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1.
BMC Pediatr ; 23(1): 239, 2023 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-37173671

RESUMO

BACKGROUND: D40LG-associated X-linked hyper-IgM syndrome with pulmonary alveolar proteinosis has rarely been reported, and its genotype-phenotypic correlation remains elusive. CASE PRESENTATION: We describe a five-month-old boy with CD40LG mutation (c.516T > A, p.Tyr172Ter) X-linked hyper-IgM syndrome with pulmonary alveolar proteinosis as the first manifestation. The patient completely recovered after immunotherapy and allogeneic hematopoietic stem cell transplantation. In addition, four previously reported patients with CD40LG mutation with pulmonary alveolar proteinosis were also analyzed. All of these patients presented with early onset of pulmonary infections and a good response to immunotherapy. The structural model of CD40LG indicated that all mutations caused the X-linked hyper-IgM syndrome with pulmonary alveolar proteinosis to be located within the tumor necrosis factor homology domain. CONCLUSIONS: A case was presented, and the characteristics of four cases of CD40LG-associated X-linked hyper-IgM syndrome with pulmonary alveolar proteinosis were summarized. The variant locations may explain the phenotypic heterogeneity of patients with the CD40LG mutation.


Assuntos
Síndrome de Imunodeficiência com Hiper-IgM Tipo 1 , Síndrome de Imunodeficiência com Hiper-IgM , Proteinose Alveolar Pulmonar , Masculino , Humanos , Lactente , Proteinose Alveolar Pulmonar/diagnóstico , Proteinose Alveolar Pulmonar/genética , Proteinose Alveolar Pulmonar/terapia , Mutação , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/complicações , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/diagnóstico , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/genética , Ligante de CD40/genética
2.
Front Immunol ; 12: 708837, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335625

RESUMO

The hyper IgM syndromes are a rare group of primary immunodeficiency. The X-linked Hyper IgM syndrome (HIGM), due to a gene defect in CD40L, is the commonest variant; it is characterized by an increased susceptibility to a narrow spectrum of opportunistic infection. A few cases of HIGM patients with Cryptococcal meningoencephalitis (CM) have been described in the literature. Herein we report the case of a young male diagnosed in infancy with HIGM who developed CM complicated by a post-infectious inflammatory response syndrome (PIIRS), despite regular immunoglobulin replacement therapy and appropriate antimicrobial prophylaxis. The patient was admitted because of a headache and CM was diagnosed through detection of Cryptococcus neoformans in the cerebrospinal fluid. Despite the antifungal therapy resulting to negative CSF culture, the patient exhibited persistent headaches and developed diplopia. An analysis of inflammatory cytokines on CSF, as well as the brain MRI, suggested a diagnosis of PIIRS. Therefore, a prolonged corticosteroids therapy was started obtaining a complete resolution of symptoms without any relapse.


Assuntos
Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/complicações , Meningite Criptocócica/etiologia , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Corticosteroides/uso terapêutico , Humanos , Masculino , Meningite Criptocócica/diagnóstico por imagem , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/imunologia , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico por imagem , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Adulto Jovem
3.
Mol Genet Genomic Med ; 9(8): e1732, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34114358

RESUMO

BACKGROUND: X-linked hyper-IgM syndrome (XHIGM) is a rare primary immunodeficiency caused by CD40 ligand defects. METHODS: We identified three patients with XHIGM in Ho Chi Minh City, Vietnam. Whole-exome sequencing, immunological analyses and western blot were performed to investigate phenotypic and genotypic features. RESULTS: Despite showing symptoms typical of XHIGM, including recurrent sinopulmonary infections, oral ulcers and otitis media, the diagnosis was significantly delayed. One patient developed anti-phospholipid syndrome, which has been documented for the first time in XHIGM syndrome. Two patients had elevated IgM levels and all of them had low IgG levels. Exome sequencing revealed mutations in the CD40LG gene: one novel splicing mutation c.156+2T>A and two previously characterised mutations (non-frameshift deletion c.436_438delTAC, stop-gain c.654C>A). Due to these mutations, the CD40 ligand was not expressed in any of the three patients, as demonstrated by western blot analysis. CONCLUSION: This is the first report of XHIGM syndrome in Vietnam indicates that an effective diagnostic strategy, such as sequencing analysis, contributes to reliable diagnosis and subsequent therapy.


Assuntos
Síndrome Antifosfolipídica/genética , Ligante de CD40/genética , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/genética , Fenótipo , Adolescente , Adulto , Síndrome Antifosfolipídica/etiologia , Síndrome Antifosfolipídica/patologia , Criança , Humanos , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/complicações , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/patologia , Masculino , Mutação
4.
Medicine (Baltimore) ; 99(24): e20505, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541472

RESUMO

INTRODUCTION: X-linked hyper-IgM syndrome is a type of primary combined immunodeficiency disorder caused by mutations in CD40 ligand. Opportunistic infections caused by P jirovecii, cytomegalovirus (CMV), or fungi are frequently the first presenting symptom of the patients with X-linked hyper-IgM syndrome. PATIENT CONCERNS: Here, we report a 10-month-old infant who presented with cyanosis and shortness of breath. The infant exhibited no medical or birth history indicating a primary immune deficiency and was first diagnosed with interstitial pneumonia and acute respiratory failure on admission. DIAGNOSES: The infant was diagnosed with Pneumocystis jirovecii pneumonia combined with CMV and fungal infection through gene sequencing by nasopharyngeal swab and G-test. Whole-exome sequencing from a blood sample was performed and identified a functional mutation across the CD40 ligand gene (NM_000074;exon1;C.86_87del) resulting in an amino acid change (P.T29Sfl*18) attributed to X-linked hyper IgM syndrome. INTERVENTIONS: The infant received continuous positive airway pressure ventilation treatment combined with trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia, ganciclovir for CMV, voriconazole for fungal infection and substitution of high-dose immunoglobulin. OUTCOMES: Six months after discharge from our hospital, the infant remained well. CONCLUSION: Opportunistic infections should be suspected in infants presenting with severe interstitial pneumonia. Primary immune deficiency diseases should also be considered in infants diagnosed with opportunistic infections.


Assuntos
Ligante de CD40/genética , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/complicações , Doenças Pulmonares Intersticiais/genética , Humanos , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/diagnóstico por imagem , Lactente , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Masculino , Tomografia Computadorizada por Raios X
5.
J Mycol Med ; 29(3): 273-277, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31409527

RESUMO

Following a fatal case of Cryptococcus neoformans meningitis in a child with X-linked hyper-immunoglobulin M syndrome (XHIGM), we evaluated the fungal isolate in an experimental infection in a mouse model with respect to microbiology, epidemiology, virulence and response to therapy. The minimum inhibitory concentrations for antifungals in the susceptibility test were 0.5mg/L for amphotericin B, 4.0mg/L for fluconazole and 0.12mg/L for voriconazole. Evaluation of pathogenicity by means of an experimental infection in BALB/c mice showed that fungus isolated from the blood and cerebrospinal fluid of the child was able to disseminate, reaching the spleen, lungs and brain, where it caused significant macroscopic alterations in the size and texture of each organ. Treatment of infected mice with amphotericin B reduced the fungal load in the spleen and lungs, but not in the brain.


Assuntos
Cryptococcus neoformans/isolamento & purificação , Cryptococcus neoformans/patogenicidade , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/complicações , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/microbiologia , Meningite Criptocócica/diagnóstico por imagem , Meningite Criptocócica/microbiologia , Anfotericina B/farmacologia , Animais , Antifúngicos/farmacologia , Pré-Escolar , Cryptococcus neoformans/efeitos dos fármacos , Modelos Animais de Doenças , Evolução Fatal , Humanos , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/diagnóstico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Tomografia Computadorizada por Raios X
6.
Medicine (Baltimore) ; 98(7): e14559, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30762803

RESUMO

RATIONALE: Pneumocystis jirovecii causes severe pneumonia in immunocompromised hosts. Human immunodeficiency virus infection, malignancy, solid organ or hematopoietic cell transplantation, and primary immune deficiency compose the risk factors for Pneumocystis pneumonia (PCP) in children, and PCP can be an initial clinical manifestation of primary immune deficiency. PATIENT CONCERNS: A 5-month-old infant presented with cyanosis and tachypnea. He had no previous medical or birth history suggesting primary immune deficiency. He was diagnosed with interstitial pneumonia on admission. DIAGNOSES: He was diagnosed with PCP, and further evaluations revealed underlying X-linked hyper-IgM syndrome. INTERVENTIONS: He was treated with trimethoprim/sulfamethoxazole for PCP, and eventually received allogeneic hematopoietic cell transplantation for hyper-IgM syndrome. OUTCOMES: Twenty months have passed after transplantation without severe complications. LESSONS: PCP should be considered in infants presenting with severe interstitial pneumonia even in the absence of evidence of immune deficiency. Primary immune deficiency should also be suspected in infants diagnosed with PCP.


Assuntos
Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/complicações , Pneumonia por Pneumocystis/complicações , Antibacterianos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Humanos , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/diagnóstico , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/terapia , Lactente , Masculino , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
7.
Curr Res Transl Med ; 67(1): 28-30, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29525420

RESUMO

Hyper IgM (HIGM) syndromes are a complex of primary immunodeficiency disorders. A 4-years-old boy with recurrent fever and chills, dyspnea, sort throat for a month was admitted to emergency department. In the current case, whole exome sequencing followed by Sanger sequencing were employed in order to screen probable functional mutations. Molecular analysis revealed a functional mutation across the CD40L gene (NM_000074: exon5: c.T464C) resulted in amino acid change p.L155P attributed to X-linked hyper IgM syndrome. The findings of the current study signify the critical role of microbial infection as well as XHIGM screening, particularly in those children cases with respiratory symptoms.


Assuntos
Ligante de CD40/genética , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/diagnóstico , Pneumopatias/diagnóstico , Mutação , Pré-Escolar , Humanos , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/complicações , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/genética , Irã (Geográfico) , Pneumopatias/genética , Masculino , Radiografia Torácica , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/genética , Sequenciamento do Exoma
10.
Medicine (Baltimore) ; 96(49): e8989, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29245273

RESUMO

INTRODUCTION: The X-linked hyper-immunoglobulin M syndrome (XHIGM) is an uncommon primary combined immunodeficiency disease caused by CD40L gene mutations. A delayed or missed diagnosis of XHIGM is common and concerning, owing to atypical immunoglobulin profile and phenotype of some patients, low recognition, and limited knowledge of clinicians on XHIGM in some underdeveloped areas. Opportunistic infections are a prominent clinical feature of XHIGM. However, toxoplasma encephalitis occurs sporadically and is extremely rare in patients with XHIGM. DIAGNOSTIC AND THERAPEUTIC PROCEDURE: A 2 years and 10 months' old male suffered from 3 times of serious infection since 1 year and 4 months of age. Although with history of recurrent respiratory infections, protracted diarrhea, persistent or intermittent neutropenia companioned with oral ulcer, and a typical immunoglobulin profile during his second disease attack, the consideration of XHIGM was still completely ignored because of our low recognition and limited knowledge of this disorder. The diagnosis of XHIGM was ultimately confirmed by detection of elevated serum IgM concentration, decreased serum IgG and IgE concentration, and identification of a mutation c.654C>A (p.C218X) in CD40L gene. Given clinical manifestation of lethargy, uncontrollable somnolence and ataxia, a cat/dog exposure history, positive serum Toxoplasma gondii (T gondii) IgM, positive cerebrospinal fluid T gondii PCR results, and typical characteristics of brain magnetic resonance imaging as multiple rings liked nodules lesions in bilateral cerebral hemisphere cortex, bilateral basal ganglia, and dorsal thalamus, the diagnosis of toxoplasmic encephalitis was considered during his third disease attack. Thereafter, oral administration of sulfadiazine and azithromycin, intravenous immunoglobulin, and subcutaneous injection of G-CSF were initiated. Regrettably, the patient abandoned the treatment because of economic factor and died 3 months after discharge. CONCLUSIONS: A more thorough clinical history and some features like recurrent respiratory infections, protracted diarrhea, and persistent or intermittent neutropenia companioned with oral ulcer could increase clinical suspicion of XHIGM. Cerebral toxoplasmosis is rare in patients with XHIGM, but still should be considered. The present study firstly reported a delayed diagnosed case of XHIGM with CD40L gene c.654C>A (p.C218X) mutant complicated with toxoplasma encephalitis in Chinese population, which highlighted the importance of CD40-CD40L interaction in cell-mediated immunity against T gondii.


Assuntos
Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/complicações , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/diagnóstico , Toxoplasmose Cerebral/complicações , Toxoplasmose Cerebral/diagnóstico , Pré-Escolar , Humanos , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/fisiopatologia , Masculino , Toxoplasmose Cerebral/fisiopatologia
11.
Pediatr Int ; 56(6): 911-914, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25521976

RESUMO

Patients with X-linked hyperimmunoglobulin M syndrome (XHIGM) have a defective CD40-CD40 ligand system and further immunoglobulin class-switching. They may present with recurrent infection and malignancy involving the liver, pancreas or biliary tract. We report here a case of poorly differentiated transitional cell carcinoma in a young man with XHIGM even on regular treatment and discuss the possible pathogenesis. Given that the triggering of the CD40-CD40 ligand system has been found to improve tumor immunogenicity in recent studies, future immunotherapy targeting the CD40 ligand for these patients may be feasible to prolong their survival.


Assuntos
Carcinoma de Células de Transição/diagnóstico , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/diagnóstico , Neoplasias Renais/diagnóstico , Adulto , Carcinoma de Células de Transição/complicações , Carcinoma de Células de Transição/terapia , Humanos , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/complicações , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/terapia , Neoplasias Renais/complicações , Neoplasias Renais/terapia , Masculino
12.
J Immunol Res ; 2014: 683160, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25215306

RESUMO

X-linked hyper-IgM syndrome (XHIGM) is one type of primary immunodeficiency diseases, resulting from defects in the CD40 ligand/CD40 signaling pathways. We retrospectively analyzed the clinical and molecular features of 20 Chinese patients diagnosed and followed up in hospitals affiliated to Shanghai Jiao Tong University School of Medicine from 1999 to 2013. The median onset age of these patients was 8.5 months (range: 20 days-21 months). Half of them had positive family histories, with a shorter diagnosis lag. The most common symptoms were recurrent sinopulmonary infections (18 patients, 90%), neutropenia (14 patients, 70%), oral ulcer (13 patients, 65%), and protracted diarrhea (13 patients, 65%). Six patients had BCGitis. Six patients received hematopoietic stem cell transplantations and four of them had immune reconstructions and clinical remissions. Eighteen unique mutations in CD40L gene were identified in these 20 patients from 19 unrelated families, with 12 novel mutations. We compared with reported mutation results and used bioinformatics software to predict the effects of mutations on the target protein. These mutations reflected the heterogeneity of CD40L gene and expanded our understanding of XHIGM.


Assuntos
Povo Asiático/genética , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/diagnóstico , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/genética , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Anemia/etiologia , Vacina BCG/efeitos adversos , Ligante de CD40/genética , Criança , Pré-Escolar , China , Testes Genéticos , Transplante de Células-Tronco Hematopoéticas , Humanos , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/complicações , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/terapia , Lactente , Pessoa de Meia-Idade , Mutação , Infecções por Mycobacterium/etiologia , Prognóstico , Transplante Homólogo , Adulto Jovem
13.
Expert Rev Clin Immunol ; 10(1): 91-105, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24308834

RESUMO

The immunoglobulin class switch recombination deficiency or hyper-IgM syndrome is characterized by normal or elevated serum IgM and low serum levels of other immunoglobulins. Since the first reported patient with hyper-IgM, more than 200 patients with this phenotype resulted from CD40 ligand deficiency have been reported. However, in addition to this common finding, they presented with different manifestations like opportunistic infections, autoimmunity and malignancies each of them are worth a detailed look. In this review, we will focus on different underlying mechanisms of these presentations to review what we have learned from our patients. In the end, we will discuss different treatment options available for these patients using this knowledge.


Assuntos
Ligante de CD40 , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1 , Switching de Imunoglobulina , Animais , Doenças Autoimunes/etiologia , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Doenças Autoimunes/terapia , Ligante de CD40/imunologia , Humanos , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/complicações , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/genética , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/imunologia , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/patologia , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/terapia , Neoplasias/etiologia , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/terapia , Infecções Oportunistas/etiologia , Infecções Oportunistas/genética , Infecções Oportunistas/imunologia , Infecções Oportunistas/patologia , Infecções Oportunistas/terapia
15.
J Clin Immunol ; 32(2): 212-20, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22193914

RESUMO

CD40 ligand (CD40L) deficiency or X-linked hyper-IgM syndrome (X-HIGM) is a well-described primary immunodeficiency in which Pneumocystis jiroveci pneumonia is a common clinical feature. We have identified an unusual high incidence of fungal infections and other not yet described infections in a cohort of 11 X-HIGM patients from nine unrelated Brazilian families. Among these, we describe the first case of paracoccidioidomycosis (PCM) in X-HIGM. The molecular genetic analysis of CD40L was performed by gene sequencing and evaluation of CD40L protein expression. Nine of these 11 patients (82%) had fungal infections. These included fungal species common to CD40L deficiency (P. jiroveci and Candida albicans) as well as Paracoccidioides brasiliensis. One patient presented with PCM at age 11 years and is now doing well at 18 years of age. Additionally, one patient presented with a simultaneous infection with Klebsiella and Acinetobacter, and one with condyloma caused by human papilloma virus. Molecular analysis revealed four previously described CD40L mutations, two novel missense mutations (c.433 T > G and c.476 G > C) resulting in the absence of CD40L protein expression by activated CD4(+) cells and one novel insertion (c.484_485insAA) within the TNFH domain leading to a frame shift and premature stop codon. These observations demonstrated that the susceptibility to fungal infections in X-HIGM extends beyond those typically associated with X-HIGM (P. jiroveci and C. albicans) and that these patients need to be monitored for those pathogens.


Assuntos
Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/complicações , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/genética , Paracoccidioidomicose/complicações , Adolescente , Adulto , Idade de Início , Sequência de Aminoácidos , Sequência de Bases , Brasil/epidemiologia , Ligante de CD40/deficiência , Ligante de CD40/genética , Ligante de CD40/metabolismo , Criança , Pré-Escolar , Estudos de Coortes , Humanos , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/diagnóstico , Isotipos de Imunoglobulinas/sangue , Isotipos de Imunoglobulinas/imunologia , Incidência , Lactente , Contagem de Linfócitos , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Masculino , Dados de Sequência Molecular , Mutação , Paracoccidioidomicose/epidemiologia , Paracoccidioidomicose/patologia , Linhagem , Alinhamento de Sequência , Adulto Jovem
16.
J Allergy Clin Immunol ; 129(3): 778-86, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22154528

RESUMO

BACKGROUND: Patients with X-linked hyper-IgM syndrome (X-HIGM) due to CD40 ligand (CD40L) mutations are susceptible to fungal pathogens; however, the underlying susceptibility mechanisms remain poorly understood. OBJECTIVE: To determine whether monocyte-derived dendritic cells (DCs) from patients with X-HIGM exhibit normal responses to fungal pathogens. METHODS: DCs from patients and controls were evaluated for the expression of costimulatory (CD80 and CD86) and MHC class II molecules and for their ability to produce IL-12 and IL-10 in response to Candida albicans and Paracoccidioides brasiliensis. We also evaluated the ability of C albicans- and P brasiliensis-pulsed mature DCs to induce autologous T-cell proliferation, generation of T helper (T(H)) 17 cells, and production of IFN-γ, TGF-ß, IL-4, IL-5, and IL-17. RESULTS: Immature DCs from patients with X-HIGM showed reduced expression of CD80, CD86, and HLA-DR, which could be reversed by exogenous trimeric soluble CD40L. Most important, mature DCs from patients with X-HIGM differentiated by coculturing DCs with fungi secreted minimal amounts of IL-12 but substantial amounts of IL-10 compared with mature DCs from normal individuals. Coculture of mature DCs from X-HIGM patients with autologous T cells led to low IFN-γ production, whereas IL-4 and IL-5 production was increased. T-cell proliferation and IL-17 secretion were normal. Finally, in vitro incubation with soluble CD40L reversed the decreased IL-12 production and the skewed T(H)2 pattern response. CONCLUSION: Absence of CD40L during monocyte/DC differentiation leads to functional DC abnormalities, which may contribute to the susceptibility to fungal infections in patients with X-HIGM.


Assuntos
Candida albicans/imunologia , Candidíase/imunologia , Células Dendríticas/metabolismo , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/imunologia , Paracoccidioides/imunologia , Paracoccidioidomicose/imunologia , Adolescente , Antígeno B7-1/genética , Antígeno B7-1/metabolismo , Antígeno B7-2/genética , Antígeno B7-2/metabolismo , Ligante de CD40/genética , Ligante de CD40/imunologia , Ligante de CD40/metabolismo , Candida albicans/patogenicidade , Candidíase/complicações , Candidíase/genética , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Proliferação de Células , Células Cultivadas , Criança , Pré-Escolar , Técnicas de Cocultura , Citocinas/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/patologia , Células Dendríticas/virologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/complicações , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/genética , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/genética , Masculino , Mutação/genética , Paracoccidioides/patogenicidade , Paracoccidioidomicose/complicações , Paracoccidioidomicose/genética , Células Th17/imunologia , Células Th17/metabolismo , Células Th17/patologia
17.
Pediatr Neurol ; 41(6): 419-27, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19931163

RESUMO

Patients with CD40 ligand deficiency are susceptible to central nervous system infections, but to date the neurologic progression or long-term outcome of central nervous system complications have not been reported in detail. Characterizing the central nervous system complications of immune deficiencies can lead to the identification of new pathogens. For this study, clinical data were reviewed on patients with both CD40 ligand deficiency and neurodegeneration, identified from a larger cohort of 31 patients. Five patients had progressive neurologic and cognitive decline in the absence of clinical signs of acute fulminant encephalitis, with anatomic brain abnormalities and high mortality (60%). Despite multiple evaluations, no pathogens were identified in four patients, all of whom were on standard intravenous immunoglobulin therapy at illness presentation. This clinical phenotype of progressive decline without acute fulminant encephalitis is similar to chronic enteroviral encephalitis in X-linked agammaglobulinemia, another condition with severe humoral immune defects. Whether infection secondary to subtherapeutic levels of central nervous system immunoglobulin G (IgG), inadequately protective levels of serum IgG, or impaired CD40 ligand-dependent IgG-independent antiviral responses contributed remains undetermined. Emerging gene-chip techniques applied in patients with primary immune deficiencies may identify heretofore unknown viruses. Prospective neurocognitive and evaluation of patients with CD40 ligand deficiency may identify affected patients before overt clinical signs appear.


Assuntos
Ligante de CD40/deficiência , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/complicações , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/patologia , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/patologia , Encéfalo/patologia , Pré-Escolar , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/terapia , Progressão da Doença , Seguimentos , Humanos , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/terapia , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Lactente , Imageamento por Ressonância Magnética , Masculino , Doenças Neurodegenerativas/terapia
18.
Clin Immunol ; 129(3): 455-61, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18805740

RESUMO

X-linked hyper-immunoglobulin M syndrome (XHIGM) is a primary immunodeficiency disorder characterized by severe defects of both cellular and humoral immunity due to impaired expression of CD40 ligand on activated T lymphocytes. Patients with XHIGM usually present with a wide variety of infections caused by common and opportunistic pathogens including Pneumocystis jirovecii. In addition, subjects with XHIGM have an increased risk for hepatocellular and bile duct carcinomas, which are rarely observed in other primary immunodeficiencies. We present here clinical, immunological, and molecular findings of four patients with CD40 ligand deficiency associated with neuroendocrine carcinoma (NEC). NEC developed as a rapidly disseminated solid cancer leading to death in three patients. Data presented here and published previously suggest that CD40 ligand deficiency may predispose patients for the development of NEC. Histochemical findings suggested that CD56, in addition to cytokeratin and chromogranin A, may be a useful marker for early detection of NEC. We conclude that patients with XHIGM should be carefully followed to diagnose and treat NEC, a formidable neuroendocrine cancer.


Assuntos
Carcinoma Neuroendócrino/complicações , Neoplasias do Sistema Digestório/complicações , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/complicações , Adolescente , Ligante de CD40/deficiência , Ligante de CD40/genética , Ligante de CD40/imunologia , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/imunologia , Criança , DNA/química , DNA/genética , Neoplasias do Sistema Digestório/genética , Neoplasias do Sistema Digestório/imunologia , Evolução Fatal , Humanos , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/genética , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/imunologia , Isotipos de Imunoglobulinas/sangue , Masculino
19.
Arch Pathol Lab Med ; 132(5): 847-50, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18466034

RESUMO

Gastroenteropancreatic neuroendocrine tumors are uncommon tumors representing 2% of all gastrointestinal tumors. We report a case of a 21-year-old man with X-linked hyperimmunoglobulin M (hyper-IgM) syndrome who presented with diarrhea and jaundice. An ultrasound and magnetic resonance imaging showed multiple variable-sized lesions in the liver and peripancreatic lymphadenopathy. The morphologic and immunohistochemical features of the biopsies from the liver and lymph node were consistent with poorly differentiated neuroendocrine carcinoma. Hyper-IgM syndrome is a rare primary immunodeficiency disease characterized by low serum IgG, IgA, and IgE levels with normal or elevated IgM levels. These patients are at a higher risk for developing malignancies, particularly adenocarcinoma of the gastrointestinal tract and lymphoma. A review of the literature of gastroenteropancreatic neuroendocrine tumors is presented with the discussion of a possible relationship of these tumors with immunodeficiency.


Assuntos
Neoplasias Gastrointestinais/patologia , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/patologia , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Adulto , Biomarcadores Tumorais/análise , Cromossomos Humanos X/genética , Neoplasias Gastrointestinais/química , Neoplasias Gastrointestinais/complicações , Humanos , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/complicações , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/metabolismo , Hospedeiro Imunocomprometido , Masculino , Tumores Neuroendócrinos/química , Tumores Neuroendócrinos/complicações , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/complicações
20.
Ideggyogy Sz ; 60(5-6): 263-8, 2007 May 30.
Artigo em Húngaro | MEDLINE | ID: mdl-17578275

RESUMO

Progressive multifocal leukoencephalopathy is a rare disease caused by the reactivation of an opportunistic agent, JC virus almost in every cases in immunodeficient conditions. The disease is characterized by multifocal demyelinating lesions of the central nervous system and causes death within a few months. The authors report two patients: a 67 year-old male treated because of chronic lymphoid leukemia, and a 19 year-old male having a hereditary immunodeficiency, X-linked hyper IgM syndrome. In both cases continuously progressive right, later both hemispheric signs were detected. Cerebrospinal fluid was not helpful. Brain MRI showed bilateral large, white matter lesion. The progression was not influenced by the treatment, finally both patient died ten and six weeks after the appearance of first complaints. The diagnosis was confirmed by brain biopsy and autopsy in both cases. Our cases demonstrate that progressive multifocal leukoencephalopathy can develop in various immunodeficiencies.


Assuntos
Encéfalo/patologia , Vírus JC/isolamento & purificação , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/etiologia , Adulto , Idoso , Antivirais/uso terapêutico , Encéfalo/virologia , Quimioterapia Combinada , Evolução Fatal , Humanos , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/complicações , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Leucoencefalopatia Multifocal Progressiva/imunologia , Leucoencefalopatia Multifocal Progressiva/patologia , Leucoencefalopatia Multifocal Progressiva/virologia , Masculino , Infecções por Polyomavirus/complicações , Infecções Tumorais por Vírus/complicações
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