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1.
Iran J Allergy Asthma Immunol ; 18(2): 225-229, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31066259

RESUMO

Hyperimmunoglobulin E syndrome (HIGE) is considered as a phagocytic or a newly classified complex and heterogeneous primary immunodeficiency disease with symptoms such as increased levels of immunoglobulin E, eczema, and, recurrent lung and skin infections. In this paper, we have presented a rare case of this syndrome. A 9-year-old Iranian girl presented with a history of pruritic maculopapular rash who was eventually diagnosed as a case of HIGE. In her recent admission, she had dysphonia, stridor and huge cauliflower cutaneous lesions on her neck, finger and vocal cords, which did not respond to intravenous antibiotics, and ultimately required surgical removal.


Assuntos
Fatores de Troca do Nucleotídeo Guanina/genética , Herpes Simples/diagnóstico , Imunoglobulinas Intravenosas/uso terapêutico , Síndrome de Job/diagnóstico , Mutação/genética , Simplexvirus/fisiologia , Pele/patologia , Prega Vocal/patologia , Antibacterianos/uso terapêutico , Criança , Resistência a Medicamentos , Disfonia , Feminino , Herpes Simples/tratamento farmacológico , Humanos , Imunoglobulina E/metabolismo , Síndrome de Job/tratamento farmacológico , Laringoscopia , Sons Respiratórios , Pele/virologia
6.
Immunol Allergy Clin North Am ; 39(1): 49-61, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30466772

RESUMO

Improvement in genetic testing has allowed specific delineation of several distinct clinical causes characterized by the hyperimmunoglobulin E (IgE) phenotype of eczema, recurrent infections, and elevated serum IgE. Mutations in STAT3, DOCK8, PGM3, ERBIN, IL6ST, and CARD11 cause clinical phenotypes that can present in this manner. This article focuses on loss of function STAT3 mutations causing autosomal-dominant hyper-IgE syndrome and dedicator of cytokinesis 8 deficiency, with discussion of other more recently described diseases.


Assuntos
Síndrome de Job/diagnóstico , Síndrome de Job/etiologia , Fenótipo , Animais , Biomarcadores , Terapia Combinada , Diagnóstico por Imagem , Suscetibilidade a Doenças , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Síndrome de Job/metabolismo , Síndrome de Job/terapia , Resultado do Tratamento
7.
Immunol Cell Biol ; 97(4): 368-379, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30264496

RESUMO

Hyper IgE syndromes comprise a group of rare primary immunodeficiency disorders characterized by a triad of atopic dermatitis, recurrent skin and lung infections along with elevated IgE levels. Job syndrome or autosomal dominant hyper IgE syndrome because of heterozygous loss-of-function mutations with dominant negative effect in signal transducer and activator of transcription-3 is the prototype of these disorders. However, several other genetically characterized immunodeficiency disorders have been identified over the past decade and joined the umbrella of hyper IgE syndromes including autosomal recessive mutations in the DOCK8, ZNF431 and PGM3 genes and heterozygous mutations with dominant negative effect in the CARD11 gene. Moreover, a number of phenotypically distinct immunodeficiency disorders can mimic hyper IgE syndromes, adding to the diagnostic challenge. Herein, we will concisely review these disorders, their molecular bases, highlighting key distinguishing clinical and laboratory findings and therapeutic options.


Assuntos
Síndrome de Job/genética , Genes Dominantes , Humanos , Síndrome de Job/diagnóstico , Síndrome de Job/imunologia , Síndrome de Job/terapia , Mutação/genética , Fenótipo , Fator de Transcrição STAT3/genética , Transcrição Genética
8.
BMJ Case Rep ; 20182018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30413445

RESUMO

Hyperimmunoglobulin E syndrome is a rare multisystem inherited disorder characterised by high serum IgE levels, skin disorder causing eczema, dermatitis, recurrent staphylococcal infections and pulmonary infections and various skeletal and connective tissue abnormalities. Common presentation is with recurrent skin and sinopulmonary infections. Several features unrelated to immune system such as characteristic facial features, hyperextensibility of joints, multiple bone fractures and craniosynostosis have been described in the literature. We describe a rare presentation of this disease with invasive aspergillosis presenting as mediastinal mass with extension to mediastinal structures and pulmonary vasculature.


Assuntos
Síndrome de Job/complicações , Síndrome de Job/diagnóstico , Mediastino/diagnóstico por imagem , Aspergilose Pulmonar/complicações , Aspergilose Pulmonar/diagnóstico , Adolescente , Antifúngicos/uso terapêutico , Biópsia , Broncoscopia , Diagnóstico Diferencial , Humanos , Síndrome de Job/cirurgia , Masculino , Mediastino/cirurgia , Aspergilose Pulmonar/tratamento farmacológico , Radiografia Intervencionista , Tomografia Computadorizada por Raios X , Voriconazol/uso terapêutico
9.
Curr Allergy Asthma Rep ; 18(10): 51, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-30112673

RESUMO

PURPOSE OF REVIEW: The hyper IgE syndromes (HIES) comprise a group of rare primary immunodeficiency disorders (PIDDs), which are characterized by extremely high serum IgE levels, eczema, recurrent skin and pulmonary infections. Both autosomal dominant (AD) HIES due to STAT3 mutations and autosomal recessive (AR) HIES due to PGM3, SPINK5, DOCK8 and TKY2 mutations have been reported. Here, we aim to summarize and compare the major clinical manifestations of different subtypes of HIES. We will also discuss otitis media, which usually do not get enough attention in HIES. Update and familiarity with these clinical features will help to make a better diagnose, assessment and treatment of HIES. RECENT FINDINGS: Although hyper serum IgE levels have been identified in PGM3 deficiency and Comel-Netherton syndrome, PGM3 and SPINK5 genes were not included in the list of genetic etiologies of AR-HIES by the Expert Committee of the International Union of Immunological Societies until 2015. The identification of these HIES-causing genes greatly promoted the pathogenic mechanism studies of HIES. Also, in recent years, more clinical manifestations, which were often not of concern in HIES patients, have been shown to be highly related to HIES. For example, a significantly high frequency of vascular and gastrointestinal abnormities has been reported in STAT3-deficient AD-HIES patients. These new findings might help to provide new clues to the functional study of these HIES-related genes. This review summarizes and compares the major clinical manifestations of different subtypes of HIES, and we suggest that the incidence and severity of otitis media should not be underestimated in HIES patients.


Assuntos
Síndrome de Job , Gastroenteropatias/complicações , Gastroenteropatias/etiologia , Humanos , Síndrome de Job/complicações , Síndrome de Job/diagnóstico , Síndrome de Job/genética , Mutação , Otite Média/complicações , Infecções Respiratórias/complicações , Dermatopatias/complicações
10.
Oral Surg Oral Med Oral Pathol Oral Radiol ; 126(5): e252-e257, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30126807

RESUMO

Hyperimmunoglobulin E syndrome (HIES) is a rare heterogeneous primary immunodeficiency disorder characterized by infections of the lung and skin, elevated serum immunoglobulin E, and involvement of soft and bony tissues. Autosomal dominant HIES and related disorders are caused by defects in the Janus activated kinase-signal transducer and activator of transcription signaling pathway, leading to reduced numbers of T helper cell type 17 and impaired production of interleukin (IL)-17 A, IL-17 F, and IL-22. In addition, neutrophils have chemotactic defects, resulting in impaired responses at skin and lung sites. We report here a case of orofacial granulomatosis-like disease in a teenage boy ultimately found to have autosomal dominant HIES caused by a heterozygous mutation in the STAT3 gene.


Assuntos
Granulomatose Orofacial/genética , Síndrome de Job/genética , Fator de Transcrição STAT3/deficiência , Fator de Transcrição STAT3/genética , Criança , Diagnóstico Diferencial , Glucocorticoides/uso terapêutico , Granulomatose Orofacial/diagnóstico , Granulomatose Orofacial/tratamento farmacológico , Humanos , Síndrome de Job/diagnóstico , Síndrome de Job/tratamento farmacológico , Masculino , Mutação , Triancinolona/uso terapêutico
11.
Mamm Genome ; 29(7-8): 603-617, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30094507

RESUMO

Spectacular progress has been made in the characterization of human hyper-IgE syndrome (HIES) over the last 50 years. HIES is a primary immunodeficiency defined as an association of atopy in a context of very high serum IgE levels, characteristic bacterial and fungal diseases, low-level clinical and biological inflammation, and various non-hematopoietic developmental manifestations. Somewhat arbitrarily, three disorders were successively put forward as the underlying cause of HIES: autosomal dominant (AD) STAT3 deficiency, the only disorder corresponding to the original definition of HIES, and autosomal recessive (AR) DOCK8 and PGM3 deficiencies, in which atopy and high serum IgE levels occur in a context of manifestations not seen in patients with typical HIES. Indeed, these three disorders disrupt different molecular pathways, affect different cell types, and underlie different clinical phenotypes. Surprisingly, several other inherited inborn errors of immunity in which serum IgE levels are high, sometimes almost as high as those in HIES patients, are not considered to belong to the HIES group of diseases. Studies of HIES have been further complicated by the lack of a high serum IgE phenotype in all mouse models of the disease other than two Stat3 mutant strains. The study of infections in mutant mice has helped elucidate only some forms of HIES and infection. Mouse models of these conditions have also been used to study non-hematopoietic phenotypes for STAT3 deficiency, tissue-specific immunity for DOCK8 deficiency, and cell lineage maturation for PGM3 deficiency. We review here the history of the field of HIES since the first clinical description of this condition in 1966, together with the three disorders commonly referred to as HIES, focusing, in particular, on their mouse models. We propose the restriction of the term "HIES" to patients with an AD STAT3-deficiency phenotype, including the most recently described AR ZNF341 deficiency, thus excluding AR DOCK8 and PGM3 deficiencies from the definition of this disease.


Assuntos
Suscetibilidade a Doenças , Síndrome de Job/etiologia , Síndrome de Job/metabolismo , Animais , Formação de Anticorpos/genética , Formação de Anticorpos/imunologia , Biomarcadores , Modelos Animais de Doenças , Predisposição Genética para Doença , Fatores de Troca do Nucleotídeo Guanina/deficiência , Humanos , Imunoglobulina E/imunologia , Síndrome de Job/diagnóstico , Fenótipo , Fosfoglucomutase/deficiência , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais
12.
Biosens Bioelectron ; 117: 613-619, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30005381

RESUMO

Multiplexed biosensors hold great promise for early diagnosis of diseases where the detection of multiple biomarkers is required. Hyper Immunoglobulin E syndromes (HIES) are rare primary immunodeficiency disorders associated with mutations either in the signal transducer and activator of transcription 3 (STAT3), dedicator of cytokinesis 8 DOCK8) or phosphoglucomutase 3 (PGM3) genes. Yet, the diagnosis of HIES is challenged by the complexity of the existing laboratory assays. Here, we report for the first time the development of a multiplexed electrochemical immunosensor for the simultaneous detection of DOCK8, STAT3 and PGM3 proteins. The immunosensor was constructed on carbon array electrodes that were first modified by electrodeposition of gold nanoparticles (AuNPs). The array electrodes were then used to immobilize specific antibodies for the three proteins after the functionalization of the electrodes with cysteamine/glutaraldehyde linkers. The simultaneous detection of the DOCK8, PGM3 and STAT3 proteins was successfully realized by the immunosensor with respective limits of detections of 3.1, 2.2 and 3.5 pg/ml. The immunosensor has shown good sensitivity as well as selectivity against other proteins such as cystic fibrosis transmembrane conductance regulator (CFTR) and Duchenne Muscular Dystrophy (DMD). Moreover, the immunosensor was successfully applied in human serum samples showing capability to distinguish the HIES from the control samples.


Assuntos
Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Análise Química do Sangue/instrumentação , Análise Química do Sangue/métodos , Síndrome de Job/diagnóstico , Ouro/química , Fatores de Troca do Nucleotídeo Guanina/sangue , Humanos , Síndrome de Job/sangue , Nanopartículas Metálicas/química , Fosfoglucomutase/sangue , Fator de Transcrição STAT3/sangue
13.
Clin Immunol ; 195: 36-44, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30048691

RESUMO

In the past few years, several genes were shown to be implicated in various forms of the Hyper Immunoglobulin E syndrome. The present study is the first to describe a cohort of DOCK8 deficiency patients from Egypt. The study included 15 patients with features of combined immunodeficiency (CID) suggestive of DOCK8 deficiency. Flow cytometry was used for evaluation of DOCK8 expression and studying different immunological characteristics of those patients including evaluation of Th17, Tregs, T and B lymphocytes differentiation and the effect of the DOCK8 deficiency on the activation of the STAT3. Diagnosis was confirmed by mutational analysis. Profound defects in Th17 cells and Tregs were observed in all patients with impaired STAT3 phosphorylation, indicating that DOCK8 plays a pivotal role in the STAT3 signaling pathway. These findings together with decrease in memory B cells and defective DOCK8 expression by flow cytometry can confirm the diagnosis.


Assuntos
Linfócitos B/imunologia , Biomarcadores/metabolismo , Citometria de Fluxo/métodos , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Síndrome de Job/diagnóstico , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Diferenciação Celular , Criança , Pré-Escolar , Estudos de Coortes , Egito , Feminino , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Memória Imunológica , Masculino , Fosforilação/genética , Fator de Transcrição STAT3/metabolismo , Deleção de Sequência/genética , Transdução de Sinais
14.
Front Immunol ; 9: 1080, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29868029

RESUMO

Background: Hyper-IgE syndrome (HIES) caused by loss-of-function (LOF) mutations in STAT3 gene (STAT3 LOF HIES) is associated with dental and facial abnormalities in addition to immunological defects. The role of STAT3 in the pathogenesis of the dental/facial features is, however, poorly elucidated. Objectives: Since mechanism of cellular resorption of mineralized tissues such as bone and teeth are similar, we attempted to study the expression of genes involved in bone homeostasis in STAT3 LOF HIES. Methods: Peripheral blood mononuclear cells from healthy controls (HCs), STAT3 LOF HIES patients, STAT3-/- PC-3 cells and STAT3+/+ LNCaP cells were stimulated with IL-6 and quantitative PCR array was performed to study the relative mRNA expression of 43 pre-selected genes. PCR array finding were further evaluated after stattic induced STAT3 inhibition. Results: Osteopontin (OPN) gene was seen to be significantly upregulated after IL-6 stimulation in HC (mean fold change 18.6, p = 0.01) compared with HIES subjects. Inhibition of STAT3 signaling by stattic followed by IL-6 stimulation abrogated the OPN response in HCs suggesting that IL-6-induced STAT3 signaling regulates OPN expression. Bioinformatics analysis predicted the presence of STAT3 response element TTCCAAGAA at position -2005 of the OPN gene. Conclusion: Regulation of OPN gene through IL-6-mediated STAT3 activation and its significant dysregulation in STAT3 LOF HIES subjects could make OPN a plausible candidate involved in the pathogenesis of dental/facial manifestations in HIES.


Assuntos
Regulação da Expressão Gênica , Síndrome de Job/genética , Mutação com Perda de Função , Osteopontina/genética , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transcrição Genética , Adolescente , Adulto , Sítios de Ligação , Linhagem Celular Tumoral , Pré-Escolar , Biologia Computacional/métodos , Elementos Facilitadores Genéticos , Perfilação da Expressão Gênica , Humanos , Interleucina-6/metabolismo , Síndrome de Job/diagnóstico , Síndrome de Job/imunologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Masculino , Fenótipo , Fosforilação , Estudos Prospectivos , Ligação Proteica , Elementos de Resposta , Proteína 3 Supressora da Sinalização de Citocinas/genética
15.
Vasc Endovascular Surg ; 52(5): 375-377, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29552943

RESUMO

Hyper-IgE syndrome also known as Job syndrome is characterized by elevation of circulating immunoglobulin (IgE) levels and is usually associated with recurrent bacterial infections of the skin and sinopulmonary tract. Though bacterial pulmonary abscess and pneumatocele formation have been described, pulmonary artery pseudoaneurysm in Job syndrome has not been reported in literature. Our report describes a case of large pulmonary artery pseudoaneurysm in a child with Job syndrome, who presented with massive hemoptysis. Emergent endovascular management was performed with percutaneous coil occlusion of the feeding artery.


Assuntos
Falso Aneurisma/cirurgia , Embolização Terapêutica , Síndrome de Job/complicações , Artéria Pulmonar , Falso Aneurisma/complicações , Falso Aneurisma/diagnóstico por imagem , Criança , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Síndrome de Job/diagnóstico , Artéria Pulmonar/diagnóstico por imagem , Resultado do Tratamento
16.
Rev Med Interne ; 39(5): 332-338, 2018 May.
Artigo em Francês | MEDLINE | ID: mdl-29397233

RESUMO

Hyper-IgE may be found under many pathological conditions. The role of IgE is essentially associated with the occurrence of allergic manifestations, which may be accompanied by an increase of their serum levels. Elevation of total IgE has also been reported in association with certain rare genetic immune deficiencies called hyper-IgE syndromes. Other circumstances such as infectious diseases, tumors or autoimmune diseases may also be accompanied by an excessive synthesis of IgE. Considering the diversity of these situations, discussion of the prognostic value of total IgE is useful to the internist.


Assuntos
Imunoglobulina E/sangue , Síndrome de Job/diagnóstico , Citocinas/sangue , Humanos , Medicina Interna , Síndrome de Job/terapia
18.
J Pediatr Hematol Oncol ; 40(6): e380-e382, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-28902078

RESUMO

BACKGROUND: Hyper-immunoglobulin E syndrome (HIES) is a rare primary immunodeficiency disease characterized by recurrent infections and elevated levels of serum immunoglobulin E, usually over 2000 IU/mL. Recurrent and chronic infection of the epidermis and squamous epithelium may also be a cause of squamous cell carcinoma (SCC). SCC is rare with HIES. CASE REPORT: A 17-year-old male patient who was diagnosed as HIES was admitted with purulent right ear discharge. The patient had a history of eczema starting from the age of 7 months and a history of recurrent middle ear infection starting from the age of 5. Biopsy specimens were taken from the lesion in the external auditory canal, and the lesion was reported as SCC. CONSLUSION: Patients with autosomal recessive HIES are at an increased risk for infections and malignancies. SCC should be considered in the differential diagnosis of the patients presenting with recurrent middle ear infections and immunodeficiency.


Assuntos
Carcinoma de Células Escamosas , Neoplasias da Orelha , Síndrome de Job , Neoplasias Cutâneas , Adolescente , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Neoplasias da Orelha/diagnóstico , Neoplasias da Orelha/genética , Neoplasias da Orelha/patologia , Humanos , Síndrome de Job/diagnóstico , Síndrome de Job/genética , Síndrome de Job/patologia , Masculino , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia
19.
Eur Ann Allergy Clin Immunol ; 49(5): 231-234, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28884991

RESUMO

Summary: We describe the case of a 24-year-old male with hyper-IgE syndrome (HIES) which was diagnosed at 4 years of age and died from a very rare cardiac complication. He had typical clinical and laboratory manifestations of HIES, including total serum IgE as high as > 100,000 IU/mL. Stem cell transplantation was not available. During the 20-year follow-up, he suffered numerous various infections of the skin and deep organs, partial lung resection, as well as multiple bone fractures. At age 24, he developed acute decompensated heart failure associated with elevated serum troponin I and brain natriuretic protein. Two-dimensional echocardiogram revealed global hypokinesis of the left ventricle with estimated ejection fraction 20-25%, and catheterization revealed ectasia of multiple coronary arteries. Endomyocardial biopsy showed lymphocytic myocarditis, focal necrosis, mild fibrosis, and myxoid degeneration, but cultures were negative. The patient improved on corticosteroid therapy and was discharged on heart failure therapy and external defibrillator. Six weeks later, he developed supraventricular tachycardia and persistent global hypokinesis and was treated with amiodarone. A trial of intravenous immunoglobulin was initiated and was repeated as outpatient every four weeks for four times. However, his cardiac function did not improve and he developed severe hypotension and pulseless electrical activity arrest. Resuscitation was unsuccessful. To the best of our knowledge, this is the first reported case of HIES complicated with lymphocytic myocarditis. Both immunologists and cardiologists need to be aware of such a complication and practice caution in using immunosuppressants when the patient's immune status is markedly compromised.


Assuntos
Hipergamaglobulinemia/imunologia , Imunoglobulina E/imunologia , Síndrome de Job/imunologia , Miocardite/imunologia , Biópsia , Evolução Fatal , Humanos , Hipergamaglobulinemia/complicações , Hipergamaglobulinemia/diagnóstico , Hospedeiro Imunocomprometido , Imunoglobulina E/sangue , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Síndrome de Job/complicações , Síndrome de Job/diagnóstico , Masculino , Miocardite/diagnóstico , Miocardite/fisiopatologia , Miocardite/terapia , Resultado do Tratamento , Adulto Jovem
20.
J Neurovirol ; 23(4): 632-636, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28643229

RESUMO

We, herein, report a 23-year-old male with a rare inherited immunodeficiency disease, hyperimmunoglobulin IgE syndrome (HIES), who developed progressive multifocal leukoencephalopathy (PML) and lymphoma simultaneously. Primary immunodeficiency of the patient has remained undiagnosed until adulthood. PML is a severe demyelinating disease of the central nervous system caused by John Cunningham virus. HIES is a rare, inherited immunodeficiency characterized by high serum levels of IgE, recurrent staphylococcal infection, eczema, and hypereosinophilia. PML may accompany primary immunodeficiency syndromes, but the association with HIES is exceedingly rare. We discuss the imaging findings, medical management, and a review of related literature on primary immunodeficiency cases complicating with PML.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Eczema/diagnóstico , Síndrome Hipereosinofílica/diagnóstico , Síndrome de Job/diagnóstico , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Linfoma/diagnóstico , Eczema/tratamento farmacológico , Eczema/imunologia , Eczema/patologia , Evolução Fatal , Humanos , Síndrome Hipereosinofílica/tratamento farmacológico , Síndrome Hipereosinofílica/imunologia , Síndrome Hipereosinofílica/patologia , Imunoglobulina E/sangue , Vírus JC/isolamento & purificação , Vírus JC/patogenicidade , Síndrome de Job/tratamento farmacológico , Síndrome de Job/imunologia , Síndrome de Job/patologia , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Leucoencefalopatia Multifocal Progressiva/imunologia , Leucoencefalopatia Multifocal Progressiva/patologia , Linfoma/tratamento farmacológico , Linfoma/imunologia , Linfoma/patologia , Masculino , Falha de Tratamento , Adulto Jovem
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