Células asesinas naturales con el receptor de antígeno quimérico (CAR-NK): terapia emergente contra el cáncer / Chimeric antigen receptor-natural killer cells: novel therapy against cancer

Resumen Una de las herramientas más novedosas en inmunoterapias adoptivas contra leucemias y tumores malignos es el uso del receptor de antígeno quimérico "CAR". El receptor CAR ha sido ampliamente utilizada en células T (células CAR-T) potenciando su eficacia en el reconocimiento y eliminación de tumores, obteniéndose a la fecha terapias basadas en esta tecnología. No obstante, las células CAR-T llegan a repercutir negativamente en la salud del paciente, presentando el síndrome neurológico de efecto inmune asociado a células (ICANS) y el síndrome de lanzamiento de citocinas (SLC). Como consecuencia, el paciente necesita ser hospitalizado durante la terapia. Además, el coste de manufactura y terapia es elevado, siendo una tecnología limitada a un sector muy bajo de la población. En este trabajo, mencionamos el empleo de una terapia emergente de células asesinas naturales (NK) con el receptor CAR (CAR-NK), que cuentan con muchas ventajas por encima de las células CAR-T. Las células CAR-NK conservan su capacidad citotóxica en contra de tumores gracias a su acción dependiente de receptores activadores e inhibidores, por lo que el receptor CAR, solo estimula sus habilidades y persistencia. Sumado a esto, el coste de una terapia de células CAR-NK podría resultar redituable debido a la capacidad de las células CAR-NK de eliminar múltiples células tumorales sin generar daño colateral en el paciente. Aquí analizamos las características de los múltiples receptores CAR y los fenotipos de células NK que han sido utilizados durante múltiples ensayos (NK-92, células NK de sangre cordal y periférica, y células NK iPSC).

Abstract One of the novel and effective devices against leukemia and solid tumors in adoptive immunotherapies is the use of the chimeric antigen receptor "CAR". CAR technology has been widely used in T-cells (CAR-T cells) empowering its efficacy on the identification and elimination of tumor cells, getting today certain drugs based on this technology. Nevertheless, CAR-T cells can have a negative impact on patient health, causing in many cases immune effector cell-associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS). As a consequence, the patient will have to be hospitalized for the duration of therapy. Moreover, the cost of manufacture and therapy is quite expensive, limiting its use to a low range of people. On the other hand, we analyze the advantages of Natural Killer cells with the CAR receptor (CAR-NK), which have many plusses over CAR-T cells. CAR-NK cells retain their cytotoxic abilities against tumor cells due their activator/ inhibitor receptors balance. Thus, the CAR receptor technology just increases their skills and persistence. Furthermore, CAR-NK therapy could be more profitable since CAR-NK can eliminate multiple tumor cells without generating collateral damage on patient health. Here, we discuss the characteristics of the multiples CAR receptors in general and the NK types cells that have been used in trials demonstrating their viable emerging therapy (NK-92, cord and peripheral blood NK cells, and iPSC-derived NK cells).

Sepsis por escherichia coli de inicio infrecuente en paciente con linfoma de células T y NK / Sepsis By Escherichia Coli Of Uncommon Starting In Patient With T And NK Cell Lymphoma

La sepsis se da en presencia de un foco infeccioso; en este caso por Escherichia coli (E.coli), las cuales poseen toxinas que pueden causar daños severos en la funcionalidad y morfología del organismo, viéndose empeorado en pacientes con enfermedades que afecten al sistema inmunitario; como es este caso en presencia de neoplasia hematológica. Paciente femenina de 42 años , con diagnóstico de Linfoma no Hodgkin de células T-NK presenta una placa necrótica en el paladar, temperatura por encima de 38°C, frecuencia respiratoria superando las 20 respiraciones por minutos y frecuencia cardíaca superando los 90 latidos por minuto, al examen de cultivo faríngeo positivo a E.coli, urocultivo negativo, confirmando punto partida infeccioso faríngeo; tratada con amikacina vía endovenosa durante 7 días con buena respuesta a la antibioticoterapia . Se reporta un caso infrecuente por este tipo de bacteria en zona bucal y revisión del tema.

Sepsis occurs in the presence of an infectious focus; in this case by Escherichia coli (E. coli), that toxins can cause severe damage to the organism's functionality and morphology, being worsened in patients with diseases that affect the immune system; as is this case in the presence of hematological malignancy. A 42-year-old female patient with a diagnosis of T-NK non-Hodgkin lymphoma presented with a necrotic plaque on the palate, temperature above 38 ° C, respiratory rate exceeding 20 breaths per minute, and heart rate exceeding 90 beats per minute. , on examination of a positive pharyngeal culture for E. coli, negative urine culture, confirming a pharyngeal infectious starting point; Treat with amikacin endovenously for 7 days with good response to antibiotic therapy. An infrequent case is reported for this type of bacteria in the oral area and a review of the subject.

Linfoma de células T/NK extranasal primario en íleon / Natural Killer/T cell primary extranasal ileum lymphoma

RESUMEN El linfoma extranodal de células T/NK extranasal (NKTL) primario del tracto gastrointestinal es poco frecuente y tiene carácter agresivo. Presentamos el caso de un paciente inmunocompetente de 51 años que ingresa por dolor abdominal de dos meses de evolución. En la colonoscopía, se hallaron ulceraciones ileales, por lo que se le realizaron estudios para descartar enfermedad de Crohn y tuberculosis intestinal, posteriormente presentó obstrucción intestinal. En la laparotomía exploratoria, se encontró un conglomerado ganglionar en mesenterio. La anatomía patológica confirmó el diagnóstico de NKTL primario en íleon. Se inició quimioterapia y el paciente pidió alta voluntaria dada su precaria condición. Dos meses después del alta el paciente fallece. Este linfoma ha sido reportado principalmente en Asia y posiblemente sea el primer caso reportado en Perú. Tiene un pronóstico funesto con una supervivencia global de ocho meses. Por ello, es necesario un diagnóstico precoz e iniciar la terapia oportunamente.

ABSTRACT Primary extranodal Natural Killer / T cell lymphoma (NKTL) on gastrointestinal tract is an uncommon and aggressive neoplasm. We present the case of a 51-year-old immunocompetent patient with a 2-month history of abdominal pain. Colonoscopy findings showed ileal ulcerations, so studies were carried out to rule out Crohn's disease and intestinal tuberculosis. Later, he developed intestinal obstruction. Exploratory laparotomy found a nodal conglomerate in the mesentery. Anatomical pathology confirmed the diagnosis of primary NKTL on the ileum. Chemotherapy was initiated but the patient asked for voluntary discharge because of his precarious condition. Two months after discharge the patient died. This lymphoma has been reported mainly in Asia and is possibly the first case in Peru. It has a dismal prognosis with overall survival of 8 months. Therefore, it is necessary to get an early diagnosis and begin therapy in a timely manner.

SMILE en linfoma de células NK/T extranodal en recaída / SMILE in relapsed extranodal NK / T cell lymphoma

Introducción: El linfoma extranodal de células NK/T, tipo nasal es una variedad agresiva que se presenta con mayor frecuencia en Asia Oriental y América Latina. El régimen de tratamiento SMILE, basado en dexametasona, metotrexato, ifosfamida, L-asparaginasa y etopósido, mostró tasas de respuestas objetivas adecuadas en estudios de fase 1/2. Objetivo: presentar el primer reporte de la aplicación del protocolo SMILE en Cuba. Presentación del caso: paciente de 47 años de edad, blanca que presentó recaída temprana de linfoma extranodal de células NK/T tipo nasal en partes blandas de la pared anterior izquierda del tórax. Recibió quimioterapia SMILE por 4 ciclos y en la evaluación al final del tratamiento se comprobó que hubo una respuesta completa de la enfermedad(AU)

Introduction: Extranodal lymphoma of NK / T cells, nasal type is an aggressive variety that occurs most frequently in East Asia and Latin America. The SMILE treatment regimen, based on dexamethasone, methotrexate, ifosfamide, L-asparaginase and etoposide, showed adequate objective response rates in phase 1/2 studies. Objective: to present the first report of the application of the SMILE protocol in Cuba. Case presentation : 47-year-old white patient who presented early relapse of extranodal lymphoma of nasal NK / T cells in soft parts of the left anterior wall of the thorax. He received SMILE chemotherapy for 4 cycles and the evaluation at the end of the treatment showed that there was a complete response of the disease(AU)

Evaluation of immunological parameters in pregnant women: low levels of B and NK cells / Avaliação dos parâmetros imunológicos em mulheres gestantes: baixos níveis de células B e NK

Abstract Objective To describe the immunological and hematological reference intervals of low-risk pregnant women. Methods A cross-sectional retrospective database analysis of a basic and translational study analyzing the hematological evaluation blood counts and immunophenotyping of TCD3 + , TCD4 + , TCD8 + , B, and natural killer (NK) cells of the peripheral blood in 79 low-risk pregnant women and of 30 control women from the state of Pernambuco, Brazil, was performed. Results No significant differences were detected between the hematological profiles of the 2nd and 3rd trimesters. Nevertheless, the median level of B cells decreased significantly in the 2nd (174 x 103 μL; p < 0.002) and 3rd trimesters (160 x 103 μL; p < 0.001), compared with the control group (296 x 103 μL). Similarly, the median level of NK cells was lower in the 2nd (134 x 103 μL; p < 0.0004) and 3rd trimesters (100 x 103 μL, p < 0.0004), compared with the control group (183 x 103 μL). In contrast, relative TCD4+ and TCD8+ levels increased in the 2nd and 3rd trimesters compared with the controls (TCD4 + : 2nd trimester = 59%; p < 0.001; 3rd trimester = 57%; p < 0.01; control = 50%; and TCD8 + : 2nd trimester = 31%; p < 0.001; 3rd trimester = 36%; p < 0.01; control = 24%). Conclusion Low-risk pregnant women have ~ 40% less B and NK cells in the peripheral blood, compared with non-pregnant women. These parameters may improve health assistance for mothers and contribute to define reference values for normal pregnancies.

Resumo Objetivo Descrever o intervalo de referência imunológico e hematológico de gestantes de baixo risco. Métodos Realizou-se uma análise retrospectiva, de um estudo básico e translacional, analisando o perfil hematológico e a imunofenotipagem das células TCD3 + , TCD4 + , TCD8 + , B e natural killer (NK) do sangue periférico de 79 gestantes de baixo risco e de 30 mulheres (controles) do estado de Pernambuco, Brasil. Resultados Não observamos diferenças significativas entre os perfis hematológicos do 2° e 3° trimestres. No entanto, houve redução das células B no 2° (média = 174 x 103 μL; p < 0,002) e no 3° trimestres (160 x 103 μL; p < 0,001), comparado como grupo controle (296 x 103 μL). A mediana das células NK foi menor no 2° (134 x 103 μL; p < 0,0004) e no 3° trimestres (100 x 103 μL; p < 0,0004), comparado com o grupo controle (183 x 103 μL). Porém, o percentual de TCD4+ e de TCD8+ aumentou no 2° e 3° trimestres em relação aos controles (TCD4 + : 2° trimestre = 59%; p < 0,001; 3° trimestre = 57%; p < 0,01; controle = 50%; e TCD8 + : 2° trimestre = 31%; p < 0,001; 3° trimestre = 36%; p < 0,01; controle = 24%). Conclusão Mulheres grávidas de baixo risco têm ~ 40% menos células B e NK no sangue periférico em comparação com mulheres não grávidas. Estes parâmetros podem melhorar a assistência à saúde das mães e contribuir para a definição de valores de referência para gestações normais.

Accurate diagnose and management of advanced nasal type extranodal nk/t cell lymphoma. a case report

ABSTRACT Extranodal natural killer (NK)/T-cell lymphoma, nasal type, is a rare entity in otorhinolaryngology. Its management requires skilled physicians in order to suspect this disease and making a proper diagnosis at early stages. This paper reports the case of a 31-year-old male patient, with one month of nasal obstruction, recurrent sinusitis, palatal ulceration and a necrotizing lesion. Histopathology reported lymphoid infiltrate polymorph angiocentric growth pattern and extensive areas of necrosis. Immunohistochemistry confirmed the phenotype for T/NK cells: positive CD3, BCL2, CD4 and CD56. IgG for Epstein-Barr virus was also positive. The initial staging was T4, N1, M0, Eastern Cooperative Oncology Group (ECOG) scale was 1, with intermediate risk, and low International Prognostic Index (IPI); based on this results, the patient was referred to oncology to initiate treatment. After a ten-month follow-up, the patient's condition improved, with complete remission of nasal and palate injuries; no relapse has occurred to date. This case is a clear example of the importance of early diagnostic through multiple biopsies in order to establish a specific treatment to decrease complication rates and improve prognosis.

Immunotherapy with natural killer cells: a possible approach for the treatment of Acute Myeloid Leukemia also in Brazil / Imunoterapia com células natural killer: um caminho possível para o tratamento da Leucemia Mielóide Aguda também no Brasil

SUMMARY The allogeneic hematopoietic stem cell transplantation (HSCT) can cure intermediate and high-risk acute myeloid leukemia. Even with the development of strategies to reduce HSCT toxicity, this is still a complex treatment with high morbidity and mortality. Knowledge of the graft versus leukemia effect of HSCT has prepared the way for the development of Adoptive Immunotherapy or in vitro expansion of activated lymphocytes without alloreactivity, with subsequent intravenous infusion. The infusion of genetically modified T lymphocytes and haploidentical natural killer cells has been tested as an alternative to HSCT with very interesting results worldwide and in Brazil, as we not only have the technology of in vitro expansion of clinical grade lymphocytes available, but also do it according to the Good Manufacturing Practices that have been determined internationally.

RESUMO O transplante de células-tronco hematopoéticas (TCTH) alogênico é curativo para leucemia mielóide aguda de risco intermediário e alto. Mesmo com o desenvolvimento de estratégias para minorar a toxicidade do TCTH, este ainda é um tratamento complexo com elevada morbi-mortalidade. O conhecimento sobre o efeito enxerto contra leukemia do TCTH pavimentou o caminho para o desenvolvimento da Imunoterapia Adotiva ou expansão in vitro de linfócitos ativados, sem alo-reatividade, com posterior infusão endovenosa. A infusão de Linfócitos T geneticamente modificados e de células Natural Killer haploidenticas tem sido testada como alternativa ao TCTH com resultados bastante interessantes no mundo e no Brazil já que não apenas dominamos a tecnologia de expansão in vitro de linfócitos em grau clínico, como o fazemos segundo as Boas Práticas de Manufatura determinadas internacionalmente.

Chronic active EBV infection: the experience of the Samsung Medical Center in South Korea / Infección crónica activa por virus de Epstein-Barr: experiencia del Centro Médico Samsung en Corea del Sur

Abstract Background: Chronic active EBV infection (CAEBV) of T-cell or NK-cell type is an EBV+ polyclonal, oligoclonal or often monoclonal lymphoproliferative disorder (LPD) recognized as representing the spectrum of EBV-associated T-cell and NK-cell LPD with different clinical presentations; one systemic and two cutaneous disorders including hydroa vacciniforme-like T-cell LPD and mosquito bite hypersensitivity. The systemic form of the disease is characterized by fever, persistent hepatitis, hepatosplenomegaly and lymphadenopathy, which shows varying degrees of clinical severity depending on the immune response of the host and the EBV viral load. Case reports: We described the clinicopathological findings of two children with CAEBV with a brief review of the literature. Conclusions: Recognition of the disease is important for adequate management of the patient. EBV analysis should be included in the principal diagnostic tests for febrile children.

Resumen Introducción: La infección crónica activa (CA) de células T o células tipo NK por virus de Epstein-Barr (VEB) es un desorden linfoproliferativo (DLP) VEB+ policlonal, oligoclonal o, frecuentemente, monoclonal reconocido como representación del espectro del DLP de células T y células NK asociado con VEB que tiene diversas presentaciones clínicas: un padecimiento sistémico y dos cutáneos que incluyen el DLP de células T que semeja hidroa vacciniforme y la hipersensibilidad por picadura de mosquito. Los síntomas de la enfermedad sistémica incluyen fiebre, hepatitis persistente, hepatoesplenomegalia y linfadenopatías que muestran diferente grado de severidad clínica, dependiendo de la respuesta inmune del hospedero y de la carga viral del VEB. Casos clínicos: Se describen los hallazgos clínico-patológicos de dos niños con CAVEB y una breve revisión de la literatura. Conclusiones: Es importante reconocer esta enfermedad para proporcionar el manejo adecuado al paciente. El análisis de VEB debería incluirse como una de las principales pruebas diagnósticas en niños con fiebre.

Efeitos do ácido fólico não metabolizado na metilação global do DNA, na expressão de RNAm dos genes de DHFR, MTHFR, interferon-γ, TNF-α e interleucina-8, e na citotoxicidade das células NK / Effects of unmetabolized folic acid on global DNA methylation, on mRNA expression of DHFR, MTHFR, interferon-α, TNF-α and interleukin-8 genes, and on NK cells cytotoxicity

Com o início da fortificação de farinhas com ácido fólico (AF) no Brasil, a partir 2004, a população passou a estar exposta de modo compulsório a maiores quantidades desta vitamina. Sabe-se que o AF na sua forma sintética pode não ser completamente convertido para formas metabolicamente ativas, levando ao aparecimento de uma fração não metabolizada no organismo. Este fato é mais preocupante nos indivíduos que além da fortificação, fazem uso terapêutico dessa vitamina, como em pacientes com anemias hemolíticas (esferocitose hereditária (EH), ß-talassemia heterozigótica (ß-TH), entre outras). O objetivo desse estudo foi avaliar se as concentrações séricas de AF não metabolizado (UMFA) afetam a metilação global do DNA; a expressão de RNAm de genes da DHFR, MTHFR, interferon-γ, TNF-α e interleucina (IL)-8; e a citotoxicidade de células NK. Foram incluídos 27 pacientes com EH, 50 indivíduos com ß-talassemia heterozigótica (ß-TH) e 136 indivíduos saudáveis. Outros 30 indivíduos saudáveis foram incluídos num estudo de intervenção com 5mg/dia de AF durante 90 dias. Foram realizadas as análises de: ácido fólico sérico, eritrocitário e UMFA, vitamina B12, homocisteína total; expressões de RNAm dos genes de MTHFR, DHFR, IFN-γ, TNF-α e IL-8; citotoxicidade das células NK; metilação global do DNA e citocinas séricas IL6, IL-8, IL10, IFN-γ e TNF-α. Resultados: Os pacientes EH apresentaram maiores concentrações de AF (sérico, eritrocitário e UMFA) que seus controles, sendo que 55,5% (método microbiológico) e 74,1% (método LC-MS/MS) apresentaram concentrações suprafisiológicas da vitamina, e 74,1% apresentaram concentrações aumentadas de UMFA. No grupo ß-TH foi observado maiores concentrações de folato eritrocitário comparado ao controle e 22% dos indivíduos tinham concentrações suprafisiológicas de AF. No estudo de intervenção, após 45 e 90 dias de uso de AF as concentrações suprafisiológicas estavam presentes em 93,3% dos indivíduos e 100% deles apresentavam concentrações aumentadas de UMFA. Não foram observadas diferenças nas taxas de metilação global do DNA entre os grupos EH e ß-TH quando comparados aos seus controles e não foi verificada correlação entre metilação global e concentrações de UMFA. Tanto EH quanto ß-TH apresentaram maior expressão de RNAm de IL-8, quando comparados aos seus controles. No grupo de intervenção houve maior expressão de IL-8 após 45 dias de uso de AF quando comparado ao período pré-intervenção. Foi mostrada uma correlação inversa entre as concentrações de folato eritrocitário com o número de células NK no grupo EH e com a capacidade citotóxica das células NK no grupo total (EH + controle). No grupo intervenção foi observado menor número e menor capacidade citotóxica das células NK após 90 dias de uso de AF. Conclusões: O uso de AF 5mg/dia foi associado com aumento expressivo das concentrações de folato sérico, eritrocitário, UMFA, na expressão de RNAm de genes da citocina inflamatória IL-8 e redução do número e da citotoxicidade das células NK. Dessa forma, altas doses de AF podem resultar em alterações de componentes do sistema imune podendo prejudicar os mecanismos de vigilância celular das células NK. Os nossos achados sugerem que é importante o acompanhamento terapêutico dos pacientes que fazem uso de AF, especialmente aqueles indivíduos que fazem uso crônico desta vitamina por longo tempo, como os pacientes com anemias hemolíticas, mulheres que desejam engravidar e gestantes

With the beginning of the fortification of flour with folic acid (FA) in Brazil, since 2004, the population has been exposed compulsorily to larger amounts of this vitamin. It is known that FA in its synthetic form can not be completely converted to metabolically active forms, leading to the appearance of an unmetabolized fraction in the body. This fact is more worrying in subjects beyond fortification, make therapeutic use of this vitamin, such as patients with hemolytic anemia (hereditary spherocytosis (HS), ß-thalassemia heterozygotic (ß-TH), among others). The aim of this study was to evaluate if serum concentrations of unmetabolized FA (UMFA) affect the global DNA methylation; mRNA expression of DHFR, MTHFR, interferon-γ, TNF-α and interleukin (IL)-8 genes; and on cytotoxicity of NK cells. It was included 27 patients EH, 50 subjects ß-TH and 136 healthy subjects. Another 30 healthy subjects were included in an intervention study with 5 mg/FA daily during 90 days. Analyzes performed were: serum and erythrocyte folate, and UMFA, vitamin B12, tHcy; mRNA expression of MTHFR, DHFR, IFN-γ, TNF-α and IL-8 genes; cytotoxicity of NK cells; global DNA methylation and serum cytokines IL6, IL-8, IL10, IFN-γ and TNF-α. Results: EH patients presented higher FA concentrations (serum, erythrocytes and UMFA) than controls ones, and 55.5% (microbiologic method) and 74.1% (LC-MS/MS method) showed supraphysiologic concentrations of vitamin, and 74.1% presented increased concentrations of UMFA. In ß-TH group, it was observed higher erythrocyte folate concentrations compared with the control and 22% of subjects had supraphysiological concentrations of FA. In the intervention study, after 45 and 90 days of FA use, supraphysiological concentrations were present in 93.3% of subjects and 100% of them showed increased concentrations of UMFA. It was not observed differences in global methylation of DNA between EH and ß-TH groups when compared to their controls and it was not observed significant correlation between global DNA methylation and UMFA levels. Both EH and ß-TH showed higher mRNA expression of IL-8 gene, when compared to controls. In the intervention group, there was higher mRNA expression of IL-8 gene after 45 days of FA use when compared to pre-intervention period. It was demonstrated an inverse correlation between erythrocyte folate levels and the number of NK cells in EH group; and cytotoxic capacity of NK cells on total group (EH + control). In intervention group, it was observed fewer number and lower cytotoxic capacity of NK cells after 90 days of AF use. Conclusions: The use of AF 5mg daily was associated with a significant increase in serum and erythrocytes folate levels, accompanied by increase in UMFA levels, an increase in mRNA expression of IL-8 gene, and reduction of the number and the cytotoxicity capacity of NK cells. Thus, high doses of AF can result in modifications of the immune system components, which may damage the cell surveillance mechanisms of NK cells. Our findings suggest that is important the therapeutic follow up of patients that are using AF, especially those subjects with chronic use of this vitamin, such as patients with hemolytic anemia, women who wish to become pregnant and pregnant women

Analysis of risk factors associated to cytomegalovirus infection in dentistry students / Análisis de factores de riesgo asociados a la infección por citomegalovirus en estudiantes de odontología

The purpose of the study was to analyze the association between cytomegalovirus (CMV) infection in dental students with occupational risk factors and a genetic trait (NKG2C gene deletion). Study design: Case-control study. 176 students were included and divided in two groups according to CMV serological results: those with CMV infection (case group) and those without prior infection (control group). Demographic, occupational, and the presence of NKG2C gene deletion were compared between both groups. Results: The presence of CMV IgG antibodies was detected in 104 (59.1 percent) students (case group) while 72 (40.9 percent) students were CMV negative (control group). The frequency of patient contact, the use of protective barriers, and the number of reported accidents was compared between the study groups; no significant differences were noted. The appropriate use of infection-control measures was observed in the majority of students in both study groups. In the case group the frequency of NKG2C deletion was 9.7 percent compared to 5.6 percent in the control group (p=0.33). Conclusion: No association between the presence of CMV infection with occupational and genetic risk factors was found in this population. Dentists should be aware of the CMV prevalence and risks factors associated to this infection, particularly among child-bearing age dentist women...

El objetivo de este estudio fue analizar la asociación entre la infección por citomegalovirus (CMV) en estudiantes de odontología con factores de riesgo ocupacionales y un polimorfismo genético (deleción del gen NKG2C). Diseño del Estudio: Estudio de casos y controles. 176 estudiantes fueron incluidos y divididos en dos grupos de acuerdo al resultado serológico para CMV: aquellos con la infección por CMV (grupo de casos) y aquellos que no presentaron infección por CMV (grupo control). Las características demográficas, ocupacionales y la presencia de la deleción del gen NKG2C fueron comparadas entre ambos grupos. Resultados: La presencia de anticuerpos IgG de CMV fue detectada en 104 (59.1 por ciento) estudiantes (grupo de casos) mientras que 72 (40.9 por ciento) estudiantes fueron negativos a CMV (grupo control). Se comparó la frecuencia de contacto con el paciente, el uso de barreras protectoras y el número de accidentes ocupacionales reportados entre los grupos de estudio. No fueron detectadas diferencias significativas. El uso apropiado de las medidas de control de infección fue observado en la mayoría de los estudiantes de ambos grupos. En el grupo de casos la frecuencia de la deleción de NKG2C observada fue de 9.7 por ciento comparada con un 5.6 por ciento en el grupo control (p=0.33). Conclusión: No se encontró asociación entre la infección por CMV con los factores de riesgo ocupacionales y genéticos de esta población. Los dentistas deben conocer la frecuencia de la infección por CMV, así como los factores de riesgo asociados, particularmente las mujeres odontólogas en edad fértil...

Linfoma de células T/Natural Killer extranodal, tipo nasal / Extranodal Natural Killer /T-cell lymphoma, nasal type

Introducción: El linfoma de células T/Natural Killer (T/NK) extranodal, tipo nasal, es un linfoma extra-ganglionar poco frecuente, con extensión a lo largo de la línea media facial, rápidamente progresivo, catastrófico y de mal pronóstico, por lo que también se le conoce como "granuloma letal de la línea media". Objetivo: El propósito de este artículo es revisar la literatura disponible y actualizada sobre el linfoma de células T/NK extranodal, tipo nasal: manifestaciones clínicas, estándares de enfoque, diagnóstico, pronóstico y tratamiento. Diseño: Revisión Narrativa de la literatura. Metodología: Revisión de la literatura mediante búsqueda selectiva por términos MeSH: Extranodal Natural Killer /T cell lymphoma, nasal type, lethal midline granuloma, de las bases de datos: MEDLINE, Current Contents, Cochrane, Pubmed y Scielo, entre los años 2000 y 2014. Resultados: Se revisaron 36 artículos según los requerimientos de los objetivos. El linfoma de células T/NK es una neoplasia rápidamente progresiva, destructiva y de mal pronóstico excepto en los casos donde el diagnóstico ha sido oportuno. Conclusiones: El diagnóstico y tratamiento tempranos del linfoma de células T/NK extranodal, tipo nasal, son las únicas herramientas para mejorar el mal pronóstico y gran afectación en la calidad de vida de los pacientes con esta enfermedad.

"Introduction: Extranodal nasal Natural Killer (NK) /T-cell lymphoma, nasal type, is an extranodal lymphoma, infrequent, with extension along facial midline, rapidly progressive, catastrophic and with poor prognosis, also known as "lethal midline granuloma". Objectives: The purpose of this article is to review the current literature available about Extranodal nasal NK/T-cell lymphoma, nasal type: Clinical manifestations, approach standards, diagnosis, prognosis and treatment. Methodology: Literature review by selective MeSH search terms: Extranodal Natural Killer / T cell lymphoma, nasal type, lethal midline granuloma of databases: MEDLINE, Current Contents, Cochrane, PubMed and SciELO, between 2000 and 2014. Results: 36 articles were reviewed according to the requirements of the objectives. Extranodal NK/T cell lymphoma, nasal type, is a rapidly progressive neoplasia, destructive and with poor prognosis except in cases where diagnosis has been timely. Conclusions: Early diagnosis and treatment of Extranodal NK/T cell lymphoma, nasal type, are the only tools to improve the poor prognosis and high impairment in quality of life of patients with this disease.

Linfoma extranodal de células t asesinas naturales tipo nasal. Reporte de caso / Nasal nk/t-cell extranodal lymphoma. Case report

El granuloma letal de la línea media también llamado linfoma nasal de células T asesinas naturales es una entidad poco frecuente que afecta hombres jóvenes en su gran mayoría, su etiología es desconocida sin embargo, está relacionado con el virus del Epstein-Barr. Se caracteriza por un curso rápidamente progresivo y pobre respuesta al tratamiento. El diagnóstico suele ser difícil y tardío y su pronóstico malo. Objetivo: Presentar un caso de un paciente de 29 años de edad con esta patología que se presentó en el Hospital Universitario San Ignacio. Diseño: Reporte de caso. Materiales y métodos: Se presenta el caso de un paciente de 29 años de edad con ocho meses de obstrucción nasal por masa de crecimiento progresivo, friable, con costras y rinorrea fétida en fosa nasal derecha; había recibido múltiples esquemas antibióticos extrainstitucionales sin mejoría. Tras un largo proceso se realizó diagnóstico de Linfoma No Hodgkin Nasal de células T NK con un trasfondo de tipo inflamatorio. Resultados: Se evidenció una evolución tórpida; se documentó ascitis requiriendo posteriormente colocación de catéter peritoneal; durante procedimiento presenta paro cardiorrespiratorio, ingresa a Unidad de cuidados intensivos; fallece 8 horas después. Conclusiones: Esta enfermedad es poco frecuente; dada su presentación su diagnóstico suele ser difícil y tardío. Es importante que el otorrinolaringólogo se encuentre familiarizado con esta entidad ya que suele ser el especialista que tiene el primer contacto con el paciente y de este depende la confi rmación y el tratamiento de dicha patología...

The lethal midline granuloma, also known as lymphoma T/NK is a rare entity that affects mostly young men, its etiology is unknown but is related to the Epstein-Barr virus. It is characterized by a rapidly progressive course and poor response to treatment. The diagnosis is often diffi cult and delayed and poor prognosis. Objective: To present a case of a patient of 29 years with this disease who presented at the “Hospital Universitario San Ignacio”. Design: Case report. Materials and Methods: We present the case of a 29 year old man with eight months of nasal obstruction ought to a friable mass of progressive growth, with crusts and fetid rhinorrhea in right nasal fossa; he had received multiple antibiotics without improvement. After a long process the diagnosis of non-Hodgkin lymphoma Nasal NK T cells with an infl ammatory background was performed. Results: A torpid evolution was observed; subsequently documented ascites was documented requiring peritoneal catheter placement; during surgery, he suffered cardiac arrest, was admitted in the intensive care unit; and died 8 hours later. Conclusions: This disease is rare and diagnosis is often diffi cult and delayed because of its presentation. It is important that the otolaryngologist includes this entity as a differential diagnosis because this is the specialist who often has the fi rst contact with the patient and confi rmation as well as treatment of this disease may depend on the ear, nose, and throat specialist...

Selenium and vitamin E enriched diet increases NK cell cytotoxicity in cattle / Dieta enriquecida com selênio e vitamina E aumenta a citotoxicidade de células NK em bovinos

A number of studies has shown that antioxidants, fatty acids and trace minerals may modulate different immune cell activities, and that their deficiency may be associated with diseases and impaired immune responses. In innate immunity, natural killer (NK) cells have a central role, killing virally infected and cancerous cells, and also secreting cytokines that shape adaptive immune responses. Thus, the aim of this study was to evaluate the effect of enriched diets in selenium plus vitamin E and/or canola oil on complete blood count and on NK cell cytotoxicity from blood lymphocytes of Nellore bulls. Bulls that received selenium plus vitamin E had (P=0.0091) higher NK cell cytotoxicity than control bulls. This result positively correlated with serum selenium levels. To the best of our knowledge, this is the first study that showed immunostimulatory effects of selenium plus vitamin E on NK cell cytotoxicity of Nellore bulls.(AU)

Vários estudos demonstraram que antioxidantes, ácidos graxos e minerais podem modular a atividade de diferentes células do sistema imunológico e que as suas carências podem estar associadas a doenças e a respostas imunes comprometidas. Na imunidade inata, os linfócitos natural killer (NK) têm um papel central matando células infectadas por vírus e células cancerígenas, ao mesmo tempo em que também secretam citocinas que modulam as respostas imunes adaptativas. Assim, o objetivo deste estudo foi avaliar o efeito de dietas enriquecidas em selênio e vitamina E e/ou óleo de canola no hemograma e na citotoxicidade das células NK do sangue de bovinos da raça Nelore. Os animais que receberam selênio e vitamina E tiveram (P = 0,0091) maior citotoxicidade das células NK do que os animais do grupo controle. Este resultado foi positivamente correlacionado com os níveis de selênio no sangue. Para o melhor do nosso conhecimento, este é o primeiro estudo que mostrou efeitos imunoestimulatórios do selênio e vitamina E sobre a citotoxicidade das células NK de bovinos Nelore.(AU)

Expresión de TLR2, 4, 9 y presencia de células tipo NK CD56 positivas en lesiones de pacientes con diferentes formas de clínicas de leismaniasis cutánea americana / Expression of TLR2, 4, 9 and presence NK type CD56 positive cells lesions of patients with different clinical forms of American cutaneous leishmaniasis

La leishmaniasis cutánea americana (LCA) presenta varias manifestaciones clínicas e inmunitarias: La leishmaniasis cutánea localizada (LCL), cuya respuesta inmunitaria es tipo Th1, la leishmaniasis cutánea difusa (LCD) con una respuesta Th2, y la leishmaniasis cutánea intermedia (LCI) cuya respuesta inmunitaria es exacerbada con un patrón mixto de citocinas. Se ha demostrado la importancia de los receptores tipo toll (TLR) en la respuesta inmunitaria frente a Leishmania promoviendo la transcripción y síntesis de citocinas inflamatorias. El reconocimiento de componentes del parásito por los TLRs activa a macrófagos, células dendríticas y células NK. En este estudio, evaluamos la presencia TLR2, TLR4, TLR9 y células tipo NK (NK y NKT CD56+) en las lesiones de pacientes con LCL, LCI y LCD mediante inmunocitoquímica. Las lesiones de LCL y LCD mostraron una alta densidad de células TLR2 y TLR4+ con respecto a LCI, mientras que LCD mostró una mayor densidad de células TLR9+. Se observó también la expresión de TLR2 en los queratinocitos y el TLR9 se localizó en el interior de los macrófagos infectados asociado con los parásitos. La densidad de células CD56+ fue mayor en LCL en comparación con LCI y LCD. Los resultados demuestran la participación de los TLR2, 4 y 9 en la respuesta inmunitaria durante la LCA, mostrando evidencia del reconocimiento del parásito por TLR9 y una mayor densidad de células NK en LCL que se puede asociar a la respuesta Th1 que prevalece en estos pacientes.

American cutaneous leishmaniasis (ACL) has several clinical and immunological manifestations: localized cutaneous leishmaniasis (LCL) that produces a Th1 immune response, diffuse cutaneous leishmaniasis (DCL) that produces a Th2 response, and intermediate cutaneous leishmaniasis (ICL) that promotes an exacerbated immune response with a mixed pattern of cytokines. The importance of toll-like receptors (TLRs) to the immune response has been demonstrated against Leishmania, as these promote the transcription and synthesis of inflammatory cytokines. Parasite components are recognized by TLRs leading to the activation of macrophages, dendritic cells and NK cells. In this study, we evaluated the presence of TLR2, TLR4, TLR9 and NK/NKT CD56+ cells by immunocytochemistry in the lesions of patients with LCL, ICL and DCL. LCL and DCL lesions showed higher densities of TLR2 and TLR4 cells than ICL, while DCL showed an increase in TLR9 + cell density. The expression of TLR2 in keratinocytes was also observed, and TLR9 was located inside the infected macrophages in contact with the parasites. NK cell density was higher in LCL compared with ICL and DCL. These results demonstrate the participation of TLR2, 4 and 9 in the immune response during ACL, and show evidence of parasite recognition by TLR9 and increased CD56+ cell density in LCL associated with the Th1 response which prevails in these patients.

Increased frequency of NK and gamma delta 1 T cells in a cohort of patients with sepsis * / Incremento en la frecuencia de células NK y células T gamma delta 1 en una cohorte de pacientes con sepsis

Introduction: The mechanisms involved in the immunopathogenesis of sepsis are not well established. The clinical and therapeutic relevance of several soluble mediators has been described and the contribution of cellular components with immunoregulatory roles has begun to be elucidated. Objective: To describe changes in the frequency and production of IFN- γ and IL-10 occurring in NK cells and γδ T lymphocytes in a cohort of patients with different manifestations of septic syndrome. Materials and methods: This was a prospective cohort study. Patients with sepsis (n=26), and severe sepsis (n=83) from adult emergency rooms and intensive care units, as well as healthy volunteers (n=8), were included. For all participants, the frequency and phenotype of NK cells and γδ T lymphocytes and the percentage of IFN- γ and IL-10 positive NK and γδ T cells were evaluated by flow cytometry. The NK cells were phenotyped based on the expression of CD56 and CD16 and the γδ T cells on the expression of d 1 and d 2 chains. Results: Patients with sepsis and severe sepsis exhibited an increase in the frequency of NK cells with changes in the proportion of the CD56 bright /CD16¯, CD56 bright /CD16 dim and CD56 dim CD16¯ subpopulations; these cells showed a proinflammatory cytokine profile. A decrease in the V d 2 subset of γδ T lymphocyte s was also observed. Conclusions: Our results indicate a role for NK and γδ T cells during sepsis, however, their exact contribution in the pathogenesis of sepsis syndrome requires further studies.

Introducción: Los mecanimos involucrados en la inmunopatogénesis de las sepsis no han sido claramente establecidos. La importancia clínica y terapéutica de diferentes mediadores solubles ha sido descrita y la contribución de componentes celulares con propiedades inmunorreguladoras ha empezado a dilucidarse. Objetivo: Describir los cambios en la frecuencia y en la producción de IFN- γ e IL-10 que se observa en células NK y linfocitos T γδ en una cohorte de pacientes con diferentes manifestaciones del síndrome séptico. Materiales y métodos: Estudio de cohorte prospectiva, donde pacientes con sepsis (n = 26) y sepsis grave (n = 83) provenientes de las salas de emergencias y unidades de cuidado intensivo, y controles sanos (n = 8) fueron incluidos. Tanto la frecuencia y fenotipo de las células NK y T γδ como el porcentaje de células IFN- γ+ e IL-10+ fueron evaluados mediante citometría de flujo. Las células NK fueron fenotipificadas con base en la expresión de las moléculas CD56 y CD 16 y los T γδ con base en la expresión de las cadenas δ1 y δ2. Resultados: En los pacientes con sepsis y sepsis grave se observó un incremento en la frecuencia de las células NK con cambios en las proporciones de las subpoblaciones CD56 bright /CD 16 ¯, CD56 bright /CD16 dim y CD56 dim CD16¯; en estas células se observó un perfil de citocinas proinflamarias. Se observó una reducción en el porcentaje de células Vδ2. Conclusiones: Los resultados sugieren un papel de las células NK y linfocitos T γδ durante la sepsis; sin embargo, su contribución en la patogénesis de este síndrome requiere estudios adicionales.

Virus como inductores de neoplasias cutáneas / Viruses as agents inducing cutaneous neoplasms

El rol oncogénico de los virus en las neoplasias cutáneas es conocido por el hombre desde hace más de un siglo, cuando se atribuía el origen de la verruga vulgar al virus papiloma humano (VPH). En la actualidad, las neoplasias inducidas por virus pueden agruparse en tumores sólidos y procesos linfoproliferativos. Destacan entre los primeros el VPH, del cual ahora conocemos numerosos serotipos, cada uno vinculado a una neoplasia específica, el herpesvirus humano tipo 8 que produce el sarcoma de Kaposi y el poliomavirus vinculado al carcinoma de Merkel. Entre los procesos linfoproliferativos debemos mencionar al virus linfotrópico de células T humanas tipo 1 (HTLV-1) responsable de los linfomas de células T, en los cuales el compromiso cutáneo es inespecífico, con un amplio espectro de presentaciones clínicas y, que por consiguiente, plantean un reto para el diagnóstico diferencial. En este grupo también se encuentra el virus Epstein Barr vinculado a los linfomas nasales de Células NK/T y a los linfomas tipo Hidroa, de reciente descripción. En esta era en la que lo genético y lo molecular priman en las investigaciones en cáncer, no podemos dejar de lado el concepto de neoplasia como resultado de la infección por un agente viral, lo que abre una nueva veta de posibilidades de tratamiento anticanceroso basado en medicamentos antivirales.

The oncogenic role of viruses in cutaneous neoplasms has been known by humankind for more than a century, when the origin of the common wart, or verruca vulgaris, was attributed to the human papilloma virus (HPV). Currently, virus-induced cutaneous neoplasms may be grouped into solid tumors and lymphoproliferative disorders. HPV, from which various serotypes are now known, each being linked to a specific neoplasm, the human herpes virus type 8 producing Kaposi sarcoma, and the Merkel cell polyomavirus, highlight among the first group. Regarding the lymphoproliferative disorders, we should mention the human T-lymphotropic virus type I (HTLV-1), which is responsible for the T-cell lymphomas, in which the cutaneous manifestations are non-specific and have a wide spectrum, thus posing a challenge for differential diagnosis. The Epstein Barr virus, linked to nasal lymphomas of NK/T-cells and Hydroa-like cutaneous lymphomas, is also part of this group. In an era in which the genetic and molecular aspects of cancer research prevail, we may not leave behind the concept of neoplasms as a result an infection with a viral agent, which opens a wide array of new possibilities for cancer treatment based on antiviral drugs.

Efecto de la proteína E2 del virus de hepatitis C sobre la activación de células NK / Effect of E2 protein of hepatitis C virus on the activation of NK cells

En estudios previos, se ha descrito un disminución de la activación y actividad citotóxica de las células NK en los pacientes infectados con hepatitis C; sin embargo, se desconoce el mecanismo por el cual éste fenómeno ocurre. En el presente reporte se estudió el efecto de la proteína E2 de la envoltura del virus o de la estimulación de su receptor con el anticuerpo anti-CD81 sobre la fosforilación de tirosinas, serinas, las enzimas: proteína quinasa C y fosfoinositol 3 quinasa, el factor de transcrición Nfkb y el intercambiador de nueclotidos VAV de células NK de controles normales estimulados con anti-CD16. Ambos, la proteína E2 y anti-CD81, combinado o por separado inducen una disminución de la fosforilación de tirosinas y serinas, así como una marcada disminución de la fosforilación de PKC, NFkB, PI3K y en menor grado VAV. Se concluye que la proteína E2 sola y en conjunto con anti-CD81 inducen señales inhibitorias responsables de la disminución en la activación de las células NK de pacientes infectados por el VHC y que éste fenómeno puede ser responsable de la cronicidad que se reporta en dicha enfermedad

The decrease in NK cell activation and cytotoxic activity in patients infected with hepatitis C virus has been described; however, the mechanism by whcih this phenomenon occurs is not known. In the present report, the effect of the E2 protein of the virus envelope or the stimulation of its receptor CD81 with the antibody anti-CD81 on the phosphorylation of tyrosines, serine, the enzymes protein kinase C, phosphoinositol kinase 3 (PI3K), the transcription factor NfkB and the nucleotide exchange protein VAV was assessed in NK cells from normal controls stimulated with anti-CD16. Both the protein E2 and anti-CD81 by themselves or combined, generated a decrease in tyrosine, serine, and a marked decrease in the phosphorylation of PKC, NfkB, PI3k and in less extent in VAV. It is concluded that the E2 protein alone and combined with anti-CD81 induce inhibitory signals responseible for the decrease in the activation of NK cells of infected HCV patients and it could be responsible for the chronicity observed in this disease

Alterações das células natural killer (NK) na síndrome mielodisplásica (SMD) / [Changes in natural killer (NK) cells in syndrome myelodysplastic syndrome (MDS)]

A síndrome mielodisplásica (SMD) compreende um grupo heterogêneo de doenças clonais da medula óssea (MO), caracterizadas por vários graus de citopenias periféricas, que pode evoluir para leucemia mielóide aguda (LMA). Tem sido discutida a possibilidade de a SMD ser mediada por mecanismos autoimunes. As células natural killer (NK) poderiam ter um papel na fisiopatologia e progressão da SMD, mas até o momento pouco se sabe sobre o assunto. Estas células são importantes componentes do sistema imune inato e possuem funções realizadas por dois subtipos distintos: as CD56dim são responsáveis pela atividade citotóxica natural contra células tumorais e infectadas por vírus e as CD56bright pela produção de citocinas imunoregulatórias. As funções destas células são controladas por um conjunto de receptores ativadores e inibidores que reconhecem as células alvo e pertencem a três famílias principais: receptores de citotoxicidade natural (NCR), lectina tipo C e receptores de células assassinas semelhantes a imunoglobulinas (KIR). O objetivo foi estudar alterações do comportamento das células NK em pacientes com SMD. Como a SMD é mais frequente em idosos e relativamente rara na infância, primeiramente foram avaliados os parâmetros de interesse em crianças, adultos e idosos saudáveis. Foi observada nos idosos saudáveis uma redução de expressão de receptores ativadores da família NCR em células NK e aumento da expressão de receptores da família KIR no subtipo CD56bright. As crianças apresentaram alterações semelhantes. Houve redução da expressão de NKG2D nos linfócitos T de idosos. A análise do genótipo KIR revelou que KIR2DL5 e KIR2DS3 estavam associados aos idosos...

Myelodysplastic syndrome (MDS) comprise a heterogeneous group of clonal disorders of bone marrow (BM), characterized by varying degrees of peripheral cytopenias that can develop into acute myeloid leukemia (AML). Recently, has been discussed the possibility that MDS may be mediated by autoimmune mechanisms. Natural killer cells (NK) cells could play a role in the pathophysiology and progression of MDS, but so far little is known about the subject. These cells are important components of the innate immune system and its functions are performed by two distinct subtypes: the CD56dim cells are responsible for natural cytotoxicity against tumor and cells virally infected while CD56bright cells are in charge by production of immunoregulatory cytokines. The functions of these cells are controlled by a set of inhibitory and activating receptors that recognize the target cells. There are three main families of NK cells receptors: natural cytotoxicity receptors (NCR), C-type lectin receptors and killer cell immunoglobulin-like receptors (KIR). The objective was to study changes in the performance of NK cells in MDS patients. As MDS is more common in the elderly and relatively rare in childhood, firstly the parameters of interest were evaluated in healthy children, adults and elderly. Healthy elderly presented a decrease of expression of activating receptors of NCR family in NK cells and increased expression of KIR receptors in CD56bright subset. Children showed similar results. NKG2D expression was decreased on T cells of elderly. Analysis of KIR genotype revealed that KIR2DL5 and KIR2DS3 were significantly associated with old age. Cytotoxic activity was preserved from childhood through old age, suggesting that the increase of the absolute number of CD56dim , observed in elderly, may represent a compensatory mechanism for the receptor expression alterations. In MDS patients, for the first time, was observed an increase of CD56dim and reduction of CD56bright subsets...

Patogenia do envolvimento esplênico na leptospirose grave com síndrome de choque séptico / The pathogeny of the splenic lesion in severe leptospirosis with septic shock syndrom

A leptospirose é a zoonose mais comum, distribuída em todas as regiões do mundo e causada por bactérias virulentas do gênero Leptospira spp. A apresentação clínica da leptospirose varia de uma doença febril inespecífica a quadros graves com insuficiência renal aguda, icterícia, hemorragias graves, choque cardiovascular e falência de múltiplos órgãos. Pouco se sabe sobre a resposta imune do hospedeiro e os mecanismos patogênicos associados com a leptospirose grave com hemorragia pulmonar e choque cardiovascular. O baço tem sido estudado e considerado nos últimos anos como um órgão essencial na fisiopatologia da sepse/choque séptico, uma vez que nele ocorre perda de células da imunidade, secundária à apoptose. Objetivos: descrever os achados histológicos e a resposta imune in situ do baço de pacientes falecidos por leptospirose com hemorragia pulmonar e choque refratário, comparando-os com dois grupos controles, um formado por pacientes falecidos por choque séptico causado por bactérias Gram-positivas/-negativas e um segundo, formado por vítimas de trauma. Metodologia: retrospectivamente, 11 baços de pacientes com leptospirose grave e 10 baços de pacientes com choque séptico foram obtidos por necrópsia e comparados com 12 baços de vítimas de trauma abdominal fechado (controles normais), obtidos por esplenectomia. Os achados histológicos da polpa vermelha e da polpa branca esplênica foram analisados por meio de escore semi-quantitativo. A reação de imunohistoquímica (IH) foi empregada para a marcação de células NK, S100+, CD68+, TCD4+, TCD8+ e CD20+, bem como para células expressando caspase-3, TNF, IFN, IL-1, IL-2r, IL-6, IL-12, IL-10, IL-4 e TGF. A contagem de células marcadas foi realizada utilizando-se gratículo sobre 10 campos da polpa vermelha e 10 campos da polpa branca, escolhidos aleatoriamente. IH também foi realizada nos baços dos casos de leptospirose para a detecção de antígenos de Leptospira spp. Resultados: os baços de pacientes do grupo...

Leptospirosis is the most common worldwide zoonosis caused by virulent bacteria from the genus Leptospira spp. The clinical presentation of leptospirosis ranges from unspecific febrile illness to severe forms with acute renal failure, jaundice, hemorrhages, shock and multi organ failure. Little is known about the hosts immune response and the pathogenic mechanisms involved in severe leptospirosis. In recent years the spleen has been considered a pivotal organ in the patophysiology of the sepsis/septic shock because immune cells are lost due to apoptosis in this organ Objectives: describe and compare the splenic histological features and the immune response in situ in patients who died of pulmonary hemorrhage and shock caused by leptospirosis, with spleens from patients who suffered from Grampositive/- negative septic shock and abdominal trauma. Methodology: in retrospect, 11 spleen tissue samples from patients with leptospirosis and 10 spleens from patients with septic shock were obtained by necropsy, and compared with 12 spleens obtained by splenectomy from patients with abdominal trauma. The histological features in the red pulp and white pulp were analyzed by a semi quantitative score. Immunohistochemistry (IH) methods for NK , S100+, CD68+, TCD4+, TCD8+, CD20+ cells, caspase-3, TNF, IFN, IL-1, IL-2r, IL-6, IL-12, IL- 10, IL-4 and TGF were carried out and the stained cells were counted using a grid scale in ten fields of red pulp and white pulp chosen randomly. Also, IH was performed for Leptospira antigens in the leptospirosis patients. Results: the trauma group was totally different from the leptospirosis and septic shock patients which demonstrated strong similarities in the histological analysis: diffuse congestion in the red pulp with a moderate to intense infiltration of plasma cells, and polymorph nuclear cells, and follicles with marked atrophy. The Leptospira antigen was positive in eight (72,7%) spleen tissue samples from the...

Presentación testicular de un linfoma no Hodking tipo NK nasal y revisión de la literatura / Testicular presentation of a nasal type NK non Hodgkin lymphoma and review of the literature

Objetivos: Comunicar un caso de un tumor de células NK de tipo nasal originado en el testículo y realizar una revisión de la literatura publicada. Método/Resultado: Presentamos un paciente de 68 años de la edad, sin historia urológica previa, que acudió a nuestra consulta refiriendo desde hace 11 meses clínica de inflamación del teste derecho y afectación de la piel escrotal con mala respuesta a tratamiento antibiótico. Se realizó una orquiectomía por vía inguinal y se resecó la piel afectada. El diagnóstico histológico definitivo fue de linfoma no Hodgkin tipo NK nasal de células grandes. Posteriormente fue derivado al servicio de hematología que realizó un estudio de extensión confirmando con un frotis sanguíneo el diagnóstico de linfoma y tras estudiar al paciente se realizó un tratamiento sistémico con 3 ciclos de CHOP y profilaxis intratecal. Tras 20 meses de seguimiento desde el inicio de los síntomas el paciente no ha presentado afectación ganglionar o de algún otro órgano. Conclusiones: Los linfomas de células T/NK nasales son tumores poco frecuentes en nuestro medio siendo su presentación extra nasal toda una rareza y encontrado en la literatura revisada sólo 12 casos de esta presentación testicular. Es esencial el estudio anatomopatológico mediante inmunohistoquímica para clasificar dichos linfomas, ya que este tipo se caracteriza por una rápida diseminación sistémica y mala respuesta al tratamiento.

Objectives: To report a case of a nasal type NK cell tumor originated in the testicle and review the published literature. Method/Results: We report a 68 years old patient, without previous urological history, who came to our clinic referring clinical inflammation of the right testicle with scrotal skin involvement for eleven months, with poor response to antibiotic treatment. Inguinal orchiectomy was performed with resection of the affected skin. The definitive histologic diagnosis was nasal type NK large cell non-Hodgkin lymphoma. He was subsequently referred to Hematology which conducted an extension study and confirmed the lymphoma diagnosis with a blood smear. After staging, the patient underwent systemic treatment with 3 cycles of CHOP and intrathecal prophylaxis. After 20 months follow up from the onset of symptoms the patient has had no lymph node or other organ involvement. Conclusions: Nasal type T/NK cell lymphoma tumors are infrequent being extranasal presentation a rarity. We found only 12 cases of this testicular presentation in the literature. Pathological analysis using immunohistochemistry is essential to classify these lymphomas, as rapid systemic spread and poor response to treatment is characteristic is essential to classify these lymphomas, as rapid systemic spread and poor response to treatment is characteristic.