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1.
Artigo em Inglês | MEDLINE | ID: mdl-31568798

RESUMO

Genetic testing has become an integral component of the diagnostic evaluation of patients with suspected primary immunodeficiency diseases. Results of genetic testing can have profound impact on clinical management decisions. Clinical providers must therefore demonstrate proficiency in interpreting genetic data. Because of the need for increased knowledge regarding this practice, the American Academy of Allergy, Asthma, and Immunology Primary Immunodeficiency Diseases Committee established a Work Group that reviewed and summarized information concerning appropriate methods, tools, and resources for evaluating variants identified by genetic testing. Strengths and limitations of tests frequently ordered by clinicians were examined. Summary statements and tables were then developed to guide the interpretation process. Finally, the need for research and collaboration was emphasized. Greater understanding of these important concepts will improve the diagnosis and management of patients with suspected primary immunodeficiency diseases.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31472268

RESUMO

Allergy and immunology practitioners are often consulted to evaluate patients with primary immune deficiency disorders (PIDD), in part because of improved awareness and diagnostic evaluation of these once considered rare diseases. This Yardstick provides information regarding state-of-the-art genetic testing to assist in the evaluation of patients with suspected or confirmed immunodeficiencies. Advances in gene sequencing technology has led to increased accessibility to genetic testing, which is essential for diagnosis, treatment, prognosis, and reproductive/family counseling. Methods that allow simultaneous sequence of several genes, known as targeted gene. sequencing (TGS), whole exome sequencing (WES), and whole genome sequencing (WGS), are currently being offered by clinical laboratories. Fluorescent in situ hybridization (FISH) and chromosomal microarray (CMA) are used to detect duplications or deletions of chromosomal regions. Each of these methods has advantages and disadvantages in the diagnostic workup of PIDD. Counseling on genetic implications to patients and their families is necessary before and after test results are available. Interpretation of results requires understanding of both genetic and immunological mechanisms of disease, especially when a newly described gene variant is reported and its association with disease has not been previously demonstrated.

4.
Allergy Asthma Proc ; 40(2): 129-132, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30819283

RESUMO

Background: Common variable immune deficiency (CVID) is a primary immune deficiency due to defective B-cell maturation. Objective: To improve recognition of noninfectious complications of CVID and increase awareness of appropriate interventions for noninfectious complications of CVID. Methods: To review the diagnosis and treatment of CVID with infectious and noninfectious complications. Results: A case of a woman with CVID with autoimmunity and gastrointestinal complications is presented with a discussion of the recognition and treatment of infectious and noninfectious complications. Conclusion: Patients with CVID must be monitored for noninfectious complications, e.g., inflammatory disease of the lung and gastrointestinal tract, because these are associated with decreased survival.

5.
Immunol Allergy Clin North Am ; 39(1): xi-xii, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30466777
7.
Clin Chem ; 62(1): 287-92, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26585925

RESUMO

BACKGROUND: A hemizygous deletion of 1.5-3 Mb in 22q11.2 causes a distinct clinical syndrome with variable congenital defects. Current diagnostic methods use fluorescent in situ hybridization (FISH) or comparative genomic hybridization by microarray to detect the deletion. Neither method is suitable for newborn screening (NBS), since they cannot be performed on dried blood spots (DBS). We developed a MALDI-TOF-MS assay that uses DBS to measure the hemizygous deletion of UFD1L, located within the 22q11.2 region. METHODS: We used DBS from 54 affected patients, previously tested by FISH or microarray, and 100 cord blood samples to evaluate the performance of the MALDI-TOF-MS assay. With a single primer pair, a 97-base oligonucleotide within UFD1L was amplified, as was a sequence on chromosome 18 that differs by 2 nucleotides. A multiplexed, single-base extension reaction created allele-specific products for MALDI-TOF-MS detection. The products were spotted onto a silicon chip, and the height of the spectral peaks identified the relative amounts of target and reference gene. RESULTS: The median ratio of the spectral peak for each UFD1L target:reference base was 0.96 and 0.99 for controls, compared with 0.35 and 0.53 for 22q11 deletion syndrome patients. There was 100% concordance between FISH/microarray and MALDI-TOF-MS in all patients with 22q11.2 deletion syndrome. CONCLUSIONS: This method can be reliably performed with DBS and is suitable for high sample throughput. This assay may be considered for use in population-based NBS for 22q11.2 deletion.


Assuntos
DNA/genética , Teste em Amostras de Sangue Seco , Deleção de Genes , Hemizigoto , Proteínas/genética , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
8.
J Allergy Clin Immunol ; 136(5): 1186-205.e1-78, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26371839

RESUMO

The American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma & Immunology (ACAAI) have jointly accepted responsibility for establishing the "Practice parameter for the diagnosis and management of primary immunodeficiency." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion.


Assuntos
Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/terapia , Comitês Consultivos , Animais , Ensaios Clínicos como Assunto , Gerenciamento Clínico , Medicina Baseada em Evidências , Humanos
9.
Eur Arch Psychiatry Clin Neurosci ; 265(6): 519-24, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25267002

RESUMO

22q11 deletion syndrome (22qDS), also known as DiGeorge syndrome, is a copy number variant disorder that has a diverse clinical presentation including hypocalcaemia, learning disabilities, and psychiatric disorders. Many patients with 22q11DS present with signs that overlap with autism spectrum disorder (ASD) yet the possible physiological mechanisms that link 22q11DS with ASD are unknown. We hypothesized that early childhood hypocalcemia influences the neurobehavioral phenotype of 22q11DS. Drawing on a longitudinal cohort of 22q11DS patients, we abstracted albumin-adjusted serum calcium levels from 151 participants ranging in age from newborn to 19.5 years (mean 2.5 years). We then examined a subset of 20 infants and toddlers from this group for the association between the lowest calcium level on record and scores on the Communication and Symbolic Behavior Scales-Developmental Profile Infant-Toddler Checklist (CSBS-DP ITC). The mean (SD) age at calcium testing was 6.2 (8.5) months, whereas the mean (SD) age at the CSBS-DP ITC assessment was 14.7 (3.8) months. Lower calcium was associated with significantly greater impairment in the CSBS-DP ITC Social (p < 0.05), Speech (p < 0.01), and Symbolic domains (p < 0.05), in regression models adjusted for sex, age at blood draw, and age at the psychological assessment. Nevertheless, these findings are limited by the small sample size of children with combined data on calcium and CSBS-DP ITC, and hence will require replication in a larger cohort with longitudinal assessments. Considering the role of calcium regulation in neurodevelopment and neuroplasticity, low calcium during early brain development could be a risk factor for adverse neurobehavioral outcomes.


Assuntos
Síndrome da Deleção 22q11 , Cálcio/sangue , Hipocalcemia , Transtornos do Neurodesenvolvimento , Habilidades Sociais , Síndrome da Deleção 22q11/sangue , Síndrome da Deleção 22q11/fisiopatologia , Adolescente , Adulto , Transtorno do Espectro Autista/sangue , Transtorno do Espectro Autista/fisiopatologia , Criança , Pré-Escolar , Transtornos da Comunicação/sangue , Transtornos da Comunicação/fisiopatologia , Feminino , Humanos , Hipocalcemia/sangue , Hipocalcemia/fisiopatologia , Lactente , Estudos Longitudinais , Masculino , Transtornos do Neurodesenvolvimento/sangue , Transtornos do Neurodesenvolvimento/fisiopatologia , Adulto Jovem
10.
J Pediatr Gastroenterol Nutr ; 58(5): 561-8, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24792626

RESUMO

OBJECTIVES: Inflammatory bowel disease (IBD) is heritable, but a total of 163 variants commonly implicated in IBD pathogenesis account for only 25% of the heritability. Rare, highly penetrant genetic variants may also explain mendelian forms of IBD and some of the missing heritability. To test the hypothesis that rare loss-of-function mutations can be causative, we performed whole exome sequencing (WES) on 5 members of a 2-generation family of European ancestry presenting with an early-onset and atypical form of IBD. METHODS: WES was performed for all of the 5 family members; the mother and 3 male offspring were affected, whereas the father was unaffected. Mapping, annotation, and filtering criteria were used to reduce candidate variants. For functional testing we performed forkhead box P3 (FOXP3) staining and a T-cell suppression assay. RESULTS: We identified a novel missense variant in exon 6 of the X-linked FOXP3 gene. The c.694A>C substitution in FOXP3 results in a cysteine-to-glycine change at the protein position 232 that is completely conserved among all vertebrates. This variant (heterozygous in the mother and hemizygous in all 3 affected sons) did not impair FOXP3 protein expression, but significantly reduced the ability of the host's T regulatory cells to suppress an inappropriate autoimmune response. The variant results in a milder immune dysregulation, polyendocrinopathy, enteropathy, and X-linked phenotype with early-onset IBD. CONCLUSIONS: Our study illustrates the successful application of WES for making a definitive molecular diagnosis in a case of multiply affected families, with atypical IBD-like phenotype. Our results also have important implications for disease biology and disease-directed therapeutic development.


Assuntos
Exoma/genética , Fatores de Transcrição Forkhead/genética , Doenças Inflamatórias Intestinais/genética , Mutação , Eczema/genética , Feminino , Fatores de Transcrição Forkhead/análise , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Genótipo , Humanos , Lactente , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/patologia , Masculino , Mutação de Sentido Incorreto/genética , Linhagem , Fenótipo , Poliendocrinopatias Autoimunes/genética , Análise de Sequência de DNA , Linfócitos T Reguladores/imunologia
11.
J Fam Psychol ; 26(2): 171-8, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22353006

RESUMO

Low-income African American children have disproportionately higher asthma morbidity and mortality. Education alone may not address barriers to asthma management due to psychosocial stress. This study evaluated the efficacy of a home-based family intervention integrating asthma education and strategies to address stress using a community-based participatory research model. Children age 8 to 13 with poorly controlled asthma and their caregivers were recruited from an urban hospital and an asthma camp. Caregivers with elevated scores on a stress measure were enrolled. Forty-three families were randomized to the 4- to 6-session Home Based Family Intervention (HBFI) or the single session of Enhanced Treatment as Usual (ETAU). All families received an asthma action plan and dust mite covers; children performed spirometry and demonstrated MDI/spacer technique at each home visit. The HBFI addressed family-selected goals targeting asthma management and stressors. Asthma management, morbidity, family functioning, and caregiver stress were assessed at baseline, postintervention, and 6 months after the intervention. ED visits and hospitalizations were ascertained by medical record review for a year after intervention completion. Only one child (5%) in HBFI had an asthma-related hospitalization compared to 7 patients (35%) in ETAU in the year following intervention. Participants in both groups demonstrated improved asthma management and family functioning, and reduced ED visits, symptom days, missed school days, and caregiver stress, but there were no differential treatment effects. The results suggest that a home-based intervention addressing medical and psychosocial needs may prevent hospitalizations for children with poorly controlled asthma and caregivers under stress.


Assuntos
Asma/terapia , Cuidadores/psicologia , Terapia Familiar/métodos , Adolescente , Adulto , Afro-Americanos/etnologia , Asma/economia , Asma/etnologia , Cuidadores/economia , Cuidadores/educação , Criança , Pesquisa Participativa Baseada na Comunidade/economia , Terapia Familiar/economia , Feminino , Seguimentos , Humanos , Entrevista Psicológica , Masculino , Educação de Pacientes como Assunto/economia , Projetos Piloto , Pobreza/economia , Estresse Psicológico/economia , Estresse Psicológico/psicologia , Estresse Psicológico/terapia , Resultado do Tratamento
12.
J Asthma ; 47(3): 317-22, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20394517

RESUMO

OBJECTIVE: The study aims to assess medication adherence and asthma management behaviors and their modifiable predictors in low-income children with persistent asthma. METHODS: The authors conducted a cohort study of 143 children ages 6 to 11 prescribed a daily inhaled controller medicine that could be electronically monitored. Children were recruited from clinics or the emergency department of an urban children's hospital. Data were collected at baseline (T1) and 1 year later (T2). Outcome measures were adherence to controller medications as measured by electronic monitoring devices, observed metered-dose inhaler and spacer technique, exposure to environmental tobacco smoke, and attendance at appointments with primary health care provider. RESULTS: Medication adherence rates varied across medications, with higher rates for montelukast than for fluticasone. Eleven percent to 15% of children demonstrated metered dose inhaler and spacer technique suggesting no drug delivery, and few (5% to 6%) evidenced significant exposure to environmental tobacco smoke. Less than half of recommended health care visits were attended over the study interval. Few psychosocial variables were associated with adherence at T1 or in the longitudinal analyses. Fluticasone adherence at T2 was predicted by caregiver asthma knowledge. CONCLUSIONS: A substantial number of low-income children with persistent asthma receive less than half of their prescribed inhaled controller agent. Patients without Medicaid, with low levels of caregiver asthma knowledge, or with caregivers who began childrearing at a young age may be at highest risk for poor medication adherence.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Adesão à Medicação , Adulto , Afro-Americanos , Idoso , Criança , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade
13.
Adolesc Med State Art Rev ; 20(1): 121-48, ix-x, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19492695

RESUMO

Recurrent infections are a common problem in pediatrics. For most children the frequency of infection decreases over time, but recurring, severe, or unusual infections may be a sign of a primary immunodeficiency disease. Primary immunodeficiency diseases are a heterogeneous group of more than 120 disorders thataffect various parts of the immune system, leading to an increased susceptibility to infection. Many primary immunodeficiency diseases are not diagnosed until late childhood or adolescence. This article will review the diagnosis and treatment of those primary immunodeficiencies that are most likely to present with clinical signs and symptoms during adolescence and young adulthood.


Assuntos
Síndromes de Imunodeficiência , Adolescente , Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/terapia
14.
Lancet ; 370(9596): 1443-52, 2007 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-17950858

RESUMO

Velocardiofacial syndrome, DiGeorge syndrome, and some other clinical syndromes have in common a high frequency of hemizygous deletions of chromosome 22q11.2. This deletion syndrome is very common, affecting nearly one in 3000 children. Here, we focus on recent advances in cardiac assessment, speech, immunology, and pathophysiology of velocardiofacial syndrome. The complex medical care of patients needs a multidisciplinary approach, and every patient has his own unique clinical features that need a tailored approach. Patients with chromosome 22q11.2 deletion syndrome might have high level of functioning, but most often need interventions to improve the function of many organ systems.


Assuntos
Síndrome de DiGeorge , Qualidade de Vida , Animais , Síndrome de DiGeorge/epidemiologia , Síndrome de DiGeorge/genética , Síndrome de DiGeorge/fisiopatologia , Feminino , Humanos , Masculino , Camundongos , Prevalência
15.
J Infus Nurs ; 29(4): 206-13, 2006 Jul-Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16858253
16.
J Pediatr Hematol Oncol ; 28(1): 53-6, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16394896

RESUMO

Monoclonal gammopathies result in hypergammaglobulinemia due to uncontrolled immunoglobulin production by a B-cell clonal population. They have been reported in patients with severe combined immune deficiency (SCID) after hematopoietic cell transplant, and also in normal children and in adults over 50 years of age. Generally they are benign, but malignant transformation does occur. The authors report an unusual case of a monoclonal IgA gammopathy occurring in an infant with SCID, prior to transplantation, due to engraftment of maternal B cells. Transplacental passage of maternal cells may occur more frequently than previously estimated. Persistence of activated B cells occurred even after treatment with rituximab and could pose a risk for the development of malignancies such as multiple myeloma.


Assuntos
Imunoglobulina A/sangue , Troca Materno-Fetal/imunologia , Paraproteinemias/etiologia , Paraproteinemias/patologia , Imunodeficiência Combinada Severa/imunologia , Anticorpos Monoclonais/sangue , Linfócitos B/imunologia , Linfócitos B/patologia , Pré-Escolar , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Linfonodos/imunologia , Linfonodos/patologia , Masculino , Gravidez , Imunodeficiência Combinada Severa/patologia , Imunodeficiência Combinada Severa/terapia
18.
J Immunol ; 174(4): 1787-90, 2005 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-15699104

RESUMO

T cell involvement in Ab responses to thymus-independent type 2 Ags is an immunologic enigma. The identity of these cells and the mechanisms of their TCR engagement to carbohydrate molecules remain unknown. We measured IgG Ab production after immunization with pneumococcal polysaccharides in mice with disruptions in selected genes of the T cell pathway. Nonclassical MHC class I-like CD1 molecules and MHC class I-dependent CD8+ cells were found to be essential. Our findings set forth a new paradigm for humoral responses in which CD1 expression as well as a subset of CD8+ cells are required to provide helper function for Ab production against thymus-independent type 2 polysaccharides, similar to MHC class II-restricted CD4+ cells for protein Ags.


Assuntos
Anticorpos Antibacterianos/biossíntese , Antígenos CD1/fisiologia , Linfócitos T CD8-Positivos/imunologia , Polissacarídeos Bacterianos/imunologia , Streptococcus pneumoniae/imunologia , Animais , Apresentação do Antígeno/genética , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/metabolismo , Antígenos CD1/genética , Antígenos CD1/imunologia , Antígenos CD1/metabolismo , Antígenos T-Independentes/fisiologia , Imunoglobulina G/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Polissacarídeos Bacterianos/administração & dosagem , Polissacarídeos Bacterianos/metabolismo
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