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1.
Indian Pediatr ; 55(8): 693-697, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30218520

RESUMO

We present the case of a 3-month-old girl who was admitted with complaints of loose stools and respiratory distress. She also had a history of rash and alopecia. Laboratory investigations revealed lymphopenia with reduced immunoglobulin G and immunoglobulin A. Lymphocyte subset analysis by flow cytometry revealed T-B+NK+ severe combined immunodeficiency (SCID). She died due to severe pneumonia, shock and pulmonary hemorrhage. Autopsy findings revealed disseminated cytomegalovirus infection in the lung, liver, adrenals and heart. Thymus was found to be dysplastic and showed characteristic histopathologic features of SCID.


Assuntos
Diarreia/etiologia , Insuficiência Respiratória/etiologia , Imunodeficiência Combinada Severa/diagnóstico , Evolução Fatal , Feminino , Humanos , Lactente , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/genética
3.
Rev Med Interne ; 39(4): 297-306, 2018 Apr.
Artigo em Francês | MEDLINE | ID: mdl-29273180

RESUMO

Deficiency of adenosine deaminase 2 (DADA2) is a recently described auto-inflammatory disorder. It is an autosomal recessive inherited disease, caused by mutations in the ADA2 gene (formerly known as CECR1) encoding ADA2 enzyme. Besides its role in the purine metabolism, it has been postulated that ADA2 may act as a growth factor for endothelial cells and in the differenciation of monocytes. Thus, deficiency of ADA2 would lead to endothelial damage and a skewing of monocytes into M1 pro-inflammatory macrophage, causing DADA2 manifestations. Three core clinical features have been described: inflammatory-vascular signs, hematologic abnormalities and immunodeficiency. Clinically, patients display intermittent fever, cutaneous vascular manifestations, such as livedo, ischemic strokes, arthralgia and abdominal pain crisis. Corticosteroids and immunosuppressive agents (i.e. cyclophosphamide, azathioprine, ciclosporin, methotrexate) appear to be poorly effective. Although the mechanism has not been elucidated, anti-TNF agents have been proven efficient in DADA2 and should therefore be used as first line therapy for vasculitis. Role of anti-platelet and anticoagulant therapies in stroke-prophylaxis remains to be discussed, as those patients display a high risk of intracranial bleeding.


Assuntos
Adenosina Desaminase/deficiência , Agamaglobulinemia/diagnóstico , Peptídeos e Proteínas de Sinalização Intercelular/genética , Imunodeficiência Combinada Severa/diagnóstico , Adenosina Desaminase/genética , Agamaglobulinemia/complicações , Agamaglobulinemia/tratamento farmacológico , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Mutação , Fenótipo , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/tratamento farmacológico , Vasculite/tratamento farmacológico , Vasculite/etiologia
4.
Virology ; 513: 108-113, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29055819

RESUMO

Understanding the dynamics of acute viral infection is crucial for developing strategies to prevent and control infection. In this study, lentiviral dynamics in a host without adaptive immunity were examined in order to determine kinetic parameters of infection and quantify the effect of neutralizing antibodies in preventing infection, using mathematical modeling of data from equine infectious anemia virus (EIAV) infection of horses with severe combined immunodeficiency (SCID). Estimated parameters were used to calculate the basic reproductive number and virus doubling time and found that the rate that antibodies neutralized virus was ~18 times greater than the virus clearance rate. These results establish EIAV replication kinetics in SCID horses and the minimal efficacy of antibodies that blocked infection. Furthermore, they indicate that EIAV is at most mildly cytopathic. This study advances our understanding of EIAV infection and may have important implications for the control of other viral infections, including HIV.


Assuntos
Anemia Infecciosa Equina/prevenção & controle , Anemia Infecciosa Equina/virologia , Vírus da Anemia Infecciosa Equina/imunologia , Vírus da Anemia Infecciosa Equina/isolamento & purificação , Carga Viral , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Cavalos , Modelos Teóricos , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/veterinária
5.
Intervirology ; 61(5): 247-254, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30726837

RESUMO

BACKGROUND: Human cosaviruses (HCoSVs) are newly discovered enteric viruses in the Picornaviridae family. They have been described in non-polio acute flaccid paralysis, diarrheal patients, and healthy individuals. They remain rarely documented in immunodeficient patients. OBJECTIVES: This study reports iterative excretion of HCoSVs in a patient with major histocompatibility complex (MHC) class II combined immunodeficiency, a relatively common primary immunodeficiency in consanguineous settings. METHODS: A total of 35 samples were collected from a patient followed for oral polio vaccine strains detection in stool samples during a 57-month period. Detection of HCoSVs in stools was performed by nested RT-PCR in the 5' noncoding region. The genotype identification and screening for recombinant strains was performed by sequencing in the VP1 and 3D genomic regions followed by phylogenetic analysis. RESULTS: The patient was infected with HCoSVs twice at a 3-year interval. The excreted viruses belonged to 2 different genotypes with 2 probable recombinant viruses. During HCoSV infections, the patient was also excreting Sabin-related polioviruses. CONCLUSIONS: This study describes excretion kinetics and genetic characteristics of HCoSVs in a patient with combined immunodeficiency due to MHC class II expression defect. The patient did not have concomitant symptoms related to the HCoSV infection.


Assuntos
Genótipo , Infecções por Picornaviridae/diagnóstico , Infecções por Picornaviridae/virologia , Picornaviridae/classificação , Picornaviridae/isolamento & purificação , Imunodeficiência Combinada Severa/complicações , Pré-Escolar , Técnicas de Genotipagem , Humanos , Estudos Longitudinais , Masculino , Picornaviridae/genética , Reação em Cadeia da Polimerase , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA
6.
Blood ; 130(25): 2718-2727, 2017 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-29021228

RESUMO

The Primary Immune Deficiency Treatment Consortium (PIDTC) is enrolling children with severe combined immunodeficiency (SCID) to a prospective natural history study. We analyzed patients treated with allogeneic hematopoietic cell transplantation (HCT) from 2010 to 2014, including 68 patients with typical SCID and 32 with leaky SCID, Omenn syndrome, or reticular dysgenesis. Most (59%) patients were diagnosed by newborn screening or family history. The 2-year overall survival was 90%, but was 95% for those who were infection-free at HCT vs 81% for those with active infection (P = .009). Other factors, including the diagnosis of typical vs leaky SCID/Omenn syndrome, diagnosis via family history or newborn screening, use of preparative chemotherapy, or the type of donor used, did not impact survival. Although 1-year post-HCT median CD4 counts and freedom from IV immunoglobulin were improved after the use of preparative chemotherapy, other immunologic reconstitution parameters were not affected, and the potential for late sequelae in extremely young infants requires additional evaluation. After a T-cell-replete graft, landmark analysis at day +100 post-HCT revealed that CD3 < 300 cells/µL, CD8 < 50 cells/µL, CD45RA < 10%, or a restricted Vß T-cell receptor repertoire (<13 of 24 families) were associated with the need for a second HCT or death. In the modern era, active infection continues to pose the greatest threat to survival for SCID patients. Although newborn screening has been effective in diagnosing SCID patients early in life, there is an urgent need to identify validated approaches through prospective trials to ensure that patients proceed to HCT infection free. The trial was registered at www.clinicaltrials.gov as #NCT01186913.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Reconstituição Imune , Imunodeficiência Combinada Severa/terapia , Pré-Escolar , Feminino , Genótipo , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Reconstituição Imune/genética , Lactente , Recém-Nascido , Infecção/etiologia , Masculino , Triagem Neonatal , Estudos Prospectivos , Fatores de Risco , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/mortalidade , Análise de Sobrevida , Doadores de Tecidos
7.
Clin Immunol ; 183: 198-200, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28917720

RESUMO

JAK3 is a tyrosine kinase essential for signaling downstream of the common gamma chain subunit shared by multiple cytokine receptors. JAK3 deficiency results in T-B+NK- severe combined immune deficiency (SCID). We report a patient with SCID due to a novel mutation in the JAK3 JH4 domain. The function of the JH4 domain remains unknown. This is the first report of a missense mutation in the JAK3 JH4 domain, thereby demonstrating the importance of the JH4 domain of JAK3 in host immunity.


Assuntos
Janus Quinase 3/metabolismo , Osteomielite/genética , Imunodeficiência Combinada Severa/genética , Coluna Vertebral/patologia , Evolução Fatal , Feminino , Humanos , Lactente , Janus Quinase 3/genética , Mutação , Osteomielite/complicações , Domínios Proteicos , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/patologia
8.
Toxicol Pathol ; 45(5): 593-603, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28782456

RESUMO

We report the identification, pathogenesis, and transmission of a novel polyomavirus in severe combined immunodeficient F344 rats with null Prkdc and interleukin 2 receptor gamma genes. Infected rats experienced weight loss, decreased fecundity, and mortality. Large basophilic intranuclear inclusions were observed in epithelium of the respiratory tract, salivary and lacrimal glands, uterus, and prostate gland. Unbiased viral metagenomic sequencing of lesioned tissues identified a novel polyomavirus, provisionally named Rattus norvegicus polyomavirus 2 (RatPyV2), which clustered with Washington University (WU) polyomavirus in the Wuki clade of the Betapolyomavirus genus. In situ hybridization analyses and quantitative polymerase chain reaction (PCR) results demonstrated viral nucleic acids in epithelium of respiratory, glandular, and reproductive tissues. Polyomaviral disease was reproduced in Foxn1rnu nude rats cohoused with infected rats or experimentally inoculated with virus. After development of RatPyV2-specific diagnostic assays, a survey of immune-competent rats from North American research institutions revealed detection of RatPyV2 in 7 of 1,000 fecal samples by PCR and anti-RatPyV2 antibodies in 480 of 1,500 serum samples. These findings suggest widespread infection in laboratory rat populations, which may have profound implications for established models of respiratory injury. Additionally, RatPyV2 infection studies may provide an important system to investigate the pathogenesis of WU polyomavirus diseases of man.


Assuntos
Infecções por Polyomavirus , Polyomavirus , Infecções Tumorais por Vírus , Animais , Feminino , Pulmão/virologia , Masculino , Metagenômica , Polyomavirus/genética , Polyomavirus/isolamento & purificação , Polyomavirus/patogenicidade , Infecções por Polyomavirus/complicações , Infecções por Polyomavirus/genética , Infecções por Polyomavirus/transmissão , Infecções por Polyomavirus/virologia , Ratos , Análise de Sequência de DNA , Imunodeficiência Combinada Severa/complicações , Distribuição Tecidual , Infecções Tumorais por Vírus/complicações , Infecções Tumorais por Vírus/genética , Infecções Tumorais por Vírus/transmissão , Infecções Tumorais por Vírus/virologia , Carga Viral/genética
9.
Pediatr Rheumatol Online J ; 15(1): 67, 2017 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-28830446

RESUMO

BACKGROUND: Loss-of-function CECR1 mutations cause polyarteritis nodosa (PAN) with childhood onset, an autoinflammatory disorder without significant signs of autoimmunity. Herein we describe the unusual presentation of an autoimmune phenotype with constitutive type I interferon activation in siblings with adenosine deaminase 2 (ADA2) deficiency. CASE PRESENTATION: We describe two siblings with early-onset recurrent strokes, arthritis, oral ulcers, discoid rash, peripheral vascular occlusive disease and high antinuclear antibody titers. Assessment of interferon signatures in blood revealed constitutive type I interferon activation. Aicardi-Goutières syndrome (AGS) was suspected, but no mutation in the known AGS genes were detected. Whole exome sequencing identified compound heterozygosity for a known and a novel mutation in the CECR1 gene. Functional consequences of the mutations were demonstrated by marked reduction in ADA2 catalytic activity. CONCLUSIONS: Our findings demonstrate that ADA2 deficiency can cause an unusual autoimmune phenotype extending the phenotypic spectrum of PAN. Constitutive interferon I activation in patient blood suggests a possible role of type I interferon in disease pathogenesis which may have therapeutic implications.


Assuntos
Adenosina Desaminase/deficiência , Agamaglobulinemia/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Interferon Tipo I/metabolismo , Poliarterite Nodosa/genética , Imunodeficiência Combinada Severa/genética , Adenosina Desaminase/genética , Agamaglobulinemia/complicações , Agamaglobulinemia/diagnóstico , Criança , Pré-Escolar , Humanos , Lactente , Interferon Tipo I/genética , Masculino , Mutação , Linhagem , Fenótipo , Poliarterite Nodosa/complicações , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/diagnóstico
12.
Clin Genet ; 92(6): 664-668, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28657137

RESUMO

Otofaciocervical syndrome (OFCS) is a rare disorder characterized by facial anomalies, cup-shaped low-set ears, preauricular fistulas, hearing loss, branchial defects, skeletal anomalies, and mild intellectual disability. Autosomal dominant cases are caused by deletions or point mutations of EYA1. A single family with an autosomal recessive form of OFCS and a homozygous missense mutation in PAX1 gene has been described. We report whole exome sequencing of 4 members of a consanguineous family in which 2 children, showing features of OFCS, expired from severe combined immunodeficiency (SCID). To date, the co-occurrence of OFCS and SCID has never been reported. We found a nonsense homozygous mutation in PAX1 gene in the 2 affected children. In mice, Pax1 is required for the formation of specific skeletal structures as well as for the development of a fully functional thymus. The mouse model strongly supports the hypothesis that PAX1 depletion in our patients caused thymus aplasia responsible for SCID. This report provides evidence that bi-allelic null PAX1 mutations may lead to a multi-system autosomal recessive disorders, where SCID might represent the main feature.


Assuntos
Síndrome Brânquio-Otorrenal/genética , Deficiência Intelectual/genética , Mutação , Fatores de Transcrição Box Pareados/genética , Imunodeficiência Combinada Severa/genética , Animais , Sequência de Bases , Síndrome Brânquio-Otorrenal/complicações , Síndrome Brânquio-Otorrenal/imunologia , Síndrome Brânquio-Otorrenal/patologia , Criança , Consanguinidade , Modelos Animais de Doenças , Exoma , Família , Feminino , Expressão Gênica , Genes Recessivos , Humanos , Lactente , Deficiência Intelectual/complicações , Deficiência Intelectual/imunologia , Deficiência Intelectual/patologia , Masculino , Camundongos , Marrocos , Fatores de Transcrição Box Pareados/imunologia , Linhagem , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/imunologia , Imunodeficiência Combinada Severa/patologia , Timo/anormalidades , Timo/imunologia , Timo/metabolismo
13.
Microb Pathog ; 109: 114-119, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28552805

RESUMO

Severe combined immunodeficiency (SCID) is a potentially fatal primary immunodeficiency (PID) that is caused by mutations in genes such as IL2RG, JAK3, IL7RA, RAG1, RAG2, and ADA. The products of these genes are involved in the development of several immune cells such as T, B and natural killer (NK) cells. Most of the SCID forms are autosomal recessive with the exception of IL2RG defects that cause an X-linked SCID. Among the different SCID types, there is a rare SCID form called leaky SCID, which is less severe when compared to the other classical SCID phenotypes. Leaky SCID can be caused by hypomorphic mutations in RAG1 and RAG2 that result in only partial loss of enzymatic function of the proteins respectively encoded by these genes. Here we report a novel missense mutation (c. 307C > T/p.H103Y) in the RAG1 gene in a patient with leaky SCID. In addition, we characterize the clinical and immunological features of this patient that developed along with other severe and recurrent infections such as mycobacterial diseases (BCGitis and pulmonary tuberculosis), the first occurrence of Chromobacterium violaceum in a patient with SCID. Understanding the increased susceptibility to mycobacteria presented by the patient, in which a functional investigation of IL-12/IFN-γ axis was performed, which demonstrated reduced production of IFN-γ in the supernatans of peripheral blood mononuclear cell cultures from the patient compared with those from healthy subjects. In conclusion, our data expands the molecular and clinical spectrum associated with the leaky SCID phenotype.


Assuntos
Chromobacterium/patogenicidade , Proteínas de Homeodomínio/genética , Mutação de Sentido Incorreto , Mycobacterium/patogenicidade , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/imunologia , Linfócitos B/imunologia , Vacina BCG , Proteínas de Ligação a DNA/genética , Feminino , Variação Genética , Humanos , Interferon gama/metabolismo , Subunidade gama Comum de Receptores de Interleucina/metabolismo , Interleucina-12/metabolismo , Leucócitos Mononucleares , Pulmão/microbiologia , Pulmão/patologia , Mycobacterium tuberculosis/patogenicidade , Proteínas Nucleares/genética , Paquistão , Linhagem , Fenótipo , Estrutura Terciária de Proteína , Alinhamento de Sequência , Linfócitos T/imunologia , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/complicações
14.
Clin Immunol ; 178: 74-78, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28161407

RESUMO

Major histocompatibility complex (MHC) class I deficiency syndrome is a rare primary immunodeficiency caused by mutations in the peptide transporter complex associated with antigen presentation (TAP) gene which plays a crucial role in intracellular peptide antigen presentation. A few cases have been reported to date. Recurrent sinopulmonary infections and skin ulcers are the main characteristics of the syndrome. Here we report two siblings diagnosed with TAP1 deficiency syndrome associated only with recurrent sinopulmonary infections with the description of a novel mutation leading to a premature stop codon in TAP1 gene and review of the relevant literature. Both of the siblings had recurrent sinopulmonary infections since childhood, responded to antibiotherapy well, neither of them had hospitalization history because of infections. One had chronic hepatitis B infection which may possibly be related to TAP1 gene defect.


Assuntos
Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/genética , Mutação da Fase de Leitura , Imunodeficiência Combinada Severa/genética , Adolescente , Adulto , Bronquiectasia/etiologia , Bronquiectasia/imunologia , Feminino , Hepatite B Crônica/etiologia , Hepatite B Crônica/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Masculino , Recidiva , Infecções Respiratórias/etiologia , Infecções Respiratórias/imunologia , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/imunologia , Irmãos , Adulto Jovem
15.
Acta Neuropathol ; 133(1): 139-147, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27770235

RESUMO

Routine childhood vaccination against measles, mumps and rubella has virtually abolished virus-related morbidity and mortality. Notwithstanding this, we describe here devastating neurological complications associated with the detection of live-attenuated mumps virus Jeryl Lynn (MuVJL5) in the brain of a child who had undergone successful allogeneic transplantation for severe combined immunodeficiency (SCID). This is the first confirmed report of MuVJL5 associated with chronic encephalitis and highlights the need to exclude immunodeficient individuals from immunisation with live-attenuated vaccines. The diagnosis was only possible by deep sequencing of the brain biopsy. Sequence comparison of the vaccine batch to the MuVJL5 isolated from brain identified biased hypermutation, particularly in the matrix gene, similar to those found in measles from cases of SSPE. The findings provide unique insights into the pathogenesis of paramyxovirus brain infections.


Assuntos
Encéfalo/virologia , Encefalite Viral/virologia , Vacina contra Caxumba/efeitos adversos , Vírus da Caxumba/isolamento & purificação , Biópsia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Doença Crônica , Encefalite Viral/complicações , Encefalite Viral/diagnóstico por imagem , Encefalite Viral/terapia , Evolução Fatal , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Vírus da Caxumba/genética , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/diagnóstico por imagem , Imunodeficiência Combinada Severa/terapia
16.
Pediatr Pulmonol ; 52(2): E4-E6, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27875026

RESUMO

CHARGE (coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, and ear anomalies/deafness) syndrome is a rare genetic disorder caused by CHD7 mutation and is related to immunodeficiency. A 6-month-old girl with right lung agenesis, congenital heart defects, and ear anomalies developed repeated and serious respiratory infection for a short period. She was clinically diagnosed with typical CHARGE syndrome with severe combined immunodeficiency (T-, B+, NK-); however, CHD7 mutation was not detected. Disseminated BCG infection did not resolve despite administration of anti-tuberculosis drugs and intravenous immune globulins, and she subsequently died of acute respiratory distress syndrome. Pediatr Pulmonol. 2017;52:E4-E6. © 2016 Wiley Periodicals, Inc.


Assuntos
Adjuvantes Imunológicos/efeitos adversos , Vacina BCG/efeitos adversos , Síndrome CHARGE/complicações , Síndrome do Desconforto Respiratório do Recém-Nascido/etiologia , Imunodeficiência Combinada Severa/imunologia , Tuberculose Pulmonar/etiologia , Anormalidades Múltiplas/diagnóstico por imagem , Evolução Fatal , Feminino , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico por imagem , Humanos , Lactente , Pulmão/anormalidades , Pulmão/diagnóstico por imagem , Pneumopatias/complicações , Pneumopatias/diagnóstico por imagem , Mutação , Mycobacterium bovis , Síndrome do Desconforto Respiratório do Recém-Nascido/imunologia , Imunodeficiência Combinada Severa/complicações , Tomografia Computadorizada por Raios X , Tuberculose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/imunologia
17.
J Innate Immun ; 9(2): 193-202, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27988511

RESUMO

Influenza A viruses (IAV) infect many host species, including humans and pigs. Severe combined immunodeficiency (SCID) is a condition characterized by a deficiency of T, B, and/or natural killer (NK) cells. Animal models of SCID have great value for biomedical research. Here, we evaluated the pathogenesis and the innate immune response to the 2009 H1N1 pandemic IAV (H1N1pdm09) using a recently identified line of naturally occurring SCID pigs deficient in T and B lymphocytes that still have functional NK cells. SCID pigs challenged with H1N1pdm09 showed milder lung pathology compared to the non-SCID heterozygous carrier pigs. Viral titers in the lungs and nasal swabs of challenged SCID pigs were significantly higher than in carrier pigs 7 days postinfection, despite higher levels of IL-1ß and IFN-α in the lungs of SCID pigs. The lower levels of pulmonary pathology were associated with the T and B cell absence in response to infection. The higher viral titers, prolonged shedding, and delayed viral clearance indicated that innate immunity was insufficient for controlling IAV in pigs. This recently identified line of SCID pigs provides a valuable model to understand the immune mechanisms associated with influenza protection and recovery in a natural host.


Assuntos
Endonucleases/metabolismo , Vírus da Influenza A Subtipo H1N1/fisiologia , Influenza Humana/imunologia , Pulmão/fisiologia , Mutação/genética , Infecções por Orthomyxoviridae/imunologia , Imunodeficiência Combinada Severa/imunologia , Animais , Linfócitos B/fisiologia , Modelos Animais de Doenças , Endonucleases/genética , Feminino , Humanos , Imunidade Inata , Pulmão/virologia , Masculino , Proteínas Nucleares/genética , Infecções por Orthomyxoviridae/complicações , Imunodeficiência Combinada Severa/complicações , Suínos , Linfócitos T/fisiologia , Carga Viral
18.
J. investig. allergol. clin. immunol ; 27(5): 299-304, 2017. tab
Artigo em Inglês | IBECS | ID: ibc-167248

RESUMO

Introduction: Severe combined immunodeficiency (SCID) is a life-threatening pediatric disease. We report on the clinical evaluation, immunological assessment, molecular analysis, and outcomes of SCID patients in a tertiary referral center in Iran. Methods: From January 2006 to December 2015, we performed a prospective cohort study in which initial screening and advanced immunological tests were carried out on patients suspected of having SCID. Genetic analysis was also performed to confirm the diagnosis. Results: A total of 63 patients were diagnosed with SCID (43 male [68.3%]). The median age at onset and diagnosis and diagnostic delay were 40 and 110 and 60 days respectively. A total of 49 patients (77.8%) had a history of BCG vaccination, and of these, onethird experienced BCG-associated complications. The most common clinical manifestations were pneumonia, recurrent oral candidiasis, chronic diarrhea, and failure to thrive. Of the thirteen patients who underwent hematopoietic stem cell transplantation, 8 survived and 5 died before they could receive the transplant. Most patients (34.9%) were classified as having T–B–NK+ SCID and had a mutation in the RAG2 or RAG1 gene. Conclusion: Autosomal recessive SCID is the most common type in Iranian patients. Providing high-quality training to physicians and patients’ families to reduce the diagnostic delay should be prioritized. It is also important to raise awareness of live vaccination and to expand stem cell donor registries to speed up the transplantation process (AU)


Introducción: La inmunodeficiencia combinada severa (SCID) es una grave enfermedad pediátrica que puede comprometer la vida del paciente. El artículo recoge la evaluación clínica e inmunológica, el análisis molecular y la supervivencia de los pacientes con SCID atendidos en un hospital de referencia de Irán. Métodos: Desde enero de 2006 a diciembre de 2015, se realizó un estudio prospectivo en los pacientes con SCID en el que se realizó un screening inicial junto a diferentes análisis inmunológicos. Se realizó un análisis genético para confirmar el diagnóstico. Resultados: Sesenta y tres pacientes fueron diagnosticados de SCID, cuarenta y tres (63,8%) de los mismos eran varones. La mediana de la edad de inicio de la enfermedad, diagnóstico y retraso en su diagnóstico, fueron de 40, 110 y 60 días respectivamente. Cuarenta y nueve pacientes (77,8%) recibieron vacunación con BCG y un tercio de los mismos presentó complicaciones como consecuencia de la misma. Las manifestaciones clínicas más frecuentes de estos pacientes fueron: neumonía, candidiasis oral recidivante, diarrea crónica y retraso en el crecimiento. Ocho de los treces pacientes que recibieron trasplante de progenitores hematopoyéticos, lograron sobrevivir. Los restantes pacientes fallecieron antes de poder recibir dicho trasplante. El 34,9% de los pacientes tuvieron T-B-NK+ SCID y la mayoría de los pacientes eran portadores de mutaciones en los genes RAG2 o RAG1. Conclusión: La variante autosómica recesiva de la SCID es la forma más común en los pacientes iraníes. Se debe considerar prioritario proporcionar una formación adecuada a los médicos y las familias para reducir el retraso en el diagnóstico. Es igualmente importante concienciar para evitar la vacunación con gérmenes vivos y expandir los registros de donantes de células madre para agilizar el trasplante de estos pacientes (AU)


Assuntos
Humanos , Recém-Nascido , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/diagnóstico , Transplante de Células-Tronco/métodos , Triagem Neonatal/métodos , Estudos Prospectivos , Estudos de Coortes , Inquéritos e Questionários , Citometria de Fluxo/métodos , Análise Estatística
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