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BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor recently approved to induce and maintain remission in ulcerative colitis (UC). AIMS: Considering the number of anti-TNF non-responders, this study aims to assess the effectiveness and safety of tofacitinib in a cohort of multi-failure patients with moderate-to-severe UC at 52 weeks. METHODS: From January 2021 to March 2023, we performed a prospective multicenter study observing adult patients with moderate-to-severe UC starting tofacitinib after an anti-TNF failure for a 52-week-long period. Effectiveness and safety were assessed in terms of colectomy rate, clinical remission and response, endoscopic remission, steroid-free clinical remission, and rate of adverse events. RESULTS: We included 58 patients with UC with an age of 42 ± 14.4 years, 59% males, 96.6% left-sided or pancolitis, who were failure to a single (65.5%) or more than one anti-TNF (34.5%). Only 6 (10.3%) patients underwent colectomy. Colectomy was clinically associated with the necessity and the number of extra cycles of tofacitinib 10 mg bid at W8 (p = 0.023) and W24 (p = 0.004), and with a higher partial Mayo score at W8 (p = 0.025). At W52, clinical remission, clinical response, and steroid-free clinical remission were 53.4%, 43.1%, and 48.3%, respectively. Of 22 performed colonoscopies at W52, 11 (50%) showed endoscopic remission. Adverse events occurred in 14 (24.1%) patients, but only 2 (3.4%) led to tofacitinib discontinuation. CONCLUSIONS: In a real-life setting of patients with anti-TNF refractory UC, tofacitinib has proved to be effective in preventing colectomy and inducing clinical and endoscopic remission at 52 weeks with a good safety profile.
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Colectomia , Colite Ulcerativa , Piperidinas , Pirimidinas , Humanos , Colite Ulcerativa/cirurgia , Colite Ulcerativa/tratamento farmacológico , Pirimidinas/uso terapêutico , Masculino , Feminino , Colectomia/efeitos adversos , Piperidinas/uso terapêutico , Piperidinas/efeitos adversos , Piperidinas/administração & dosagem , Adulto , Pessoa de Meia-Idade , Estudos Prospectivos , Itália/epidemiologia , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Inibidores de Janus Quinases/uso terapêutico , Inibidores de Janus Quinases/efeitos adversos , Indução de Remissão , Resultado do Tratamento , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversosRESUMO
OBJECTIVES: The number of susceptibility loci currently associated with vasculitis is lower than in other immune-mediated diseases due in part to small cohort sizes, a consequence of the low prevalence of vasculitides. This study aimed to identify new genetic risk loci for the main systemic vasculitides through a comprehensive analysis of their genetic overlap. METHODS: Genome-wide data from 8467 patients with any of the main forms of vasculitis and 29 795 healthy controls were meta-analysed using ASSET. Pleiotropic variants were functionally annotated and linked to their target genes. Prioritised genes were queried in DrugBank to identify potentially repositionable drugs for the treatment of vasculitis. RESULTS: Sixteen variants were independently associated with two or more vasculitides, 15 of them representing new shared risk loci. Two of these pleiotropic signals, located close to CTLA4 and CPLX1, emerged as novel genetic risk loci in vasculitis. Most of these polymorphisms appeared to affect vasculitis by regulating gene expression. In this regard, for some of these common signals, potential causal genes were prioritised based on functional annotation, including CTLA4, RNF145, IL12B, IL5, IRF1, IFNGR1, PTK2B, TRIM35, EGR2 and ETS2, each of which has key roles in inflammation. In addition, drug repositioning analysis showed that several drugs, including abatacept and ustekinumab, could be potentially repurposed in the management of the analysed vasculitides. CONCLUSIONS: We identified new shared risk loci with functional impact in vasculitis and pinpointed potential causal genes, some of which could represent promising targets for the treatment of vasculitis.
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Vasculite Sistêmica , Vasculite , Humanos , Antígeno CTLA-4 , Reposicionamento de Medicamentos , Predisposição Genética para Doença/genética , Vasculite Sistêmica/genética , Vasculite/tratamento farmacológico , Vasculite/genética , Proteínas Reguladoras de Apoptose/genéticaRESUMO
PURPOSE: Vessel wall imaging (VWI) with black-blood (BB) technique can demonstrate aneurysmal enhancement preluding to growth/rupture in treatment-naive cerebral aneurysms. Interestingly, recent works showed that BB enhancement may also occur in endovascularly treated aneurysms, though its meaning is controversial. Hypothesizing a flow-related mechanism of BB enhancement, we explored its relationship with incomplete occlusion status and coil packing density at DSA. METHODS: We analyzed the subjects undergoing 3T MRI between January 2017 and October 2020 for a previous aneurysmal coiling. All the MRI studies included pre- and post-contrast 3D BB sequences. The presence of intra-aneurysmal pre-contrast BB signal was assessed. BB enhancement (when present) was classified as follows: (1) enhancement at the neck, (2) intrasaccular/intra-coil enhancement, and (3) peripheral enhancement. Coil packing density and aneurysmal occlusion status (according to the modified Raymond-Roy classification, MRRC) were determined on post-treatment DSA and compared with BB findings using generalized linear mixed-effect model and ANOVA. Significant p values were <0.05. RESULTS: Forty-eight aneurysms from 44 patients were eligible for analysis. Pre-contrast BB signal was observed in 50% of the aneurysms and showed a relationship with baseline aneurysmal size. BB enhancement was detectable in 31 aneurysms (65%), being significantly associated with incomplete aneurysmal occlusion and reduced coil packing density at DSA. CONCLUSION: BB enhancement of coiled aneurysms is related with increasing degrees of post-coiling aneurysmal remnants and with loose coil packing density at DSA. This supports a hemodynamic interpretation of BB enhancement in long-term coiled aneurysms.
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Embolização Terapêutica , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/terapia , Resultado do Tratamento , Embolização Terapêutica/métodos , Imageamento por Ressonância Magnética/métodos , HemodinâmicaRESUMO
PURPOSE OF REVIEW: Large vessel vasculitides (LVVs) are inflammatory conditions of the wall of large-sized arteries, mainly represented by giant cell arteritis (GCA) and Takayasu arteritis (TA). The inflammatory process within the vessel wall can lead to serious consequences such as development of aneurysms, strokes and blindness; therefore, early diagnosis and follow-up of LVV are fundamental. However, the arterial wall is poorly accessible and blood biomarkers are intended to help physicians not only in disease diagnosis but also in monitoring and defining the prognosis of these conditions, thus assisting therapeutic decisions and favouring personalised management. The field is the object of intense research as the identification of reliable biomarkers is likely to shed light on the mechanisms of disease progression and arterial remodelling. In this review, we will discuss the role of blood biomarkers in LVVs in the light of the latest evidence. RECENT FINDINGS: In clinical practice, the most widely performed laboratory investigations are the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). However, these indices may be within normal limits during disease relapse and they are not reliable in patients receiving interleukin-6 (IL-6) receptor inhibitors. New biomarkers struggle to gain traction in clinical practice and no molecule with good accuracy has been identified to date. IL-6, a pro-inflammatory cytokine that drives CRP synthesis and increases the ESR, is one of the most promising biomarkers in the field. IL-6 analysis is increasingly performed, and serum levels are more sensitive than ESR for active GCA and might reflect persistent inflammation with high risk of relapse in patients on IL-6 receptor inhibitors. A future with biomarkers that reflect different disease features is an important aspiration. Accordingly, intense effort is being made to identify IL-6-independent inflammatory biomarkers, such as S100 proteins, pentraxin-3 and osteopontin. Moreover, metalloproteinases such as MMP2/9 and angiogenic modulators such as VEGF, YLK-40 and angiopoietins are being studied as markers of arterial remodelling. Lastly, biomarkers indicating organ damage may guide prognostic stratification as well as emergency therapeutic decisions: the most promising biomarkers so far identified are NT-proBNP, which reflects myocardial strain; pentraxin-3, which has been associated with recent optic nerve ischemia; and endothelin-1, which is associated with ischaemic complications. Currently, the use of these molecules in clinical practice is limited because of their restricted availability, lack of sufficient studies supporting their validity and associated costs. Further evidence is required to better interpret their biological and clinical value.
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Arterite de Células Gigantes , Arterite de Takayasu , Biomarcadores/sangue , Citocinas/sangue , Arterite de Células Gigantes/sangue , Arterite de Células Gigantes/diagnóstico , Humanos , Prognóstico , Arterite de Takayasu/sangue , Arterite de Takayasu/diagnóstico , Vasculite/sangue , Vasculite/diagnósticoRESUMO
The signals that control endothelial plasticity in inflamed tissues have only been partially characterized. For example, it has been shown that inadequate vasculogenesis in systemic sclerosis (SSc) has been associated with an endothelial defect. We used a genetic lineage tracing model to investigate whether endothelial cells die or change phenotypically after fibrosis induction and whether signals released by cells of the innate immune system and in the blood of patients influence their commitment. We observed that in the lineage-tracing transgenic mice Cdh5-CreERT2::R26R-EYFP, endothelial-derived cells (EdCs) underwent fibrosis after treatment with bleomycin, and EdCs retrieved from the lung showed expression of endothelial-to-mesenchymal transition (EndoMT) markers. Liposome-encapsulated clodronate was used to assess macrophage impact on EdCs. Clodronate treatment affected the number of alternatively activated macrophages in the lung, with upregulated expression of EndoMT markers in lung EdCs. Endothelial fate and function were investigated in vitro upon challenge with serum signals from SSc patients or released by activated macrophages. Sera of SSc patients with anti-Scl70 Abs, at higher risk of visceral organ fibrosis, induced EndoMT and jeopardized endothelial function. In conclusion, EdCs in SSc might be defective because of commitment to a mesenchymal fate, which is sustained by soluble signals in the patient's blood. Macrophages contribute to preserve the endothelial identity of precursor cells. Altered macrophage-dependent plasticity of EdCs could contribute to link vasculopathy with fibrosis.
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Endotélio/fisiologia , Inflamação/imunologia , Pulmão/patologia , Macrófagos/fisiologia , Células-Tronco Mesenquimais/fisiologia , Escleroderma Sistêmico/imunologia , Animais , Autoanticorpos/metabolismo , Diferenciação Celular , Linhagem da Célula , Plasticidade Celular , Células Cultivadas , Ácido Clodrônico , DNA Topoisomerases Tipo I , Fibrose , Humanos , Imunidade Inata , Camundongos , Camundongos Transgênicos , Neovascularização Patológica , Proteínas Nucleares/imunologiaRESUMO
OBJECTIVES: Takayasu arteritis commonly results in severe arterial injury with stenoses, occlusions and occasionally aneurysms. Arterial disease may compromise organ blood flow and result in significant cardiovascular morbidity and premature mortality. Involvement of the supra-aortic arteries is common, and in its most severe form may compromise cerebral blood supply, resulting in signs of cerebral ischaemia including visual impairment, dysphasia, transient hemiparesis, loss of consciousness and stroke. In addition to combination immunosuppression, the management paradigm for symptomatic cerebral ischaemia includes revascularization. The invasive nature of this surgery, the risk of complications and the relatively high rate of re-stenosis is of concern to patients and their physicians alike. The aim of this study was to determine whether combined immunosuppression with early escalation to biologic therapy improved outcomes and reduced the need for high risk surgical intervention. METHODS: A retrospective review of 145 Takayasu arteritis patients attending Imperial College Healthcare between 2010-2018 was conducted to identify those with cerebral ischaemia secondary to supra-aortic disease and to analyse their treatment and outcomes. RESULTS: Eight patients (5.5%) were identified. Seven patients received long-term combined immunosuppressive therapy and six were prescribed biologics. The data revealed a higher than expected comprehensive response to therapy, with significant falls in disease activity, the cerebral ischaemia score and the prednisolone dose required, over a median follow-up of 37 months. Serial imaging analysis detected no arterial disease progression after the initiation of optimal therapy. Only one patient required surgical intervention for persistent neurological symptoms. CONCLUSION: Early use of biologic therapy in those with supra-aortic Takayasu arteritis presenting with cerebral ischaemia may reduce the numbers of patients requiring surgical intervention and improve outcomes.
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Terapia Biológica , Isquemia Encefálica/etiologia , Isquemia Encefálica/terapia , Arterite de Takayasu/complicações , Adulto , Feminino , Humanos , Estudos Retrospectivos , Adulto JovemRESUMO
Recent advances have shown impressive results by anti-interleukin 1 (IL-1) agents in refractory idiopathic recurrent pericarditis. PURPOSE OF REVIEW: We critically discuss the current state of the art of therapy of relapsing pericarditis, with a focus on new pharmacological approaches and on specific clinical settings such as pregnancy, pediatric patients, and secondary forms of relapsing pericarditis. RECENT FINDINGS: Antagonism of the IL-1 is highly effective in idiopathic recurrent pericarditis with autoinflammatory features. Currently, available anti-IL-1 agents are anakinra and canakinumab. Rilonacept is another IL-1 antagonist, currently studied in the phase-3 clinical trial RHAPSODY. Available data suggest similar efficacy and safety profiles of these three agents, although only anakinra has been tested in randomized clinical trials. These agents have slightly different pharmacological properties, being canakinumab a specific IL-1ß antagonist while anakinra and rilonacept are unselective IL-1α and IL-1ß blockers. To date, there is no evidence that specificity against IL-1ß affects safety and efficacy in patients with relapsing pericarditis, although it has been proposed that unspecific blockage might be useful in severe disease. Anakinra is the first anti-IL-1 agent with well-documented efficacy and safety in adult and pediatric patients with idiopathic relapsing pericarditis. Other anti-IL-1 agents are currently under study. Future research should clarify the optimal duration of therapy and tapering schedule of treatment with these agents. Moreover, biomarkers would be required to understand which patients will benefit from early administration of IL-1 blockers due to refractoriness to conventional therapy and which others will suffer from recurrences during the tapering of these agents. Lastly, future studies should focus on the subjects with the autoimmune or the pauci-inflammatory phenotype of idiopathic refractory pericarditis.
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Pericardite , Adulto , Biomarcadores , Criança , Humanos , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-1 , RecidivaRESUMO
Although outcomes in Takayasu arteritis (TAK) are improving, diagnosis is typically delayed and significant arterial injury accrues. While wider use of non-invasive imaging is impacting this, the onus remains with clinicians to consider a diagnosis of TAK earlier. Meanwhile, morbidity and mortality in TAK remains increased. Herein we review the current situation, outline recent advances and summarize remaining challenges. Understanding of disease pathogenesis remains poor. However, recent genetic data and identification of pathogenic cytokines may facilitate the search for biomarkers capable of distinguishing active and inactive disease, inflammatory and non-inflammatory arterial remodelling. Imaging is critical for TAK, and each modality has important strengths and limitations. Dependence upon CS therapy remains too high. However, the impact of combination immunosuppressive therapy is now recognized, biologic therapies are increasingly available and new agents offer promise. Multicentre clinical trials are now required, and these will depend upon development of defined clinical and imaging end-points.
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Arterite de Takayasu/diagnóstico , Arterite de Takayasu/terapia , Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Biomarcadores/sangue , Angiografia por Tomografia Computadorizada , Progressão da Doença , Predisposição Genética para Doença , Humanos , Imunossupressores/uso terapêutico , Angiografia por Ressonância Magnética , Índice de Gravidade de Doença , Arterite de Takayasu/etiologiaRESUMO
PURPOSE: The object of this study was to assess whether 18F-fluorodeoxyglucose PET/CT (FDG PET/CT) provides novel information in patients with Takayasu's arteritis (TA) in addition to that provided by current activity assessment, to analyse the effects of possible confounders, such as arterial grafts, and to verify whether PET/CT could be informative in lesions <4 mm thick. METHODS: We studied 30 patients with TA, evaluated from October 2010 to April 2014 by both PET/CT and magnetic resonance imaging (MRI). All arterial lesions were evaluated by PET both qualitatively (positive/negative) and semiquantitatively (maximum standardized uptake value, SUVmax), and the thickness of lesions in the MRI field of view was evaluated. In a per-patient analysis, the relationships between the PET data and acute-phase reactants and NIH criteria for active TA were evaluated. In a per-lesion analysis, the relationships between the PET features of each lesion and MRI morphological data were evaluated. The effects of the presence of arterial grafts were also evaluated. RESULTS: Increased FDG uptake was seen in 16 of 30 patients (53%) and in 46 of 177 vascular lesions (26%). Significant periprosthetic FDG uptake was seen in 6 of 7 patients (86%) with previous vascular surgery and in 10 of 11 of grafts (91%). Graft-associated uptake influenced the PET results in three patients (10%) and the SUVmax values in five patients (17%). Of 39 lesions with significant FDG uptake, 15 (38%) were <4 mm thick. Lesion thickness was correlated with lesion SUVmax in FDG-avid lesions only. FDG arterial uptake was not associated with systemic inflammation or NIH criteria. CONCLUSIONS: PET/CT reveals unique and fundamental features of arterial involvement in TA. PET/CT may be useful in the assessment of local inflammatory and vascular remodelling events independent of systemic inflammation during follow-up, even in lesions in which the arterial wall is <4 mm. The presence of arterial grafts is a potential confounder. Prospective studies are required to correlate PET findings with relevant clinical outcomes.
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Artérias/diagnóstico por imagem , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Arterite de Takayasu/diagnóstico por imagem , Adulto , Idoso , Artérias/metabolismo , Transporte Biológico , Biomarcadores/metabolismo , Feminino , Fluordesoxiglucose F18/metabolismo , Humanos , Inflamação/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Arterite de Takayasu/metabolismo , Arterite de Takayasu/fisiopatologia , Adulto JovemRESUMO
OBJECTIVES: An ill-defined hyperintense edge and hypointense core on diffusion-weighted imaging (DWI) is typical of progressive multifocal leukoencephalopathy (PML). We aimed to investigate whether a b-value of 3,000 s/mm2 (b3000) can improve visualisation of PML, or provide different structural information compared to 1,000 s/mm2 (b1000). METHODS: We retrospectively identified HIV-positive patients with confirmed PML studied under a clinical protocol including both b1000 and b3000 DWI. The rim and core of each PML lesion and normal-appearing white matter (NAWM) were outlined on trace-weighted DWI. Signal intensities, apparent diffusion coefficient (ADC) values and volumes were measured and compared between b1000 and b3000. RESULTS: Nine lesions from seven patients were analysed. The rim and core were better visualised on b3000, with higher signal of the rim and lower signal of the core compared to NAWM. The hyperintense rim had non-restricted average ADCs, but included foci of low ADC on both b3000 and b1000. Despite similar total lesion volumes, b3000 displayed significantly larger core and smaller rim volumes than b1000. CONCLUSION: b3000 improves visualisation of this important PML hallmark. Moreover, b3000 partly reclassifies tissue from rim into core, and might provide potentially more accurate biomarkers of PML activity and prognosis. KEY POINTS: ⢠B3000 improves contrast resolution between lesion rim, core and normal-appearing white matter. ⢠B3000 improves identification of the typical rim-and-core pattern of PML lesions. ⢠B3000 and b1000 similarly identify lesions, but b3000 results in smaller rims and larger cores. ⢠B3000 excludes some high diffusion components from rim, reclassifying them into core. ⢠B3000 DWI may provide more precise PML biomarkers of disease activity and tissue damage.
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Infecções Oportunistas Relacionadas com a AIDS/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Leucoencefalopatia Multifocal Progressiva/diagnóstico por imagem , Infecções Oportunistas Relacionadas com a AIDS/patologia , Adulto , Idoso , Imagem de Difusão por Ressonância Magnética/métodos , Progressão da Doença , Feminino , Humanos , Leucoencefalopatia Multifocal Progressiva/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
Drug induced exfoliative dermatitis (ED) are a group of rare and severe drug hypersensitivity reactions (DHR) involving skin and usually occurring from days to several weeks after drug exposure. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Overall, T cells are the central player of these immune-mediated drug reactions. Here we provide a systematic review on frequency, risk factors, pathogenesis, clinical features and management of patients with drug induced ED.
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Recurrent pericarditis, an inflammatory syndrome with a pathogenesis not fully elucidated, often presents diagnostic challenges. This study aims to assess the correlation of D-Dimer (D-D) and procalcitonin (PCT) levels with clinical, laboratory and imaging features in recurrent idiopathic pericarditis. We analyzed 412 patients with idiopathic recurrent pericarditis from 2019 to 2023 in our referral center. D-D and PCT values were obtained from emergency room in other Italian facilities. Among the cohort, PCT levels were assessed in 50 of 412 patients (12.1%), with only 4 showing marginal elevation. D-D levels were measured in 48 of 412 patients (11.6%), with 33 of them exhibiting elevated values. None of these patients had venous thromboembolism, and elevated D-D levels were significantly associated with pleural effusion, fever, higher CRP, increased white blood cell counts, higher neutrophil counts, reduced relative lymphocyte counts. Multivariate analysis revealed fever as the sole correlate of elevated D-D. PCT elevation was infrequent and unrelated to any variables. In idiopathic recurrent pericarditis unrelated to specific conditions, we observed a close association between elevated D-D levels and non-specific inflammation markers, including fever, increased CRP, and neutrophil leukocytosis. PCT levels were typically normal or mildly elevated.
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OBJECTIVE: The aim of this study was to assess whether circulating histone-specific T cells represent tools for precision medicine in systemic lupus erythematosus (SLE). METHODS: Seroprevalence of autoantibodies and HLA-DR beta (DRB) 1 profile were assessed among 185 patients with SLE and combined with bioinformatics and literature evidence to identify HLA-peptide autoepitope couples for ex vivo detection of antigen-specific T cells through flow cytometry. T cell differentiation and polarization was investigated in patients with SLE, patients with Takayasu arteritis, and healthy controls carrying HLA-DRB1*03:01 and/or HLA-DRB1*11:01. SLE Disease Activity Index 2000 and Lupus Low Disease Activity State were used to estimate disease activity and remission. RESULTS: Histone-specific CD4+ T cells were selectively detected in patients with SLE. Among patients with a history of anti-DNA antibodies, 77% had detectable histone-specific T cells, whereas 50% had lymphocytes releasing cytokines or upregulating activation markers after in vitro challenge with histone peptide antigens. Histone-specific regulatory and effector T helper (Th) 1-, Th2-, and atypical Th1/Th17 (Th1*)-polarized cells were significantly more abundant in patients with SLE with quiescent disease. In contrast, total Th1-, Th2-, and Th1*-polarized and regulatory T cells were similarly represented between patients and controls or patients with SLE with active versus quiescent disease. Histone-specific effector memory T cells accumulated in the blood of patients with quiescent SLE, whereas total effector memory T cell counts did not change. Immunosuppressants were associated with expanded CD4+ histone-specific naive T (TN) and terminally differentiated T cells. CONCLUSION: Histone-specific T cells are selectively detected in patients with SLE, and their concentration in the blood varies with disease activity, suggesting that they represent innovative tools for patient stratification and therapy.
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Linfócitos T CD4-Positivos , Histonas , Lúpus Eritematoso Sistêmico , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Histonas/imunologia , Histonas/metabolismo , Linfócitos T CD4-Positivos/imunologia , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/imunologia , Autoanticorpos/imunologia , Anticorpos Antinucleares/imunologia , Estudos de Casos e Controles , Células Th1/imunologiaRESUMO
AIMS: To identify peripheral blood cellular correlates of active pericarditis and to verify whether peripheral blood neutrophils, lymphocytes and the neutrophil to-lymphocyte ratio (NLR) are associated with disease phenotype or prognosis. METHODS: Observational prospective study on a cohort of 63 patients with idiopathic pericarditis followed for 12 months after each pericarditis recurrence. Two distinct analyses were performed: the "index attack" analysis focused on the first pericarditis episode in each patient, while the "all attacks" analysis included all episodes occurring during the study. RESULTS: Absolute and relative neutrophilia and lymphopenia, together with high NLR, were observed during active pericarditis, as compared with disease remission, at both analyses. Neutrophils showed a positive correlation with plasma C-reactive protein levels, while lymphocyte count showed a negative correlation. Relative neutrophil count was higher, and lymphocyte count lower in patients with pleural effusion; a higher NLR and lower absolute lymphocyte count were observed in those with peritoneal involvement. No correlations were found between peripheral blood neutrophil or lymphocyte counts and size of pericardial effusion, or with the presence of myocardial involvement. Peripheral neutrophilia, lymphopenia and NLR during acute attacks predicted the number of recurrences in the following 12 months. CONCLUSIONS: Peripheral blood neutrophilia and lymphopenia are typical of acute idiopathic pericarditis. Acute attacks of pericarditis are associated with neutrophilia and lymphopenia, as compared with disease remission. During acute attacks, neutrophilia and lymphopenia reflect the extent of serosal inflammation and could help to customize therapeutic management after remission has been achieved.
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Doenças da Medula Óssea , Linfopenia , Pericardite , Humanos , Neutrófilos , Estudos Prospectivos , Linfopenia/diagnóstico , Linfócitos , Contagem de Linfócitos , Prognóstico , Inflamação , Pericardite/diagnóstico , Pericardite/terapia , Estudos RetrospectivosRESUMO
OBJECTIVES: This cohort study describes a systemic phenotype of pericarditis, comparing this phenotype with other forms of pericarditis. PATIENTS AND METHODS: Patients in our center were enrolled in a prospectively maintained registry from 2019 to 2022. 412 patients with idiopathic recurrent pericarditis were analyzed. "Systemic inflammatory" subset was defined as the presence of all the following criteria: fever ≥38C°, CRP ≥2 times normal values, pleural effusion detected with any imaging techniques. The absence of any of the 3 criteria was defined as "isolated" subset. RESULTS: We found that 211 (51.2%) of 412 patients (188 female) presented the systemic subset and the variables significantly associated with this subset in univariate analysis (p<0.001) were: higher mean age: 45.5 (±SD 17.2) vs 39.9 (±SD 16.4) years, higher mean CRP values: 128.8 vs 49.9 mg/L, higher proportion of pericardiocentesis: 19% vs 1.5%, higher mean leukocyte count: 13,143.3 vs 9910.3/mm3, higher mean neutrophils number: 10,402.5 vs 6779.8 /mm3 and lower mean lymphocyte count: 1693.9 vs 2079.3 /mm3. As results the neutrophil-to-lymphocyte ratio was higher in systemic inflammatory phenotype: 6.6 vs 3.4 (p< 0.001). Anti-IL1 therapy was started more frequently in the systemic subgroup (26%) than in the isolated subset (7.5%) (p < 0.001). On multivariate analysis neutrophil count and lymphopenia were statistically associated with the systemic subset (p < 0.001). CONCLUSION: This results demonstrate the relevance of the systemic inflammatory phenotype, characterized by pleural effusions, confirming its analogy with autoinflammatory diseases, thus possibly requiring an eventual escalation of therapy to IL-1 inhibitors.
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Doenças Hereditárias Autoinflamatórias , Pericardite , Derrame Pleural , Humanos , Feminino , Estudos de Coortes , Proteína C-Reativa/análise , Derrame Pleural/complicações , Febre , Doenças Hereditárias Autoinflamatórias/complicaçõesRESUMO
OBJECTIVE: It is unclear why activated platelets and platelet-derived microparticles (MPs) accumulate in the blood of patients with systemic sclerosis (SSc). This study was undertaken to investigate whether defective phagocytosis might contribute to MP accumulation in the blood of patients with SSc. METHODS: Blood samples were obtained from a total of 81 subjects, including 25 patients with SSc and 26 patients with stable coronary artery disease (CAD). Thirty sex- and age-matched healthy volunteers served as controls. Studies were also conducted in NSG mice, in which the tail vein of the mice was injected with MPs, and samples of the lung parenchyma were obtained for analysis of the pulmonary microvasculature. Tissue samples from human subjects and from mice were assessed by flow cytometry and immunochemical analyses for determination of platelet-neutrophil interactions, phagocytosis, levels and distribution of P-selectin, P-selectin glycoprotein ligand 1 (PSGL-1), and HMGB1 on platelets and MPs, and concentration of byproducts of neutrophil extracellular trap (NET) generation/catabolism. RESULTS: Activated P-selectin+ platelets and platelet-derived HMGB1+ MPs accumulated in the blood of SSc patients but not in the blood of healthy controls. Patients with CAD, a vasculopathy independent of systemic inflammation, had fewer P-selectin+ platelets and a negligible number of MPs. The expression of the receptor for P-selectin, PSGL-1, in neutrophils from SSc patients was significantly decreased, raising the possibility that phagocytes in SSc do not recognize activated platelets, leading to a failure of phagocytosis and continued neutrophil release of MPs. As evidence of this process, activated platelets were not detected in the neutrophils from SSc patients, whereas they were consistently present in the neutrophils from patients with CAD. HMGB1+ MPs elicited generation of NETs, which were only detected in the plasma of SSc patients. In mice, P-selectin-PSGL-1 interaction resulted in platelet phagocytosis in vitro and influenced the ability of MPs to elicit NETs, endothelial activation, and migration of leukocytes through the pulmonary microvasculature. CONCLUSION: The clearance of activated platelets via PSGL-1 limits the undesirable effects of MP-elicited neutrophil activation. This balance is disrupted in patients with SSc. Its reconstitution might curb vascular inflammation and prevent fibrosis.
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Plaquetas/fisiologia , Micropartículas Derivadas de Células , Glicoproteínas de Membrana/fisiologia , Fagocitose , Escleroderma Sistêmico/sangue , Adulto , Idoso , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-IdadeRESUMO
This review summarizes the currently available evidence on the management of acute and recurrent pericarditis during pregnancy, focusing on the safety of diagnostic procedures and treatment options for the mother and fetus. Family planning should be addressed in women with recurrent pericarditis of reproductive age and adjustment of therapy should be considered before a planned pregnancy. The treatment of pericarditis in pregnancy is similar to that for non-pregnant women but considers current knowledge on drug safety during pregnancy and lactation. The largest case series on this topic described 21 pregnancies with idiopathic recurrent pericarditis. Pregnancy should be planned in a phase of disease quiescence. Non-steroidal anti-inflammatory drugs can be used at high dosages until the 20th week of gestation (except low-dose aspirin 100 mg/die). Colchicine is allowed until gravindex positivity; after this period, administration of this drug during pregnancy and lactation should be discussed with the mother if its use is important to control recurrent pericarditis. Prednisone is safe if used at low-medium doses (2.5-10 mg/die). General outcomes of pregnancy in patients with pericarditis are good when the mothers are followed by a multidisciplinary team with experience in the field.