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1.
J Exp Med ; 221(5)2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38557723

RESUMO

CD4+ T cells are vital for host defense and immune regulation. However, the fundamental role of CD4 itself remains enigmatic. We report seven patients aged 5-61 years from five families of four ancestries with autosomal recessive CD4 deficiency and a range of infections, including recalcitrant warts and Whipple's disease. All patients are homozygous for rare deleterious CD4 variants impacting expression of the canonical CD4 isoform. A shorter expressed isoform that interacts with LCK, but not HLA class II, is affected by only one variant. All patients lack CD4+ T cells and have increased numbers of TCRαß+CD4-CD8- T cells, which phenotypically and transcriptionally resemble conventional Th cells. Finally, patient CD4-CD8- αß T cells exhibit intact responses to HLA class II-restricted antigens and promote B cell differentiation in vitro. Thus, compensatory development of Th cells enables patients with inherited CD4 deficiency to acquire effective cellular and humoral immunity against an unexpectedly large range of pathogens. Nevertheless, CD4 is indispensable for protective immunity against at least human papillomaviruses and Trophyrema whipplei.


Assuntos
Linfócitos T CD4-Positivos , Linfócitos T Auxiliares-Indutores , Humanos , Linfócitos T CD8-Positivos , Ativação Linfocitária , Antígenos HLA , Isoformas de Proteínas/metabolismo
2.
Rheumatology (Oxford) ; 63(1): 103-110, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-37074923

RESUMO

OBJECTIVE: Stratifying the risk of death in SSc-related interstitial lung disease (SSc-ILD) is a challenging issue. The extent of lung fibrosis on high-resolution CT (HRCT) is often assessed by a visual semiquantitative method that lacks reliability. We aimed to assess the potential prognostic value of a deep-learning-based algorithm enabling automated quantification of ILD on HRCT in patients with SSc. METHODS: We correlated the extent of ILD with the occurrence of death during follow-up, and evaluated the additional value of ILD extent in predicting death based on a prognostic model including well-known risk factors in SSc. RESULTS: We included 318 patients with SSc, among whom 196 had ILD; the median follow-up was 94 months (interquartile range 73-111). The mortality rate was 1.6% at 2 years and 26.3% at 10 years. For each 1% increase in the baseline ILD extent (up to 30% of the lung), the risk of death at 10 years was increased by 4% (hazard ratio 1.04, 95% CI 1.01, 1.07, P = 0.004). We constructed a risk prediction model that showed good discrimination for 10-year mortality (c index 0.789). Adding the automated quantification of ILD significantly improved the model for 10-year survival prediction (P = 0.007). Its discrimination was only marginally improved, but it improved prediction of 2-year mortality (difference in time-dependent area under the curve 0.043, 95% CI 0.002, 0.084, P = 0.040). CONCLUSION: The deep-learning-based, computer-aided quantification of ILD extent on HRCT provides an effective tool for risk stratification in SSc. It might help identify patients at short-term risk of death.


Assuntos
Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Humanos , Prognóstico , Reprodutibilidade dos Testes , Capacidade Vital , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/epidemiologia , Pulmão , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico por imagem , Tomografia Computadorizada por Raios X
3.
J Autoimmun ; 139: 103093, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37536165

RESUMO

BACKGROUND: The landscape of polyarteritis nodosa (PAN) has substantially changed during the last decades. Recent data regarding causes, characteristics, and prognosis of systemic PAN in the modern era are lacking. METHODS: This retrospective study included patients with systemic PAN referred to the French Vasculitis Study Group between 2005 and 2019. Characteristics, associated conditions and outcomes were collected, and predictors of relapse and death were analyzed. RESULTS: 196 patients were included. Main clinical symptoms were constitutional (84%), neurological (59%), skin (58%) and musculoskeletal (58%) manifestations. Secondary PAN accounted for 55 (28%) patients, including myelodysplastic syndrome (9%), solid cancer (7%), lymphoma (4%) and autoinflammatory diseases (4%). No patient had active HBV infection. All treated patients (98.5%) received glucocorticoids (GCs), alone (41%) or in combination with immunosuppressants (59%), with remission achieved in 90%. Relapses were independently associated with age >65 years (HR 1.85; 95% CI1.12-3.08), gastrointestinal involvement (1.95; 95% CI1.09-3.52) and skin necrotic lesions (HR 1.95; 95%CI 1.24-3.05). One-, 5- and 10-year overall survival rates were 93%, 87% and 81%, respectively. In multivariate analyses, age >65 years (HR 2.80; 95%CI 1.23-6.37), necrotic purpura (HR 4.16; 95%CI 1.62-10.70), acute kidney injury (HR 4.89; 95% 1.71-13.99) and secondary PAN (HR 2.98; 95%CI 1.29-6.85) were independently associated with mortality. CONCLUSION: Landscape of PAN has changed during the last decades, with the disappearance of HBV-PAN and the emergence of secondary PAN. Relapse rate remains high, especially in aged patients with gastrointestinal and cutaneous necrosis, as well as mortality.


Assuntos
Poliarterite Nodosa , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Poliarterite Nodosa/diagnóstico , Poliarterite Nodosa/epidemiologia , Poliarterite Nodosa/etiologia , Recidiva , Prognóstico
4.
JAMA Netw Open ; 5(7): e2220925, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35802372

RESUMO

Importance: Older patients are underrepresented in studies of rituximab for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Little is known about outcomes and adverse events associated with the use of rituximab therapy among patients 75 years and older with ANCA-associated vasculitis. Objective: To examine outcomes and adverse events associated with the use of rituximab therapy in patients 75 years and older with ANCA-associated vasculitis, specifically granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Design, Setting, and Participants: This multicenter cohort study involved 93 patients 75 years and older with ANCA-associated vasculitis from 36 university and nonuniversity hospitals in France. Data were obtained from the French Vasculitis Study Group database between January 1, 2000, and July 1, 2018, and a call for observation sent to French Vasculitis Study Group members on June 6, 2019. Data analysis was performed from November 15 to December 31, 2021. Inclusion criteria included a diagnosis of GPA or MPA according to European Medicines Agency classification criteria and receipt of treatment with rituximab after age 75 years. Patients were excluded if they were missing relevant clinical or biological data. Data on race and ethnicity were not reported because inclusion of this information was not authorized by the ethics committee. Exposure: At least 1 infusion of rituximab as induction or maintenance therapy. Main Outcomes and Measures: Occurrence of remission, relapse, drug discontinuation, death, and serious infections (including types of serious infections). Results: Of 238 patients screened, 93 were included (median [IQR] age, 79.4 [76.7-83.1] years; 51 women [54.8%]); 52 patients (55.9%) had a diagnosis of GPA, and 41 (44.1%) had a diagnosis of MPA. Thirty patients (32.3%) received rituximab as induction therapy in combination with high-dose glucocorticoid regimens, 27 (29.0%) received rituximab as maintenance therapy, and 36 (38.7%) received rituximab as both induction and maintenance therapy. The median (IQR) follow-up was 2.3 (1.1-4.0) years. Among 66 patients who received rituximab as induction therapy, 57 (86.4%) achieved remission, and 2 (3.0%) experienced relapses. The incidence of serious infection was significantly higher when rituximab was used as induction therapy vs maintenance therapy (46.6 [95% CI, 24.8-79.7] per 100 patient-years vs 8.4 [95% CI, 3.8-15.9] per 100 patient-years; P = .004). Most infections (12 of 22 [54.5%]) were gram-negative bacterial infections. The incidence of death was 19.7 (95% CI, 7.2-42.9) per 100 patient-years among those who received rituximab as induction therapy and 5.3 (95% CI, 1.9-11.6) per 100 patient-years among those who received rituximab as maintenance therapy. Conclusions and Relevance: In this cohort study, rituximab therapy was associated with achievement and maintenance of remission in most patients 75 years and older with ANCA-associated vasculitis. The incidence of serious infections and death was high when rituximab was used as induction therapy in combination with high-dose glucocorticoid regimens but not when rituximab was used as maintenance therapy. Efforts might focus on reducing serious infections during the first months of therapy.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Anticorpos Anticitoplasma de Neutrófilos , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/induzido quimicamente , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Anticorpos Anticitoplasma de Neutrófilos/uso terapêutico , Estudos de Coortes , Feminino , Glucocorticoides , Humanos , Recidiva , Rituximab/efeitos adversos , Resultado do Tratamento
5.
J Clin Med ; 11(5)2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35268324

RESUMO

Fabry disease is an X-linked lysosomal disease in which defects in the alpha-galactosidase A enzyme activity lead to the ubiquitous accumulation of glycosphingolipids. Whereas the classic disease is characterized by neuropathic pain, progressive renal failure, white matter lesions, cerebral stroke, and hypertrophic cardiomyopathy (HCM), the non-classic phenotype, also known as cardiac variant, is almost exclusively characterized by HCM. Circulating sphingosine-1-phosphate (S1P) has controversially been associated with the Fabry cardiomyopathy. We measured serum S1P levels in 41 patients of the FFABRY cohort. S1P levels were higher in patients with a non-classic phenotype compared to those with a classic phenotype (200.3 [189.6−227.9] vs. 169.4 ng/mL [121.1−203.3], p = 0.02). In a multivariate logistic regression model, elevated S1P concentration remained statistically associated with the non-classic phenotype (OR = 1.03; p < 0.02), and elevated lysoGb3 concentration with the classic phenotype (OR = 0.95; p < 0.03). S1P levels were correlated with interventricular septum thickness (r = 0.46; p = 0.02). In a logistic regression model including S1P serum levels, phenotype, and age, age remained the only variable significantly associated with the risk of HCM (OR = 1.25; p = 0.001). S1P alone was not associated with cardiac hypertrophy but with the cardiac variant. The significantly higher S1P levels in patients with the cardiac variant compared to those with classic Fabry suggest the involvement of distinct pathophysiological pathways in the two phenotypes. S1P dosage could allow the personalization of patient management.

6.
EClinicalMedicine ; 46: 101362, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35350097

RESUMO

Background: In moderate-to-severe COVID-19 pneumonia, dexamethasone (DEX) and tocilizumab (TCZ) reduce the occurrence of death and ventilatory support. We investigated the efficacy and safety of DEX+TCZ in an open randomized clinical trial. Methods: From July 24, 2020, through May 18, 2021, patients with moderate-to-severe COVID-19 pneumonia requiring oxygen (>3 L/min) were randomly assigned to receive DEX (10 mg/d 5 days tapering up to 10 days) alone or combined with TCZ (8 mg/kg IV) at day 1, possibly repeated with a fixed dose of 400 mg i.v. at day 3. The primary outcome was time from randomization to mechanical ventilation support or death up to day 14, analysed on an intent-to-treat basis using a Bayesian approach. ClinicalTrials.gov number, NCT04476979. Findings: A total of 453 patients were randomized, 3 withdrew consent, 450 were analysed, of whom 226 and 224 patients were assigned to receive DEX or TCZ+DEX, respectively. At day 14, mechanical ventilation or death occurred in 32/226 (14%) and 27/224 (12%) in the DEX and TCZ+DEX arms, respectively (hazard ratio [HR] 0·85, 90% credible interval [CrI] 0·55 to 1·31). At day 14, the World health Organization (WHO) clinical progression scale (CPS) was significantly improved in the TCZ+DEX arm (OR 0·69, 95% CrI, 0·49 to 0.97). At day 28, the cumulative incidence of oxygen supply independency was 82% in the TCZ+DEX arms and 72% in the DEX arm (HR 1·36, 95% CI 1·11 to 1·67). On day 90, 24 deaths (11%) were observed in the DEX arm and 18 (8%) in the TCZ+DEX arm (HR 0·77, 95% CI 0·42-1·41). Serious adverse events were observed in 25% and 21% in DEX and TCZ+DEX arms, respectively. Interpretation: Mechanical ventilation need and mortality were not improved with TCZ+DEX compared with DEX alone. The safety of both treatments was similar. However, given the wide confidence intervals for the estimate of effect, definitive interpretation cannot be drawn. Funding: Programme Hospitalier de Recherche Clinique [PHRC COVID-19-20-0151, PHRC COVID-19-20-0029], Fondation de l'Assistance Publique - Hôpitaux de Paris (Alliance Tous Unis Contre le Virus) and from Fédération pour la Recherche Médicale" (FRM). Tocilizumab was provided by Roche.

7.
Am J Public Health ; 112(2): 262-270, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35080948

RESUMO

We explored how air quality management processes associated with Assembly Bill 617 (AB 617) in West Oakland, California, represent a shift in power relationships between government agencies and communities toward the goal of addressing legacies of environmental injustice. We drew from a statewide assessment of community engagement in AB 617's first year, and an analysis of the West Oakland AB 617 process. The first comprised 2 statewide surveys (n = 102 and n = 106), 70 key informant interviews, observation of all AB 617 first-year sites, and analysis of related planning documents. The second comprised 2 rounds of interviews (n = 22 and n = 23, with a total of 19 individuals) and extensive participant observation. Several factors are necessary for pursuing environmental justice: (1) invest in community partnerships and collaborations, (2) honor community knowledge and data, (3) ensure that community constituents share power in environmental governance, and (4) adopt explicit racial justice frameworks. Although still a work in progress, AB 617 offers important lessons for community and policy organizations nationwide engaged in environmental justice. (Am J Public Health. 2022;112(2):262-270. https://doi.org/10.2105/AJPH.2021.306592).


Assuntos
Conservação dos Recursos Naturais/legislação & jurisprudência , Exposição Ambiental/legislação & jurisprudência , Política Ambiental/legislação & jurisprudência , Política de Saúde/legislação & jurisprudência , Poluição do Ar/estatística & dados numéricos , California , Defesa do Consumidor/legislação & jurisprudência , Humanos
9.
Eur J Haematol ; 107(2): 190-201, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34288162

RESUMO

BACKGROUND: A high prevalence of pulmonary embolism (PE) has been described during COVID-19. Our aim was to identify predictive factors of PE in non-ICU hospitalized COVID-19 patients. METHODS: Data and outcomes were collected upon admission during a French multicenter retrospective study, including patients hospitalized for COVID-19, with a CT pulmonary angiography (CTPA) performed in the emergency department for suspected PE. Predictive factors significantly associated with PE were identified through a multivariate regression model. RESULTS: A total of 88 patients (median [IQR] age of 68 years [60-78]) were analyzed. Based on CTPA, 47 (53.4%) patients were diagnosed with PE, and 41 were not. D-dimer ≥3000 ng/mL (OR 8.2 [95% CI] 1.3-74.2, sensitivity (Se) 0.84, specificity (Sp) 0.78, P = .03), white blood count (WBC) ≥12.0 G/L (29.5 [2.3-1221.2], Se 0.47, Sp 0.92, P = .02), and ferritin ≥480 µg/L (17.0 [1.7-553.3], Se 0.96, Sp 0.44, P = .03) were independently associated with the PE diagnosis. The presence of the double criterion D-dimer ≥3000 ng/mL and WBC ≥12.0 G/L was greatly associated with PE (OR 21.4 [4.0-397.9], P = .004). CONCLUSION: The white blood count, the D-dimer and ferritin levels could be used as an indication for CTPA to confirm PE on admission in non-ICU COVID-19 patients.


Assuntos
COVID-19/complicações , Ferritinas/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Contagem de Leucócitos , Embolia Pulmonar/sangue , Embolia Pulmonar/complicações , COVID-19/virologia , França , Humanos , Admissão do Paciente , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação
10.
J Bone Jt Infect ; 6(5): 131-134, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34084701

RESUMO

We describe a 79-year-old man with spondylodiscitis and unknown pathogen, treated with cefazolin and rifampicin. He developed a massive digestive hemorrhage. Prothrombin time was prolonged with severe vitamin-K-dependent clotting-factor deficiency. Severe bleeding can occur during cefazolin and rifampicin use. This deficiency should be assessed before prescribing cefazolin-rifampicin and prothrombin time monitored.

11.
Medicine (Baltimore) ; 100(21): e26023, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032722

RESUMO

ABSTRACT: To assess tocilizumab (TCZ) efficacy associated to standard of care (SOC) compared to SOC alone in severe coronavirus associated disease 2019 (COVID-19) patients. In a matched case-control study from 3 French Hospital COVID-19 Departments, 27 patients with severe COVID-19 treated with TCZ and SOC were matched for baseline epidemiological and clinical features and compared to 27 severe COVID-19 patients treated with SOC alone. Baseline characteristics of the study population were comparable between groups. Eleven patients (20%) died. TCZ was not associated with clinical improvement as compared to SOC regarding oxygen-free status (44% vs 63%) and death (18.5% vs 22%), despite a higher decrease of the C-reactive protein at Day 7 (10.7 vs 52 mg/L; P < 10-3). Compared to the 43 patients alive at the end-of follow-up, patients who died were older (78 vs 64 years; P < 10-3), with 82% of them older than 72 years vs only 23% of live patients (P < 10-3). Age (OR = 1.15; 95%CI = 1.04-1.3; P = .008) and age over 72 years (OR) = 14.85; 95%CI = 2.7-80; P = .002) were independently associated with mortality. TCZ in addition to SOC for severe COVID-19 patients did not reduce mortality, subsequent need for invasive mechanical ventilation nor did it shorten the time of oxygen support, despite better control of the inflammatory response. More powerful and randomized controlled trials are warranted to determine if TCZ is effective in the management of COVID-19.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Tratamento Farmacológico da COVID-19 , COVID-19/terapia , Respiração Artificial/estatística & dados numéricos , Padrão de Cuidado/estatística & dados numéricos , Fatores Etários , Idoso , COVID-19/diagnóstico , COVID-19/mortalidade , COVID-19/virologia , Estudos de Casos e Controles , Feminino , Seguimentos , França/epidemiologia , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/administração & dosagem , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Resultado do Tratamento
12.
Viruses ; 13(5)2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33926038

RESUMO

The incidence of pulmonary embolism (PE) is high during severe Coronavirus Disease 2019 (COVID-19). We aimed to identify predictive and prognostic factors of PE in non-ICU hospitalized COVID-19 patients. In the retrospective multicenter observational CLOTVID cohort, we enrolled patients with confirmed RT-PCR COVID-19 who were hospitalized in a medicine ward and also underwent a CT pulmonary angiography for a PE suspicion. Baseline data, laboratory biomarkers, treatments, and outcomes were collected. Predictive and prognostics factors of PE were identified by using logistic multivariate and by Cox regression models, respectively. A total of 174 patients were enrolled, among whom 86 (median [IQR] age of 66 years [55-77]) had post-admission PE suspicion, with 30/86 (34.9%) PE being confirmed. PE occurrence was independently associated with the lack of long-term anticoagulation or thromboprophylaxis (OR [95%CI], 72.3 [3.6-4384.8]) D-dimers ≥ 2000 ng/mL (26.3 [4.1-537.8]) and neutrophils ≥ 7.0 G/L (5.8 [1.4-29.5]). The presence of these two biomarkers was associated with a higher risk of PE (p = 0.0002) and death or ICU transfer (HR [95%CI], 12.9 [2.5-67.8], p < 0.01). In hospitalized non-ICU severe COVID-19 patients with clinical PE suspicion, the lack of anticoagulation, D-dimers ≥ 2000 ng/mL, neutrophils ≥ 7.0 G/L, and these two biomarkers combined might be useful predictive markers of PE and prognosis, respectively.


Assuntos
COVID-19/patologia , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Neutrófilos/patologia , Embolia Pulmonar/virologia , Idoso , COVID-19/sangue , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , Embolia Pulmonar/sangue , Embolia Pulmonar/patologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/genética , Tromboembolia Venosa/sangue , Tromboembolia Venosa/patologia , Tromboembolia Venosa/virologia
13.
J Scleroderma Relat Disord ; 6(1): 87-95, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35382246

RESUMO

Objective: To explore pharmacokinetic/pharmacodynamic relationship between mycophenolic acid area under the curve and clinical response at 1 year on skin involvement or interstitial lung disease in patients with systemic sclerosis. Method: Retrospective, monocentric study based on French Scleroderma Database in patients receiving mycophenolate mofetil who experienced a limited sampling strategy to estimate individual mycophenolic acid area under the curve plus two pulmonary function tests and skin evaluation after 1 month and 1 year. Efficacy criterions were variations of modified Rodnan skin score, forced vital capacity, and diffusing lung capacity for carbon monoxide at 1 year. Results: We included 52 patients; mean age was 49 years (range 17-79), and 36 (69%) were females. Fifty patients (96%) had skin sclerosis, 39 (75%) had diffuse skin involvement with a median modified Rodnan skin score of 14 (0-38). Thirty-eight (76%) had interstitial lung disease, with median forced vital capacity and diffusing lung capacity for carbon monoxide of 81% (37-127) and 56% (28-103) from predicted values, respectively. Twenty-five (51%) patients had pulmonary fibrosis. Mycophenolate mofetil was given for 10 months (0-173) at a median dose of 2000 mg/day (500-3000). In the entire population, no relationship was found between area under the curve and modified Rodnan skin score (p = 0.085), forced vital capacity (p = 0.80), or diffusing lung capacity for carbon monoxide (p = 0.72) variations at 1 year. Conclusion: In this retrospective study, we failed to document any relationship between mycophenolic acid area under the curve and skin involvement or interstitial lung disease evolution. Routine monitoring of mycophenolic acid in systemic sclerosis patients treated with mycophenolate mofetil cannot be recommended based on our results.

14.
Rheumatology (Oxford) ; 60(5): 2157-2168, 2021 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-33026090

RESUMO

OBJECTIVES: To characterize lymphocytes dysregulation in patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). METHODS: Using flow cytometry, we analysed B- and T-cell subsets in peripheral blood from 37 untreated patients with active disease (29 GPA and 8 MPA) and 22 healthy controls (HCs). RESULTS: GPA patients had increased Th2 (1.8 vs 1.0%, P = 0.02), Th9 (1.1 vs 0.2%, P = 0.0007) and Th17 (1.4 vs 0.9%, P = 0.03) cells compared with HC. Patients with MPO-ANCAs had significantly more CD21- B cells than HC or PR3-ANCA patients (6.9 vs 3.3% and 4.4%, P = 0.01). CD69 expressing B cells were significantly higher in GPA and MPA (3.0 and 5.9 vs 1.4%, P = 0.02 and P = 0.03, respectively) compared with HC, whereas B-cell activating factor-receptor expression was decreased in GPA and MPA (median fluorescence intensity ratio 11.8 and 13.7 vs 45.1 in HC, P < 0.0001 and P = 0.003, respectively). Finally, IL-6-producing B cells were increased in GPA vs HC (25.8 vs 14.9%, P < 0.0001) and decreased in MPA vs HC (4.6 vs 14.9%, P = 0.005), whereas TNF-α-producing B cells were lower in both GPA and MPA patients compared with controls (15 and 8.4 vs 30%, P = 0.01 and P = 0.006, respectively). CONCLUSION: Skewed T-cell polarization towards Th2, Th9 and Th17 responses characterizes GPA, whereas B-cell populations are dysregulated in both GPA and MPA with an activated phenotype and a decreased B-cell activating factor-receptor expression. Finally, inflammatory B cells producing IL-6 are dramatically increased in GPA, providing an additional mechanism by which rituximab could be effective.


Assuntos
Linfócitos B/imunologia , Granulomatose com Poliangiite/sangue , Poliangiite Microscópica/sangue , Linfócitos T/imunologia , Linfócitos B/metabolismo , Citocinas/metabolismo , Citometria de Fluxo , Granulomatose com Poliangiite/imunologia , Granulomatose com Poliangiite/metabolismo , Humanos , Poliangiite Microscópica/imunologia , Poliangiite Microscópica/metabolismo , Linfócitos T/metabolismo
15.
Ocul Immunol Inflamm ; 29(2): 290-298, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-31671003

RESUMO

Background: This study aimed to assess the diagnostic relevance of CD4/CD8 ratio in cerebrospinal fluid (CSF) for the etiological diagnosis work-up of uveitis.Methods: We consecutively included patients who were referred to our department for the diagnostic workup of intermediate and/or posterior uveitis. Etiological diagnoses were established in a blind manner regarding CD4/CD8 ratio.Results: Fifty-two patients were included. A diagnosis of ocular sarcoidosis was made in 15 (29%) patients, 21% had another determined diagnosis while 50% remained of undetermined origin. Median CD4/CD8 ratio in CSF was 4.57 (IQR 3.39-5.47) in ocular sarcoidosis, 1.74 (1.60-3.18) in uveitis due to other determined cause (P = .008), and 2.83 (2.34-3.54) in those with uveitis of undetermined origin (P = .007). CD4/CD8 ratio >3.23 was associated with a diagnosis of ocular sarcoidosis.Conclusion: Determination of CD4/CD8 ratio in CSF can be useful for diagnosis work-up since a CD4/CD8 ratio >3.23 in CSF is associated with ocular sarcoidosis.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Imunofenotipagem/métodos , Sarcoidose/imunologia , Uveíte/diagnóstico , Adulto , Biomarcadores/líquido cefalorraquidiano , Relação CD4-CD8 , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sarcoidose/líquido cefalorraquidiano , Sarcoidose/complicações , Uveíte/líquido cefalorraquidiano , Uveíte/etiologia
18.
Rev Prat ; 70(5): 537-540, 2020 May.
Artigo em Francês | MEDLINE | ID: mdl-33058644

RESUMO

Fabry disease. Fabry disease is an X-linked disorder in which lysosomal alpha-galactosidase A is lacking, leading to enzyme-substrate accumulation and tissues dysfunction. Acroparesthesia, angiokeratoma, familial nephropathy or hypertrophic cardiomyopathy should suggest Fabry disease. Enzymatic assay allows diagnosis in men but genetic assay is needed for women. Enzyme replacement therapy is available since 2001 and a pharmacologic chaperone since 2016.


Maladie de Fabry. La maladie de Fabry est une maladie rare, monogénique, liée à l'X, où un déficit enzymatique en alpha-galactosidase A lysosomale provoque l'accumulation intracellulaire de son substrat à l'origine de dysfonctions d'organe. On doit l'évoquer aussi bien chez l'homme que chez la femme, en particulier devant des acroparesthésies à électropyogramme normal, des angiokératomes, une insuffisance rénale familiale ou une cardiopathie hypertrophique possiblement isolée et sans obstacle à l'éjection. Le diagnostic se fait par dosage enzymatique chez l'homme et par analyse génétique chez la femme. Trois traitements sont disponibles : deux enzymothérapies substitutives depuis 2001, une molécule chaperon depuis 2016.


Assuntos
Doença de Fabry , Nefrite Hereditária , Terapia de Reposição de Enzimas , Doença de Fabry/diagnóstico , Doença de Fabry/genética , Doença de Fabry/terapia , Feminino , Humanos , Masculino , alfa-Galactosidase/genética , alfa-Galactosidase/uso terapêutico
19.
Blood ; 136(20): 2290-2295, 2020 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-32959052

RESUMO

Anti-CD20 monoclonal antibodies are widely used for the treatment of hematological malignancies or autoimmune disease but may be responsible for a secondary humoral deficiency. In the context of COVID-19 infection, this may prevent the elicitation of a specific SARS-CoV-2 antibody response. We report a series of 17 consecutive patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms, negative immunoglobulin G (IgG)-IgM SARS-CoV-2 serology, and positive RNAemia measured by digital polymerase chain reaction who were treated with 4 units of COVID-19 convalescent plasma. Within 48 hours of transfusion, all but 1 patient experienced an improvement of clinical symptoms. The inflammatory syndrome abated within a week. Only 1 patient who needed mechanical ventilation for severe COVID-19 disease died of bacterial pneumonia. SARS-CoV-2 RNAemia decreased to below the sensitivity threshold in all 9 evaluated patients. In 3 patients, virus-specific T-cell responses were analyzed using T-cell enzyme-linked immunospot assay before convalescent plasma transfusion. All showed a maintained SARS-CoV-2 T-cell response and poor cross-response to other coronaviruses. No adverse event was reported. Convalescent plasma with anti-SARS-CoV-2 antibodies appears to be a very promising approach in the context of protracted COVID-19 symptoms in patients unable to mount a specific humoral response to SARS-CoV-2.


Assuntos
Anticorpos Antivirais/imunologia , Linfócitos B/patologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Soros Imunes/administração & dosagem , Linfopenia/terapia , Pneumonia Viral/imunologia , Adulto , Idoso , Linfócitos B/imunologia , Transfusão de Componentes Sanguíneos , COVID-19 , Infecções por Coronavirus/sangue , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Feminino , França , Neoplasias Hematológicas/complicações , Humanos , Imunização Passiva , Linfopenia/etiologia , Linfopenia/patologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/terapia , Pneumonia Viral/virologia , SARS-CoV-2 , Soroterapia para COVID-19
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