Identification of hepatitis B virus genotypes detected in Lahaul & Spiti district of Himachal Pradesh, India

Background & objectives: Infection by hepatitis B virus (HBV) results in acute or chronic hepatitis. Based on sequence differences of eight per cent or more, HBV is divided into 10 genotypes (A to J) and 35 sub-genotypes. Molecular characterization of the circulating HBV genome has helped in understanding the epidemiology and its clinical importance. Spiti valley in Himachal Pradesh, which shares its border with Tibet, is one of the most HBV prevalent areas in India. Since information about the circulating genotype/s of HBV in this area is limited, this study was conducted to identify the circulating HBV genotypes. Methods: The surface and partial reverse transcriptase gene regions were sequenced using 14 hepatitis B surface antigen-positive samples. Results: Out of the 14 hepatitis B surface antigen-positive samples 11 sample gave quality sequence for further analysis. All the 11 samples belonged to subtype ayw2. The phylogenetic and recombination analysis revealed that five out of 11 samples were of genotype CD1 and the rest six were of genotype D3. Interpretation & conclusions: The CD1 recombinant sub-genotype might have immigrated during past or present transcontinental migration between the adjacent countries. Further studies using full-genome sequencing and high sample size will be helpful to understand this epidemiology and to combat the high prevalence of HBV in the area.

Decreased CD1a + and CD83 + cells in tonsillar squamous cell carcinoma regardless of HPV status

Abstract Dendritic cells (DCs) are specialized antigen-presenting cells that play a critical role in the immune response against human papillomavirus (HPV) infection, and represent a therapeutic target in cancer. Objective: To identify and quantify DCs in tonsillar squamous cell carcinoma (TSCC) under the influence of HPV infection. Methodology: CD1a and CD83 antibodies were used to identify immature dendritic cells and mature dendritic cells by immunohistochemistry in 33 primary TSCC and 10 normal tonsils (NTs), respectively. For the TSCC samples, the number of DCs per area was evaluated in the intra- and peritumoral compartments. For the NTs, the quantification of DCs was evaluated in the intra- and peritonsillar compartments. HPV detection methods were determined according to the ASCO Clinical Practice Guidelines from the College of American Pathologists Guideline (2018). Results: There were fewer intratumoral CD1a+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.05). In the peritumoral compartment, there were fewer CD83+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.001). The quantification of DCs subtypes showed no statistical differences between HPV-positive and HPV-negative TSCC groups (p>0.137). Patients with HPV-positive TSCC had significantly better overall survival rate than those with HPV-negative TSCC (p=0.004). Conclusion: Tumor activity contributes to DC depletion regardless of intralesional HPV positivity. An improved prognosis has been reported in patients with HPV-positive TSCC.

Effects of prenatal tobacco smoke on cerebellum histomorphological changes at critical developmental stages in CD-1 mice / Efectos del humo de tabaco en los cambios histomorfológicos del cerebelo en las etapas críticas del desarrollo prenatal en ratones CD-1

SUMMARY: In this study the consequences of prenatal exposure to tobacco smokes on the histo-morphological changes of cerebellum was assessed by comparing the smoker mice to the nonsmoker mice. A total of 30 pregnant cd-1 mice were divided into three groups of 10 mice each and with two replicates per group (5 mice each). Following acclimation for five days, the mice were placed in a special modified smoking machine for 2 hours per day over a two- and three-week period for group two and group three, respectively. Group one was considered as a control group. Mice in the control group were exposed simultaneously to fresh air from the room, while those in the treatment groups were exposed to tobacco smoke from six commercial filter cigarettes, containing 0.8 mg of nicotine, 10 mg of tar, and 10 mg of carbon monoxide, for three 1-hour exposure periods every day for three weeks. The mice in the control group were exposed to room air for three 1-hour periods every day for the same period of three weeks. The results from this study showed a correlation between maternal smoking and histological changes in Neuron purkinjense (Purkinje cells) of the cerebellum. They also showed that prenatal smoking period may have caused more damage in the histology and structure of Neuron purkinjense in some juvenile mice. An increased incidence of morphology damage of the cerebellum's Neuron purkinjense' structures was also observed in fetuses with prolonged exposure to tobacco smoking. Exposure of in utero maternal smoking may interfere with brain biological development parameters, giving rise to structural abnormalities of the cerebellum. This study concluded that tobacco smoke exposure to pregnant mice may affect neurodevelopment which may induce behavioural changes as a result of reduced cerebellar size and function.

RESUMEN: Se evaluaron los efectos producidos por la exposición prenatal al humo de tabaco en ratones expuestos y no expuestos y los cambios histomorfológicos observados en el cerebelo en ambos grupos. Un total de 30 ratones cd-1 preñados se dividieron en tres grupos de 10 ratones cada uno y con dos réplicas por grupo (5 ratones cada uno). Después de la aclimatación durante cinco días, los ratones se colocaron en una máquina de fumar modificada, especial durante 2 horas al día, durante un período de dos y tres semanas para el grupo dos y el grupo tres, respectivamente. El grupo uno se consideró como grupo control. Los ratones del grupo de control fueron expuestos simultáneamente al aire limpio de la habitación, mientras que los grupos de tratamiento fueron expuestos al humo de tabaco de seis cigarrillos comerciales, que contenían 0,8 mg de nicotina, 10 mg de alquitrán y 10 mg de monóxido de carbono. durante tres períodos de 1 hora diariamente, durante tres semanas. Los ratones del grupo de control se expusieron al aire ambiente durante tres períodos de 1 hora todos los días durante el mismo período de tres semanas. Los resultados de este estudio mostraron una correlación entre el tabaquismo materno y los cambios histológicos en las neuronas purkinjenses (células de Purkinje). Se observó además que el período de tabaquismo prenatal puede haber causado mayor daño en la histología y estructura de las neuronas purkinjenses en algunos ratones jóvenes. También se observó una mayor incidencia de daño morfológico de las estructuras de las neuronas purkinjenses del cerebelo en fetos con exposición prolongada al tabaquismo. La exposición al tabaquismo materno en el útero puede interferir con los parámetros de desarrollo biológico del cerebro, dando lugar a anomalías estructurales del cerebelo. Este estudio concluyó que la exposición al humo del tabaco en ratones preñados puede afectar el desarrollo neurológico, lo que puede inducir cambios de comportamiento como resultado de la reducción del tamaño y la función del cerebelo.

Análise de células dendríticas, mastócitos e vascularização na doença periodontal biofilme induzida em idosos / Analysis of dendritic cells, mast cells and vasculature in biofilm-induced periodontal disease in the elderly

A microbiota e o sistema imune do idoso apresentam algumas alterações, favorecendo ao aparecimento de infecções e doenças inflamatórias. A doença periodontal é um exemplo, permeando entre fase imediata e tardia, pode ter alterações em sua evolução com o envelhecimento humano. Compreender a doença periodontal e sua relação com o ciclo da vida é importante para a prevenção, tratamento e cura. Este estudo tem como objetivo avaliar a quantidade de mastócitos (triptase), células dendríticas imaturas (CD1a), células dendríticas maduras (CD83) e vasos sanguíneos (CD34) em 154 tecidos periodontais saudáveis e doentes (27 idosos e 127 adultos). Foi utilizada a técnica de imunoistoquímica através da imunomarcação do CD1a, CD83, triptase e CD34, sendo contabilizados em 5 campos de maior número de células positivas, no aumento de 1000x. Para o CD34, ainda foram calculadas a área e o perímetro microvascular para todos os vasos sanguíneos presentes, e dos vasos com presença do endotélio vascular alto. Não houve diferença na imunomarcação das células dendríticas, dos mastócitos e na quantidade de vasos sanguíneos nos tecidos gengivais, entre os casos de gengiva clinicamente saudável, gengivite induzida por biofilme e periodontite estágios II, III e IV, avaliando isoladamente os grupos etários: adultos e idosos. As células dendríticas imaturas são mais numerosas no idoso com o quadro clínico de gengivite e periodontite. Os adultos com gengivite induzida por biofilme possuem maior quantidade de vasos sanguíneos que o grupo idoso. A área microvascular e o perímetro microvascular dos vasos sanguíneos com o endotélio vascular alto apresentaram maiores nos idosos nos casos de gengivite. Este estudo concluiu que nesta amostra não houve diferença na quantidade de células dendríticas imaturas e maduras, mastócitos na doença periodontal dentro dos grupos etário, porém as células dendríticas imaturas estão mais presentes no idoso podendo estar relacionado a algum decréscimo funcional. Em relação aos vasos sanguíneos, há presença de HEVs em adultos e idosos, não havendo diferença entre os diagnósticos. Nos idosos com gengivite há um aumento da área microvascular e perímetro microvascular, necessitando de estudos que justifiquem esta diferença (AU).

The elderly's microbiota and immune system show some changes, favoring the onset of infections and inflammatory diseases. Periodontal disease is an example, permeating between immediate and adaptative stages, it can have changes in its evolution with human aging. Understanding periodontal disease and its relationship with the life cycle is important for prevention, treatment and cure. This study aims to assess the amount of mast cells (tryptase), immature dendritic cells (CD1a), mature dendritic cells (CD83) and blood vessels (CD34) in 154 healthy and sick periodontal tissues (27 elderly and 127 adults). The immunohistochemistry technique was used through the immunostaining of CD1a, CD83, tryptase and CD34, being counted in 5 fields with a greater number of positive cells, in the 1000x increase. For CD34, the microvascular area and perimeter were also calculated for all blood vessels present, and for vessels with the presence of high vascular endothelium. There was no difference in the immunostaining of dendritic cells, mast cells and the amount of blood vessels in the gingival tissues, between cases of clinically healthy gingiva, biofilm-induced gingivitis and stages II, III and IV periodontitis, evaluating the age groups: adults and elderly. Immature dendritic cells are more numerous in the elderly with the clinical picture of gingivitis and periodontitis. Adults with biofilm-induced gingivitis have a greater amount of blood vessels than the elderly group. The microvascular area and the microvascular perimeter of the blood vessels with the high vascular endothelium were larger in the elderly in cases of gingivitis. This study concluded that in this sample there was no difference in the amount of immature and mature dendritic cells, mast cells in periodontal disease within the age groups, however, immature dendritic cells are more present in the elderly and may be related to some functional decrease. Regarding blood vessels, there are HEVs in adults and the elderly, with no difference between diagnoses. In the elderly with gingivitis there is an increase in the microvascular area and microvascular perimeter, requiring studies that justify this difference (AU).

Erdheim-Chester disease with multisystemic involvement: a diagnostic challenge

Erdheim–Chester disease (ECD) is a rare, non-inherited, non- Langerhans form of histiocytosis of unknown origin, first described in 1930. This entity is defined by a mononuclear infiltrate consisting of lipid laden, foamy histiocytes that stain positively for CD68. Individuals affected by this disease are typically adults between their 4th and 6th decades of life. The multi systemic form of ECD is associated with significant morbidity, which may arise due to histiocytic infiltration of critical organ systems. Among the more common sites of involvement are the skeleton, central nervous system, cardiovascular system, lungs, kidneys (retroperitoneum) and skin. The most common presenting symptom of ECD is bone pain. Bilateral symmetric increased tracer uptake on 99mTc bone scintigraphy affecting the periarticular regions of the long bones is highly suggestive of ECD. However, definite diagnosis of ECD is established only once CD68(+), CD1a(−) histiocytes are identified within a biopsy specimen with aid of clinical and radiological data. Here we present a rare case of Erdheim-Chester disease in a 46 year male patient based on clinical data, radiological data, histopathological and immunohistochemistry findings.

CD24⁺ Cell Depletion Permits Effective Enrichment of Thymic iNKT Cells While Preserving Their Subset Composition

Invariant NKT (iNKT) cells are a small subset of thymus-generated T cells that produce cytokines to control both innate and adaptive immunity. Because of their very low frequency in the thymus, in-depth characterization of iNKT cells can be facilitated by their enrichment from total thymocytes. Magnetic-activated cell sorting (MACS) of glycolipid antigen-loaded CD1d-tetramer-binding cells is a commonly used method to enrich iNKT cells. Surprisingly, we found that this procedure also dramatically altered the subset composition of enriched iNKT cells. As such, NKT2 lineage cells that express large amounts of the transcription factor promyelocytic leukemia zinc finger were markedly over-represented, while NKT1 lineage cells expressing the transcription factor T-bet were significantly reduced. To overcome this limitation, here, we tested magnetic-activated depletion of CD24⁺ immature thymocytes as an alternative method to enrich iNKT cells. We found that the overall recovery in iNKT cell numbers did not differ between these 2 methods. However, enrichment by CD24⁺ cell depletion preserved the subset composition of iNKT cells in the thymus, and thus permitted accurate and reproducible analysis of thymic iNKT cells in further detail.

Langerhans' cell histiocytosis diagnosed due to dermatological perianal lesion / Histiocitose de células de Langerhans diagnosticada por lesão perianal dermatológica

Abstract Langerhans' cell histiocytosis is a rare disease characterized by proliferation of Langerhans cells in the body. It affects mainly males, predominantly in childhood. Ulcerated plaques are one of the cutaneous forms of presentation. Diagnostic confirmation is done through immunohistochemistry. As therapeutic options, topical corticosteroids and chemotherapy are good choices. The case is reported of a male patient, aged 14, with perianal ulceration. He consulted a coloproctologist, who performed a biopsy of the region and started local triamcinolone applications. Immunohistochemistry diagnosed Langerhans' cells histiocytosis. Further investigation revealed diabetes insipidus, osteolytic lesions in the skull and lower limbs, enlarged liver, and encephalic alterations. Chemotherapy was started with Vinblastine, with significant improvement of the lesions.

Resumo A histiocitose de células de Langerhans é uma doença rara caracterizada pela proliferação de células de Langerhans no corpo. A doença afeta principalmente os homens, predominantemente na infância. Placas ulceradas são uma das formas cutâneas de apresentação. A confirmação diagnóstica é feita através de análise imuno-histoquímica. Como opções terapêuticas, corticosteroides tópicos e quimioterapia são boas escolhas. O caso aqui relatado é de um paciente do sexo masculino, com idade de 14 anos, com ulceração perianal. Ele consultou um coloproctologista, que realizou uma biópsia da região e iniciou o tratamento com aplicações locais de triancinolona. A análise imunohistoquímica diagnosticou histiocitose de células de Langerhans. Outros exames revelaram diabetes insipidus, lesões osteolíticas no crânio e nos membros inferiores, aumento do fígado e alterações encefálicas. A quimioterapia foi iniciada com vimblastina, com melhora significativa das lesões.

Homozygosity for the CD1E*02 allele is associated with a resistance to Plasmodium falciparum malaria infection in Gabonese school children

OBJECTIVE@#To explore the possible association between polymorphisms in CD1 genes and both asymptomatic and mild Plasmodium falciparum infection.@*METHODS@#Two clusters of 85 school children, from the village of Dienga (Gabon) were investigated. The first group was analysed for the prevalence and the multiplicity of asymptomatic P. falciparum infection, whereas the second group was screened for the frequency of malarial attacks.@*RESULTS@#Our findings showed that homozygosity for the CD1E*02 allele was associated with a low frequency of malarial attacks. Furthermore, a strong association between CD1E*02 homozygotes and the resistance to multiple malarial attacks was identified. The CD1A*01 allele showed a weak association with a small number of malarial attacks.@*CONCLUSION@#Our results suggest a possible role of CD1E polymorphisms in malaria protection among school children and that CD1e molecules are involved in anti-malarial immunity.

Isolated Pulmonary Langerhans Cell Histiocytosis in an Infant Diagnosed by CD1a Immunostaining of Bronchoalveolar Lavage Cells: A Case Report and Literature Review / 임상소아혈액종양

Isolated pulmonary Langerhans cell histiocytosis (LCH) is a very rare disease in childhood. We report a case of a 5-month-old girl with isolated pulmonary LCH, who was transferred due to incidental chest x-ray finding of multiple cystic lesions without any clinical symptoms. Chest computed tomography (CT) finding suggested that pulmonary LCH was likely, but evaluations including lung biopsy were negative. At a follow-up visit three months later, we performed bronchoalveolar lavage (BAL) fluid analysis and confirmed the presence of CD1a-positive cells, thereby confirming diagnosis of pulmonary LCH. After completing eight months of chemotherapy, yearly follow-up evaluations were performed and there has been no evidence of reactivation of the disease for four years. Based on our case, we suggest that BAL with immunohistochemical staining can be a valuable modality to eliminate the possibility of infection and other infiltrating disorders, and diagnose pulmonary LCH in case of suspicious pulmonary lesions.

Homozygosity for the CD1E*02 allele is associated with a resistance to Plasmodium falciparum malaria infection in Gabonese school children

Objective To explore the possible association between polymorphisms in CD1 genes and both asymptomatic and mild Plasmodium falciparum infection. Methods Two clusters of 85 school children, from the village of Dienga (Gabon) were investigated. The first group was analysed for the prevalence and the multiplicity of asymptomatic P. falciparum infection, whereas the second group was screened for the frequency of malarial attacks. Results Our findings showed that homozygosity for the CD1E*02 allele was associated with a low frequency of malarial attacks. Furthermore, a strong association between CD1E*02 homozygotes and the resistance to multiple malarial attacks was identified. The CD1A*01 allele showed a weak association with a small number of malarial attacks. Conclusion Our results suggest a possible role of CD1E polymorphisms in malaria protection among school children and that CD1e molecules are involved in anti-malarial immunity.

Histiocitose de células de Langerhans: relato de um caso / Langerhans cell histiocytosis: case report

A histiocitose de células de Langerhans corresponde a um grupo heterogêneo de desordens caracterizadas pela proliferação monoclonal de células dendríticas. Predomina na infância e pode afetar qualquer órgão. Relata-se caso de paciente, sexo feminino, 44 anos, apresentando placas espessas, exsudativas, com escamas aderentes aos pelos, localizadas no couro cabeludo, semelhantes a dermatite seborreica, além de fístulas nas axilas, regiões inframamárias e inguinais de evolução há 16 anos. Realizou-se biópsia da lesão cutânea seguida de imunohistoquímica que concluiu diagnóstico de Histiocitose de células de Langerhans. Investigação sistêmica evidenciou acometimento pulmonar concomitante. Até o presente momento existem poucas publicações sobre envolvimento cutâneo em adultos, assim como não há protocolos de tratamento para os mesmos, necessitando maiores estudos para melhor manejo desses pacientes.

Langerhans cell histiocytosis corresponds a heterogeneous group of disorders characterized by monoclonal dendritic cells proliferation, it predominates in childhood which may affect any organ of the body. The case reports of a female patient, aged 44, presenting thick plates with scales adhering to the hairs, scalp located, similar to seborrheic dermatitis, besides fistulas in axillas, inguinal and infra mammary regions. The hypothesis of Langerhans cell histiocytosis was confirmed by cutaneous biopsy and immunohistochemistry. Systemical investigation accused pulmonary involvement. Until now are few publications about adult cutaneous cases, so none treatment protocols are avaible for them. More specific studies are demanded for better management of these patients.

Isolated Pulmonary Langerhans Cell Histiocytosis in an Infant Diagnosed by CD1a Immunostaining of Bronchoalveolar Lavage Cells: A Case Report and Literature Review / 임상소아혈액종양

Isolated pulmonary Langerhans cell histiocytosis (LCH) is a very rare disease in childhood. We report a case of a 5-month-old girl with isolated pulmonary LCH, who was transferred due to incidental chest x-ray finding of multiple cystic lesions without any clinical symptoms. Chest computed tomography (CT) finding suggested that pulmonary LCH was likely, but evaluations including lung biopsy were negative. At a follow-up visit three months later, we performed bronchoalveolar lavage (BAL) fluid analysis and confirmed the presence of CD1a-positive cells, thereby confirming diagnosis of pulmonary LCH. After completing eight months of chemotherapy, yearly follow-up evaluations were performed and there has been no evidence of reactivation of the disease for four years. Based on our case, we suggest that BAL with immunohistochemical staining can be a valuable modality to eliminate the possibility of infection and other infiltrating disorders, and diagnose pulmonary LCH in case of suspicious pulmonary lesions.

Mecanismos de activación de las células T asesinas naturales invariantes (iNKT) / Mecanismos de ativação das células T assassinas naturais invariantes (iNKT) / Activation mechanisms of invariant natural killer T cells (iNKTs)

Aunque se ha logrado un conocimiento amplio acerca de las células T asesinas naturales (iNKT), aún no existe consenso sobre sus mecanismos de activación. Dichas células reconocen diferentes antígenos glicolipídicos presentados por medio de la molécula CD1d, los cuales pueden ser endógenos, exógenos derivados de organismos como bacterias y sintéticos desarrollados para aplicaciones clínicas. Existe mucho interés en entender cómo estas distintas variantes glicolipídicas inducen diferentes tipos de polarización, pero ha sido muy difícil llegar a un consenso, debido a que la respuesta depende de varios factores como la naturaleza, la internalización y el procesamiento de los glicolípidos. Además, la activación de las células iNKT la determinan el tipo y estado de activación de la célula presentadora de antígeno, las moléculas coestimuladoras, los mecanismos de transactivación y la localización de los complejos CD1d-glicolípido en distintas microrregiones de la membrana plasmática, como las balsas lipídicas. Esta revisión explora la evidencia sobre los factores que afectan la activación de las células iNKT con el fin de entender su potencial inmunomodulador.

A great amount of knowledge on natural killer T cells (iNKTs) is now available, but a consensus about their activation mechanisms has not been reached. These cells recognize different glycolipid antigens through the CD1d molecule. Such antigens may be endogenous, derived from bacteria (foreign) and synthetic, the latter have been developed for clinical applications. There exists much interest in understanding how these different glycolipid compounds induce different types of polarization, but it has been difficult to reach a consensus due to the fact that responses depend on different factors such as: the nature of the molecule, the internalization process and the presentation of the glycolipids. Moreover, activation of iNKT cells is determined by the type and state of the antigen presenting cell, the co-stimulatory molecules, the transactivation mechanisms and the location of the glycolipid-CD1d complexes on the plasma membrane, such as the lipid rafts. This review explores the evidence about the factors that affect activation of iNKT cells in order to understand their immune-modulatory potential.

Ainda que se conseguiu um conhecimento amplo a respeito das células T assassinas naturais (iNKT), ainda não existe consenso sobre seus mecanismos de ativação. Ditas células reconhecem diferentes antígenos glicolipídicos apresentados por meio da molécula CD1d, os quais pode ser: endógenos, exógenos derivados de organismos como bactérias e sintéticos desenvolvidos para aplicações clínicas. Existe muito interesse em entender como estas diferentes variantes glicolipídicas induzem diferentes tipos de polarização, mas foi muito difícil chegar a um consenso, devido a que a resposta depende de vários fatores como a natureza, a internalização e o processamento dos glicolípidos. Ademais, a ativação das células iNKT a determinam o tipo e estado de ativação da célula apresentadora de antígeno, as moléculas co-estimuladoras, os mecanismos de transativação e a localização dos complexos CD1d-glicolípido em diferentes microrregiões da membrana plasmática, como as balsas lipídicas. Esta revisão explora a evidência sobre os fatores que afetam a ativação das células iNKT com o fim de entender seu potencial imunomodulador.

Study on the endometrial dendritic cells populations during the normal menstrual cycle / 重庆医学

Objective To investigate the number and distribution of dendritic cells in normal endometrium of reproductive age during the normal menstrual cycle .Methods Normal endometrial samples were collected from 40 women of reproductive age . 20 endometrium samples at the proliferative phase (day 6th to 10th) and 20 endometrium samples at the window of implantation(day 20th to 24th) were obtained .These patients underwent intrauterine exploration before IVF and ET resulting from tubal resec-tion or male factor infertility .Endometrial tissue was collected with a pipelle aspirator .Sections were stained with hematoxylin-eosin (HE) to identify the morphological characteristics of endometrial tissues .The Envision two-step immunohistochemical staining technique was used to detect the expression of CD1a and CD83 in the endometrium .Normal human skin and tonsil were used as pos-itive control tissues for CD1a and CD83 ,respectively .The serum levels of ovarian steroid hormones were measured to analyze their relationship with the expression of CD1a and CD83 .Results CD1a + DCs were found in all samples of window of implantationand most samples of the proliferative phase (18/20 ,90% ) .DCs showed irregular shape with different processes and were buffy in cell membrane ,mainly in stroma around grand and blood vessels .The density of CD1a + DCs at the window of implantation were (18 .2 ± 5 .76)cells/mm2 ,significantly higher than that at the proliferative phase [(6 .5 ± 4 .05)cells/mm2 ,P 0 .05) .Conclusion Increased CD1a+ immature DCs at the window of implantation in endometri-um may play an important role in the establishment of maternal-fetal tolerance .

Perfil das células T Natural Killer (NKT)de indivíduos asmáticos desafiadas com antígenos solúvel do ovo de schistosoma mansoni / Natural Killer T cell (NKT) profile of asthmatic individuals challenged with soluble schistosoma mansoni egg antigens

INTRODUÇÃO: A asma é uma doença inflamatória crônica, caracterizada por hiper-reatividade das vias aéreas inferiores e por limitação variável e reversível ao fluxo aéreo. Apresenta manifestações clínicas na forma de sibilância, dispneia, sensação de aperto no peito e tosse, podendo ser considerada como atópica ou não atópica, de acordo com seus aspectos imunopatogênicos. Células do sistema imune, como neutrófilos, macrófagos, células dendríticas e as células T Natural Killer (NKT), apresentam importante papel no desenvolvimento ou regulação da resposta inflamatória da asma. Desta forma é possível que antígenos com propriedades regulatórias, como no caso dos antígenos de ovo do Schistosoma mansoni (SEA), sejam capazes de alterar o perfil destas células e regular a resposta imune da asma. OBJETIVOS: Avaliar a frequência de NKT e expressão de moléculas de ativação e coestimulação, além de citocinas nestas células, em indivíduos com asma. METODOLOGIA: Trata-se de um estudo de corte transversal realizado com 24 voluntários, sendo 14 indivíduos asmáticos e 10 voluntários não asmáticos. Células mononucleares de sangue periférico (PNMC)...

INTRODUCTION: Asthma is a chronic inflammatory disease characterized by hyperreactivity of lower airways and variable limitation and reversible airflow. The main clinical manifestations are wheezing, breathlessness, chest pain that feel like tightness and coughing, being considered as atopic or non-atopic, according to its immunopathogenic aspect. Immune cells, such as neutrophils, macrophages, dendritic cells and Natural Killer T cells (NKT) play an important role in the regulation or development of inflammatory response of asthma. Thus, it is possible that antigens with regulatory properties, such as Schistosoma mansoni soluble egg antigen (SEA), are able to alter the profile of these cells and regulate the immune response of asthma. AIM: To evaluate the frequency of NKT cells, expression of activation and costimulatory markers, as well as cytokine expression in NKT cells from individuals with asthma. METHODOLOGY: This is a cross-sectional study of 24 volunteers, of which 14 were asthmatic and 10 nonasthmatic volunteers. Peripheral blood mononuclear cells (PBMC)...

Adult Langerhans cell histiocytosis:A case report and literature review / 吉林大学学报(医学版)

Objective:To study the clinical and pathological features of Langerhans cell histiocytosis (LCH), and to provide the reference for its diagnosis and treatment.Methods:The manifestation of one LCH patient was retrospectively analyzed.The features of the LCH patients were explored by analyzing the results of skin biopsy, radiological test and follow-up.The associated literatures were reviewed.Results:The patient presented the typical symptoms gradually,including polycystic lung,skin ulcer,diabetes insipidus,and lactation.The skin pathological findings showed the densely distributed mononuclear cell infiltration in dermis and the immunohistological staining result showed positive CD1a. The patient was follwed up for 7 years and died of heart and lung failure. Conclusion:LHC has various manifestations and should be confirmed by clinical features,pathological features and imaging examination.The adult patients with multisystem and vital organ involvement suggest the poor prognosis.

Murine invariant natural killer T cells recognize glycolipids derived from extracts of the lichen Stereocaulon ramulosum / Células T asesinas naturales invariantes murinas reconocen glicolipidos derivados de extractos del liquen Stereocaulon ramulosum

Background: Invariant natural killer T cells (iNKT) can be activated by certain types of glycolipids that have the potential to generate adjuvant effects which could be used to develop effective and safe immunotherapies. Many of these glycolipids have been isolated from natural organisms, but there is a great amount of these organisms completely unexplored as a source of these types of compounds. Some of these organisms are lichens which are complex symbiotic organisms that have been showed to contain glycolipids. Objectives: We decide to test if glycolipids isolated from lichens would be able to activate iNKT cells in vitro and in vivo. Methods: We have used extracted glycolipids from 43 different species of lichens from Colombia. We have used iNKT hybridoma cells, C57BL/6 mice, IL-2 ELISA and the B16 melanoma to test for the adjuvant capabilities of glycolipids isolated from lichens. Results: In this study we have found two glycolipids with the capacity to activate iNKT cells in vivo. One of the glycolipids was able to activate iNKT cells in vivo, and was competent to induce protection against the B16 melanoma in the mouse model. Conclusions: We propose a possible chemical structure for a novel glycolipid called ß-GalCer-lich (1) derived from the lichen Stereocaulon ramulosum.

Antecedentes: Las células asesinas naturales T (iNKT) pueden ser activadas por ciertos tipos de glicolípidos que tienen el potencial para generar efectos adyuvantes los cuales pueden ser usados para desarrollar inmunoterapias efectivas. Muchos de estos glicolípidos han sido aislados de organismos naturales, pero hay una gran cantidad de organismos completamente inexplorados como fuente de este tipo de compuestos. Algunos de estos organismos son los líquenes, los cuales son organismos simbiontes complejos para los que se ha mostrado que contienen glicolípidos. Objetivos: Nosotros decidimos probar si los glicolípidos aislados de líquenes podrían ser capaces de activar alas celulas iNKT in vitro e in vivo. Metodos: Nosotros hemos extraído glicolípidos de 43 especies de líquenes de Colombia. Nosotros hemos usado células de un hibridoma de iNKTs, ratones C57BL/6, ELISA para IL-2 y el melanoma B16 para probar la capacidad adyuvante de los glicolipidos aislados de los líquenes. Resultados: En este estudio nosotros hemos encontrado dos glicolípidos con la capacidad de activar iNKTs in vitro. Uno de los glicolípidos fue capaz de activar células iNKT in vivo, y fue competente para inducir protección contra el melanoma B16 en el modelo de ratón. Conclusiones: Nosotros proponemos una posible estructura química para el nuevo glicolípido llamado ß-GalCer-lich (1) derivado del liquen Stereocaulon ramulosum.

A Case of Gastric Langerhans Cell Histiocytosis with Spontaneous Regression

A 44-year-old male was followed-up with esophagogastroduodenoscopy due to an esophageal submucosal tumor. On the lesser curvature of the gastric low body, a 0.5 cm sized round elevated lesion with hyperemia was noticed. Two pieces of biopsy were taken from this lesion for histopathologic examination. Histology showed Langerhans cell infiltration. Immunohistochemical staining was positive for CD1a antigen, which confirmed the diagnosis of Langerhans cell histiocytosis. There was no evidence of other organ involvement. The lesions spontaneously disappeared 4 months later without any treatment. We report a very rare case of gastric Langerhans cell histiocytosis.

A case of S100-positive atypical juvenile xanthogranuloma: a longitudinal observation and review of the literature / 中华皮肤科杂志

A 3-year-old boy presented with a 3-month history of brown-yellow papules scattered on the trunk.The first skin biopsy showed a dermal infiltrate of many mononuclear histiocytes,eosinophilic granulocytes and a small number of lymphocytes.Immunohistochemical examination of the lesions demonstrated positive reactions with anti-CD68,-S100 and-CD1a (partial) antibodies.After the biopsy,the skin lesions gradually turned dark and partially regressed leaving hyperpigmentation,but new lesions continuously appeared.Four months later,a second biopsy was performed,and showed a dermal infiltrate of histiocytes with eosinophilic granulocytes and a few multinucleated giant cells.Immunohistochemistry showed that the histiocytes stained positive for CD68,but negative for S100 and CD1a.Based on the above findings,the patient was diagnosed with juvenile xanthogranuloma.

Subpoblaciones de linfocitos B y su expresión de CD1d en pacientes con lupus eritematoso sistémico / B cell subsets and their expression of CD1d in patients with systemic lupus erythematosus

Resumen Introducción: Los linfocitos B (LB) se consideran el centro de la desregulación inmune en pacientes con lupus eritematoso sistémico (LES), principalmente, por su producción de autoanticuerpos. Recientemente, se demostró la existencia de LB, incluidos en los B transicionales, con capacidad reguladora (Breg) y fenotipo CD19+CD24hiCD38hi. En humanos se demostró la importancia de CD80 y CD86 en su función reguladora. El papel de CD1d aún no ha sido evaluado. Objetivo: Evaluar la frecuencia de LB maduros, memoria y transicionales, en controles y pacientes con LES, además de la expresión de CD1d y correlacionarla con la actividad de la enfermedad medida por SLEDAI (Systemic Lupus Erythematosus Disease Activity Index). Materiales y métodos: Se evaluó por citometría de flujo la frecuencia de subpoblaciones de LB basados en la expresión de CD19, CD24 y CD38, además de CD1d, en controles con otras enfermedades autoinmunes (OEA), individuos sanos y pacientes con LES, y se correlacionó con SLEDAI. Resultados: Se evidenció una disminución significativa en el porcentaje de LB de memoria en pacientes LES y OEA, sin alteraciones en las subpoblaciones de LB maduros y transicionales. La expresión de CD1d no evidenció diferencias significativas en ninguna de las subpoblaciones ni se correlacionó con SLEDAI. Conclusión: La disminución de la subpoblación de memoria fue previamente descrita en LES y se ha asociado a algunos tipos de tratamiento. Aunque CD1d se ha asociado a la función de Breg en murinos, no hubo diferencias significativas en su expresión en las subpoblaciones y queda por clarificar su papel en la función de las Breg humanas.

Abstract Introduction: B lymphocytes are considered the center of immune dysregulation in Systemic Lupus Erythematosus (SLE). It has recently been demonstrated that there is a B cell with regulatory capacities (Breg) included in transitional B lymphocytes with the phenotype CD19+CD24hiCD38hi. The importance of CD80 and CD86 in the regulatory function of the Bregs has been demonstrated in humans, but the role of CD1d has not been evaluated. Objective: To evaluate the frequency of mature, memory and transitional B cells in SLE patients and controls, the expression of CD1d among these cells, and its correlation with the activity of the disease measured using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Materials and methods: The frequency of the B cell subsets was evaluated by flow cytometry based on the expression of CD19, CD24 and CD38, as well as CD1d in these cells in SLE patients and controls, and were correlated with the activity of the disease measured using the SLEDAI. Results: A significant reduction in the percentage of memory B cells was observed in SLE patients and other autoimmune conditions, with no changes in the mature or transitional B cell subsets. Similarly, no significant differences were observed in the expression of CD1d in any of the subsets, nor was there any correlation with the SLEDAI. Conclusion: The reduction of the memory subset has been previously described in SLE, and has been associated with some types of treatment. The expression of CD1d in all the subsets was observed, but its role in the regulatory function of the CD19+CD24hiCD38hi cells is still not clear.