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1.
Life Sci ; 241: 117168, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31838133

RESUMO

AIM: Immunosenescence is the decline of the host immune system due to aging, resulting in various complications. The splenic lymphoid nodule is the pivotal compartment involved in immunosenescence. In this study, we investigated the important changes in the splenic immune cell populations of aged rats (18-24 months) in comparison with young rats (3-5 months). MATERIALS AND METHODS: We, also, studied the effects of aging on the activities of total superoxide dismutase (T-SOD) and malondialdehyde (MDA) levels in spleen of both groups, besides the changes of the splenic architecture. Furthermore, immunohistochemical staining was performed to detect the aging effects in T cells, B cells, macrophages, granulocytes, mast cells, proliferating cells, apoptotic cells, and cells positive for interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and Toll-like receptor 4 (TLR4). KEY FINDINGS: The aged rats had significantly lower spleen/body weight ratios and smaller splenic nodules, indicating a decline in general immunity in them. With aging, T-SOD activities were decreased, while MDA levels were increased, exhibiting that oxidative stress increases in spleens. In addition, the aged group also had significantly fewer T and B cells, macrophages, granulocytes, IL-6 and TLR4 immuno-positive cells, and proliferating cells in the periarterial lymphatic sheaths, marginal zone, and lymphoid follicles compared with the young group. On the other hand, the number of mast cells and apoptotic cells was significantly increased with age. Therefore, we can conclude that cellular immunity and humoral immunity were crumpled with age.


Assuntos
Linfócitos B/imunologia , Imunidade Celular/imunologia , Imunossenescência/imunologia , Estresse Oxidativo/imunologia , Baço/imunologia , Linfócitos T/imunologia , Animais , Linfócitos B/metabolismo , Linfócitos B/patologia , Células Cultivadas , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Wistar , Baço/metabolismo , Baço/patologia , Superóxido Dismutase/metabolismo , Linfócitos T/metabolismo , Linfócitos T/patologia
2.
Medicine (Baltimore) ; 98(50): e18300, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852109

RESUMO

RATIONALE: Kimura disease (KD) is a rare, chronic inflammatory disorder characterized by subcutaneous granuloma in the head and neck region, as well as increased eosinophil counts and high serum immunoglobulin E (IgE) levels. Kimura disease is suspected to be an IgE-mediated disease, associated with an allergic response, in which antigen-specific B cells are stimulated to undergo specific IgE class switching with disease-specific CD4+ T (Th) cells help. Thus, exploration of the Th cells in affected tissues with KD is a highly promising field of the investigation. However, there have been no reports with direct evidence to implicate Th cells in affected lesions with KD. Here we quantitatively demonstrate that CD4+ GATA3+ T cells and interleukin (IL)-4+ IgE+ c-kit+ mast cells prominently infiltrate in affected lesion with KD. PATIENT CONCERNS: A 56-year-old Japanese man who exhibited painless swelling in the left parotid region. DIAGNOSES: Diagnosis of KD was made based on characteristic histopathologic findings, in conjunction with peripheral eosinophilia and elevated serum IgE levels. INTERVENTIONS: The patient underwent corticosteroid therapy and had been followed for 2 years. OUTCOMES: We report a rare case of KD of the parotid region in a 56-year-old man, followed by corticosteroid therapy for 2 years. The mass decreased in size and skin itchiness decreased after therapy. He was discharged without any complications. Furthermore, we quantitatively demonstrate the dominance of CD4+ GATA3+ T cells in affected tissues of KD and detect IL-4+ IgE+ c-kit+ mast cells in lesions by multicolor staining approaches. LESSONS: The findings from this case suggest that peripheral blood eosinophilia might serve as a marker of recurrent disease, long-term follow-up is necessary due to the possibility of recurrent. Interactions among expanded IgE+ B cells, CD4+ GATA3+ T cells, eosinophils, and activated mast cells might play a critical role in the pathogenesis of KD.


Assuntos
Hiperplasia Angiolinfoide com Eosinofilia/imunologia , Linfócitos B/imunologia , Eosinófilos/imunologia , Imunoglobulina E/sangue , Mastócitos/imunologia , Hiperplasia Angiolinfoide com Eosinofilia/sangue , Hiperplasia Angiolinfoide com Eosinofilia/diagnóstico , Linfócitos B/patologia , Biópsia , Eosinófilos/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Mastócitos/patologia , Pessoa de Meia-Idade
3.
Genes Dev ; 33(23-24): 1673-1687, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31699777

RESUMO

Knockout of the ubiquitously expressed miRNA-17∼92 cluster in mice produces a lethal developmental lung defect, skeletal abnormalities, and blocked B lymphopoiesis. A shared target of miR-17∼92 miRNAs is the pro-apoptotic protein BIM, central to life-death decisions in mammalian cells. To clarify the contribution of miR-17∼92:Bim interactions to the complex miR-17∼92 knockout phenotype, we used a system of conditional mutagenesis of the nine Bim 3' UTR miR-17∼92 seed matches. Blocking miR-17∼92:Bim interactions early in development phenocopied the lethal lung phenotype of miR-17∼92 ablation and generated a skeletal kinky tail. In the hematopoietic system, instead of causing the predicted B cell developmental block, it produced a selective inability of B cells to resist cellular stress; and prevented B and T cell hyperplasia caused by Bim haploinsufficiency. Thus, the interaction of miR-17∼92 with a single target is essential for life, and BIM regulation by miRNAs serves as a rheostat controlling cell survival in specific physiological contexts.


Assuntos
Linfócitos B/citologia , Proteína 11 Semelhante a Bcl-2/metabolismo , Sobrevivência Celular/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Hematopoese/genética , MicroRNAs/metabolismo , Regiões 3' não Traduzidas/genética , Animais , Linfócitos B/patologia , Proteína 11 Semelhante a Bcl-2/genética , Técnicas de Inativação de Genes , Pulmão/embriologia , Camundongos , MicroRNAs/genética , Mutação , Estresse Fisiológico
4.
Medicine (Baltimore) ; 98(39): e17311, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574860

RESUMO

Immune infiltration of nasopharyngeal carcinoma (NPC) is closely associated with the patients' prognosis. However, previous studies have not interpreted the difference of infiltrating immune cells in NPC.We comprehensively analyzed the tumor-infiltrating immune cells present in NPC for the first time, which was based on a scientific deconvolution algorithm (CIBERSORT) and the gene expression data of GSE64634. The fractions of 22 immune cells were assessed to reveal the associations between normal samples and NPC samples.Profiles of immune infiltration vary significantly between normal samples and NPC samples, and the variation could characterize the individual differences. NPC samples contained a higher proportion for M1 macrophages, whereas memory B cells and CD4 memory resting T cells were relatively lower.Our data suggest that the differences in the infiltrating immune cells in NPC and these differences would probably facilitate patient consultation and individualized treatment.


Assuntos
Linfócitos do Interstício Tumoral , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Adulto , Algoritmos , Linfócitos B/imunologia , Linfócitos B/patologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , China , Correlação de Dados , Feminino , Expressão Gênica , Humanos , Memória Imunológica , Linfócitos do Interstício Tumoral/classificação , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/patologia , Prognóstico , Reprodutibilidade dos Testes
5.
PLoS Pathog ; 15(9): e1008030, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31518366

RESUMO

Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with multiple human malignancies. EBV drives B-cell proliferation, which contributes to the pathogenesis of multiple lymphomas. Yet, knowledge of how EBV subverts host biosynthetic pathways to transform resting lymphocytes into activated lymphoblasts remains incomplete. Using a temporal proteomic dataset of EBV primary human B-cell infection, we identified that cholesterol and fatty acid biosynthetic pathways were amongst the most highly EBV induced. Epstein-Barr nuclear antigen 2 (EBNA2), sterol response element binding protein (SREBP) and MYC each had important roles in cholesterol and fatty acid pathway induction. Unexpectedly, HMG-CoA reductase inhibitor chemical epistasis experiments revealed that mevalonate pathway production of geranylgeranyl pyrophosphate (GGPP), rather than cholesterol, was necessary for EBV-driven B-cell outgrowth, perhaps because EBV upregulated the low-density lipoprotein receptor in newly infected cells for cholesterol uptake. Chemical and CRISPR genetic analyses highlighted downstream GGPP roles in EBV-infected cell small G protein Rab activation. Rab13 was highly EBV-induced in an EBNA3-dependent manner and served as a chaperone critical for latent membrane protein (LMP) 1 and 2A trafficking and target gene activation in newly infected and in lymphoblastoid B-cells. Collectively, these studies identify highlight multiple potential therapeutic targets for prevention of EBV-transformed B-cell growth and survival.


Assuntos
Linfócitos B/virologia , Ácidos Graxos/biossíntese , Herpesvirus Humano 4/patogenicidade , Ácido Mevalônico/metabolismo , Alquil e Aril Transferases/metabolismo , Linfócitos B/patologia , Proliferação de Células , Sobrevivência Celular , Colesterol/biossíntese , Infecções por Vírus Epstein-Barr/metabolismo , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Antígenos Nucleares do Vírus Epstein-Barr/metabolismo , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/fisiologia , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Redes e Vias Metabólicas , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Proteínas Virais/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo
7.
Presse Med ; 48(7-8 Pt 1): 842-849, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31447330

RESUMO

Hairy cell leukemia (HCL) is a well-defined entity. Proliferation with hair cells, morphological aspects of hairy cells are easy to identify. Hairy cells express markers CD11c, CD25, CD103 and CD123. In 80% of cases, a BRAFV600E mutation is highlighted. In the absence of a BRAFV600E mutation, the differential diagnosis with other hair cell proliferations can be difficult, especially with the variant form of hairy leukemia, diffuse lymphoma of the red pulp of the spleen or splenic lymphoma of the marginal zone. Purine analogues (PNA) with or without anti-CD20 antibodies remain the first-line reference treatment. In case of relapse or resistance to PNA, BRAF inhibitors, with or without MEK inhibitors, are proposed in patients with the mutation. In the absence of BRAFV600E mutation, moxetumomab-pasudotox represents an interesting alternative. A multidisciplinary discussion is always necessary. In complex cases, expert advice is desirable.


Assuntos
Leucemia de Células Pilosas , Linfócitos B/patologia , Proliferação de Células , Diagnóstico Diferencial , Humanos , Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/epidemiologia , Leucemia de Células Pilosas/patologia , Leucemia de Células Pilosas/terapia , Linfoma de Zona Marginal Tipo Células B/patologia , Fatores de Risco , Baço/patologia , Neoplasias Esplênicas/patologia
8.
Presse Med ; 48(7-8 Pt 1): 792-806, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31447335

RESUMO

Chronic lymphoproliferative disorders should be classified according to the revised 2016 WHO classification. Biopsies are not mandatory for all chronic lymphoproliferative disorders as blood or bone marrow cytologroachical approach can be sufficient for some lymphoma entities. Diagnostic is based on a multidiscplinary approach taking into account clinical presentation, histopathological, cytological, immunophenotypical features (immunohistochemistry and Flow cytometry) and molecular pattern (translocation by FISH, Mutations landscape by NGS, and genomic abnormalities by CGH array). An important heterogeneity of clinical presentation and prognosis arises within the same lymphoma subtype. Clinical evolution is characterized by relapses, cytological progression and transformation into diffuse large B cell lymphoma, aggressive lymphoma or high-grade lymphomas.


Assuntos
Linfócitos B/patologia , Leucemia Linfocítica Crônica de Células B/classificação , Leucemia Linfocítica Crônica de Células B/patologia , Transtornos Linfoproliferativos/classificação , Transtornos Linfoproliferativos/patologia , Doença Crônica , Diagnóstico Diferencial , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Transtornos Linfoproliferativos/diagnóstico , Síndrome
10.
Hematol Oncol ; 37(4): 483-486, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31408541

RESUMO

In absence of red blood cells disease or immune defect, parvovirus B19 (PVB-19) is usually considered as a benign condition. Here, we report the case of a 10-year-old boy, previously healthy, presenting with a PVB-19 infection revealed by a bicytopenia and a voluminous axillary adenopathy. Pathophysiology examination showed reactional lymphoid population. Nine months later and in the absence of remission, a new biopsy of the same adenopathy revealed a Hodgkin lymphoma with area of T-cell rich aggressive large B-cell lymphoma. This case suggests PVB-19 as potential trigger of this malignant childhood hemopathy. Although no definitive conclusion can be drawn, our clinical case questions the role of PVB-19 in lymphomagenesis.


Assuntos
Eritema Infeccioso/complicações , Doença de Hodgkin/etiologia , Linfoma de Células B/etiologia , Neoplasias Primárias Múltiplas/etiologia , Viremia/complicações , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfócitos B/patologia , Medula Óssea/patologia , Medula Óssea/virologia , Criança , Eritema Infeccioso/sangue , Eritema Infeccioso/patologia , Eritema Infeccioso/virologia , Doença de Hodgkin/patologia , Humanos , Linfoma de Células B/patologia , Masculino , Neoplasias Primárias Múltiplas/patologia , Pancitopenia/etiologia , Pseudolinfoma/etiologia , Indução de Remissão , Rituximab/administração & dosagem , Linfócitos T/patologia , Sequenciamento Completo do Exoma
11.
J Cancer Res Clin Oncol ; 145(11): 2803-2811, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31463716

RESUMO

BACKGROUND: Flow cytometry (FCM) plays a crucial role in the differential diagnosis of Burkitt lymphoma/leukemia (BL) and B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The presence of surface IgM (sIgM) alone or with light chain restriction indicates a mature blast phenotype (BIV by EGIL) and is usually observed in BL. However, sIgM expression could also be detected in transitional BCP-ALL cases. These similarities in immunophenotype and ambiguous correspondence with other laboratory findings may challenge the correct BL diagnostics. METHODS: We retrospectively reviewed the available data from immunophenotypic, morphological, cytogenetic, and molecular genetic studies of 146 children (85 boys and 61 girls) with a median age of 10 years (range 0-18 years) who were diagnosed with BL and BCP-ALL. The blasts' immunophenotype was studied by multicolor FCM. The conventional cytogenetic analysis included G-banded karyotyping and fluorescence in situ hybridization (FISH). RESULTS: In 54 children classified as BIV-ALL according to the EGIL, it was demonstrated that sIgM in a minority of cases can be associated with various types of BCP-ALL. Analysis of the antigen expression profile of 105 patients with verified BL (n = 21) and BCP-ALL (n = 84) showed significant differences in BL and the sIgM(+) vs BCP-ALL immunophenotype. Thus, even in cases of ambiguous sIgM expression, these two diseases could be reliably discriminated by complex immunophenotyping. Moreover, 10 patients (7 boys and 3 girls) with BL leukemic cells did not express sIgM, and they were diagnosed with BL on the basis of other laboratory and clinical signs. CONCLUSIONS: In conclusion, our study shows that BIV subtype is heterogeneous group of leukemia including not only the BL, but also BCP-ALL. In ambiguous cases, only a combination of multiple immunophenotypic, cytomorphologic, and genetic diagnostic technologies can allow the precise discrimination of BL and BCP-ALL and selection of the appropriate treatment scheme.


Assuntos
Linfócitos B/patologia , Citometria de Fluxo/métodos , Imunofenotipagem/métodos , Cariotipagem/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/classificação , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Estudos Retrospectivos
12.
Surg Pathol Clin ; 12(3): 719-731, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31352984

RESUMO

Technical advances in diagnostic modalities have led to the characterization of indolent lymphoid disorders similar to the in situ lesions described in epithelial malignancies. These early and indolent lymphoid lesions share clinicopathologic characteristics with well-characterized lymphoid malignancies such as chronic lymphocytic leukemia and follicular lymphoma. The in situ lesions have an indolent clinical course with only a minor subset shown to progress to frank malignancies. In addition to the in situ lesions, new indolent lymphoproliferative disorders have been recently characterized. Diagnosis and characterization of these indolent lesions is necessary to prevent overtreatment with aggressive therapeutic regimens.


Assuntos
Linfoma Folicular/patologia , Transtornos Linfoproliferativos/patologia , Linfócitos B/patologia , Diagnóstico Diferencial , Humanos , Imunofenotipagem/métodos , Leucemia Linfocítica Crônica de Células B/patologia , Linfocitose/patologia , Linfoma de Célula do Manto/patologia , Prognóstico
14.
Acta Med Acad ; 48(1): 45-56, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31264432

RESUMO

The aim of study was to summarize recent developments in laboratory work-up of lymphomas and discuss their clinical relevance. Diagnosis of lymphoma requires tissue biopsy with adequate work-up by pathologists. Recent developments in laboratory testing have raised the bar for establishing the diagnosis: more and more testing seems to be required, while the lines between research and clinical practice are being blurred. Academic medical practice is designed to push boundaries and test new hypotheses, which eventually result in improved patient care. Ability to (relatively) cheaply screen for multiple genomic abnormalities using new technologies is luring. Often, however, no change in patient management is pursued based on these results. It is therefore useful to review which testing is truly necessary from the patient's point of view. CONCLUSIONS: The laboratory work-up of lymphomas in a regular clinical practice requires relatively few tests. Many new tests have prognostic value, but do not necessarily contribute to the patient management.


Assuntos
Linfócitos B/patologia , Técnicas de Laboratório Clínico/métodos , Linfoma de Células B/diagnóstico , Neoplasias/diagnóstico , Biópsia , Doença Crônica , Testes Genéticos , Genômica , Humanos , Linfoma de Células B/genética , Linfoma de Células B/patologia , Neoplasias/genética , Neoplasias/patologia , Prognóstico
15.
J Clin Exp Hematop ; 59(2): 48-55, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257345

RESUMO

In the current revised 4th edition of the World Health Organization (WHO) classification, 'other iatrogenic immunodeficiency-associated lymphoproliferative disorders (Oii-LPDs)' is listed in the last section in the chapter on immunodeficiency-associated lymphoproliferative disorders. Oii-LPDs cover a broad spectrum from benign lesions to lymphoma, and correspond to one of the subtypes in the WHO classification for immunocompetent patients.The WHO classification does not clearly indicate the histological subtype of this disease category; however, the framework of subtype classification is similar to the classification of post-transplant lymphoproliferative disorders, and recent studies have attempted to subcategorize Oii-LPDs that fit this unique disease type. In this review, we provide an overview of B-cell-type Oii-LPDs regarding their histopathology and immunophenotype, genetics and clinical behaviors.


Assuntos
Linfócitos B/patologia , Síndromes de Imunodeficiência/patologia , Imunossupressores/efeitos adversos , Transtornos Linfoproliferativos/patologia , Animais , Linfócitos B/efeitos dos fármacos , Humanos , Doença Iatrogênica/epidemiologia , Síndromes de Imunodeficiência/induzido quimicamente , Síndromes de Imunodeficiência/classificação , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/classificação
16.
J Clin Exp Hematop ; 59(2): 64-71, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257347

RESUMO

Epstein-Barr virus (EBV)-positive mucocutaneous ulcers (EBVMCUs) were first described as a lymphoproliferative disorder in 2010. Clinically, EBVMCUs are shallow, sharply circumscribed, unifocal mucosal or cutaneous ulcers that occur in immunosuppressed patients, including those with advanced age-associated immunosenescence, iatrogenic immunosuppression, primary immune disorders, and HIV/AIDS-associated immune deficiencies. In general, patients exhibit indolent disease progression and spontaneous regression. Histologically, EBVMCUs are characterized by the proliferation of EBV-positive, variable-sized, atypical B-cells. According to conventional histopathologic criteria, EBVMCUs may diagnosed as lymphomas. However, EBVMCUs are recognized as pseudomalignant lesions because they spontaneously regress without anti-cancer treatment. Therefore, overtreatment must be carefully avoided and multilateral differentiation is important. In this article, we reviewed previously reported EBVMCUs focusing on their clinical and pathological aspects in comparison with other EBV-positive B-cell neoplasms.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/isolamento & purificação , Úlcera Cutânea/etiologia , Úlcera Cutânea/virologia , Animais , Linfócitos B/patologia , Linfócitos B/virologia , Gerenciamento Clínico , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/patologia , Humanos , Prognóstico , Pele/patologia , Pele/virologia , Úlcera Cutânea/diagnóstico , Úlcera Cutânea/patologia
17.
Immunol Rev ; 290(1): 39-59, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31355492

RESUMO

By increasing disease-free survival and offering the potential for long-term cure, chimeric antigen receptor (CAR) T-cell therapy has dramatically expanded therapeutic options among those with high-risk B-cell malignancies. As CAR T-cell utilization evolves however, novel challenges are generated. These include determining how to optimally integrate CAR T cells into standard of care and overcoming mechanisms of resistance to CAR T-cell therapy, such as evolutionary stress induced on cancer cells leading to immunophenotypic changes that allow leukemia to evade this targeted therapy. Compounding these challenges are the limited ability to determine differences between various CAR T-cell constructs, understanding the generalizability of trial outcomes from multiple sites utilizing unique CAR manufacturing strategies, and comparing distinct criteria for toxicity grading while defining optimal management. Additionally, as understanding of CAR behavior in humans has developed, strategies have appropriately evolved to proactively mitigate toxicities. These challenges offer complimentary insights and guide next steps to enhance the efficacy of this novel therapeutic modality. With a focus on B-cell malignancies as the paradigm for effective CAR T-cell therapy, this review describes advances in the field as well as current challenges and future directions.


Assuntos
Imunoterapia Adotiva , Leucemia de Células B/imunologia , Leucemia de Células B/terapia , Linfoma de Células B/imunologia , Linfoma de Células B/terapia , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Animais , Antígenos CD19/imunologia , Antígenos de Neoplasias/imunologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos B/patologia , Modelos Animais de Doenças , Humanos , Leucemia de Células B/diagnóstico , Linfoma de Células B/diagnóstico , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos Quiméricos/genética , Resultado do Tratamento
18.
World Neurosurg ; 131: 87-89, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31356970

RESUMO

BACKGROUND: Intraorbital and intracerebral cavernous malformation (CM) lesions are considered independent entities. Purely cerebral CMs have variable biology with recent evidence depicting inflammation as an important player and a risk factor for aggressiveness. We describe a case of concomitant left intraaxial and extraaxial CMs, linked by the ipsilateral basal vein, where the extraaxial component has developed an aggressive behavior. CASE DESCRIPTION: A 35-year-old female patient presented with a rapid and progressive exophthalmos and loss of vision on the left eye. Cranial magnetic resonance and angiography examinations demonstrated a left craniofacial CM and large intraorbital component. The lesion was connected through a large basal vein to a cerebral intraventricular CM. Transconjunctival resection showed typical findings of CM. A complete histopathology and immunostaining analysis was performed and revealed a clear acute lymphomononuclear reaction with a predominant immune cellular inflammation. CONCLUSIONS: A case of intraorbital and extracranial cavernomatous mass, connected to a cerebral intraventricular CM through a large basal vein, has presented with an aggressive course. A complete histopathologic and immunohistochemical analysis of the orbital mass has pictured a clear immune-cellular inflammatory reaction adding to the amounting evidence of association between inflammation and site aggressiveness in the setting of CMs.


Assuntos
Veias Cerebrais/diagnóstico por imagem , Neoplasias do Ventrículo Cerebral/diagnóstico por imagem , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Orbitárias/diagnóstico por imagem , Adulto , Linfócitos B/imunologia , Linfócitos B/patologia , Angiografia Cerebral , Feminino , Hemangioma Cavernoso do Sistema Nervoso Central/imunologia , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Humanos , Inflamação/imunologia , Inflamação/patologia , Macrófagos/imunologia , Macrófagos/patologia , Imagem por Ressonância Magnética , Neoplasias Primárias Múltiplas/imunologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias Orbitárias/imunologia , Neoplasias Orbitárias/patologia , Neoplasias Orbitárias/cirurgia , Plasmócitos/imunologia , Plasmócitos/patologia
19.
PLoS Pathog ; 15(6): e1007840, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31173604

RESUMO

BLyS/BAFF is recognized for its role in B-cell ontogenesis, as well as cell fate decision towards the first-line/innate marginal zone (MZ) B-cell pool. Excess BLyS/BAFF is associated with hyperglobulinemia and increased frequencies of activated precursor-like MZ B-cells. Herein, we show that HIV highly-exposed seronegative (HESN) commercial sex workers (CSWs) had lower soluble BLyS/BAFF levels and relative frequencies of BLyS/BAFF expressing cells in their genital mucosa when compared to those from HIV-infected CSWs and HIV-uninfected non-CSWs. Furthermore, we identified genital innate and/or marginal zone (MZ)-like CD1c+ B-cells that naturally bind to fully glycosylated gp120, which frequencies were lower in HESNs when compared to HIV-infected CSWs and HIV-uninfected non-CSWs. Although genital levels of total IgA were similar between groups, HESNs had lower levels of total IgG1 and IgG3. Interestingly, HIV-gp41 reactive IgG1 were found in some HESNs. Low genital levels of BLyS/BAFF observed in HESNs may allow for controlled first-line responses, contributing to natural immunity to HIV.


Assuntos
Antígenos CD1/imunologia , Fator Ativador de Células B/imunologia , Linfócitos B/imunologia , Genitália Feminina/imunologia , Glicoproteínas/imunologia , Soronegatividade para HIV/imunologia , HIV-1/imunologia , Imunidade Inata , Profissionais do Sexo , Adulto , Linfócitos B/patologia , Feminino , Anticorpos Anti-HIV/imunologia , Humanos , Imunoglobulina G/imunologia , Pessoa de Meia-Idade
20.
Iran J Immunol ; 16(2): 127-141, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31182687

RESUMO

BACKGROUND: We have previously reported the aberrant expression of Fibromodulin (FMOD) in patients with chronic lymphocytic leukemia (CLL). Although FMOD has been considered as a cytoplasmic or secretory protein, we discovered the cell surface expression of FMOD in leukemic B cells via anchoring with glycosylphosphatidylinositol (GPI). OBJECTIVE: To evaluate FMOD as a new biomarker in CLL patients in comparison with healthy individuals. METHODS: A monoclonal antibody was generated against human FMOD. The cell surface expression of FMOD in 52 CLL patients and 45 healthy individuals were compared by flow cytometry. A bacterial phosphatidylinositol-specific phospholipase C (PI-PLC) was used to determine the cell surface localization of FMOD using ELISA and flow cytometry techniques. Annexin V-FITC and propidium iodide (PI) was used to detect apoptosis induction in CLL PBMCs following in vitro incubation with anti-FMOD mAb. RESULTS: The results demonstrated the widespread cell surface expression of GPI-anchored FMOD in CLL patients (median: 79.9 %), although healthy individuals had low FMOD expression (median: 6.2 %) (p≤0.0001). The cut-off value of FMOD expression was estimated with high sensitivity and specificity at 17.9 %. Furthermore, in vitro apoptosis induction of leukemic cells following incubation with anti-FMOD mAb showed a direct apoptosis of CLL cells (27.9%) with very low effect on healthy PBMCs (6%). CONCLUSION: The membrane-anchoring of FMOD by means of a GPI moiety in leukemic cells supports FMOD as a highly potential diagnostic and therapeutic target in CLL patients.


Assuntos
Linfócitos B/patologia , Fibromodulina/metabolismo , Leucemia Linfocítica Crônica de Células B/diagnóstico , Proteínas de Membrana/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Apoptose , Linfócitos B/metabolismo , Linhagem Celular Tumoral , Feminino , Fibromodulina/química , Fibromodulina/imunologia , Regulação Neoplásica da Expressão Gênica , Glicosilfosfatidilinositóis/química , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Masculino , Proteínas de Membrana/química , Proteínas de Membrana/imunologia , Pessoa de Meia-Idade , Ligação Proteica , Sensibilidade e Especificidade
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