RESUMO
Primary effusion lymphoma (PEL) is a rare B-cell non-Hodgkin lymphoma associated with Kaposi Sarcoma-associated herpesvirus (KSHV/HHV8) infection. Lymphoma cells are coinfected with Epstein-Barr virus (EBV) in 60-80% of cases. Tools allowing a reliable PEL diagnosis are lacking. This study reports PEL diagnosis in 4 patients using a Flow-Fluorescence in situ hybridization (FlowFISH) technique that allowed detection of differentially expressed EBV and HHV8 transcripts within the same sample, revealing viral heterogeneity of the disease. Moreover, infected cells exhibited variable expressions of CD19, CD38, CD40, and CD138. Therefore, FlowFISH is a promising tool to diagnose and characterize complex viral lymphoproliferations.
Assuntos
Herpesvirus Humano 4 , Herpesvirus Humano 8 , Hibridização in Situ Fluorescente , Linfoma de Efusão Primária , Humanos , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/isolamento & purificação , Hibridização in Situ Fluorescente/métodos , Linfoma de Efusão Primária/virologia , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Masculino , Idoso , Pessoa de Meia-Idade , Feminino , Infecções por Herpesviridae/virologia , Infecções por Herpesviridae/diagnóstico , Infecções por Vírus Epstein-Barr/virologia , Infecções por Vírus Epstein-Barr/complicações , Idoso de 80 Anos ou maisRESUMO
Langerhans cell histiocytosis (LCH) and the non-LCH neoplasm Erdheim-Chester disease (ECD) are heterogeneous neoplastic disorders marked by infiltration of pathologic macrophage-, dendritic cell-, or monocyte-derived cells in tissues driven by recurrent mutations activating MAPK signaling. Although recent data indicate that at least a proportion of LCH and ECD patients have detectable activating kinase mutations in circulating hematopoietic cells and bone marrow-based hematopoietic progenitors, functional evidence of the cell of origin of histiocytosis from actual patient materials has long been elusive. Here, we provide evidence for mutations in MAPK signaling intermediates in CD34+ cells from patients with ECD and LCH/ECD, including detection of shared origin of LCH and acute myelomonocytic leukemia driven by TET2-mutant CD34+ cell progenitors in one patient. We also demonstrate functional self-renewal capacity for CD34+ cells to drive the development of histiocytosis in xenotransplantation assays in vivo. These data indicate that the cell of origin of at least a proportion of patients with systemic histiocytoses resides in hematopoietic progenitor cells prior to committed monocyte/macrophage or dendritic cell differentiation and provide the first example of a patient-derived xenotransplantation model for a human histiocytic neoplasm.
Assuntos
Células da Medula Óssea/patologia , Proteínas de Ligação a DNA/genética , Doença de Erdheim-Chester/patologia , Células-Tronco Hematopoéticas/patologia , Histiocitose de Células de Langerhans/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas/genética , Adulto , Alelos , Animais , Antígenos CD34/genética , Antígenos CD34/imunologia , Células da Medula Óssea/imunologia , Transplante de Medula Óssea , Diferenciação Celular , Proteínas de Ligação a DNA/imunologia , Células Dendríticas/imunologia , Células Dendríticas/patologia , Dioxigenases , Doença de Erdheim-Chester/genética , Doença de Erdheim-Chester/imunologia , Expressão Gênica , Células-Tronco Hematopoéticas/imunologia , Histiocitose de Células de Langerhans/genética , Histiocitose de Células de Langerhans/imunologia , Humanos , Imunofenotipagem , Macrófagos/imunologia , Macrófagos/patologia , Camundongos , Monócitos/imunologia , Monócitos/patologia , Mutação , Proteínas Proto-Oncogênicas/imunologia , Proteínas Proto-Oncogênicas B-raf/imunologia , Transplante HeterólogoRESUMO
The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 12th workshop on hematopoietic stem cell transplantation clinical practices harmonization procedures on September 2021 in Lille, France. In the absence of specific national or international recommendation, the French working group for autologous stem Cell transplantation in Auto-immune Diseases (MATHEC) proposed guidances for vaccinations of patients undergoing autologous hematopoietic stem cell transplantation for autoimmune disease, including in the context of SARS-Cov-2 pandemic.
Assuntos
Doenças Autoimunes , COVID-19 , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Medula Óssea , Transplante Autólogo , COVID-19/prevenção & controle , SARS-CoV-2 , Doenças Autoimunes/terapia , Sociedades Médicas , Vacinação , FrançaRESUMO
BACKGROUND: Behçet's disease (BD) is a rare form of vasculitis involving both veins and arteries of all calibers. Psychological symptoms and cognitive impairment appear to be frequent, but few data are available. METHODS: All consecutive patients in our center fulfilling the 2013 BD criteria underwent a psychometric evaluation with auto- (SCL-90-R and Modified Fatigue Index) and hetero-questionnaires (MINI). A standardized test battery assessed cognitive dysfunction. Data were correlated with BD activity as well as quality of life (SF-36). RESULTS: We included 20 consecutive patients (16 men, four women) with a median [IQR] age of 38 (30.0-45.5) and a median disease duration of 7 years (1.8-11.0). Five patients had an abnormal brain MRI. The SCL-90-R questionnaire highlighted eight psychopathological profiles (42.1%) that correlated with altered quality of life and more severe fatigue. The most frequent symptoms were anxiety (9/19, 47.4%), somatization (8/19, 42.1%) and phobia (5/19, 26.3%). Psychopathological symptoms appeared to be more severe, but not more frequent, in neuro-Behçet's patients. Based on standardized cognitive evaluation, nine patients had cognitive impairment defined by three or more altered tests. Notably, 6/9 patients did not have any complaint of memory loss and were thus considered ansognostic. CONCLUSION: Cognitive involvement was significantly associated with BD activity score (BSAS) but not with brain MRI abnormalities.
RESUMO
BACKGROUND: Patients with systemic lupus erythematosus (SLE) exhibit a high risk for cardiovascular diseases (CVD) which is not fully explained by the classical Framingham risk factors. SLE is characterized by major metabolic alterations which can contribute to the elevated prevalence of CVD. METHODS: A comprehensive analysis of the circulating metabolome and lipidome was conducted in a large cohort of 211 women with SLE who underwent a multi-detector computed tomography scan for quantification of coronary artery calcium (CAC), a robust predictor of coronary heart disease (CHD). FINDINGS: Beyond traditional risk factors, including age and hypertension, disease activity and duration were independent risk factors for developing CAC in women with SLE. The presence of coronary calcium was associated with major alterations of circulating lipidome dominated by an elevated abundance of ceramides with very long chain fatty acids. Alterations in multiple metabolic pathways, including purine, arginine and proline metabolism, and microbiota-derived metabolites, were also associated with CAC in women with SLE. Logistic regression with bootstrapping of lipidomic and metabolomic variables were used to develop prognostic scores. Strikingly, combining metabolic and lipidomic variables with clinical and biological parameters markedly improved the prediction (area under the curve: 0.887, p < 0.001) of the presence of coronary calcium in women with SLE. INTERPRETATION: The present study uncovers the contribution of disturbed metabolism to the presence of coronary artery calcium and the associated risk of CHD in SLE. Identification of novel lipid and metabolite biomarkers may help stratifying patients for reducing CVD morbidity and mortality in SLE. FUNDING: INSERM and Sorbonne Université.
RESUMO
Lymphomas localized in the kidney are a rare entity that may be challenging to diagnose. We analyzed data from 10 patients with renal involvement of lymphoma diagnosed between 2009 and 2019 on fine needle biopsy from our tertiary center, and compared these with findings of 160 cases reported in the literature. Diffuse large B-cell lymphoma was the main histology subtype (40 and 38% in our sample and in the literature, respectively), followed by low-grade B-cell lymphomas, mostly from the marginal zone (MZ). Altogether, 106 patients had urological inaugural symptoms and 64 had general symptoms. Patients with urological presentation more often had renal masses than diffuse infiltration (p < 0.001), unilateral tumors (p = 0.0036) and low-grade B-cell lymphomas (17 vs 6%, p = 0.043). In both groups, nearly one-fourth of patients had diffuse (stage IV) lymphomas. Overall survival did not differ by the presence of urological/systemic symptoms, stage or aggressive lymphoma status. Notably, 3 of 10 patients from our series had MZ lymphomas associated with primary Sjögren syndrome revealed by acute kidney injury, including one where the autoimmune disease was detected. Lymphoproliferative disorders localized in the kidney are a challenging condition that can lead to detection of aggressive or diffuse lymphomas.