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1.
J Neurol ; 267(2): 561-571, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31705291

RESUMO

BACKGROUND: Anti-MAG polyneuropathy (anti-MAG PN) is an immune-mediated peripheral sensorimotor neuropathy characterized by distal demyelination and ataxia. However, this disorder, unlike other immune-mediated neuropathies, is difficult to treat in most cases. METHOD: We retrospectively collected all anti-MAG PN patients followed in two hospitals for a period of 12 years to determine prognostic factors, especially those that indicated a good response to the various therapeutic strategies used. RESULTS: Forty-seven patients were included in the study; of these, 61% had a classical 'distal demyelinating pattern', 34.2% had a 'CIDP-like pattern', and the others had an 'axonal pattern'. The most commonly used treatments were intravenous immunoglobulin (IVIg) as the first-line treatment and rituximab as the second- or third-line treatment. No prognostic factor was identified for IVIg, but electrophysiological parameters at onset were better in patients with a good response to rituximab than in non-responder patients, even though mild or high disability was observed in nearly half the patients at last examination. CONCLUSION: Even though disability seems to progress in most cases despite the treatments used, our results suggest that an early electrophysiological reduction in sensory nerves could be considered a 'red flag' for the prompt initiation of rituximab to try to delay long-term disability.

2.
Autoimmun Rev ; 18(9): 102359, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31323362

RESUMO

OBJECTIVE: The aim of this study is to compare the frequency of remission, according to DORIS definitions, of inception patients from two European SLE cohorts, with a special focus on the differences between the therapeutic schemes of both Units. METHODS: Inception patients enrolled after 2000 from the longitudinal Cruces Lupus Cohort (CC) and Bordeaux Lupus Cohort (BC) were included. The main endpoint was the achievement of clinical remission on treatment (ClinROnT). ClinROnT was assessed yearly from the 1st until the 5th year following the diagnosis of SLE. RESULTS: 173 patients, 92 CC and 81 BC, were studied. The clinical presentation of both cohorts was similar, with no significant differences in the mean SLEDAI score at diagnosis (6.6 vs. 8.1, p = 0.06). Patients from CC were treated more frequently with hydroxychloroquine (mean 57 vs. 43 months), methotrexate (24% vs. 11%) and pulse methyl-prednisolone (42% vs. 26%), and received lower doses of oral prednisone (average dose during the follow up 2.3 vs. 7.2 mg/d, p < 0.001). Patients in CC were more likely to achieve ClinROnT at year one, 84% vs. 43% (p < 0.001). Prolonged ClinROnT during the 5 years of follow up was more frequent in CC: 70% vs. 28%, p < 0.001. Patients in CC were also more likely to achieve ClinROnT after controlling for baseline SLEDAI (adjusted HR 1.69, 95%CI 1.21-2.35) and for the presenting clinical manifestations (adjusted HR 1.72, 95% CI 1.2-2.4). CONCLUSION: Prolonged ClinROnT was achievable by using a therapeutic regime consisting of lower doses of oral prednisone and maximizing the use of hydroxychloroquine, pulse methyl-prednisolone and methotrexate.


Assuntos
Imunossupressores/administração & dosagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Prednisona/administração & dosagem , Administração Oral , Adulto , Estudos de Coortes , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , França/epidemiologia , Glucocorticoides/administração & dosagem , Humanos , Hidroxicloroquina/administração & dosagem , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Metotrexato/administração & dosagem , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Indução de Remissão , Espanha/epidemiologia , Resultado do Tratamento , Adulto Jovem
3.
Artigo em Inglês | MEDLINE | ID: mdl-31254159

RESUMO

Systemic lupus erythematosus (SLE) is a systemic and potentially fatal autoimmune disease. SLE pathophysiology is complex and involves the interplay between the innate and adaptive immune systems, with a particularly significant role for type I interferons. Recently, the participation of other actors such as platelets and IgE has been described in SLE. On the one hand, platelets activated by different stimuli (antiphospholipid antibodies, immune complexes…) participate in immune dysregulation through direct interactions with immune cells. On the other hand, autoreactive IgE can activate basophils, promoting a Th2 environment and subsequent antibody production by plasma cells. In synergy with IgG, IgE is also able to activate plasmacytoid DCs (pDCs) increasing interferon alpha production. Mirroring the IgG paradox, total nonautoreactive IgE is described as a potential regulator of IFNα production. This review summarizes recent and novel data on innate immunity in SLE pathophysiology with a focus on platelets and IgE, as they represent novel players in immune dysregulation and potential therapeutic targets.

5.
JCI Insight ; 3(24)2018 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-30568041

RESUMO

Tregs are impaired in human systemic lupus erythematosus (SLE) and contribute to effector T cell activation. However, the mechanisms responsible for the Treg deficiency in SLE remain unclear. We hypothesized that the OX40L/OX40 axis is implicated in Treg and regulatory follicular helper T (Tfr) cell dysfunction in human SLE. OX40L/OX40 axis engagement on Tregs and Tfr cells not only specifically impaired their ability to regulate effector T cell proliferation, but also their ability to suppress T follicular helper (Tfh) cell-dependent B cell activation and immunoglobulin secretion. Antigen-presenting cells from patients with active SLE mediated Treg dysfunction in an OX40L-dependent manner, and OX40L-expressing cells colocalized with Foxp3+ cells in active SLE skin lesions. Engagement of the OX40L/OX40 axis resulted in Foxp3 downregulation in Tregs, and expression in SLE Tregs correlated with the proportion of circulating OX40L-expressing myeloid DCs. These data support that OX40L/OX40 signals are implicated in Treg dysfunction in human SLE. Thus, blocking the OX40L/OX40 axis appears to be a promising therapeutic strategy.


Assuntos
Lúpus Eritematoso Sistêmico/imunologia , Ligante OX40/imunologia , Receptores OX40/imunologia , Linfócitos T Reguladores/imunologia , Células Apresentadoras de Antígenos , Doenças Autoimunes/imunologia , Proliferação de Células , Citocinas , Células Dendríticas/imunologia , Regulação para Baixo , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Imunidade Celular/imunologia , Ativação Linfocitária , Masculino , Células Mieloides/imunologia , Ligante OX40/metabolismo , Receptores OX40/metabolismo , Linfócitos T , Linfócitos T Auxiliares-Indutores , Linfócitos T Reguladores/metabolismo
6.
Front Immunol ; 9: 1637, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30065726

RESUMO

T follicular helper (Tfh) cells are a distinct subset of CD4+ T lymphocytes, specialized in B cell help and in regulation of antibody responses. They are required for the generation of germinal center reactions, where selection of high affinity antibody producing B cells and development of memory B cells occur. Owing to the fundamental role of Tfh cells in adaptive immunity, the stringent control of their production and function is critically important, both for the induction of an optimal humoral response against thymus-dependent antigens but also for the prevention of self-reactivity. Indeed, deregulation of Tfh activities can contribute to a pathogenic autoantibody production and can play an important role in the promotion of autoimmune diseases. In the present review, we briefly introduce the molecular factors involved in Tfh cell formation in the context of a normal immune response, as well as markers associated with their identification (transcription factor, surface marker expression, and cytokine production). We then consider in detail the role of Tfh cells in the pathogenesis of a broad range of autoimmune diseases, with a special focus on systemic lupus erythematosus and rheumatoid arthritis, as well as on the other autoimmune/inflammatory disorders. We summarize the observed alterations in Tfh numbers, activation state, and circulating subset distribution during autoimmune and some other inflammatory disorders. In addition, central role of interleukin-21, major cytokine produced by Tfh cells, is discussed, as well as the involvement of follicular regulatory T cells, which share characteristics with both Tfh and regulatory T cells.

7.
Front Immunol ; 9: 1702, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30083163

RESUMO

Systemic sclerosis (SSc) is a heterogeneous autoimmune disease characterized by three interconnected hallmarks (i) vasculopathy, (ii) aberrant immune activation, and (iii) fibroblast dysfunction leading to extracellular matrix deposition and fibrosis. Blocking or reversing the fibrotic process associated with this devastating disease is still an unmet clinical need. Although various components of innate immunity, including macrophages and type I interferon, have long been implicated in SSc, the precise mechanisms that regulate the global innate immune contribution to SSc pathogenesis remain poorly understood. Recent studies have identified new innate immune players, such as pathogen-recognition receptors, platelet-derived danger-associated molecular patterns, innate lymphoid cells, and plasmacytoid dendritic cells in the pathophysiology of SSc, including vasculopathy and fibrosis. In this review, we describe the evidence demonstrating the importance of innate immune processes during SSc development with particular emphasis on their role in the initiation of pathology. We also discuss potential therapeutic options to modulate innate immune cells or signaling in SSc that are emerging from these recent advances.

8.
AIDS ; 32(12): 1651-1660, 2018 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-29762168

RESUMO

BACKGROUND: The widespread introduction of combination antiretroviral therapy (cART) has increased survival of HIV-infected patients. However, the prevalence of age-related comorbidities remains higher than that of the general population, suggesting that individuals with HIV suffer from accelerated aging. Immune activation, senescence and inflammation could play an important role in this process. METHODS: The CIADIS (Chronic Immune Activation anD Senescence) sub-study analyzed biomarkers of activation, differentiation and senescence of T cells in a cellular-CIADIS-weighted score, whereas biomarkers of inflammation were analyzed in a soluble CIADIS-weighted score using principal component analysis. Adjusted logistic regression and Cox proportional hazard models were used to determine the association between CIADIS-weighted scores and the presence of multimorbidity, time to occurrence of the first new age-related comorbidity and time to death, over a 3-year follow-up period. RESULTS: Of 828 patients with an undetectable viral load, a higher cellular-CIADIS-weighted score and higher TNFRI levels were independently associated with the presence of multimorbidity (OR 1.3; 95% CI 1.0-1.6; P = 0.02), but the soluble CIADIS-weighted score was not (OR = 1.1; 95% CI 0.9-1.3; P = 0.33). A higher cellular CIADIS-weighted score (hazard ratio 2.2; P < 0.01), higher levels of CD8 activation and a lower CD4/CD8 ratio were associated with a higher risk of age-related comorbidities. Only TNFRI was associated with mortality in a 3-year period. CONCLUSION: The cellular CIADIS-weighted score was independently associated with both multimorbidity at inclusion and the risk of new age-related comorbidity during a 3- year follow-up. TNFRI was associated a higher risk for mortality.


Assuntos
Envelhecimento , Infecções por HIV/complicações , Infecções por HIV/patologia , Inflamação/patologia , Mortalidade , Multimorbidade , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Medição de Risco , Análise de Sobrevida , Carga Viral
9.
Autoimmun Rev ; 17(6): 625-635, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29635077

RESUMO

Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are two phenotypically distincts inflammatory systemic diseases. However, SLE and SSc share pathogenic features such as interferon signature, loss of tolerance against self-nuclear antigens and increased tissue damage such as fibrosis. Recently, platelets have emerged as a major actor in immunity including auto-immune diseases. Both SLE and SSc are characterized by strong platelet system activation, which is likely to be both the witness and culprit in their pathogenesis. Platelet activation pathways are multiple and sometimes redundant. They include immune complexes, Toll-like receptors activation, antiphospholipid antibodies and ischemia-reperfusion associated with Raynaud phenomenon. Once activated, platelet promote immune dysregulation by priming interferon production by immune cells, providing CD40L supporting B lymphocyte functions and providing a source of autoantigens. Platelets are actively implicated in SLE and SSc end-organ damage such as cardiovascular and renal disease and in the promotion of tissue fibrosis. Finally, after understanding the main pathogenic implications of platelet activation in both diseases, we discuss potential therapeutics targeting platelets.


Assuntos
Plaquetas/fisiologia , Lúpus Eritematoso Sistêmico/etiologia , Escleroderma Sistêmico/etiologia , Anticorpos Antifosfolipídeos/sangue , Complexo Antígeno-Anticorpo/sangue , Plaquetas/imunologia , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Doença de Raynaud/sangue , Doença de Raynaud/imunologia , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/imunologia
10.
Joint Bone Spine ; 85(6): 663-668, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29631068

RESUMO

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that primarily affects women of childbearing age. While the impact of hydroxychloroquine (HCQ) on SLE activity and neonatal lupus occurrence has been evaluated in several studies, its role on prematurity and intrauterine growth restriction (IUGR) remains uncertain. The aim of this study was to assess the impact of HCQ exposure on prematurity and IUGR during pregnancy in women with SLE. METHODS: We conducted a systematic review and a meta-analysis comparing prematurity and IUGR in SLE pregnancies exposed or not exposed to HCQ. The odds ratio of IUGR and prematurity were calculated and compared between pregnancies in each group according HCQ treatment. RESULTS: Six studies were included (3 descriptive cohort studies and 3 case series) totalling 870 pregnancies. Of the SLE pregnancies, 308 were exposed to HCQ and were compared to 562 not exposed to HCQ. There was no statistical difference for prematurity or IUGR between groups. CONCLUSION: This meta-analysis failed to prove the efficacy of HCQ in the prevention of prematurity as well as IUGR during SLE pregnancies. Due to the heterogeneity of the studies, these results should be interpreted cautiously.


Assuntos
Retardo do Crescimento Fetal/prevenção & controle , Hidroxicloroquina/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Complicações na Gravidez , Nascimento Prematuro/prevenção & controle , Antirreumáticos/uso terapêutico , Feminino , Retardo do Crescimento Fetal/etiologia , Humanos , Recém-Nascido , Lúpus Eritematoso Sistêmico/complicações , Gravidez
11.
Clin Exp Rheumatol ; 36(3): 490-493, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29533748

RESUMO

OBJECTIVES: Guidelines for preventing Pneumocystis pneumonia (PCP) in HIV patients are based on CD4 below 200/mm3. Such cut-off value is suggested to guide prophylaxis in non-HIV conditions (NHIV) especially in autoimmune and inflammatory diseases (AD). We aimed to determine if CD4 could be used to guide PCP prophylaxis in AD. METHODS: CD4 and lymphocyte-count were retrospectively studied in patients diagnosed with PCP between January 2013 and February 2016. RESULTS: 129 patients were included. The median CD4-count was 302/mm3 in AD, which was significantly higher than in HIV patients (19/mm3; p<0.0001). Fifty percent (n=10) of AD patients had CD4 counts greater than 300/mm3. CONCLUSIONS: Prophylaxis for PCP cannot rely solely on CD4-count in NHIV patients especially in AD.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/terapia , Imunossupressores/efeitos adversos , Linfopenia/tratamento farmacológico , Pneumonia por Pneumocystis/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Doenças Autoimunes/complicações , Doenças Autoimunes/imunologia , Contagem de Linfócito CD4 , Crioglobulinemia/complicações , Crioglobulinemia/tratamento farmacológico , Crioglobulinemia/imunologia , Dermatomiosite/complicações , Dermatomiosite/tratamento farmacológico , Dermatomiosite/imunologia , Gerenciamento Clínico , Feminino , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/tratamento farmacológico , Arterite de Células Gigantes/imunologia , Infecções por HIV/complicações , Hepatite Autoimune/complicações , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/imunologia , Humanos , Hospedeiro Imunocomprometido , Linfopenia/etiologia , Linfopenia/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/imunologia , Neoplasias/terapia , Transplante de Órgãos , Pneumonia por Pneumocystis/etiologia , Pneumonia por Pneumocystis/imunologia , Guias de Prática Clínica como Assunto , Estudos Retrospectivos
12.
Joint Bone Spine ; 85(2): 155-163, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29288864

RESUMO

OBJECTIVES: To determine whether subclinical atherosclerosis is increased in patients with systemic lupus erythematosus (SLE) compared to healthy individuals, using carotid intima-media thickness (CIMT), carotid plaque (CP) presence or flow-mediated dilatation (FMD). METHODS: A systematic literature search was performed using MedLine, Embase and Cochrane databases. Two reviewers independently screened the articles to identify studies that compared the rates of atherosclerosis in SLE patients versus healthy controls. The results were pooled in a meta-analysis. Factors influencing the CIMT, CP or FMD results were collected. RESULTS: Of the 203 articles initially identified, 68 were selected for the meta-analysis. Compared to healthy controls, SLE patients had a significantly increased CIMT (mean difference [MD] of 0.08mm, 95% CI [0.06-0.09], P<0.05), more CP (odds ratio 2.01, 95% CI [1.63-2.47], P<0.05) and decreased FMD (MD -3.96%, 95% CI [-5.37 to -2.54)], P<0.05). There was marked heterogeneity among the studies. However, the results of the meta-analysis that included only the CIMT per new international recommendations also showed an increased CIMT in SLE patients, but the heterogeneity was low (MD 0.04mm, 95% CI [0.02-0.06], P<0.05; I2=23%). CONCLUSION: SLE patients exhibit increased subclinical atherosclerosis compared to healthy controls. CIMT is a promising measure for cardiovascular risk evaluations because non-invasive, non-radiation-based, reproducible. Thus, CIMT can be proposed as an alternative to the reliable CP evaluation and to FMD, which is influenced by independent factors such as smoking. Future studies should focus on reducing the heterogeneity of these measures using standardized procedures.


Assuntos
Aterosclerose/epidemiologia , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Adulto , Aterosclerose/fisiopatologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
PLoS One ; 12(11): e0188943, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29190827

RESUMO

BACKGROUND: Bevacizumab, an anti-VEGF monoclonal antibody, has recently emerged as a new option for severe forms of hereditary hemorrhagic telangiectasia (HHT). Its utilization in this orphan disease has rapidly spread despite the lack of randomized trials and international guidelines. The objective of this study is to report the main clinical data (baseline characteristics, dose schedule, efficacy, adverse events and deaths) of HHT patients treated by intravenous bevacizumab in France. METHODS: Retrospective observational study of HHT patients treated with bevacizumab for a severe form of the disease in the 14 centers of the French HHT network. RESULTS: Forty-six patients (median age: 68 years) were treated between March 2009 and May 2015. Ten patients were treated for high output cardiac failure, 20 patients for severe hemorrhages and 16 for both indications. The standard protocol (6 infusions of 5mg/kg every 2 weeks) was initially used in 89% of the cases but diverse strategies were subsequently applied. A clinical improvement was noted by the referent physician for 74% of the patients with a median effect's duration of 6 months. Wound healing complications led to 2 amputations. Arthralgia/arthritis and arterial hypertension occurred in 5 patients each. One third of the patients were dead at the time of the final update, coherently with age and the poor prognosis of these highly symptomatic patients. CONCLUSION: Intravenous bevacizumab seems to provide a clinical benefice in severe HHT patients. Precautions concerning wound healing and vascular pathologies must be respected. Prospective double blinded versus placebo trials are needed.


Assuntos
Bevacizumab/uso terapêutico , Telangiectasia Hemorrágica Hereditária/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
AIDS ; 31(17): 2355-2365, 2017 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-29068834

RESUMO

OBJECTIVE: To evaluate the predictive value of soluble suppression of tumorigenicity 2 (sST2), a decoy receptor of IL-33 involved in several inflammatory and immune diseases, for death in HIV infection. DESIGN: Patients enrolled in the ANRS CO3 Aquitaine Cohort, a prospective hospital-based cohort of HIV-1-infected patients, who had a plasma sample available in the biobank were systematically eligible. METHODS: sST2, soluble CD14 (sCD14) and IL-6 were measured using Luminex multiplex bead-based technology (R&D Systems) and a Bio-Plex 200 instrument (BioRad). Predictive capacities of sST2, sCD14, IL-6 and of the Veterans Aging Cohort Study clinical score at baseline on overall mortality were compared using multivariable Cox proportional hazards models. RESULTS: During a median follow-up of 7.2 years [interquartile range (IQR): 6.0; 7.9], 93 deaths from all causes (incidence rate 9.9 per 1000 patient-years; 95% confidence interval 7.9-11.9) were reported in 1414 patients. The median sST2 baseline concentration was 22.9 ng/ml (IQR: 17.7; 30.3) and was higher (30.8 ng/ml, IQR: 21.5; 42.1) in patients who died as compared with those who stayed alive (22.6 ng/ml; IQR: 17.5; 29.6) (P < 10). An increased risk of death of 21% for a concentration 10.0 ng/ml higher of sST2 remained after adjustment for sCD14, IL-6 and Veterans Aging Cohort Study score (adjusted hazard ratio: 1.21; P < 10). The predictive capacity of sST2 was confirmed in a validation cohort (n = 386, 31 deaths) with an improved area c-index from 0.804 without sST2 to 0.811 with sST2. CONCLUSION: sST2 is a new valuable biomarker to evaluate the risk of all-cause mortality in HIV disease.


Assuntos
Biomarcadores/sangue , Infecções por HIV/mortalidade , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Soro/química , Adulto , Feminino , Humanos , Interleucina-6/sangue , Receptores de Lipopolissacarídeos/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Medição de Risco , Análise de Sobrevida
15.
Arthritis Res Ther ; 19(1): 238, 2017 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-29065901

RESUMO

BACKGROUND: The aim of this study was to identify the most reliable biomarkers in the literature that could be used as flare predictors in systemic lupus erythematosus (SLE). METHODS: A systematic review of the literature was performed using two databases (MEDLINE and EMBASE) through April 2015 and congress abstracts from the American College of Rheumatology and the European League Against Rheumatism were reviewed from 2010 to 2014. Two independent reviewers screened titles and abstracts and analysed selected papers in detail, using a specific questionnaire. Reports addressing the relationships between one or more defined biological test(s) and the occurrence of disease exacerbation were included in the systematic review. RESULTS: From all of the databases, 4668 records were retrieved, of which 69 studies or congress abstracts were selected for the systematic review. The performance of seven types of biomarkers performed routinely in clinical practice and nine types of novel biological markers was evaluated. Despite some encouraging results for anti-double-stranded DNA antibodies, anti-C1q antibodies, B-lymphocyte stimulator and tumour necrosis factor-like weak inducer of apoptosis, none of the biomarkers stood out from the others as a potential gold standard for flare prediction. The results were heterogeneous, and a lack of standardized data prevented us from identifying a powerful biomarker. CONCLUSIONS: No powerful conclusions could be drawn from this systematic review due to a lack of standardized data. Efforts should be undertaken to optimize future research on potential SLE biomarkers to develop validated candidates. Thus, we propose a standardized pattern for future studies.


Assuntos
Fator Ativador de Células B/análise , Biomarcadores/análise , Complemento C1q/análise , Citocina TWEAK/análise , Lúpus Eritematoso Sistêmico/metabolismo , Anticorpos Antinucleares/análise , Anticorpos Antinucleares/imunologia , Fator Ativador de Células B/imunologia , Proteína C-Reativa/análise , Proteína C-Reativa/imunologia , Complemento C1q/imunologia , Citocina TWEAK/imunologia , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Prognóstico , Sensibilidade e Especificidade
16.
Curr Rheumatol Rep ; 19(8): 48, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28718063

RESUMO

PURPOSE OF REVIEW: Current knowledge on the role of platelets and platelet-derived microparticles (PMPs) on the immune system has been fast-growing. Systemic lupus erythematosus (SLE) is a systemic auto-immune disorder characterized by a loss of tolerance toward nuclear auto-antigens. Although recent studies allowed a better understanding of SLE pathogenesis, there is an urgent need for the development of new treatments and the identification of new biomarkers to assess the disease activity. We describe here the state-of-the-art knowledge linking platelets and PMPs to SLE. RECENT FINDINGS: Platelet system activation is a key event in the pathogenesis of SLE. Circulating immune complexes, anti-phospholipid antibodies, and infectious agents such as virus are the main activators of platelets in SLE. Platelet activation can be monitored through different ways such as P-selectin expression, mean platelet volume, or circulating PMP levels, suggesting their potential use as biomarkers. Upon activation, platelets promote type I interferon production, NETosis, dendritic cell activation, and T and B lymphocyte activation, all essential events contributing to the development of SLE. Of interest, platelets also play a fundamental role in SLE organ disease such as the development of cardiovascular, thrombotic, and renal diseases. Finally, we review current knowledge on drugs targeting platelet activation and their potential impact on SLE pathogenesis. Platelets play a major role in SLE pathogenesis and organ disease and represent a great potential for novel biomarkers and drug development.


Assuntos
Autoimunidade/fisiologia , Plaquetas/imunologia , Micropartículas Derivadas de Células/imunologia , Lúpus Eritematoso Sistêmico/sangue , Humanos , Lúpus Eritematoso Sistêmico/imunologia
17.
AIDS ; 31(8): 1119-1128, 2017 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-28328797

RESUMO

OBJECTIVES: To assess the association among immune activation, immune senescence, inflammation biomarkers and renal function measured by estimated glomerular filtration rate (eGFR) at inclusion and its evolution over a 3-year follow-up in HIV-infected patients with undetectable viral load. DESIGN: The Chronic Immune Activation and Senescence (CIADIS) substudy consecutively included patients between October 2011 and May 2013 enrolled in the ANRS CO3 Aquitaine observational cohort. METHODS: Biomarkers of T-cell activation, differentiation and senescence were summarized in a cellular-CIADIS weighted score and inflammation biomarkers in a soluble-CIADIS weighted score using principal component analysis. Logistic regression and linear mixed models were used to determine the association between the CIADIS weighted scores and confirmed eGFR less than 60 ml/min per 1.73 m, and evolution of eGFR, respectively. RESULTS: Of 756 patients with an undetectable viral load, 76% were men, and median age was 51 years (Interquartile range: 45-57 years). In multivariable analysis, the soluble-CIADIS weighted score was independently associated with a confirmed eGFR less than 60 [odds ratio = 1.4; 95% confidence interval (CI) 1.1-1.8] but the cellular-CIADIS weighted score was not (odds ratio = 1.2; 95% CI 1.0-1.5). Only in patients with a confirmed eGFR less than 60 ml/min per 1.73 m at inclusion, a higher soluble-CIADIS weighted score (increased inflammation) was associated with a steeper decrease of renal function of -2.3 (ml/min per 1.73 m) per year (95% CI -3.6 to -1.0). CONCLUSION: At inclusion, soluble-CIADIS weighted score was independently associated with a confirmed eGFR less than 60 ml/min per 1.73 m. The soluble-CIADIS weighted score was associated with a decrease of eGFR evolution during a 3-year follow-up only in patients with a confirmed eGFR less than 60 ml/min per 1.73 m.


Assuntos
Nefropatia Associada a AIDS/patologia , Envelhecimento , Infecções por HIV/complicações , Infecções por HIV/patologia , Inflamação/patologia , Ativação Linfocitária , Resposta Viral Sustentada , Idoso , Feminino , Taxa de Filtração Glomerular , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários
18.
Rheumatology (Oxford) ; 56(7): 1200-1205, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28340056

RESUMO

Objectives: Mitochondrial DNA (mtDNA) contains sequestered damage-associated molecular patterns that might be involved in osteoimmunological pathogenesis of RA. Here, we aimed to investigate the cellular source of mtDNA and its role in RANK ligand (RANKL) expression by RA SF neutrophils. Methods: The gene expression signature of SF neutrophils was examined by proteomic quantitative analysis. Levels of mtDNA in circulating and SF neutrophils from RA patients and OA control subjects were assessed by real-time PCR. Purified neutrophils were challenged in vitro with Toll-like receptor agonists as well as mtDNA. RANKL expression by neutrophils was studied by flow cytometry. Results: SF neutrophils from RA patients displayed a gene expression signature of oxidative stress. This stress signature was associated with the release of mtDNA in SF as observed by a significant increase of mtDNA in the SF of RA patients compared with OA patients. mtDNA in RA SF was correlated with systemic inflammation as assessed by CRP concentrations. We also showed that mtDNA drives neutrophil RANKL expression to the same extent as Toll-like receptor agonists. Conclusion: Our data identify SF neutrophils as a cellular source of mtDNA that leads to a subsequent expression of RANKL. This highlights the important role of neutrophils in RA osteoimmunology.


Assuntos
Artrite Reumatoide/genética , DNA Mitocondrial/metabolismo , Regulação da Expressão Gênica , Ligante RANK/genética , Receptor Ativador de Fator Nuclear kappa-B/genética , Adulto , Idoso , Artrite Reumatoide/imunologia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Estresse Oxidativo/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Valores de Referência , Estudos Retrospectivos , Transdução de Sinais/genética
19.
Arthritis Rheumatol ; 68(11): 2784-2794, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27429171

RESUMO

OBJECTIVE: To investigate the relationship between vascular damage and fibrosis in systemic sclerosis (SSc) by testing the hypothesis that platelets contribute to skin fibrosis via the activation of human dermal microvascular endothelial cells (HDMECs) and subsequent production of profibrotic mediators. METHODS: A total of 203 SSc patients and 30 healthy donors were prospectively enrolled between 2012 and 2015 at the University Hospital of Bordeaux. Immunohistochemistry and immunofluorescence analyses were performed on skin biopsy sections from 18 SSc patients and 5 healthy donors. Serum thymic stromal lymphopoietin (TSLP) levels were measured by enzyme-linked immunosorbent assay in the entire cohort. HDMECs and fibroblasts were purified from biopsy sections. Extracellular matrix production by cultured fibroblasts was assessed by real-time quantitative polymerase chain reaction. RESULTS: Serum TSLP levels were significantly increased in SSc patients compared to healthy donors (P < 0.0001) and were associated with a higher frequency of vasculopathy (P = 0.02). The proportion of TSLP-positive dermal cells was increased in the skin of SSc patients compared with healthy donors (P < 0.0001) and was correlated with fibrosis (modified Rodnan skin thickness score) (r = 0.6146, P = 0.0001). In SSc dermis, TSLP was mainly expressed by CD31-positive endothelial cells. In vitro, activated platelets induced TSLP production by HDMECs in an interleukin-1ß-dependent manner. SSc fibroblasts responded differently according to their original TSLP environment. CONCLUSION: Taken together, these results identify HDMECs as contributors to TSLP production in SSc and suggest a potential mechanism by which platelets may profoundly affect the fibrotic process in SSc.


Assuntos
Citocinas/metabolismo , Células Endoteliais/metabolismo , Matriz Extracelular/genética , Fibroblastos/metabolismo , Escleroderma Sistêmico/metabolismo , Pele/patologia , Adulto , Plaquetas , Estudos de Casos e Controles , Células Cultivadas , Derme/irrigação sanguínea , Ensaio de Imunoadsorção Enzimática , Feminino , Fibrose , Imunofluorescência , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Interleucina-1beta/metabolismo , Masculino , Microvasos/citologia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Esclerodermia Difusa/metabolismo , Esclerodermia Difusa/patologia , Esclerodermia Limitada/metabolismo , Esclerodermia Limitada/patologia , Escleroderma Sistêmico/patologia , Pele/citologia
20.
Rheumatology (Oxford) ; 55(9): 1664-72, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27160278

RESUMO

OBJECTIVES: The aim was to assess the immunogenicity and the impact on disease activity of pneumococcal and influenza vaccines in SLE patients. METHODS: We conducted a systematic literature review and meta-analysis of studies comparing the humoral response of either pneumococcal (serotype 23F) or influenza (AH1N1, AH3N2 and B strains) vaccines between SLE patients and healthy controls, assessed by a seroconversion or a seroprotection rate 3-6 weeks after vaccination. The impact on disease activity was assessed by the comparison of the SLEDAI score before and 3-8 weeks after vaccination. Odds ratios (ORs), risk ratios and their 95% CIs were pooled using the generic inverse variance method. RESULTS: Twenty studies were included, three for pneumococcal vaccine and 17 for influenza vaccine, gathering 1665 SLE patients and 826 healthy controls. For pneumococcal vaccination, no significant difference was observed, either for seroconversion rate between SLE patients and controls or for the SLEDAI score. For influenza vaccination, the response against AH1N1 was significantly reduced in SLE patients, with a lower rate of seroconversion (OR = 0.38; 95% CI: 0.27, 0.54; P < 0.00001, I(2) = 39%) and seroprotection (OR = 0.36; 95% CI: 0.28, 0.47; P < 0.00001, I(2) = 25%). For AH3N2, only seroprotection rate was significantly lower in SLE patients (OR = 0.26; 95% CI: 0.14, 0.50; P < 0.0001, I(2) = 21%). For B strain, neither seroconversion nor seroprotection rates were significantly different. Influenza vaccine did not modify the SLEDAI score. CONCLUSION: The immunogenicity of influenza vaccine in SLE patients depends on the viral strains. A reduced immunogenicity against influenza A is noted, while the immunogenicity against the B strain is preserved. The pneumococcal vaccine against 23F serotype has a preserved immunogenicity. These vaccines have no impact on the SLEDAI score.


Assuntos
Imunogenicidade da Vacina/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Infecções Pneumocócicas/imunologia , Vacinas Pneumocócicas/imunologia , Humanos , Imunidade Celular/imunologia , Influenza Humana/prevenção & controle , Infecções Pneumocócicas/prevenção & controle , Resultado do Tratamento
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