Asociación del inmunofenotipo linfocitario de sangre periférica con la presencia de linfomas no Hodgkin / Association of peripheral blood lymphoid immunophenotype with presence of non-Hodgkin lymphomas

Introducción: Los cambios en el inmunofenotipo de los linfocitos en los pacientes con linfoma no Hodgkin están asociados con el pronóstico y las respuestas terapéuticas. Sin embargo, no se ha establecido sistemáticamente la asociación con la enfermedad y por tanto su contribución al diagnóstico. Objetivo: Evaluar la asociación del inmunofenotipo linfocitario en sangre periférica con la presencia del linfoma no Hodgkin. Métodos: Se analizaron 31 muestras de sangre periférica de pacientes con diagnóstico confirmado de linfoma no Hodgkin y de 68 individuos sanos como controles, durante el período de 2018 a 2020. Se empleó la citometría de flujo multiparamétrica para el inmunofenotipado. Se calculó el área bajo la curva y el índice de Youden para establecer puntos de corte en los porcentajes linfocitarios. La asociación de los cambios inmunofenotípicos con el linfoma no Hodgkin, se realizó mediante cálculos de Odd ratio. Resultados: El aumento de linfocitos TCD8+ y NKCD56opaco se asoció significativamente con la presencia de linfoma no Hodgkin (OR= 3,4 y 2,9; respectivamente). Por el contrario, la disminución de linfocitos TCD4+, T doble positivo, T doble negativo y NKCD56brillante también se asoció con la existencia de linfoma no Hodgkin (OR= 23,0; 10,7; 6,9 y 15,8; respectivamente). Además, la disminución del índice CD4/CD8 también fue asociada con la enfermedad. Conclusiones: Los cambios encontrados en los inmunofenotipos linfocitarios se asociaron de forma significativa con la presencia del linfoma no Hodgkin, lo cual representa una expresión sistémica de la enfermedad y sugiere su valor diagnóstico(AU)

Introduction: Lymphocyte immunophenotype changes in non-Hodgkin lymphoma patients are associated with prognosis and therapeutic responses. However, its association with the disease has not been systematically established. Therefor its contribution to the diagnosis process. Objective: To assess the association of lymphocyte immunophenotype in peripheral blood with the presence of non-Hodgkin lymphoma. Methods: 31 peripheral blood samples were analyzed from patients with a confirmed diagnosis of non-Hodgkin lymphoma and from 68 healthy individuals as controls, during the period 2018 to 2020. Multiparametric flow cytometry was used for immunophenotyping. The area under the curve and the Youden index were calculated to establish cut-off points in lymphocyte percentages. The association of immunophenotypic changes with non-Hodgkin's lymphoma was made using Odd ratio calculations. Results: The increase in TCD8+ and NKCD56dim lymphocytes from peripheral blood was significantly associated with the presence of non-Hodgkin lymphoma (OR= 3.4 and 2.9, respectively). Oppositely, the decrease in TCD4+, double positive T, double negative T and NKCD56bright lymphocytes was associated with the existence of non-Hodgkin lymphoma (OR= 23.0, 10.7, 6.9 and 15.8, respectively). Therefore, the decrease in the CD4/CD8 rate was also associated with the disease. Conclusion: The changes found in these lymphocytic immunophenotypes were significantly associated with the presence of non-Hodgkin lymphoma, which represents a systemic expression of the disease and suggests its diagnostic value(AU)

Potential targets for the hepatitis C virus-mediated autoimmune thyroiditis

2021.174934ABSTRACTIntroduction: The mechanisms by which hepatitis C virus (HCV) infection induces autoimmune thyroiditis (AIT) have been studied, and it was suggested that inflammatory cytokines during HCV infection would change the thy-roperoxidase (TPO) signaling cascade and thyroglobulin (Tg) determining autoimmune thyroid disease.Objective: To show the signaling pathway, of TPO and Tg, and their potential targets mediated HCV in individuals with hepatitis C.Methods: The mapping of the signaling pathway was based on a review study approach and performed using the automatic annotation server of the Kyoto and Genome Encyclopedia (KEGG). PathVisio is free software for analysis and design of open source routes, and was used for the graphic representation of the signaling pathway.Results: The contigs were extracted from the KEGG database and their mapped transcription represents the signa-ling pathway of the main biomolecules that triggers the AIT. The action of HCV, or its treatment can trigger AIT that is characterized by the presence of autoantibodies against TPO and Tg. In AIT, autoreactive CD4 + T lymphocytes recruit B cells and CD8 + T cells in the thyroid. The progression of the disease leads to the death of thyroid cells and hypothyroidism. Conclusion: HCV or its treatment activates several signaling pathways with thyroid cells damage resulting in AIT and secondary hypothyroidism to cellular apoptosis. (AU)

RESUMOIntrodução: Os mecanismos pelos quais a infecção com o vírus da hepatite C (HCV) induz à tireoidite autoimune (TAI) têm sido alvo de estudos. Tem sido sugerido que citocinas inflamatórias, como a elevação das interleucinas na inflamação causadas pelo HCV, alterariam a cascata de sinalização da tireoperoxidase (TPO) e tireoglobulina (Tg) determinando um quadro de doença autoimune da tireóide.Objetivo: Demonstrar a via de sinalização da TPO e da Tg e seus potenciais alvos para a TAI mediados pelo HCV em indivíduos com hepatite C.Método: O mapeamento da via de sinalização foi realizado usando o servidor de anotação automática da Enciclopé-dia Quioto de Genes e Genomas (KEGG). O PathVisio, um software gratuito de análise e desenho de vias de código aberto, foi utilizado para a representação gráfica da via de sinalização.Resultado: As sequências foram retiradas do banco de dados KEGG e sua transcrição mapeada representa a via de . sinalização das principais biomoléculas que desencadeia a TAI. A ação do HCV, ou seu tratamento pode desen-cadear a TAI que é caracterizada pela presença de autoanticorpos contra a TPO e Tg. Na TAI os linfócitos T CD4+ auto-reativos recrutam células B e células T CD8+ na tireóide. A progressão da doença leva à morte de células da tireóide e hipotireoidismo.Conclusão: O HCV ou o seu tratamento ativa várias vias de sinalização com dano na célula tireoidiana, tendo como resultado TAI e hipotireoidismo secundário a apoptose celular. (AU)

Características sociodemográficas y clínicas, según el índice CD4: CD8, de una población de personas infectadas con el VIH que consultó en la Corporación para Investigaciones Biológicas de Medellín, Colombia / Sociodemographic and clinical characteristics based on their cd4: cd8 ratio. of HIV infected persons who consulted at Corporación para Investigaciones Biológicas of Medellín, Colombia

RESUMEN Objetivo: las personas infectadas con el virus de la inmunodeficiencia humana tipo 1 (VIH-1+) con un índice CD4:CD8 menor a 1, presentan un mayor riesgo de morbilidad y mor-talidad por eventos no asociados con el SIDA. El objetivo de este trabajo fue explorar‚ en la población seleccionada‚ variables sociodemográficas y clínicas de acuerdo con dicho índice, debido a que este es más informativo que LT CD4+ y LT CD8+ por sí solos. Materiales y métodos: estudio observacional en pacientes con VIH-1+ atendidos en la Corporación para Investigaciones Biológicas (CIB). En 227 pacientes se evaluaron diferencias en edad‚ recuento de LT CD4+‚ carga viral‚ número y tipo de esquemas. Se dividieron los pacientes en dos grupos: (A con índice CD4:CD8 ≥ 1 y, B < 1). Resultados: el estudio se compuso de la siguiente forma, 71 % hombres y 29 % mujeres. El 22,5 % pertenecía al grupo A y el 77,5 % al B. La media de la edad fue 42‚8 años en el grupo A y 45 en el B (p = 0‚176). El 100 % de los individuos en el grupo A recibían tratamiento y, 97‚7 % en el B. La media de LT CD4+ fue de 772‚4 para el grupo A y, 448‚1 en el B (p = 0‚00001). En el grupo A el 90‚2 % tenían carga viral indetectable‚ en contraste con el 68‚8 % del B (p = 0‚002). El 41‚2 % en el grupo A tuvieron un solo esquema‚ en relación con el 43,8 % del B (p = 0‚744). Conclusiones: la mayoría de los pacientes presentaron un índice CD4:CD8 < 1 a pesar de haber presentado LT CD4+ aceptables. Fue más frecuente encontrar un índice < 1 en los pacientes sin un adecuado control virológico. Se requieren más estudios para determinar las variables asociadas con su normalización.

SUMMARY Introduction: Human Immunodeficiency Virus type 1 (HIV-1+) patients with a CD4:CD8 ratio < 1 presents a higher risk of morbidity and mortality due to not-associated AIDS events. The aim was to explore, in the selected population, sociodemographic and clinical variables, based on that ratio, because it is more informative than LT CD4+ and LT CD8+ by themselves. Materials and Methods: Observational, in HIV-1 infected patients attended at Biological Research Corporation. In 227 patients, age differences, LT CD4+ count, viral load, number and type of treatments were evaluated. The patients were divided in group A with a CD4:CD8 ratio equal or above to 1, and B bellow 1. Results: The study includes 71% of male and 29% of female. 22,5% were from group A and 77,5% from B. The mean of age was 42,8 years old in A and 45,3 years old in B (p=0,176). 100% of individuals from group A receive treatment, meanwhile 97,7% in B. Mean of LT CD4+ count was 772,4 cell/μL in A and 448,1 cell/μL in B (p=0,00001). In A, 90,2% had undetectable viral load vs 68,8% in B (p=0,002). 41,2% in A had only one type of treatment, vs 43,8% in B (p=0,744). Conclusion: Most of the patients had a CD4:CD8 ratio bellow to 1, despite an acceptable count of LTCD4++. To find a ratio bellow 1 in patients without an adequate virological control was more frequent. More studies to determinate variables associated with its normalization are required.

Nova mutação no gene STAT1 associada com candidíase mucocutânea crônica / New STAT1 gene mutation associated with chronic mucocutaneous candidiasis

Mutações no gene STAT1 (signal transducer and activator of transcription 1) têm sido identificadas como responsáveis pela maioria dos casos sindrômicos da candidíase mucocutânea crônica com herança autossômica dominante (AD). Nesse artigo, descrevemos uma menina de 7 anos que apresentou candidíase da mucosa oral e unhas, além de infecção disseminada da pele e couro cabeludo por Microspora gipseum. Recentemente, a paciente foi diagnosticada e tratada de meningite por Cryptococcus neoformans. Na família não existem outros casos de candidíase. A avaliação imunológica incluiu a detecção de subpopulações de linfócitos (CD3, CD4, CD8, CD20 e células NK), assim como a dosagem de IgG, IgA, IgM e IgE, subclasses de IgG e autoanticorpos. Excluindo-se discreta diminuição de CD3, CD4, CD8, NK e leve aumento de IgG1, os demais exames estiveram dentro da normalidade. O sequenciamento do exoma detectou uma rara mutação em heterozigose no exon 14 do domínio de ligação do DNA (DNA-binding domain) do gene STAT1, ocasionando um provável ganho de função (GOF) responsável pela doença (Gly384Asp). Essa variação foi também identificada pelo sequenciamento de Sanger, não estando reportada nos bancos de dados públicos e apresentando elevado potencial de dano (índice CADD=32). Será interessante contarmos com informações clínicas e estudos com outros pacientes para conhecermos mais essa mutação patológica. Além da apresentação do caso, discutiremos as formas de tratamento existentes.

STAT1 (signal transducer and activator of transcription 1) gene mutations have been identified as responsible for most syndromic cases of chronic mucocutaneous candidiasis with autosomal dominant (AD) inheritance. In this article, we described a 7-year-old girl who presented with candidiasis of the oral mucosa and nails, as well as disseminated infection of the skin and scalp caused by Microsporum gypseum. Recently, the patient was diagnosed and treated for Cryptococcus neoformans meningitis. There are no other cases of candidiasis in the family. The immunological evaluation consisted of detection of subpopulations of lymphocytes (CD3, CD4, CD8, CD20, and NK cells), as well as measurement of IgG, IgA, IgM, and IgE, IgG subclasses, and autoantibodies. Excluding a slight decrease in CD3, CD4, CD8, NK and a minimal increase in IgG1, the others were within normal limits. Exome sequencing detected a rare heterozygous variation in exon 14 of the DNA-binding domain of the STAT1 gene, causing a probable gain of function (GOF) responsible for the disease (Gly384Asp). This variation was also identified by Sanger sequencing, but it was not reported in public databases and had a high potential for damage (Combined Annotation-Dependent Depletion [CADD] score = 32). Having clinical information and conducting studies of other patients will be helpful to learn more about this pathological mutation. In addition to the presentation of the case, we will discuss the existing forms of treatment.

CD4+, CD8+ and FOXP3+ lymphocytes infiltrating oral leukoplakia: an immunohistochemical analysis / Linfócitos CD4+, CD8+ e FOXP3+ que se infiltram na leucoplasia oral: uma análise imunohistoquimica

Objetivo: Avaliar a infiltraçãdo dos linfócitos CD4+ , CD8 + e FOXP3+ e sua correlação com caracteristicas sociodemográfica, clinicopatologicas e estilo de vida de pacientes com leucoplasias bucais. Pacientes e métodos: Oitenta pacientes com diagnóstico de leucoplasia bucal foram incluidos no estudo. Análises retrospectivas foram realizadas para verificar as características sociodemográficos, clinicopatológicos e estilo de vida dos pacientes. O infiltrado linfocitário foi caracterizado por imunoistoquímica com antígenos contra de CD4+ , CD8 + e FOXP3+ . Resultados: Dos 80 pacientes incluidos neste estudo, (60%) eram homens e a idade variou de 25 a 82 anos com idade média de 58,6 anos.Trinta e oito (47.5%) eram idosos, Trinta e dois (40%) eram adultos de meia idade e apenas dez (10%) adultos jovens. Sessenta e um dos pacientes eram fumantes (76.2%) e quarenta e seis eram etilistas (57.5%). Vinte e sete (35.5%) das lesões apresentaram algum grau de displasia epitelial. O grau de displasia epitelial apresentou correlação positiva com a intensidade do consumo do alcool (p=0.008). Houve correlação positiva entre os linfócitos CD4+ e CD8+ (p=0.005). Conclusão: O infiltrado linfocitário não foi relacionado com nenhuma característica clinicopatológica das lecoplasias bucais. Entretanto, o grau de displasia está relacionado ao estilo de vida dos pacientes(AU)

Objective: To evaluate the infiltration of CD4+ , CD8+ and FOXP3+ lymphocytes and their correlation with sociodemographic, clinicopathological and lifestyle characteristics of patients with oral leukoplakia. Patients and methods: Eighty patients diagnosed with oral leukoplakia were included in the study. Retrospective analyses were performed in order to verify the sociodemographic, clinicopathologic and lifestyle characteristics. The lymphocytic infiltrate characterization was performed by immunohistochemistry with antibodies against CD4+, CD8+, and FOXP3+ markers. Results: Of 80 patients included in the study, 60% were men, and their age ranged from 25 to 82 years, with a mean of 58.6. Thirty-eight patients (47.5%) were elderly, Thirty-two (40%) middle-aged, and only ten (10%) young adults. Sixty-one of the patients were smokers (76.2%) and forty-six were alcoholics (57.5%). Twenty-seven (35.5%) of the lesions presented some degree of dysplasia. The degree of epithelial dysplasia was correlated with the intensity of alcohol consumption (p=0.008). A positive correlation was found between CD4+ and CD8+ lymphocytes (p=0.005). Conclusion: The lymphocytic infiltrate of oral leukoplakia was not correlated with any clinicopathologic characteristic. However, the degree of epithelial dysplasia was correlated with the lifestyle of the patients(AU)

Imnuno-Oncología: Recuento Histórico y Fundamentos Básicos / Imnuno-Oncology: Historical Recount and Basic Fundamentals

El sistema inmune cumple un rol fundamental en la defensa contra microorganismos y células anómalas. Históricamente, el concepto de vigilancia inmunológica se fundamenta en el control de múltiples funciones incluyendo la regulación de células cancerígenas a través de diversos mecanismos, en los cuales están involucrados: células, moléculas y tejidos del sistema inmune. El objetivo de analizar la respuesta inmune frente al cáncer, es entender los mecanismos de presentación del antígeno y los mecanismos desencadenados por el sistema adaptativo e innato que participan en la destrucción del tumor a expensas de un proceso inflamatorio agudo que podría llevar al control o destrucción del cáncer. La propuesta de esta revisión es resumir y esquematizar los aspectos cardinales de los diferentes procesos inmunológicos que participan en la fisiopatología de las enfermedades malignas, así como los mecanismos que emplea el sistema inmune para la defensa del cáncer.

The Inmune System plays an essential role in the defense of the organism against microorganisms and alters cells. Historically, the concept of immune surveillance its based in the control of multiple functions including the regulation of cancer cells through diverse mechanisms such as cells, molecules and tissue from the immune system. Therefore, it is important to understand the mechanisms of antigen presentation and other mechanisms of the innate and adaptive system which participate in the defense of the organism against the tumor. This process is enhancing by an inflammatory acute process that could lead to the control or de destruction of the tumor. The purpose of this review is to develop the cardinal aspects of the immunologic process that take part in the defense against malignant diseases, and also to explain its mechanisms.

Alta concomitância de doenças autoimunes em um paciente com síndrome de Down / High concomitance of autoimmune diseases in a patient with Down syndrome

Objetivo: Pacientes com síndrome de Down (SD) apresentam maior prevalência de doenças autoimunes (DAI). No caso apresentado, chama atenção a elevada concomitância de DAI, a apresentação clínica das mesmas e a influência na saúde mental do paciente. Descrição do caso: Relatamos o caso de paciente masculino, 25 anos, cariótipo 47,XY+21, acompanhado pelo ambulatório de SD do HC/UFPR desde o nascimento, que até o presente momento apresentou cinco DAI associadas: vitiligo generalizado, alopecia areata, doença de Hashimoto, doença celíaca e psoríase. Nesse paciente, chama atenção as cinco doenças autoimunes concomitantes e a gravidade das doenças de pele. Foi realizada a fenotipagem da sua população linfocitária, obtendose numericamente: contagem normal de linfócitos T (CD3+) e de linfócitos T (CD8+); e contagem diminuída de linfócitos T (CD4+), células natural killer e linfócitos B. Foi realizada a sua tipagem HLA e observou-se a presença de alelos HLA-DQ2 e HLA-DR3 que, de acordo com a literatura, estão associados com o aparecimento de DAI. Aos 14 anos o paciente começou a apresentar sintomas da síndrome do pânico e episódios de transtorno obsessivo compulsivo. Comentários: A associação de fatores imunológicos e genéticos faz com que pacientes com SD possam ter concomitância de DAI. Profissionais de saúde que atendem pacientes Down devem estar atentos para tais doenças.

Objective: Patients with Down syndrome (DS) show a higher prevalence of autoimmune diseases (AIDs). In the case here described, the high concomitance of AIDs stands out, as does their clinical presentation and influence on the patient's mental health. Case description: We report the case of a male patient aged 25 years, karyotype 47,XY+21, followed from birth at the DS outpatient clinic at Hospital de Clínicas ­ Universidade Federal do Paraná. Up to the present moment, the patient presented five associated AIDs: generalized vitiligo, alopecia areata, Hashimoto's disease, celiac disease and psoriasis. In this patient, attention is drawn to the five concomitant AIDs and the severity of skin diseases. Phenotypic analysis of lymphocyte populations was obtained numerically, resulting in normal counts for T (CD3+) and T (CD8+) lymphocytes, and decreased counts for T lymphocytes (CD4+), natural killer cells and B lymphocytes. HLA typing was performed and the presence of HLA-DQ2 and HLA-DR3 alleles was observed ­according to the literature, these alleles are associated with the development of AIDs. At 14 years of age, the patient started to present symptoms of panic disorder and episodes of obsessive-compulsive disorder. Comments: The association of immunological and genetic factors leads patients with DS to have concomitant AIDs. Healthcare professionals who treat patients with DS should be aware of these diseases.

Proliferación linfoide indolente cutánea CD8 positiva a propósito de tres casos con compromiso facial / Indolent CD8-positive t-cell lymphoid proliferation: on purpose three cases of facial commitment

Resumen La proliferación linfoide indolente cutánea CD8 positiva es una variante recientemente descrita de linfoma T cutáneo que se caracteriza por un nódulo, pápula o placa eritematosa de crecimiento lento que puede afectar la región facial o extrafacial. En el estudio de patología se caracteriza por un infiltrado monomorfo de linfocitosTalo largo de la dermis con presencia de zona de Grenz y ausencia de epidermotropismo. El infiltrado es característicamente CD8+ así como CD3+, TIA-1+, CD4-, CD56- CD30-, PD-1-, Granzima B- y EBER negativo. El índice de proliferación Ki-67 es inferior al 10% y se observan reordenamientos clonales de los genes del receptor de antígeno de la célula T, TCR. El seguimiento clínico es favorable y no se ha observado compromiso sistémico. Se presentan tres casos con compromiso facial (dos casos en pabellón auricular y un caso con compromiso nasal), con presentación clínica y hallaz gos histopatológicos típicos (curiosamente un caso con cambio de célula clara), y además se realizaron estudios de clonalidad.

Abstract Primary cutaneous indolent CD8-positive lymphoid proliferation is a recent variant of cutaneous T lymphoma that is characterized by nodule, papule or plaque erythematous with slow growth that can affect the facial or extrafacial region. In the histopathology study it is characterized by an infiltration of monomorphic T lymphocytes throughout the dermis with presence of Grenz zone and absence of epidermotropism. The infiltrate is characteristically CD 8+ and CD3+ TIA-1+ CD4-, CD56- CD30, PD-1, Granzyme B- and negative EBER. Ki-67 Proliferación linfoide indolente cutánea CD8 positiva a propósito de tres casos proliferation index is less than 10% and clonal T-cell receptor gene rearrangements. Clinical follow-up is favorable and has not been observed systemic involvement. We present three cases with facial involvement (two cases in ear and one case with nasal commitment) with typical clinical presentation, histopathological findings (curiously a case with clear cell change) and clonality studies.

Changes of CD8+CD28- T cell percentage in patients with multiple injuries and their clinical significance / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the correlation of the changes in CD8(+)CD28(-) T cell percentage with platelet (PLT) and D-dimer (D-D) levels in patients with multiple injuries (MI).</p><p><b>METHODS</b>Twenty-six patients with MI, 31 with a single injury (SI group) and 26 healthy individuals were examined for peripheral blood CD8(+)CD28(-) T cells and intracellular transformation growth factor-β1 (TGF-β1) and interleukin 10 (IL-10) contents using flow cytometry at 24, 48, and 72 h after the injuries. PLT and D-dimer levels were compared among the 3 groups.</p><p><b>RESULTS</b>CD8(+)CD28(-) T cells, TGF-β1 and IL-10 were significantly higher in MI group than in SI group and healthy control group (P<0.05) without significant differences between the latter 2 groups. The levels of PLT and D-D differed significantly among the 3 groups, the highest in MI group and the lowest in the control group. In MI group, CD8(+)CD28(-) T cells, TGF-β1 and IL-10 significantly increased at 48 h after the injury (P<0.05) but decreased significantly at 72 h (P<0.05) compared with the measurements at 24 h. The levels of PLT and D-D trended to decrease with time after the injuries and showed significant differences among the 3 groups at any of the 3 time points (P<0.05). CD8(+)CD28(-) T cells, TGF-β1 and IL-10 were all positively correlated with the levels of PLT and D-D in MI patients (r>0.70, P<0.05 for all comparisons).</p><p><b>CONCLUSION</b>In MI patients, CD8(+)CD28(-) T cell percentage and their cytokines tend to increase early after the injury but decrease significantly at 72 h in close relation with the changes of the coagulation function following the injuries.</p>

Analysis of Interleukin 17A in periapical abscess and granuloma lesions

Abstract Interleukin 17A (IL-17A) is a proinflammatory cytokine responsible for the initiation and propagation of inflammation. One of its actions is the recruitment of neutrophils to the site of infection. The aim of this study was to investigate whether there is association between IL-17A expression and neutrophil infiltration in periapical abscesses and periapical granulomas, as well as to find which type of T lymphocyte effector (CD4+ or CD8+) expresses IL-17A in these lesions. Elastase, CD4, CD8, and IL-17A were analyzed by immunohistochemistry and immunofluorescence, in the biopsies of periapical lesions. Abscess lesions exhibited the highest labeling area for IL-17A (p = 0.011). During double immunofluorescence staining, there were significantly more CD4+/IL-17A+ cells compared to CD8+/IL-17A+ cells, both in the abscesses (p = 0.025) and granulomas (p = 0.011). In conclusion, IL-17A was intensively expressed in periapical abscesses rich in neutrophils. The high percentage of IL-17A in these cases suggests the participation of this cytokine particularly in the acute stages of the inflammatory process of the periapical lesions.

Expressão de antígenos MHC classe I e de células CD4 e CD8 na polimiosite e dermatomiosite / MHC class I antigens, CD4 and CD8 expressions in polymyositis and dermatomyositis

Objetivo: Analisar as frequências de expressão dos antígenos de complexo principal de histocompatibilidade classe I (MHC-I) e células CD4 e CD8 no músculo esquelético na polimiosite (PM) e dermatomiosite (DM). Métodos: Estudo retrospectivo de 34 casos de PM, oito casos de DM e 29 controles com miopatias não inflamatórias. Resultados: Os antígenos MHC-I expressaram-se no sarcolema e/ou sarcoplasma em 79,4% dos casos de PM, 62,5% dos casos de DM e 27,6% dos controles (a expressão de CD4 foi observada em 76,5%, 75% e 13,8%, respectivamente). Quando os antígenos de MHC-I foram coexpressados com CD4, houve elevada suspeita de PM/DM (principalmente PM). Em 14,3% dos casos de PM/DM, observou-se a expressão isolada dos antígenos MHC-I, sem células inflamatórias. Conclusão: A expressão dos antígenos MHC-I e a positividade do CD4 podem aumentar a suspeita diagnóstica de PM/DM. Não foi observado infiltrado celular em 14,3% dos casos. .

Objective: To analyze the frequencies of the expression of major histocompatibility complex class I (MHC-I) antigens, and CD4 and CD8 cells in skeletal muscle in polymyositis (PM) and dermatomyositis (DM). Methods: This was a retrospective study of 34 PM cases, 8 DM cases, and 29 control patients with non-inflammatory myopathies. Results: MHC-I antigens were expressed in the sarcolemma and/or sarcoplasm in 79.4% of PM cases, 62.5% of DM cases, and 27.6% of controls (CD4 expression was observed in 76.5%, 75%, and 13.8%, respectively). There was a high suspicion of PM/DM (mainly PM) in participants in whom MHC-I antigens and CD4 were co-expressed. In 14.3% of PM/DM cases, we observed MHC-I antigens expression alone, without inflammatory cells. Conclusion: MHC-I antigens expression and CD4 positivity might add to strong diagnostic suspicion of PM/DM. No cellular infiltration was observed in approximately 14.3% of such cases. .

Hepatopulmonary syndrome-related changes in D-dimer, prothrombin time, fibrinogen, CD4 and CD8 in a rat model system / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To determine the changes in levels of D-dimer, prothrombin time (PT), fibrinogen (Fib), CD4 and CD8 in relation to hepatopulmonary syndrome (HPS) by using a rat model system and to assess the association with pathologic changes in lung.</p><p><b>METHODS</b>Forty male Sprague-Dawley rats were divided into equal groups for modeling of cirrhosis and HPS. The two groups were assessed by blood gas analysis, standard biochemical tests to measure D-dimer, PT, Fib, CD4 and CD8, and pathological examination of lung tissues.</p><p><b>RESULTS</b>The HPS rats showed significantly lower PaO2 than the cirrhosis rats (58.20+/-3.19 mmHg vs. 85.00+/-2.53 mmHg, P = 0.000). The HPS rats showed significantly higher levels of D-dimer, Fib and CD8 than the cirrhosis rats (0.39+/-0.09 mg/ml vs. 0.25+/-0.05 mg/ml, P = 0.000; 1.77+/-0.10 g/L vs. and 1.49+/-0.09 g/L, P = 0.010; 32.32+/-4.45/mm3 vs. 20.13+/-6.09/mm3, P = 0.014). The HPS rats showed significantly lower levels of PT, CD4 and CD4/CD8 than the cirrhosis rats (14.86+/-1.04 s vs. 16.23+/-0.75 s, P = 0.036; 20.45+/-3.86/mm3 vs. 26.75+/-5.32/mm3, P = 0.000; 0.64+/-0.09 vs. 1.32+/-0.13, P = 0.000). The lung tissues of the HPS rats showed microthrombosis in pulmonary vessels, which were not observed in lung tissues of the cirrhosis rats.</p><p><b>CONCLUSION</b>HPS-related differential levels of D-dimer, PT, Fib, CD4, CD8 and CD4/CD8 may represent a biomarker profile suggestive of incidence of thromboembolism in lung.</p>

Immunophenotyping of bone marrow biopsies in 26 patients with non-hodgkin's lymphoma, using anti-CD3, CD8, CD19 and CD20 monoclonal antibodies

Immunophenotyping with monoclonal antibodies [MoAbs] directed against lymphoid-associated antigens, immunohistochemical staining on paraffin-embedded BM biopsy material, and molecular studies of Ig genes/T-cell receptor genes or lymphoma-associated gene translocations should be used in the global approach to the patient with malignant lymphoma. 1. To determine the subtypes of non-Hodgkin lymphomas [B- or T-cell] in the bone marrow using anti-CD3, CD8 monoclonal antibodies for T-cell and anti-CD19 and CD20 for B-cells. 2. Correlation of the subtypes of NHL [B- or T-cell] with the morphology and pattern of bone marrow infiltration. A retrospective study, done in Al-Kadhymia teaching hospital during the period from 1/10/2010 to1/2/2011.The study consisted 26 adult patients, who were diagnosed as Non-Hodgkin lymphomas by undergoing a BM biopsy. Immunohistochemical staining of the paraffin-embedded sections of BM trephine biopsies was performed in all cases and used standard techniques with monoclonal anti-CD8, CD20 and dual immunofluorscence-labelled CD3, and CD19 antibodies and also all stained with Hematoxylin and Eosin [H and E] for morphologic assessment. The 26 cases of NHL comprised of 14 male [54%] and 12 female patients [46%]. The median age was [57.32] year ranged from 27-85 years. There were 23 cases of B-cell cases [88.5%] and 3 cases of T-cell lineage [11.5%] of all the cases. Among all the B-cell lymphomas, 15 cases showed interstitial infiltration in the bone marrow, while among the T-cell lymphoma two cases showed diffuse infiltration. 1. In these 26 cases NHL patients with marrow involvement, B cell phenotype comprised 88% of cases. 2. B-cell NHLs had predominance of interstitial infiltration in bone marrow biopsies in comparison with the T-cell lymphoma, in which diffuse infiltration was predominant

Histological and immunohistochemical assessment of the immunological aspect of certain cells in human palatine tonsils

Tonsils contain four specialized lymphoid compartments that together are involved in immune functions. The capacity of tonsillar lymphocytes to counter infections may be altered during one's lifetime. The classification of lymphocytes by CD antigen expression is now widely used in clinical medicine and experimental immunology. The present work was designed to study the distribution of CD4 and CD8 antigen expression in T lymphocytes in human tonsils at different periods of life. Sixty-two tonsillar specimens were obtained from still birth infants and from children aged 1-9 years. Paraffin sections were prepared and stained with H and E and with immunohistochemical stains to demonstrate CD4 and CD8 T lymphocytes. The distribution of these cells in the different components of the tonsils was evaluated with an image analyzer. The obtained data were statistically analyzed using SPSS. There was a significant increase in the distribution of stained CD4 and CD8 T lymphocytes in the interfollicular areas, mantle zones of lymphoid follicles, and partially in the germinal centers of the examined tonsils with the advancement of age. Activated T lymphocytes differentiate into several subtypes, among which are CD4 and CD8 cells. These types of T lymphocytes express surface antigens, which can interact with different foreign pathogens

Immunophenotyping related to cluster of differentiation [CD] markers in patients with atopic dermatitis

Determination of concentrations of cluster of differentiation [CD] markers in patients with atopic dermatitis and comparison with healthy individuals were carried out in this study. It was found that the mean concentrations of positive lymphocytes for AD patients reached 82.2%, 55.7%, 28.7%, and 21.9% for CD3, CD4, Cd8, and GD19, respectively, and those of healthy individuals reached 72.2, 40.3, 18.5, and 13.1 for CD3, CD4, Cd8, and CD19 respectively. We found that the mean values of CDs for AD patients high than those of healthy individuals [69.7%, 75.9%, 94.4% and 68.5%] [P<0.05]

re high than those of healthy individuals [65.7%, 75.9%, 94.4% and 68.5%] [P<0.05]

Type II enteropathy-associated T-cell lymphoma: a clinicopathologic study / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunohistochemical findings, differential diagnosis and prognosis of type II enteropathy-associated T-cell lymphoma (EATL).</p><p><b>METHODS</b>Fourteen cases of type II EATL encountered in Department of Pathology, Nanjing General Hospital were retrospectively reviewed. The clinical data, histologic features, immunohistochemical findings and follow-up information were analyzed, with literature review.</p><p><b>RESULTS</b>There were altogether 12 males and 2 females. The median age of patient was 49 years. The sites of involvement included jejunum (10 cases) and ileum/colon (4 cases). The patients often presented with an abdominal mass, abdominal pain, diarrhea and constitutional symptoms such as fever, night sweating and cachexia. There was no clinical evidence of gluten-sensitive enteropathy. Histologically, the lymphoma cells showed full-thickness infiltration of the intestinal wall. They contained round hyperchromatic nuclei and pale cytoplasm. The stroma was minimally inflamed, with or without associated coagulative necrosis. A remarkable finding was the presence of villous atrophy, cryptal hyperplasia and intraepithelial lymphocytosis. Immunohistochemical study showed that the tumor cells expressed CD3, CD43 and CD8 (14/14). Some of them were also positive for CD56 (11/14) and CD30 (2/14). The staining for CD4, CD20, CD79a and myeloperoxidase was negative. A high proliferation index was demonstrated by Ki-67 immunostain. In-situ hybridization for EBER was negative. Follow-up data were available in 9 cases. The duration of follow-up ranged from 6 months to 36 months. Seven patients died within 14 months.</p><p><b>CONCLUSIONS</b>EATL is a rare type of lymphoma with intestinal involvement. Associated enteropathy is not demonstrated, in contrast to cases encountered in Nordic countries. A correct diagnosis requires evaluation of clinical manifestations, pathologic features and ancillary study results.</p>

Expression of PD-1/PD-L1 in peripheral blood mononuclear cells in lung cancer patients and its biological significance / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the expression of co-stimulatory molecules PD-1/PD-L1 in peripheral blood mononuclear cells in lung cancer patients, and to explore its biological significance.</p><p><b>METHODS</b>One hundred and thirty-three lung cancer patients, 25 lung infection patients and 23 healthy donors were enrolled in this study. 100 µl of whole blood from these subjects were collected. Multi-color immunofluorescence staining and flow cytometry were used to detect PD-1/PD-L1 expression. The results were statistically analyzed.</p><p><b>RESULTS</b>The expression level of CD3⁺CD8⁺ T cells in the lung cancer patients was (38.83 ± 1.74)%, significantly lower than that in the control group [(43.25 ± 3.35)%, P < 0.05]. CD8⁺CD28⁺ T cell subset in the peripheral blood of lung cancer patients was (17.73 ± 1.21)% significantly lower than that of the healthy donors [(27.96 ± 2.72)%, P < 0.01]. The CD8⁺CD28⁻ T cell subset was (21.19 ± 1.92)% in the lung cancer patients, significantly higher than that of the healthy control group [(15.18 ± 2.93)%, P < 0.05]. The expression level of PD-1 on the surface of CD8⁺CD28⁺ T cells was (10.67 ± 1.12)% in the group of lung cancer patients, significantly higher than that of the control group [(5.32 ± 1.58)%, P < 0.01]. It was also found that the expression of PD-1 on CD8⁺CD28⁻ T cells was up-regulated in the group of lung cancer patients (7.46 ± 1.25)%, significantly higher than that of the healthy control group [(2.68+1.07)%, P < 0.01]. The expression level of PD-L1 on CD68⁺ cells in the lung cancer patients was (16.03 ± 2.06)%, significantly higher than that of the healthy control group [(9.32 ± 2.00)%, P < 0.05].</p><p><b>CONCLUSION</b>Up-regulation of PD-1/PD-L1 on peripheral blood cells in lung cancer patients negatively regulates the lymphocytes, inhibits the immune response for killing tumor cells, and promotes tumor development and immune escape.</p>

Antiviral effect of dietary germanium biotite supplementation in pigs experimentally infected with porcine reproductive and respiratory syndrome virus

Germanium biotite (GB) is an aluminosilicate mineral containing 36 ppm germanium. The present study was conducted to better understand the effects of GB on immune responses in a mouse model, and to demonstrate the clearance effects of this mineral against Porcine reproductive and respiratory syndrome virus (PRRSV) in experimentally infected pigs as an initial step towards the development of a feed supplement that would promote immune activity and help prevent diseases. In the mouse model, dietary supplementation with GB enhanced concanavalin A (ConA)-induced lymphocyte proliferation and increased the percentage of CD3+CD8+ T lymphocytes. In pigs experimentally infected with PRRSV, viral titers in lungs and lymphoid tissues from the GB-fed group were significantly decreased compared to those of the control group 12 days post-infection. Corresponding histopathological analyses demonstrated that GB-fed pigs displayed less severe pathological changes associated with PRRSV infection compared to the control group, indicating that GB promotes PRRSV clearance. These antiviral effects in pigs may be related to the ability of GB to increase CD3+CD8+ T lymphocyte production observed in the mice. Hence, this mineral may be an effective feed supplement for increasing immune activity and preventing disease.

Hematopathologic features of T-cell large granular lymphocytic leukemia / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the hematopathologic features of T-cell large granular lymphocytic leukemia (T-LGLL).</p><p><b>METHODS</b>A retrospective analysis of the clinical presentation, bone marrow morphology, immunophenotyping and T-cell receptor gene rearrangement status were performed in 19 patients with T-LGLL.</p><p><b>RESULTS</b>Of 19 patients, the most frequent hematological abnormalities were anemia and neutropenia (16/19 and 17/19 patients, respectively). Large granular lymphocytes (LGLs) were observed in 17 of 19 peripheral blood smears and 15 of 19 bone marrow aspirate specimens. Lymphocytosis (> 0.2) was present in 17 of 19 patients in their bone marrow aspirate specimens. Bone marrow biopsy specimens revealed lymphocytosis in 16 cases, with a mild to moderate increase of lymphocytes observed in 12 cases (12/16). The pattern of lymphoid distribution was interstitial in bone marrow sections. Intravascular distribution was seen in 8 cases. Lymphoid nodules were present in 4 cases. Flow cytometery showed an immunophenotype of CD3(+) CD4(-) CD8(+) CD56(-) CD57(+) of the tumor cells in 13 cases. Of the other 6 cases, the immunophenotypes included CD8(-) (1 case), CD56(+) (2 cases) and CD57(-) (3 cases). Immunohistochemistry showed CD3+ (10/10), CD57+ (3/3), CD8+ (6/7), TIA-1+ (6/7), granzyme B+ (4/7), perforin + (1/7), CD4- (4/4) and CD56- (9/9). Clonal T-cell receptor γ gene rearrangement by PCR was detected in 12 cases (12/17).</p><p><b>CONCLUSIONS</b>Hematopathologic features of most T-LGLL are distinct. Morphologic, immunophenotypic and molecular analysis of both peripheral blood and bone marrow specimens are essential and complementary in the diagnosis and differential diagnosis of T-LGLL.</p>