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2.
Front Immunol ; 11: 532177, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193304

RESUMO

Background: Microparticles (MPs) are vesicular structures that derive from multiple cellular sources. MPs play important roles in intercellular communication, regulation of cell signaling or initiation of enzymatic processes. While MPs were characterized in Systemic Sclerosis (SSc) patients, their contribution to SSc pathogenesis remains unknown. Our aim was to investigate the potential role of MPs in SSc pathophysiology and their impact on tissue fibrosis. Methods: Ninety-six SSc patients and 37 sex-matched healthy donors (HD) were enrolled in this study in order to quantify and phenotype their plasmatic MPs by flow cytometry. The ability of MPs purified from SSc patients and HD controls to modulate fibroblast's extra-cellular matrix genes expression was evaluated in vitro by reverse transcriptase quantitative polymerase chain reaction. Results: SSc patients exhibited a higher concentration of circulatory MPs compared to HD. This difference was exacerbated when we only considered patients that were not treated with methotrexate or targeted disease-modifying antirheumatic drugs. Total circulatory MPs were associated to interstitial lung disease, lung fibrosis and diminished lung functional capacity, but also to vascular involvement such as active digital ulcers. Finally, contrary to HD MPs, MPs from SSc patients stimulated the production of extracellular matrix by fibroblast, demonstrating their profibrotic potential. Conclusions: In this study, we provide evidence for a direct profibrotic role of MPs from SSc patients, underpinned by strong clinical associations in a large cohort of patients.

3.
Arthritis Rheumatol ; 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32951354

RESUMO

BACKGROUND: Temporal arteritis (TA) is a typical manifestation of giant cell arteritis (GCA). Rarely, ANCA-associated vasculitides (AAV) can be revealed by TA, leading to misdiagnoses of GCA and inappropriate treatments. METHODS: We retrospective included patients with TA revealing AAV (TA-AAV), and compared them with classical GCA patients. RESULTS: Fifty patients with TA-AAV (median age 70 years) were included. Thirty-three (66%) patients presented atypical symptoms for GCA (ENT, renal, pulmonary and neurological involvement in 32%, 26%, 20% and 16%, respectively). ANCA were screened at disease onset in 33 cases, and were positive in 88%, leading to diagnosis of early TA-AAV in 20 cases. AAV diagnosis was delayed in 30 cases after a median interval of 15 months. Compared to GCA, TA-AAV patients were younger (70 vs. 74 years), more frequently men (48 vs. 30%), had high frequency of atypical manifestations and higher CRP levels (10.8 vs. 7.0 mg/dL). Temporal artery biopsy (TAB) from TA-AAV showed fibrinoid necrosis and small branch vasculitis in 23% each, whereas it did not in GCA. Treatment failure-free survival was comparable between early TA-AAV and GCA, whereas those with delayed TA-AAV patients had a significant higher risk of treatment failure compared to GCA [HR 3.85 (1.97-7.51), P<0.0001)]. CONCLUSION: TA revealing AAV should be considered in case of atypical manifestations for GCA, GCs refractoriness or early relapse. Analysis of TAB for small branch vasculitis and/or fibrinoid necrosis could be useful. Detection of ANCA should be performed in case of suspected GCA with atypical clinical features and/or TAB.

4.
BMC Fam Pract ; 21(1): 163, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32787857

RESUMO

BACKGROUND: Guidelines that detail preventive measures against Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae type b, and influenza are published annually in France to decrease the risk of severe infections in immunocompromised patients. We aimed at describing adherence to these guidelines by GPs in the management of their asplenic patients in France between 2013 and 2016. METHOD: We conducted a multicenter retrospective study between January 2013 and December 2016 in three French hospitals: asplenic adults were identified and their GPs were questioned. A descriptive analysis was performed to identify the immunization coverage, type and length of antibiotic prophylaxis, number of infectious episodes, and education of patients. RESULTS: 103 patients were finally included in this study: only 57% were adequately vaccinated against Streptococcus pneumoniae or Neisseria meningitidis, 74% against Haemophilus influenzae type b, and 59% against influenza. Only 24% of patients received a combination of all four vaccinations. Two-thirds of patients received prophylactic antibiotics for at least 2 years. Overall, this study found that 50% of splenectomized patients experienced at least one pulmonary or otorhinolaryngological infection, or contracted influenza. CONCLUSIONS: These data match those reported in other countries, including Australia and the United Kingdom, meaning a still insufficient coverage of preventive measures in asplenic patients. Improved medical data sharing strategies between healthcare professionals, along with educational measures to keep patients and physicians up to date in the prevention of infections after splenectomy would improve health outcomes of asplenic patients.

5.
Am J Surg Pathol ; 44(10): 1367-1373, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32773529

RESUMO

Chronic intervillositis of unknown etiology (CIUE) is a rare placental disease characterized by intervillous infiltration of maternal macrophages and associated with poor pregnancy outcomes and a high risk of recurrence in subsequent pregnancies. Its pathophysiology remains unclear and prognostic factors have not yet been established. In addition, clear relationships between the histologic extent of lesions and the severity of perinatal outcomes have not been demonstrated. Our objectives were to validate a CIUE classification system based on the gradation of macrophagic infiltration of the intervillous space, and to attempt to correlate these results with perinatal outcomes. For this multicenter retrospective study, 3 pathologists reviewed all cases diagnosed with "intervillositis" between 1997 and 2018. Confirmed CIUE cases were semiquantitatively graded based on the percentage of macrophagic infiltrate in the intervillous space: grade 1 (5% to 10%), grade 2 (10% to 50%), and grade 3 (>50%). Multiple pregnancies and pregnancies with medical follow-up completed outside of the study centers were excluded. In total, 122 cases of CIUE in 102 patients were included in the study. Microscopic classification based on one criterion was easy to perform, and interobserver correlation was good. Grade 3 infiltration was strongly associated with poor perinatal outcomes and fetal growth restriction (P<0.0001). After delivery, only 16.1% of newborns from the grade 3 CIUE group were alive, compared with 59% from the grade 2 and 86.5% from the grade 1 group (P=0.0002). Recurrence risk was associated with CIUE gradation of the index case (P=0.004), with 95% of recurrent CIUE cases being from patients with grades 2 and 3 CIUE. In this study, conducted with the largest CIUE cohort to date, a classification based only on the degree of macrophagic infiltration of the intervillous space was validated, and this classification was shown to be strongly associated with poor perinatal outcomes and risk of recurrence.


Assuntos
Doenças Placentárias/classificação , Doenças Placentárias/patologia , Resultado da Gravidez , Adulto , Doença Crônica , Feminino , Humanos , Gravidez , Estudos Retrospectivos
6.
Clin Infect Dis ; 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32686834

RESUMO

BACKGROUND: An increased risk of cardiovascular disease (CVD) was reported in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), without identifying factors associated with atherosclerotic CVD (ASCVD) events. METHODS: HIV-HCV coinfected patients were enrolled in the ANRS CO13 HEPAVIH nationwide cohort. Primary outcome was total ASCVD events. Secondary outcomes were coronary and/or cerebral ASCVD events, and peripheral artery disease (PAD) ASCVD events. Incidences were estimated using the Aalen-Johansen method. Factors associated with ASCVD were identified using cause-specific Cox proportional hazards models. RESULTS: At baseline, median age of the study population (n=1213) was 45.4 (interquartile range [IQR] 42.1-49.0) years and 70.3% were men. After a median follow-up of 5.1 (IQR 3.9-7.0) years, the incidence was 6.98 (95% confidence interval [CI] 5.19-9.38) per 1000 person-years for total ASCVD events, 4.01 (2.78-6.00) for coronary and/or cerebral events, and 3.17 (2.05-4.92) for PAD ASCVD events. Aging (hazard ratio [HR] 1.06, 95% CI 1.01-1.12), prior CVD (HR 8.48, 95% CI 3.14-22.91), high total cholesterol (HR 1.43, 95% CI 1.11-1.83), high-density lipoprotein cholesterol (HR 0.22, 95% CI 0.08-0.63), statin use (HR 3.31, 95% CI 1.31-8.38), and high alcohol intake (HR 3.18, 95% CI 1.35-7.52) were independently associated with total ASCVD events, while undetectable baseline viral load (HR 0.41, 95%CI 0.18-0.96) with coronary and/or cerebral events. CONCLUSION: HIV-HCV coinfected patients experienced a high incidence of ASCVD events. Some traditional cardiovascular risk factors were the main determinants of ASCVD. Controlling cholesterol abnormalities and maintaining undetectable HIV viral load are essential to control cardiovascular risk.

7.
Sci Rep ; 10(1): 12611, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32724097

RESUMO

Our study aimed to assess perinatal outcomes and recurrence rate of Chronic Intervillositis of Unknown Etiology (CIUE). We conducted an observational retrospective study in a tertiary care university hospital in France from January 1, 1997 to July 31, 2018. 122 pregnancies (102 women) with CIUE were included. Cases of the Department of Histopathology placenta database were re-analysed independently by three pathologists specializing in fetal pathology. Diagnosis of CIUE was confirmed according to: (1) the presence of cellular infiltrate in the intervillous space, (2) ~ 80% of the mononuclear cells in the intervillous space positive for CD68, (3) infiltration occupying at least 5% of the intervillous space, and (4) no clinical or histopathological sign of infection. Outcomes of pregnancies with CIUE (miscarriages, stillbirths, terminations of pregnancy, live birth with or without prematurity or fetal growth restriction) and proportion of CIUE recurrence were analysed. The lost pregnancies comprised 17 (13.9%) miscarriages, 17 (13.9%) stillbirths, and 18 (14.8%) terminations of pregnancy. Of the 70 (57.4%) pregnancies that led to a live birth, 38 (54.3%) new-borns were premature and 50 (72.5%) exhibited fetal growth restriction. Among the 102 women, 23 subsequently became pregnant, half of whom (n = 11) developed recurrent CIUE. CIUE was associated with high rates of adverse perinatal outcomes, including pregnancy loss, fetal growth restriction, and preterm birth with a risk of recurrence nearly 50%.

8.
Health Qual Life Outcomes ; 18(1): 220, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32650781

RESUMO

BACKGROUND: Antiretroviral therapy has prolonged the lives of those with human immunodeficiency virus (HIV), but the effects of chronic infection on their health-related quality of life (HRQoL) remain a concern. Numerous instruments have been developed to measure HRQoL, yet evidence of their cross-cultural equivalence and continued applicability is limited. We adapted the WHOQOL-HIV BREF to French and assessed its psychometric properties in a sample of community-dwelling adults living with HIV who were mostly virally suppressed. METHODS: We conducted a cross-sectional study within the ANRS CO3 Aquitaine cohort from July 2018 to May 2019. Five hundred eighty-six participants were consecutively enrolled at their HIV-consultations and completed either a web-based (n = 406) or paper self-administered assessment (n = 180). The means and standard deviations for items and domains were computed and the presence of floor and ceiling effects assessed. We evaluated internal consistency by calculating Cronbach's alpha coefficients per domain. We assessed construct validity by performing a Confirmatory Factor Analysis (CFA). Concurrent, convergent and discriminant validity were assessed with Pearson's correlations and known-group validity was assessed according to CD4 cell count, viral load, Centers for Disease Control and Prevention clinical categories for HIV, and hospitalization of more than 48 h within 2 years of the most recent consultation using one-way analysis of variance and independent t-tests. RESULTS: Five hundred eighty-six PLWH were included in this analysis. Their median age was 55; 73% were male; 85% were of French descent; 99% were on ART and 93% were virally suppressed. We found floor effects for one and ceiling effects for 11 items. Four of the six domains showed good internal consistency (α range: 0.63-0.79). CFA showed that the WHOQOL-HIV BREF's six-domain structure produced an acceptable fit (SRMR = 0.059; CFI = 0.834; RMSEA = 0.07; 90% CI: 0.06-0.08). It showed good concurrent, convergent and discriminant validity. There was some evidence of known-group validity. The personal beliefs domain had the highest score (15.04 ± 3.35) and the psychological health domain had the lowest (13.70 ± 2.78). CONCLUSIONS: The French WHOQOL-HIV BREF has acceptable measurement properties. Its broad conceptualisation of HRQoL, going beyond physical and mental health, may be of particular value in our older, treatment-experienced and virally suppressed population. TRIAL REGISTRATION: ClinicalTrials.gov NCT03296202 (Archived by WebCite at http://www.webcitation.org/6zgOBArps ).

13.
J Invest Dermatol ; 140(7): 1427-1434.e5, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31954725

RESUMO

Systemic sclerosis (SSc) is a rare and severe connective tissue disease combining autoimmune and vasculopathy features, ultimately leading to organ fibrosis. Impaired angiogenesis is an often silent and life-threatening complication of the disease. We hypothesize that CCN3, a member of the CCN family of extracellular matrix proteins, which is an antagonist of the profibrotic protein CCN2 as well as a proangiogenic factor, is implicated in SSc pathophysiology. We performed skin biopsies on 26 patients with SSc, both in fibrotic and nonfibrotic areas for 17 patients, and collected 18 healthy control skin specimens for immunohistochemistry and cell culture. Histological analysis of nonfibrotic and fibrotic SSc skin shows a systemic decrease of papillary dermis surface as well as disappearance of capillaries. CCN3 expression is systematically decreased in the dermis of patients with SSc compared with healthy controls, particularly in dermal blood vessels. Moreover, CCN3 is decreased in vitro in endothelial cells from patients with SSc. We show that CCN3 is essential for endothelial cell migration and angiogenesis in vitro. In conclusion, CCN3 may represent a promising therapeutic target for patients with SSc presenting with vascular involvement.

14.
Autoimmun Rev ; 19(3): 102464, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31917264

RESUMO

OBJECTIVE: To describe the clinical, biological and pathological characteristics of patients with the association of SLE and thymic epithelial tumors (TET) in a retrospective multicenter series. METHODS: Cases diagnosed in France between 2000 and 2015 were collected after a call for observations from the French network for thymic epithelial tumors (RYTHMIC database) and the French National Society of Internal Medicine (SNFMI). RESULTS: Fourteen patients were identified, the majority were women (93%). The median age at diagnosis of lupus was 43.5 [range: 30-66] years and 43.5 [range: 26-73] years at diagnosis of thymoma. TET required chemotherapy and/or radiotherapy complementary to surgery in >90% cases. Lupus was diagnosed before, simultaneously, or after diagnosis of thymoma in 6, 3 and 5 cases, respectively. Among the lupus manifestations, joint involvement was predominant (78.6%), followed by autoimmune cytopenia (35.7%), cutaneous affections (28.6%), serositis (28.6%) and renal involvement (21.4%). SLE was associated with one or more AID in 5/14 patients. These characteristics were compared with those from 17 patients identified in the literature. Among them, joint and skin involvement as well as pleural/pericardial effusions occurred in >50%. SLE was controlled by prednisone and hydroxychloroquine in the majority of cases, but 7 out of 31 patients had an immunosuppressant. CONCLUSION: The association of SLE and TET is rare, and its clinical profile seems to be distinguished by the frequency of cytopenias. The management of these patients is complicated by the need to treat cancer, lupus and/or associated autoimmune diseases.


Assuntos
Lúpus Eritematoso Sistêmico/complicações , Timoma/complicações , Neoplasias do Timo/complicações , Adulto , Idoso , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Clin Rev Allergy Immunol ; 58(2): 194-212, 2020 Apr.
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.

16.
J Autoimmun ; 106: 102338, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31570253

RESUMO

BACKGROUND: Progressive fibrosing interstitial lung disease (ILD) is rarely associated with antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). This study focused on the outcomes of ILD patients with associated AAV (AAV-ILD). METHODS: AAV-ILD (cases: microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA) with ILD) were compared to AAV patients without ILD (controls). ILD was defined as a usual interstitial pneumonia (UIP) or non-specific interstitial pneumonia (NSIP) pattern. Two controls were matched to each case for age (>or ≤65 years), ANCA status (PR3-or MPO-positive) and creatininemia (≥or <150 µmol/L). RESULTS: Sixty-two cases (89% MPO-ANCA+) were included. Median age at AAV diagnosis was 66 years. ILD (63% UIP), was diagnosed before (52%) or simultaneously (39%) with AAV. Cases versus 124 controls less frequently had systemic vasculitis symptoms. One-, 3- and 5-year overall survival rates, respectively, were: 96.7%, 80% and 66% for cases versus 93.5%, 89.6% and 83.8% for controls (p = 0.008). Multivariate analyses retained age >65 years (hazard ratio (HR) 4.54; p < 0.001), alveolar haemorrhage (HR 2.25; p = 0.019) and UIP (HR 2.73; p = 0.002), but not immunosuppressant use, as factors independently associated with shorter survival. CONCLUSION: For AAV-ILD patients, only UIP was associated with poorer prognosis. Immunosuppressants did not improve the AAV-ILD prognosis. But in analogy to idiopathic pulmonary fibrosis, anti-fibrosing agents might be useful and should be assessed in AAV-ILD patients with a UIP pattern.

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