RESUMO
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD can progress to liver cirrhosis and hepatocellular carcinoma (HCC). Recently, the prognosis of NAFLD/NASH has been reported to be dependent on liver fibrosis degree. Liver biopsy remains the gold standard, but it has several issues that must be addressed, including its invasiveness, cost, and inter-observer diagnosis variability. To solve these issues, a variety of noninvasive tests (NITs) have been in development for the assessment of NAFLD progression, including blood biomarkers and imaging methods, although the use of NITs varies around the world. The aim of the Japan NASH NIT (JANIT) Forum organized in 2020 is to advance the development of various NITs to assess disease severity and/or response to treatment in NAFLD patients from a scientific perspective through multi-stakeholder dialogue with open innovation, including clinicians with expertise in NAFLD/NASH, companies that develop medical devices and biomarkers, and professionals in the pharmaceutical industry. In addition to conventional NITs, artificial intelligence will soon be deployed in many areas of the NAFLD landscape. To discuss the characteristics of each NIT, we conducted a SWOT (strengths, weaknesses, opportunities, and threats) analysis in this study with the 36 JANIT Forum members (16 physicians and 20 company representatives). Based on this SWOT analysis, the JANIT Forum identified currently available NITs able to accurately select NAFLD patients at high risk of NASH for HCC surveillance/therapeutic intervention and evaluate the effectiveness of therapeutic interventions.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Fígado/patologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Inteligência Artificial , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , BiomarcadoresRESUMO
Platelet derived growth factor (PDGF) plays a pivotal role in the remodeling of connective tissues. Emerging data indicate the distinctive role of PDGF receptor-α (PDGFRα) in this process. In the present study, the Pdgfra gene was systemically inactivated in adult mouse (α-KO mouse), and the role of PDGFRα was examined in the subcutaneously implanted sponge matrices. PDGFRα expressed in the fibroblasts of Pdgfra-preserving control mice (Flox mice), was significantly reduced in the sponges in α-KO mice. Neovascularized areas were largely suppressed in the α-KO mice than in the Flox mice, whereas the other parameters related to the blood vessels and endothelial cells were similar. The deposition of collagen and fibronectin and the expression of collagen 1a1 and 3a1 genes were significantly reduced in α-KO mice. There was a significantly decrease in the number and dividing fibroblasts in the α-KO mice, and those of macrophages were similar between the two genotypes. Hepatocyte growth factor (Hgf) gene expression was suppressed in Pdgfra-inactivated fibroblasts and connective tissue. The findings implicate the role of PDGFRα-dependent ECM and HGF production in fibroblasts that promotes the remodeling of connective tissue and suggest that PDGFRα may be a relevant target to regulate connective tissue remodeling.
Assuntos
Tecido Conjuntivo/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Animais , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/metabolismo , Contagem de Células , Colágeno/metabolismo , Tecido Conjuntivo/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibronectinas/metabolismo , Imunofluorescência , Fator de Crescimento de Hepatócito/metabolismo , Implantes Experimentais , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neovascularização Fisiológica/efeitos dos fármacos , Pele/citologia , Tamoxifeno/farmacologiaRESUMO
To develop effective drugs for hypogonadism, sarcopenia, and cachexia, we designed, synthesized, and evaluated selective androgen receptor modulators (SARMs) that exhibit not only anabolic effects on organs such as muscles and the central nervous system (CNS) but also neutral or antagonistic effects on the prostate. Based on the information obtained from a docking model with androgen receptor (AR), we modified a hit compound A identified through high-throughput screening. Among the prepared compounds, 1-(4-cyano-1-naphthyl)-2,3-disubstituted pyrrolidine derivatives 17h, 17m, and 17j had highly potent AR agonistic activities in vitro and good tissue selectivity in vivo. These derivatives increased the weight of the levator ani muscle without influencing the prostate and seminal vesicle. In addition, these compounds induced sexual behavior in castrated rats, indicating that the compounds could also act as agonists on the CNS.
Assuntos
Anabolizantes/síntese química , Androgênios/síntese química , Naftóis/síntese química , Pirrolidinas/síntese química , Receptores Androgênicos/metabolismo , Anabolizantes/farmacologia , Androgênios/farmacologia , Animais , Castração , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/metabolismo , Expressão Gênica , Humanos , Masculino , Simulação de Acoplamento Molecular , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Naftóis/farmacologia , Próstata/efeitos dos fármacos , Próstata/metabolismo , Ligação Proteica , Pirrolidinas/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores Androgênicos/genética , Comportamento Sexual Animal/efeitos dos fármacos , Relação Estrutura-Atividade , Testosterona/farmacologiaRESUMO
Syntenin-1 is an intracellular PDZ protein that binds multiple proteins and regulates protein trafficking, cancer metastasis, exosome production, synaptic formation, and IL-5 signaling. However, the functions of Syntenin-1 have not yet been clearly characterized in detail, especially in vivo. In this study, we generated a Syntenin-1 knock out (KO) mouse strain and analyzed the role(s) of Syntenin-1 in IL-5 signaling, because the direct interaction of Syntenin-1 with the cytoplasmic domain of the IL-5 receptor α subunit and the regulation of IL-5 signaling by Syntenin-1 have been reported. Unexpectedly, the number of IL-5-responding cells was normal and the levels of fecal immunoglobulins were rather higher in the Syntenin-1 KO mice. We also found that IgA and IgM production of splenic B cells stimulated in vitro was increased in Syntenin-1 KO mice. In addition, we showed that a distribution of intestinal microbial flora was influenced in Syntenin-1 KO mice. Our data indicate that Syntenin-1 negatively regulates the intestinal immunoglobulin production and has a function to maintain the intestinal homeostasis in vivo. The analysis of Syntenin-1 KO mice may provide novel information on not only mucosal immunity but also other functions of Syntenin-1 such as cancer metastasis and neural development.
Assuntos
Imunoglobulinas/biossíntese , Intestinos/imunologia , Sinteninas/metabolismo , Animais , Formação de Anticorpos/genética , Microbioma Gastrointestinal/genética , Homeostase/genética , Imunidade nas Mucosas/genética , Interleucina-5/metabolismo , Intestinos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais/genética , Sinteninas/genéticaRESUMO
BACKGROUND: Most infants with pneumothorax have underlying conditions. Pneumocystis jirovecii pneumonia (PCP) frequently occurs in patients with severe combined immunodeficiency (SCID). The aim of this study was to determine clinical features of PCP-associated pneumothorax in SCID patients. METHODS: The medical records of four SCID patients with pneumothorax were retrospectively reviewed. RESULTS: All four patients were diagnosed as having SCID at the time of contracting PCP. All patients received mechanical ventilation because of severe respiratory failure. Only one patient was successfully extubated and was alive following hematopoietic stem cell transplantation (HSCT); of the remaining patients, however, two died of respiratory failure, and one patient died of early HSCT-related complications. CONCLUSIONS: Pneumothorax associated with PCP can occur in SCID patients, and they may have a poor prognosis. If pneumothorax occurs in infants, both respiratory management and prompt investigation of the underlying conditions are needed, considering the possibility of PCP associated with SCID.
Assuntos
Pneumocystis carinii , Pneumonia por Pneumocystis/complicações , Pneumotórax/complicações , Imunodeficiência Combinada Severa/complicações , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
Wiskott-Aldrich syndrome (WAS) is caused by a mutation in the WAS gene, and it is clinically characterized by the triad of thrombocytopenia, eczema and immunodeficiency. X-linked thrombocytopenia (XLT), which is a clinically mild form of WAS, is also caused by a WAS gene mutation. Patients with WAS/XLT sometimes also have autoimmune diseases such as IgA nephropathy. Progression of IgA nephropathy may lead to chronic renal failure with a poor prognosis. Here, we describe an XLT patient who also had IgA nephropathy. The patient underwent bone marrow transplantation (BMT) because of an associated-lymphoproliferative disorder, and clinical and histological improvement in his IgA nephropathy was observed after BMT. The amount of galactose-deficient IgA in the patient's serum markedly decreased after BMT. Therefore, immunological reconstitution might improve autoimmune diseases in patients with WAS/XLT.
Assuntos
Transplante de Medula Óssea , Doenças Genéticas Ligadas ao Cromossomo X/complicações , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/terapia , Trombocitopenia/complicações , Trombocitopenia/terapia , Biópsia , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Glomerulonefrite por IGA/diagnóstico , Humanos , Imunoglobulina A/sangue , Rim/patologia , Rim/ultraestrutura , Masculino , Trombocitopenia/diagnóstico , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
Giardiasis is a common cause of diarrhea in undeveloped countries, but is very rare in developed countries. A patient with acute myelogenous leukemia and retinoblastoma presented with a high fever and severe watery diarrhea during induction chemotherapy. On microscopy, cysts were seen in her stool, suggesting Giardia intestinalis, which was confirmed on polymerase chain reaction (PCR). G. intestinalis was also detected in the patient's asymptomatic parents, who may have transmitted it to the patient. Giardiasis should be tested for in patients with severe and persistent diarrhea during chemotherapy, when other etiologies have been excluded. PCR used to amplify the DNA of G. intestinalis is rapid and sensitive.
Assuntos
Antineoplásicos/uso terapêutico , Giardíase/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Animais , DNA de Protozoário/análise , Feminino , Giardia lamblia/genética , Giardíase/diagnóstico , Giardíase/parasitologia , Humanos , Lactente , Leucemia Mieloide Aguda/complicações , Reação em Cadeia da Polimerase , Neoplasias da Retina/complicações , Retinoblastoma/complicaçõesRESUMO
The incidence of lymphoproliferative disease (LPD) is significantly higher in individuals who have congenital, acquired or iatrogenically induced immunodeficiency. Although there are a wide range of LPDs including lymphoma and leukemia, this article only covers LPDs in patients with impaired immune function, which are called immunodeficiency-associated LPDs (ID-LPDs). Three of the four ID-LPD categories recognized by WHO have been selected for discussion: LPD in primary immune disorders, post-transplant LPD and LPD in HIV infection. Because of the high incidence and mortality of ID-LPDs, careful evaluation of the morphology, immunophenotype, genotype, viral status and clinical history is required for accurate diagnosis and treatment. Recently, treatment with monoclonal antibodies (mAbs) has been widely used and developed because of its potential benefits. The aim of this review is to describe new information concerning mAb treatment in LPDs and to draw physicians' attention to mAb therapy, which should be effective for some types of LPD.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Hospedeiro Imunocomprometido , Transtornos Linfoproliferativos/terapia , Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos/uso terapêutico , Humanos , RituximabAssuntos
Agamaglobulinemia/patologia , Células Mieloides/patologia , Neutropenia/etiologia , Imunodeficiência Combinada Severa/patologia , Adenosina Desaminase/sangue , Adenosina Desaminase/deficiência , Agamaglobulinemia/sangue , Agamaglobulinemia/complicações , Pré-Escolar , Humanos , Imunodeficiência Combinada Severa/sangue , Imunodeficiência Combinada Severa/complicaçõesRESUMO
In this case report, we describe successful BMT with RIC in a patient with delayed-onset ADA deficiency. A three-yr-old Japanese boy was diagnosed with delayed-onset ADA deficiency because of recurrent bronchitis, bronchiectasia, and lymphopenia. In addition, autoimmune thyroiditis and neutropenia were present. At four yr of age, he underwent BMT with a RIC regimen, including busulfan and fludarabine, from an HLA-identical healthy sister. Engraftment after BMT was uneventful without GVHD. Decreased ADA levels in blood immediately increased following BMT, and the patient was disease-free 13 months after BMT. These results suggest that BMT with RIC may sufficiently restore immune regulation in delayed-onset ADA deficiency. A longer follow-up period is needed to confirm these observations.
Assuntos
Adenosina Desaminase/deficiência , Agamaglobulinemia/terapia , Transplante de Medula Óssea/métodos , Imunodeficiência Combinada Severa/terapia , Condicionamento Pré-Transplante/métodos , Adenosina Desaminase/imunologia , Agamaglobulinemia/imunologia , Bussulfano/administração & dosagem , Pré-Escolar , Humanos , Doadores Vivos , Masculino , Imunodeficiência Combinada Severa/imunologia , Fatores de Tempo , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/análogos & derivadosAssuntos
Transplante de Células-Tronco Hematopoéticas , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/genética , Transtornos Linfoproliferativos , Mutação , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Sequência de Aminoácidos , Sequência de Bases , Criança , Citometria de Fluxo/métodos , Genes Ligados ao Cromossomo X , Humanos , Linfócitos/metabolismo , Linfo-Histiocitose Hemofagocítica/terapia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/terapia , Transplante Homólogo , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/deficiência , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismoRESUMO
Abstract Recently, the search for stem cells has become focused on fetal appendages such as the amniotic membrane and umbilical cord. Previously, we have shown the existence of stem cells in the amniotic membrane that can differentiate into various cells. In this study, we attempt to characterize and maintain the stemness characteristics of mesenchymal stem cells (MSCs) for Wharton's jelly, an inherent tissue of the umbilical cord. Wharton's jelly cells (WJCs) were isolated, adhered to culture plates, and characterized for stem cell and surface markers expression. They expressed the embryonic stem cell markers Nanog, Oct ¾, and Sox2. On flow cytometric analysis, WJCs predominantly expressed the MSC markers CD73, CD90, and CD105 and did not express the hematopoietic lineage markers CD14, CD34, CD45, and HLA-DR. In floating culture, WJCs could maintain stemness, and they could differentiate to osteogenic, chondrogenic, and adipogenic lineages. In conclusion, WJCs satisfy the criteria of MSCs. Given that extraction of the umbilical cord is not invasive, and the umbilical cord can be obtained without ethical and technical issues, we suggest that WJCs, after maintaining stemness, have a potential contribution to medical treatment for patients, even newborns, with congenital skeletal and cartilage disorders.
Assuntos
Células-Tronco Mesenquimais/citologia , Antígenos CD/imunologia , Antígenos CD/metabolismo , Sequência de Bases , Biomarcadores/metabolismo , Células Cultivadas , Primers do DNA , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The contiguous gene syndrome involving 8p11.2 is recognized as a combined phenotype of both Kallmann syndrome and hereditary spherocytosis, because the genes responsible for these 2 clinical entities, the fibroblast growth factor receptor 1 (FGFR1) and ankyrin 1 (ANK1) genes, respectively, are located in this region within a distance of 3.2Mb. We identified a 3.7Mb deletion of 8p11.2 in a 19-month-old female patient with hereditary spherocytosis. The identified deletion included ANK1, but not FGFR1, which is consistent with the absence of any phenotype or laboratory findings of Kallmann syndrome. Compared with the previous studies, the deletion identified in this study was located on the proximal end of 8p, indicating a pure interstitial deletion of 8p11.21. This patient exhibited mild developmental delay and distinctive facial findings in addition to hereditary spherocytosis. Thus, some of the genes included in the deleted region would be related to these symptoms.
Assuntos
Anquirinas/genética , Anormalidades Craniofaciais/genética , Deficiências do Desenvolvimento/genética , Esferocitose Hereditária/genética , Anquirinas/sangue , Anquirinas/deficiência , Deleção Cromossômica , Cromossomos Humanos Par 8/genética , Feminino , Estudos de Associação Genética , Haploinsuficiência , Humanos , Hibridização in Situ Fluorescente , Lactente , Síndrome de Kallmann/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Esferocitose Hereditária/sangueRESUMO
The N-methyl-D-aspartate (NMDA)-type glutamate receptor plays a key role in excitatory synaptic transmission. The overactivation of the NMDA receptor has been implicated in the development of epileptic seizures. D-Serine is a coagonist of the NMDA receptor and its biosynthesis is catalyzed by serine racemase (SR). Here, we examined the effect of d-serine deficiency on the seizures induced by a single injection of pentylenetetrazole (PTZ) using SR knockout (KO) mice. We found that, compared with wild-type (WT) mice, SR-KO mice showed the attenuation of seizure expression in terms of a significantly shortened duration of generalized seizures and resistance to generalized clonic-tonic seizures. Consistently, immunohistochemical analysis of c-Fos demonstrated that the numbers of cells expressing c-Fos induced by high-dose PTZ in the cerebral cortex, hippocampal CA1, hippocampal CA3, and the basolateral nucleus of the amygdala in WT mice were significantly higher than those in SR-KO mice. Moreover, PTZ induced an increase in extracellular glutamate level in the dentate gyrus of WT mice at two different time phases. However, such a PTZ-induced increase in glutamate level was completely inhibited in SR-KO mice. The present findings suggest that SR may be a target for the development of new therapeutic strategies for epileptic seizures.
Assuntos
Convulsivantes/toxicidade , Suscetibilidade a Doenças/induzido quimicamente , Pentilenotetrazol/toxicidade , Racemases e Epimerases/deficiência , Convulsões/induzido quimicamente , Convulsões/genética , Aminoácidos/metabolismo , Análise de Variância , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Predisposição Genética para Doença , Ácido Glutâmico/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microdiálise , Microscopia Confocal , Proteínas Proto-Oncogênicas c-fos/metabolismo , Convulsões/patologia , Estatísticas não Paramétricas , Fatores de TempoRESUMO
Hemophagocytic lymphohistiocytosis (HLH) is a multisystem inflammatory disorder due to cytokine overproduction from excessively activated lymphocytes and macrophages. HLH has been divided into two subgroups: primary HLH and secondary HLH. Primary HLH includes PRF1, UNC13D, STX11, STXBP2, RAB27A, LYST, SH2D1A and XIAP gene mutations; and secondary HLH is associated with infections, malignancies and autoimmune diseases. Among primary HLH-related genes, SH2D1A and XIAP are genetically responsible for X-linked lymphoproliferative syndrome (XLP) due to signaling-lymphocytic-activation-molecule-associated protein (SAP) and XIAP deficiencies, respectively. XLP is characterized by extreme vulnerability to Epstein-Barr virus infection. The major clinical manifestations of XLP consist of HLH (60%), lymphoproliferative disorder (30%) and dysgammaglobulinemia (30%). Analysis of clinical phenotypes of XLP patients suggests that XLP predominantly shows familial HLH phenotypes, whereas some XLP patients present sporadic HLH. For many decades, clinicians and investigators have been concerned with possible XLP in young boys presenting with Epstein-Barr-virus-associated HLH. This review aims to describe the new knowledge about XLP and to draw the attention of the pediatrician to XLP, which should be differentiated from other forms of HLH.
Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Linfo-Histiocitose Hemofagocítica/etiologia , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/deficiência , Criança , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Linfo-Histiocitose Hemofagocítica/genética , Proteína Associada à Molécula de Sinalização da Ativação Linfocitária , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genéticaAssuntos
Neoplasias de Cabeça e Pescoço/genética , Leucemia Promielocítica Aguda/genética , Leucopenia/genética , Proteínas Nucleares/genética , Proteínas de Fusão Oncogênica/genética , Receptores do Ácido Retinoico/genética , Imunodeficiência Combinada Severa/genética , Neoplasias Cutâneas/genética , Pré-Escolar , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Lactente , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucopenia/complicações , Leucopenia/tratamento farmacológico , Masculino , Nucleofosmina , Receptor alfa de Ácido Retinoico , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
OBJECTIVE: X-linked lymphoproliferative syndrome (XLP) type 1 is a rare immunodeficiency, which is caused by mutations in SH2D1A gene. The prognosis of XLP is very poor, and hematopoietic stem cell transplantation (HSCT) is the only curative therapy. We characterized the clinical features and outcome of Japanese patients with XLP-1. METHODS: We used a combination of flow cytometric analysis and genetic analysis to identify XLP-1 and reviewed the patient characteristics and survival with HSCT. RESULTS: We identified 33 patients from 21 families with XLP-1 in Japan. Twenty-one of the patients (65%) who did not undergo a transplant died of the disease and complications. Twelve patients underwent HSCT, and 11 of these (92%) survived. CONCLUSION: We described the clinical characteristics and outcomes of Japanese patients with XLP-1, and HSCT was the only curative therapy for XLP-1. The rapid and accurate diagnosis of XLP with the combination of flow cytometric assay and genetic analysis is important.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Peptídeos e Proteínas de Sinalização Intracelular/genética , Transtornos Linfoproliferativos/diagnóstico , Adolescente , Adulto , Separação Celular , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Testes Genéticos , Humanos , Lactente , Recém-Nascido , Japão , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/mortalidade , Transtornos Linfoproliferativos/terapia , Masculino , Pessoa de Meia-Idade , Proteína Associada à Molécula de Sinalização da Ativação Linfocitária , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Acute disseminated encephalomyelitis (ADEM) is a monophasic, immune-mediated demyelinating disorder that can appear after either immunizations or, more often, infections. Magnetic resonance imaging of patients shows inflammatory lesions in the brain and spinal cord. An immune-mediated mechanism may play a role in this disease, although its precise pathogenesis remains unclear. In this study, a 2-year-old boy presented with ADEM, and he showed improvement on treatment with high-dose intravenous corticosteroids. At the age of 3 years, the presence of recurrent bronchitis, bronchiectasia, and lymphopenia suggested that the patient was suffering from combined immunodeficiency. The patient was finally diagnosed with delayed onset adenosine deaminase deficiency. Delayed onset adenosine deaminase deficiency is frequently associated with autoimmune diseases, including thyroiditis and cytopenia, both of which were observed in the patient. The ADEM in this patient may be a presentation of delayed onset adenosine deaminase deficiency.
Assuntos
Agamaglobulinemia/complicações , Encefalomielite Aguda Disseminada/etiologia , Imunodeficiência Combinada Severa/complicações , Adenosina Desaminase/deficiência , Adenosina Desaminase/imunologia , Adenosina Desaminase/metabolismo , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Pré-Escolar , Encefalomielite Aguda Disseminada/diagnóstico , Encefalomielite Aguda Disseminada/imunologia , Humanos , Isotipos de Imunoglobulinas/sangue , Isotipos de Imunoglobulinas/imunologia , Contagem de Linfócitos , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/imunologiaRESUMO
BACKGROUND: X-linked lymphoproliferative syndrome (XLP) is a rare inherited immunodeficiency by an extreme vulnerability to Epstein-Barr virus (EBV) infection, frequently resulting in hemophagocytic lymphohistiocytosis (HLH). XLP are now divided into type 1 (XLP-1) and type 2 (XLP-2), which are caused by mutations of SH2D1A/SLAM-associated protein (SAP) and X-linked inhibitor of apoptosis protein (XIAP) genes, respectively. The diagnosis of XLP in individuals with EBV-associated HLH (EBV-HLH) is generally difficult because they show basically similar symptoms to sporadic EBV-HLH. Although EBV-infected cells in sporadic EBV-HLH are known to be mainly in CD8+ T cells, the cell-type of EBV-infected cells in EBV-HLH seen in XLP patients remains undetermined. METHODS: EBV-infected cells in two patients (XLP-1 and XLP-2) presenting EBV-HLH were evaluated by in EBER-1 in situ hybridization or quantitative PCR methods. RESULTS: Both XLP patients showed that the dominant population of EBV-infected cells was CD19+ B cells, whereas EBV-infected CD8+ T cells were very few. CONCLUSIONS: In XLP-related EBV-HLH, EBV-infected cells appear to be predominantly B cells. B cell directed therapy such as rituximab may be a valuable option in the treatment of EBV-HLH in XLP patients.