RESUMEN
Patients with primary Sjögren syndrome frequently present hematologic abnormalities, consisting mainly of immune cytopenias. Pure red cell aplasia is a very rare complication of primary Sjögren syndrome. This is the first report in the literature describing the development of pure red cell aplasia combined with autoimmune hemolytic anemia in a 74-year-old woman with primary Sjögren syndrome. In our patient, despite administration of diverse therapeutic schemes, such as corticosteroids, immunomodulating agents (intravenous immune globulin), immunosuppressive drugs (cyclophosphamide), and novel treatment options (monoclonal antibody directed against the CD20 antigen), no response was achieved. The present case suggests that the possibility of comorbid connective tissue disease should be a diagnostic consideration in patients with acquired pure red cell aplasia and autoimmune hemolytic anemia. Although most of the hematologic abnormalities that occur in primary Sjögren syndrome are not clinically significant, serious and difficult-to-treat hematologic complications may also occur.
Asunto(s)
Anemia Hemolítica Autoinmune/etiología , Aplasia Pura de Células Rojas/etiología , Síndrome de Sjögren/complicaciones , Anciano , Anemia Hemolítica Autoinmune/diagnóstico , Anemia Hemolítica Autoinmune/tratamiento farmacológico , Médula Ósea/patología , Diagnóstico Diferencial , Femenino , Humanos , Aplasia Pura de Células Rojas/diagnóstico , Aplasia Pura de Células Rojas/tratamiento farmacológico , Síndrome de Sjögren/sangre , Síndrome de Sjögren/tratamiento farmacológicoRESUMEN
A potential complication of leptospirosis is cardiovascular involvement. Electrocardiographic abnormalities are frequent. Leptospirosis has been reported to be one of the infectious causes of relative bradycardia, but severe absolute sinus bradycardia has been rarely described as a potential electrocardiographic alteration. We present a case of marked sinus bradycardia (35 bpm) lasting for 4 days in a patient with anicteric leptospirosis and relative bradycardia on admission. Heart rate resolved spontaneously after control of infection by appropriate antibiotic therapy. This case points toward the need for close monitoring of vital signs and electrocardiogram in leptospirosis, especially when relative bradycardia is present on admission.
Asunto(s)
Bradicardia/etiología , Leptospirosis/complicaciones , Adulto , Antibacterianos/uso terapéutico , Electrocardiografía , Humanos , Leptospirosis/fisiopatología , Leptospirosis/terapia , MasculinoRESUMEN
We determined the intracellular expression and inducibility of heat shock proteins (Hsps) 72, 73 and 27 in the bone marrow of patients with myelodysplastic syndrome (MDS) and controls. Hsps were overexpressed in MDS marrow especially in advanced disease, providing resistance to induction of apoptosis. These data suggest that Hsps could be implicated in the progression of MDS to acute myeloid leukemia.
Asunto(s)
Médula Ósea/metabolismo , Regulación Neoplásica de la Expresión Génica/fisiología , Proteínas de Choque Térmico/biosíntesis , Proteínas de Choque Térmico/genética , Síndromes Mielodisplásicos/metabolismo , Médula Ósea/patología , Progresión de la Enfermedad , Humanos , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/patologíaRESUMEN
Aplastic anemia (AA) is a syndrome of hematopoietic failure involving increased apoptosis of stem cells. In order to investigate the molecular mechanisms participated in the process of marrow failure, we created an in vitro model of hematopoietic cell suppression, by continuous addition of TNF-alpha and IFN-gamma in an vitro long-term bone marrow culture system. An up-regulation of Fas expression was observed in CD34+ cells in cytokine treated cultures, compared to controls. This was accompanied by significant TRAIL and decreased caspase 3 mRNA expression, whereas the expression of Bcl-2 family members was low (Bcl-xl) or absent (Bcl-2, Bax). The expression of these apoptotic genes was also investigated in aplastic anemia patients. Apart from Fas mRNA expression in total marrow and/or CD34+ cells, TRAIL mRNA expression was found only in CD34+ cells in active disease while in total marrow cell compartment this remains a constant finding even in patients in remission. The above data are in agreement with previous studies proposing a major role for the extrinsic apoptosis pathway in the pathogenesis of aplastic anemia and additionally introduce TRAIL as a probable important molecule in the process.
Asunto(s)
Anemia Aplásica/metabolismo , Proteínas Reguladoras de la Apoptosis/biosíntesis , Apoptosis , Células Madre Hematopoyéticas/metabolismo , Glicoproteínas de Membrana/biosíntesis , Transducción de Señal , Factor de Necrosis Tumoral alfa/biosíntesis , Regulación hacia Arriba , Adulto , Anciano , Anemia Aplásica/patología , Antígenos CD34/biosíntesis , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Células Cultivadas , Femenino , Células Madre Hematopoyéticas/patología , Humanos , Interferón gamma/farmacología , Masculino , Persona de Mediana Edad , Transducción de Señal/efectos de los fármacos , Ligando Inductor de Apoptosis Relacionado con TNF , Factor de Necrosis Tumoral alfa/farmacología , Regulación hacia Arriba/efectos de los fármacos , Proteína X Asociada a bcl-2/biosíntesis , Proteína bcl-X/biosíntesis , Receptor fas/biosíntesisRESUMEN
Myelodysplastic syndromes (MDS) are clonal stem cell disorders, characterized by ineffective and dysplastic hematopoiesis. MDS patients have a defective immune response manifested by increased susceptibility to bacterial infections, autoimmune phenomena, and high incidence of lymphoid malignancies. Presently, we investigated the phenotype and function of monocyte-derived dendritic cells (MoDC) in 23 MDS patients and 15 controls at different stages of differentiation using the maturation stimuli tumor necrosis factor-alpha (TNF-alpha) and LPS. Monocytes from MDS patients showed low potential to differentiate into dendritic cells (DC), as determined by low cell yield and CD1a expression. MDS-MoDCs exhibited low expression of mannose receptor and reduced endocytic capacity. MDS-MoDCs showed a diminished response to TNF-alpha with low CD83, CD80, and CD54 expression and allostimulatory capacity. In patients with 5q syndrome, monocytes and MoDCs were positive for the 5q deletion, suggesting their origin from the malignant clone. Our data indicate that MoDCs in MDS display quantitative and functional abnormalities that may contribute to the defective immune response of these patients.
Asunto(s)
Diferenciación Celular/efectos de los fármacos , Células Dendríticas/efectos de los fármacos , Células Dendríticas/patología , Monocitos/efectos de los fármacos , Monocitos/patología , Síndromes Mielodisplásicos/patología , Factor de Necrosis Tumoral alfa/farmacología , Anciano , Anciano de 80 o más Años , Antígenos/metabolismo , Células Cultivadas , Células Dendríticas/metabolismo , Endocitosis , Femenino , Citometría de Flujo , Humanos , Lectinas Tipo C/metabolismo , Masculino , Receptor de Manosa , Lectinas de Unión a Manosa/metabolismo , Persona de Mediana Edad , Monocitos/metabolismo , Fenotipo , Receptores de Superficie Celular/metabolismoRESUMEN
Myelodysplastic syndrome (MDS) is a stem cell disorder characterized by ineffective haematopoiesis and blood cytopenias. The present study investigated the potential of bone marrow CD34(+) progenitors in MDS patients to proliferate and differentiate into dendritic cells (DCs) in a cytokine-supplemented liquid culture system and analysed the status of blood DC subsets in these patients. CD34(+) progenitors had low potential to generate DCs in vitro, as the number of DCs obtained from one CD34(+) cell was significantly lower compared with controls (median value 0.2 vs. 4, P = 0.003). In patients, the survival and proliferation of CD34(+) cells in culture was not correlated to the degree of apoptosis. Phenotypically and functionally CD34(+)-derived DCs were similar in MDS patients and normal subjects. The percentage of both circulating DC subsets in patients was extremely diminished compared with controls (myeloid DC: 0.10 +/- 0.10% vs. 0.35 +/- 0.13%, P < 0.001; plasmacytoid DC: 0.11 +/- 0.10% vs. 0.37 +/- 0.14%, P < 0.001). In cases with the 5q deletion both CD34-derived DCs and blood DCs harboured the cytogenetic abnormality. Our results indicate that, in MDS, the production of DCs is affected by the neoplastic process resulting in ineffective 'dendritopoiesis' with low blood DC precursor numbers. This quantitative DC defect probably contributes to the poor immune response against infectious agents and to the escape of the malignant clone from immune recognition with disease progression towards acute leukaemia.
Asunto(s)
Antígenos CD34/análisis , Células Dendríticas/patología , Células Madre Hematopoyéticas/patología , Síndromes Mielodisplásicos/patología , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis , Diferenciación Celular , División Celular , Células Cultivadas , Células Clonales/patología , Células Dendríticas/inmunología , Femenino , Células Madre Hematopoyéticas/inmunología , Humanos , Inmunofenotipificación , Prueba de Cultivo Mixto de Linfocitos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/inmunologíaRESUMEN
Excessive intramedullary apoptosis has been considered to account for the paradox of hypercellular marrow and refractory cytopenias in myelodysplastic syndrome (MDS). However, a causative relationship of apoptosis to the progenitor's defective clonogenic growth has not been sufficiently demonstrated. We investigated the degree of apoptosis and its contribution to ineffective hematopoiesis in MDS, by assessing the differential clonogenic capacity of purified "apoptotic" and "non-apoptotic" bone marrow progenitors in a short-term semisolid culture system. Although increased apoptosis was indeed detected in MDS bone marrow progenitors, there was no correlation between the existence of apoptosis and culture performance. Non-apoptotic as well as apoptotic CD34+ cells gave similar patterns of growth, both defective compared to normal. The ability of "apoptotic" CD34+ cells to proceed in colony formation as well as the abnormal growth of "non-apoptotic" progenitors are probably pointing towards the need to reconsider the role of apoptosis in the defective clonogenicity of MDS.