


Assuntos
Adipogenia , Interleucina-17/farmacologia , Células-Tronco Mesenquimais/citologia , Osteogênese , Medula Espinal/citologia , Células Estromais/citologia , Fator de Necrose Tumoral alfa/farmacologia , Adipogenia/efeitos dos fármacos , Adipogenia/genética , Idoso , Osso e Ossos/citologia , Quimiocina CCL20/metabolismo , Citocinas/metabolismo , Feminino , Humanos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Osteogênese/efeitos dos fármacos , Osteogênese/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores CCR6/metabolismo , Células Estromais/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...