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1.
Gen Thorac Cardiovasc Surg ; 67(10): 884-890, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31346956

RESUMO

OBJECTIVE: We investigated the merits and demerits of right cervical open surgery with right trans-cervical pneumomediastinal approach in mediastinoscopic esophagectomy. METHODS: Ten thoracic esophageal cancer patients were treated using this approach. Under pneumomediastinum via a right neck incision, the right cervical and upper mediastinal paraesophageal lymph nodes were dissected. The left recurrent nerve lymph nodes were dissected using a left trans-cervical pneumomediastinal approach. The subaortic arch to the left tracheobronchial lymph nodes was dissected with a combined right and left trans-cervical crossover approach. RESULTS: The average number of dissected lymph nodes among the right cervical and upper mediastinal paraesophageal lymph nodes identified with a right cervical open/right trans-cervical mediastinoscopic/right thoracoscopic approach was 3.2/4.0/0.6, respectively. The average number of dissected lymph nodes among the subaortic arch to the left tracheobronchial lymph nodes with a right trans-cervical mediastinoscopic/right thoracoscopic approach was 1.5/0.6, respectively. These findings indicate that, without using the right trans-cervical pneumomediastinal approach, it might be impossible to successfully remove some of the right cervical and upper mediastinal paraesophageal lymph nodes and the subaortic arch to the left tracheobronchial lymph nodes lymph nodes. Regarding surgical complications, one case of bilateral recurrent nerve palsy as well as two cases on the right and two cases on the left were noted. CONCLUSIONS: Although the rate of recurrent nerve palsy should still be reduced, a bilateral (especially right-sided) trans-cervical pneumomediastinal approach is an available option for achieving sufficient upper mediastinal lymph node dissection and esophagectomy.

2.
Pediatr Diabetes ; 20(7): 1035-1040, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31322807

RESUMO

Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) syndrome is an autoimmune disorder caused by the dysfunction of FOXP3, which leads to regulatory T-(Treg) cell dysfunction and subsequently autoimmunity including type 1 diabetes mellitus (T1D). Presently, allogeneic hematopoietic stem cell transplantation (HSCT) is a potential curative therapy for IPEX syndrome, but not for T1D. Generally, after complete loss of pancreatic ß-cells, HSCT cannot improve the prognosis of T1D. Here, we report the case of a 16-year-old adolescent with late-onset of FOXP3 R347H mutation associated IPEX syndrome with T1D, where insulin dependency was ameliorated following HSCT. This patient with insulin-dependent diabetes mellitus required insulin dosage of 1.28 U/kg/day for 1 month before HSCT. Although the results of glucose homeostasis before HSCT revealed impaired insulin secretion and low ΔC-peptide immunoreactivity (CPR, 1.0 ng/mL), the patient withdrew insulin infusion and remained euglycemic at 15 months after HSCT, and had normal ß-cell function with improved ΔCPR (3.4 ng/mL) at 20 months after HSCT. The present case suggests that HSCT for T1D-associated IPEX syndrome improves Treg deficiency and prevents elimination of ß-cells. We speculate that the period from the onset of T1D to HSCT could affect the therapeutic efficacy for T1D with IPEX, and early intervention with HSCT before or immediately after the onset of DM can rescue ß-cells and remit T1D completely. Our study elaborates not only the therapeutic strategy for T1D with IPEX, but also the pathogenic mechanism in general T1D.

3.
Rinsho Ketsueki ; 60(6): 708-715, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31281164

RESUMO

Lymphoproliferative disorders (LPDs) are caused by dysregulated lymphocyte proliferation and include polyclonal benign and monoclonal malignant diseases. LPDs frequently occur in immunocompromized patients, particularly those with primary immunodeficiency disease (PID), a monogenic disease. PID-associated LPD corresponds to inherited LPD. Here, we describe inherited LPD and focus on IKZF1-associated diseases and Epstein-Barr virus-associated LPD, such as ZAP70 deficiency and X-linked lymphoproliferative syndrome type 1 with somatic reversion mosaicism. Disclosing the pathogenesis of inherited LPDs would lead to a broad understanding of LPDs and development of new treatment strategies.


Assuntos
Síndromes de Imunodeficiência/complicações , Transtornos Linfoproliferativos/genética , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Humanos , Fator de Transcrição Ikaros/genética
4.
Angew Chem Int Ed Engl ; 58(30): 10168-10172, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31211481

RESUMO

Biomimetic epoxide-opening cascades of polyepoxides enable the efficient and rapid construction of polyether frameworks. Herein, we show that the epoxide-opening cascade cyclization that affords tetrahydrofuran products in acidic aqueous media produces tetrahydropyran (THP) in neutral water. THP formation proceeded by simply heating polyepoxides in neutral water and followed a different cyclization mode from those observed so far. The novel cascade cyclization in H2 O was applied to the synthesis of a new nerolidol-type sesquiterpenoid, resulting in revision of the proposed structure and determination of the absolute configuration.

5.
Clin Immunol ; 203: 9-13, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30951839

RESUMO

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is one of the inborn errors of immunity, characterized by impaired function of the regulatory T cells. Clinical manifestations of IPEX syndrome are characterized by various autoimmune diseases with autoantibodies. The comprehensive analysis for autoantibodies using human proteome microarrays in the four patients with IPEX syndrome was performed. The numbers of the highly expressed autoantibody showing relative log2 ratios greater than 1 were 1876, 513, 234 and 831 (mean: 864), respectively. Some novel autoantibodies which could explain the phenotypes of patients, adrenal dysfunction, muscular hypotonia, afibrinogenemia, enteropathy and pancytopenia were identified. Various kinds of autoantibodies targeting testis-specific antigens were also identified. Human proteome microarray is a powerful tool to understand the pathophysiology of IPEX syndrome. The larger cohort analysis using this method will provide further understanding of the impaired immune tolerance in humans.

6.
Esophagus ; 16(2): 214-219, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30737707

RESUMO

PURPOSE: A prospective trial evaluated the feasibility and safety of "mediastinoscopic esophagectomy with lymph node dissection" (MELD). METHODS: Eligible patients had thoracic esophageal squamous cell carcinoma, excluding T4, a bulky primary lesion or distant metastasis. Ten patients were enrolled and treated between September 2015 and March 2018. Additionally, to verify the integrity of the mediastinal lymph node dissection, thoracoscopic observation and lymph node dissection were followed. The primary end point was the integrity of mediastinal lymph node dissection. The secondary end points were the short-term outcomes, including mortality and morbidity. RESULTS: The median number of dissected lymph nodes in the upper mediastinal to cervical region and middle to lower mediastinal region by mediastinoscopy/thoracoscopy was 27/0.5 and 11.5/0, respectively. The median total operation time was 615 min, the median bleeding amount was 476 ml, and the median postoperative hospital stay was 15.5 days. Regarding complications of more than grade III according to the Clavien-Dindo classification, four had sputum excretion difficulty, one had pneumothorax and one had bilateral recurrent nerve palsy, but none required conversion to thoracotomy, and no operative deaths occurred. CONCLUSION: Although the rate of recurrent nerve palsy still should be reduced, our mediastinoscopic lymphadenectomy technique is closely similar to radical esophagectomy.


Assuntos
Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia/métodos , Mediastinoscopia/métodos , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Estudos de Viabilidade , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Excisão de Linfonodo/métodos , Metástase Linfática , Masculino , Neoplasias do Mediastino/cirurgia , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Prospectivos , Toracoscopia/métodos , Resultado do Tratamento
7.
J Pediatr Hematol Oncol ; 41(8): e538-e541, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30676439

RESUMO

X-linked lymphoproliferative syndrome type 1 (XLP1) is a rare congenital immunodeficiency disease. We report the case of an 18-year-old male who developed hemophagocytic lymphohistiocytosis (HLH) with neurologic complications after primary Epstein-Barr virus (EBV) infection and subsequently developed EBV-related central nervous system lymphoma (CNSL). Given the vulnerability to EBV, he was finally diagnosed with XLP1 and treated with whole-brain irradiation along with chemotherapy and subsequent allogeneic hematopoietic stem cell transplantation from a SH2D1A wild-type sibling donor. Although the prognosis for CNSL is generally dismal, reconstitution of the immune system from a normal donor contributed to the patient remaining in remission for 30 months.

8.
Rinsho Ketsueki ; 59(11): 2459-2467, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-30531144

RESUMO

Primary immunodeficiency disease (PID) is characterized by an impaired immune system along with recurrent and severe and/or opportunistic infections; these infections are frequently associated with malignancies and autoimmune disorders. Dysregulation of the adaptive immune system leads to an increased risk of malignancies. Various mechanisms contribute to increased tumor susceptibility in patients with PIDs, which are as follows: defective cell-mediated tumor surveillance, defective apoptosis, specific susceptibility to carcinogens, decreased pathogen clearance and over-active inflammatory responses, defects in cytokinesis, impaired control of virus-infected cells, defects in cell cycle control, and impaired cellular response to genotoxic agents. Moreover, some malignancies might arise owing to germline mutations in PID-causative genes. Here, we describe the close association between PIDs and malignancies, particularly hematopoietic malignancies.


Assuntos
Doenças Autoimunes , Neoplasias Hematológicas , Síndromes de Imunodeficiência , Neoplasias , Humanos , Sistema Imunitário
9.
J Exp Med ; 215(11): 2715-2724, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30337470

RESUMO

Genetic mutations account for many devastating early onset immune deficiencies. In contrast, less severe and later onset immune diseases, including in patients with no prior family history, remain poorly understood. Whole exome sequencing in two cohorts of such patients identified a novel heterozygous de novo IKBKB missense mutation (c.607G>A) in two separate kindreds in whom probands presented with immune dysregulation, combined T and B cell deficiency, inflammation, and epithelial defects. IKBKB encodes IKK2, which activates NF-κB signaling. IKK2V203I results in enhanced NF-κB signaling, as well as T and B cell functional defects. IKK2V203 is a highly conserved residue, and to prove causation, we generated an accurate mouse model by introducing the precise orthologous codon change in Ikbkb using CRISPR/Cas9. Mice and humans carrying this missense mutation exhibit remarkably similar cellular and biochemical phenotypes. Accurate mouse models engineered by CRISPR/Cas9 can help characterize novel syndromes arising from de novo germline mutations and yield insight into pathogenesis.

11.
Rinsho Ketsueki ; 59(10): 2195-2203, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-30305526

RESUMO

Primary immunodeficiencies (PIDs) are inherited disorders caused by an impaired immune system. Because the immune system effects various immune reactions, PIDs present various clinical phenotypes including increased susceptibility to infections, autoimmunity, and malignancies. For adequate diagnosis of PIDs, a systematic approach using clinical genetic sequencing is required. New technologies including next-generation sequencing have become widely available and have led to the identification of novel genetic defects underlying PIDs. In the clinical setting, the identification of genes responsible for impaired immune system function for each PID enables the proposition of more disease-specific treatment options that target the affected signaling pathway. Research on PIDs not only benefits clinical treatment, it also provides a deeper understanding of the human immune system.

12.
Laryngoscope Investig Otolaryngol ; 3(4): 263-267, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30186956

RESUMO

Objective: To assess the usefulness of modified esophagogastroduodenoscopy (EGD) for the detection of second primary malignancies of the esophagus or hypopharynx in patients with oral squamous cell carcinoma and determine the association between the oral lesion subsite and esophageal or hypopharyngeal lesion occurrence. Study Design: Retrospective review. Methods: In total, 166 patients with oral squamous cell carcinoma without any established symptoms of esophageal or hypopharyngeal squamous cell carcinoma underwent modified EGD based on the Valsalva maneuver and U-turn method, image-enhanced endoscopy, and chromoendoscopy using Lugol's iodine for diagnosis. All suspected lesions were biopsied to determine the clinical stages and duplication rates. Odds ratios for the occurrence of duplicate lesions according to the oral lesion subsite were determined. Results: In total, 37 esophageal and 16 hypopharyngeal lesions were detected. According to the Union for International Cancer Control/American Joint Committee on Cancer classification (2009), 75.7% and 5.4% esophageal lesions were classified as stage IA and IB, respectively, and 50% and 18.8% hypopharyngeal lesions as stage II and stage I, respectively. Approximately 59.1% and 50% esophageal and hypopharyngeal lesions, respectively, were successfully treated by endoscopic resection. Oral lesions involving the floor of the mouth were more frequently accompanied by second primary malignancies of the esophagus or hypopharynx. Conclusions: Modified EGD is an effective noninvasive technique for early diagnosis and treatment of second primary malignancies of the esophagus and hypopharynx in patients with oral squamous cell carcinoma. In particular, patients with floor of the mouth lesions need close monitoring for hypopharyngeal and esophageal lesions. Level of Evidence: 3b.

13.
Clin Immunol ; 195: 45-48, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30048690

RESUMO

Patients with CTLA4 mutations present with autoimmune diseases, lymphoproliferation, and hypogammaglobulinemia, and a subset of patients developed Epstein-Barr virus (EBV)-associated malignancies, suggesting an impaired immune function against EBV. Here we investigated EBV infection in individuals with CTLA4 mutations. We measured EBV viral DNA in healthy individuals, individuals with autoimmune diseases, and individuals with CTLA4 mutations. In addition, we evaluated the numbers and function of EBV-specific T cells, invariant NKT cells, and NK cells. More than half of individuals with CTLA4 mutations including asymptomatic ones had detectable EBV DNA, which is a significantly higher frequency with higher viral loads compared with healthy and disease controls. However, individuals with CTLA4 mutations had almost normal immunity against EBV. Individuals with CTLA4 mutations have an increased susceptibility to Epstein-Barr virus infections. Asymptomatic viremia occurs at high frequencies, which can be persistent and can occur in unaffected individuals.

14.
Esophagus ; 15(4): 272-280, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29948479

RESUMO

BACKGROUND: The structure of the fascia in upper mediastinum has already been reported from gross anatomical viewpoints by Sarrazin. But it is necessary to understand meticulous anatomy for thoracoscopic or mediastinoscopic surgery. So herein, we investigate histologically the thin membranous structure made of dense connective tissues. METHODS: Semi-sequential transverse sections of the mediastinum were obtained from three cadavers. Hematoxylin and eosin staining, Elastica van Gieson staining, and Masson trichrome staining were performed to identify the presence and location of the thin membranous structure made of dense connective tissues. RESULTS: The "visceral sheath" and "vascular sheath," as previously described by Sarrazin, were observed histologically. These two thin membranous structures do not surround the esophagus and trachea cylindrically. In addition, the "visceral sheath" on the right side of the upper mediastinum was unclear in comparison to the left side. The "visceral sheath" (on the left side) gradually became unclear, and seemed to almost disappear; the esophagus was found to be very close to the thoracic duct on the caudal side of the bifurcation of the trachea. Although the left recurrent nerve was located inside the "visceral sheath" in all cadavers, the left recurrent nerve lymph nodes were located inside the "visceral sheath" in cadaver 1 and between the "visceral sheath" and "vascular sheath" in cadaver 3. CONCLUSION: The "visceral sheath" around the esophagus in the upper mediastinum was histologically demonstrated; however, the findings were not constant.

15.
J Clin Invest ; 128(7): 3071-3087, 2018 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-29889099

RESUMO

Ikaros/IKZF1 is an essential transcription factor expressed throughout hematopoiesis. IKZF1 is implicated in lymphocyte and myeloid differentiation and negative regulation of cell proliferation. In humans, somatic mutations in IKZF1 have been linked to the development of B cell acute lymphoblastic leukemia (ALL) in children and adults. Recently, heterozygous germline IKZF1 mutations have been identified in patients with a B cell immune deficiency mimicking common variable immunodeficiency. These mutations demonstrated incomplete penetrance and led to haploinsufficiency. Herein, we report 7 unrelated patients with a novel early-onset combined immunodeficiency associated with de novo germline IKZF1 heterozygous mutations affecting amino acid N159 located in the DNA-binding domain of IKZF1. Different bacterial and viral infections were diagnosed, but Pneumocystis jirovecii pneumonia was reported in all patients. One patient developed a T cell ALL. This immunodeficiency was characterized by innate and adaptive immune defects, including low numbers of B cells, neutrophils, eosinophils, and myeloid dendritic cells, as well as T cell and monocyte dysfunctions. Notably, most T cells exhibited a naive phenotype and were unable to evolve into effector memory cells. Functional studies indicated these mutations act as dominant negative. This defect expands the clinical spectrum of human IKZF1-associated diseases from somatic to germline, from haploinsufficient to dominant negative.

16.
Artigo em Inglês | MEDLINE | ID: mdl-29729943

RESUMO

BACKGROUND: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a negative immune regulator. Heterozygous CTLA4 germline mutations can cause a complex immune dysregulation syndrome in human subjects. OBJECTIVE: We sought to characterize the penetrance, clinical features, and best treatment options in 133 CTLA4 mutation carriers. METHODS: Genetics, clinical features, laboratory values, and outcomes of treatment options were assessed in a worldwide cohort of CTLA4 mutation carriers. RESULTS: We identified 133 subjects from 54 unrelated families carrying 45 different heterozygous CTLA4 mutations, including 28 previously undescribed mutations. Ninety mutation carriers were considered affected, suggesting a clinical penetrance of at least 67%; median age of onset was 11 years, and the mortality rate within affected mutation carriers was 16% (n = 15). Main clinical manifestations included hypogammaglobulinemia (84%), lymphoproliferation (73%), autoimmune cytopenia (62%), and respiratory (68%), gastrointestinal (59%), or neurological features (29%). Eight affected mutation carriers had lymphoma, and 3 had gastric cancer. An EBV association was found in 6 patients with malignancies. CTLA4 mutations were associated with lymphopenia and decreased T-, B-, and natural killer (NK) cell counts. Successful targeted therapies included application of CTLA-4 fusion proteins, mechanistic target of rapamycin inhibitors, and hematopoietic stem cell transplantation. EBV reactivation occurred in 2 affected mutation carriers after immunosuppression. CONCLUSIONS: Affected mutation carriers with CTLA-4 insufficiency can present in any medical specialty. Family members should be counseled because disease manifestation can occur as late as 50 years of age. EBV- and cytomegalovirus-associated complications must be closely monitored. Treatment interventions should be coordinated in clinical trials.

17.
Int J Hematol ; 108(3): 319-328, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29777376

RESUMO

Epstein-Barr virus (EBV) is associated with several life-threatening diseases, such as lymphoproliferative disease (LPD), particularly in immunocompromised hosts. Some categories of primary immunodeficiency diseases (PIDs) including X-linked lymphoproliferative syndrome (XLP), are characterized by susceptibility and vulnerability to EBV infection. The number of genetically defined PIDs is rapidly increasing, and clinical genetic testing plays an important role in establishing a definitive diagnosis. Whole-exome sequencing is performed for diagnosing rare genetic diseases, but is both expensive and time-consuming. Low-cost, high-throughput gene analysis systems are thus necessary. We developed a comprehensive molecular diagnostic method using a two-step tailed polymerase chain reaction (PCR) and a next-generation sequencing (NGS) platform to detect mutations in 23 candidate genes responsible for XLP or XLP-like diseases. Samples from 19 patients suspected of having EBV-associated LPD were used in this comprehensive molecular diagnosis. Causative gene mutations (involving PRF1 and SH2D1A) were detected in two of the 19 patients studied. This comprehensive diagnosis method effectively detected mutations in all coding exons of 23 genes with sufficient read numbers for each amplicon. This comprehensive molecular diagnostic method using PCR and NGS provides a rapid, accurate, low-cost diagnosis for patients with XLP or XLP-like diseases.


Assuntos
Análise Mutacional de DNA/métodos , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/genética , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Hospedeiro Imunocomprometido , Lactente , Transtornos Linfoproliferativos/etiologia , Masculino , Pessoa de Meia-Idade , Mutação , Perforina/genética , Proteína Associada à Molécula de Sinalização da Ativação Linfocitária/genética , Adulto Jovem
18.
J Infect Dis ; 218(5): 825-834, 2018 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-29684201

RESUMO

Background: Some patients with genetic defects develop Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (LPD)/lymphoma as the main feature. Hypomophic mutations can cause different clinical and laboratory manifestations from null mutations in the same genes. Methods: We sought to describe the clinical and immunologic phenotype of a 21-month-old boy with EBV-associated LPD who was in good health until then. A genetic and immunologic analysis was performed. Results: Whole-exome sequencing identified a novel compound heterozygous mutation of ZAP70 c.703-1G>A and c.1674G>A. A small amount of the normal transcript was observed. Unlike ZAP70 deficiency, which has been previously described as severe combined immunodeficiency with nonfunctional CD4+ T cells and absent CD8+ T cells, the patient had slightly low numbers of CD8+ T cells and a small amount of functional T cells. EBV-specific CD8+ T cells and invariant natural killer T (iNKT) cells were absent. The T-cell receptor repertoire, determined using next generation sequencing, was significantly restricted. Conclusions: Our patient showed that a hypomorphic mutation of ZAP70 can lead to EBV-associated LPD and that EBV-specific CD8+ T cells and iNKT cells are critically involved in immune response against EBV infection.

19.
SAGE Open Med Case Rep ; 6: 2050313X17753788, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29348920

RESUMO

Wiskott-Aldrich syndrome is a rare X-linked recessive disease resulting from variations in the WAS gene. Wiskott-Aldrich syndrome is sometimes difficult to differentiate from immune thrombocytopenic purpura. A 2-month-old boy was admitted to our hospital for purpura and thrombocytopenia. His mean platelet volume was reported to be normal. Treatment with intravenous immunoglobulins failed to improve the patient's platelet count. Subsequently, an acute cytomegalovirus infection was confirmed by serological testing and antigenemia. The patient was diagnosed with immune thrombocytopenic purpura secondary to a cytomegalovirus infection. However, based on the patient's clinical course and the refractoriness of his condition, Wiskott-Aldrich syndrome was strongly suspected. Through direct sequencing of the genomic DNA of the Wiskott-Aldrich syndrome protein (WASP) gene, we identified a novel missense mutation in exon 3 of the patient's WASP gene (c. 343 C>T, p. H115T), and the patient was diagnosed with Wiskott-Aldrich syndrome at 3 months after onset. Children with Wiskott-Aldrich syndrome are often initially diagnosed with immune thrombocytopenic purpura, which can lead to inappropriate treatment and delays to life-saving definitive therapy. Our findings imply that Wiskott-Aldrich syndrome should be considered as a differential diagnosis in cases of refractory immune thrombocytopenic purpura combined with a cytomegalovirus infection.

20.
Pediatr Blood Cancer ; 65(2)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28960754

RESUMO

Autoimmune diseases in children are rare and can be difficult to diagnose.  Single causative genes have been identified for some pediatric autoimmune diseases. Such orphan diseases may not be diagnosed properly due to the variability of patients' phenotypes. Guidelines for the diagnostic process need to be developed. Fifteen patients with uncharacterized childhood autoimmune diseases with lymphoproliferation that had negative testing for autoimmune lymphoproliferative syndrome were subjected to whole-exome sequencing to identify genes associated with these conditions. Five causative genes, CTLA4, STAT3, TNFAIP3, IKZF1, and PSTPIP1, were identified. These genes should be considered as candidates for uncharacterized childhood autoimmune diseases with lymphoproliferation.


Assuntos
Doenças Autoimunes/genética , Transtornos Linfoproliferativos/genética , Proteínas de Neoplasias/genética , Adolescente , Doenças Autoimunes/complicações , Criança , Pré-Escolar , Feminino , Estudo de Associação Genômica Ampla , Humanos , Transtornos Linfoproliferativos/complicações , Masculino
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