RESUMO
We detected WU polyomavirus (WUPyV) in a bronchoalveolar lavage sample from lungs transplanted into a recipient with Job syndrome by using immunoassays specific for the WUPyV viral protein 1. Co-staining for an epithelial cell marker identified most WUPyV viral protein 1-positive cells as respiratory epithelial cells.
Assuntos
Síndrome de Job/virologia , Infecções por Polyomavirus/diagnóstico , Mucosa Respiratória/virologia , Adulto , Feminino , Células HEK293 , Humanos , Síndrome de Job/cirurgia , Transplante de Pulmão , Polyomavirus/genética , Polyomavirus/isolamento & purificação , Infecções por Polyomavirus/virologiaRESUMO
STAT3 transcription factor signaling in specific T helper cell differentiation has been well described, although the broader roles for STAT3 in lymphocyte memory are less clear. Patients with autosomal-dominant hyper-IgE syndrome (AD-HIES) carry dominant-negative STAT3 mutations and are susceptible to a variety of bacterial and fungal infections. We found that AD-HIES patients have a cell-intrinsic defect in the number of central memory CD4(+) and CD8(+) T cells compared to healthy controls. Naive T cells from AD-HIES patients had lower expression of memory-related transcription factors BCL6 and SOCS3, a primary proliferation defect, and they failed to acquire central memory-like surface phenotypes in vitro. AD-HIES patients showed a decreased ability to control varicella zoster virus (VZV) and Epstein-Barr virus (EBV) latency, and T cell memory to both of these viruses was compromised. These data point to a specific role for STAT3 in human central memory T cell formation and in control of certain chronic viruses.
Assuntos
Memória Imunológica/genética , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Linfócitos T/imunologia , Adolescente , Adulto , Apoptose/genética , Apoptose/imunologia , Sequência de Bases , Criança , Pré-Escolar , Infecções por Vírus Epstein-Barr/imunologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Herpesvirus Humano 3/imunologia , Humanos , Síndrome de Job/genética , Síndrome de Job/imunologia , Síndrome de Job/virologia , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Linfócitos T/metabolismo , Adulto JovemRESUMO
Hyper-immunoglobulin E recurrent infection syndromes (HIES) have distinct features, with identified associated mutations of STAT3, TYK2, and DOCK8. Among 197 Taiwanese patients with primary immunodeficiency on a referral-base of over 23 million inhabitants, STAT3 (R382W and Q469R) and DOCK8 mutations (exon 1-9 deletion) were identified in two patients each from six AD-HIES and five AR-HIES patients, respectively. Aside from decreased Th17 and memory B cells, characteristic facies and pneumatocele were not mutually exclusive regardless of STAT3 and DOCK8 mutations. One with novel DOCK8 deletion had notable cytomegalovirus retinitis, cerebral vasculitis, lead deposition, and amenorrhea. In adolescence, three AD-HIES patients without STAT3 mutation died of myocardial infarction, staphylococcus sepsis, and proteus sepsis while receiving chemotherapy for lymphoma. Close follow-up of the HIES phenotype rather than identifying genetic mutations should be the cornerstone of intervention at this juncture because of relatively lower percentage of identifying mutations in Taiwanese HIES (4/11; 36.5%).
Assuntos
Povo Asiático/genética , Fatores de Troca do Nucleotídeo Guanina/genética , Imunoglobulina E/imunologia , Síndrome de Job , Fator de Transcrição STAT3/genética , TYK2 Quinase/genética , Adolescente , Idoso , Pré-Escolar , Citomegalovirus/crescimento & desenvolvimento , Feminino , Frequência do Gene , Estudos de Associação Genética , Fatores de Troca do Nucleotídeo Guanina/imunologia , Humanos , Imunoglobulina E/biossíntese , Lactente , Recém-Nascido , Síndrome de Job/genética , Síndrome de Job/imunologia , Síndrome de Job/patologia , Síndrome de Job/virologia , Estudos Longitudinais , Masculino , Mutação , Fenótipo , RNA Mensageiro , Retinite/imunologia , Retinite/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição STAT3/imunologia , Análise de Sequência de DNA , TYK2 Quinase/imunologia , TaiwanRESUMO
Hyper-IgE syndrome, also known as Job's syndrome, is a rare primary immunodeficiency that was first described in 1966. This syndrome is associated with an increased risk for malignancies. Here, we report an 18-year-old woman who was frequently hospitalized since childhood because of recurrent pneumonia and urinary tract infection. Multiple erythematous papules and nodules with ulceration were found on her face and right forearm. A skin biopsy showed angiocentric and angiodestructive atypical lymphoid infiltration. In situ hybridization revealed latent Epstein- Barr virus-infected lymphoid cells. Accordingly, this indicates that Epstein-Barr virus infection may have induced the extranodal natural killer/T cell lymphoma in this patient with hyper-IgE syndrome.
Assuntos
Herpesvirus Humano 4/fisiologia , Síndrome de Job/complicações , Síndrome de Job/virologia , Linfoma Extranodal de Células T-NK/complicações , Linfoma Extranodal de Células T-NK/virologia , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/virologia , Adolescente , Feminino , Humanos , Imuno-Histoquímica , Síndrome de Job/patologia , Linfoma Extranodal de Células T-NK/patologia , Neoplasias Cutâneas/patologia , Úlcera/patologia , Úlcera/virologiaRESUMO
A 7-year-old girl presented with large soft masses rising from the nostril and from behind the ear. She had previously been diagnosed as suffering from hyper-IgE syndrome. The presence of herpes simplex virus infection within these lesions was confirmed by biopsy and immunohistochemical studies. The mass lesions did not respond to antibacterial therapy with cefazolin, but improved promptly under antiviral therapy with acyclovir. Immunological studies revealed a mild decrease in the CD4 cell population. Based on our results and on the relevant literature we propose an immunological mechanism for this unique manifestation of herpes simplex virus infection in hyper-IgE syndrome.