Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 10 de 10
Filtrar
Mais filtros










Tipo de estudo
Intervalo de ano de publicação
1.
Allergol. immunopatol ; 47(2): 141-151, mar.-abr. 2019. tab
Artigo em Inglês | IBECS | ID: ibc-180802

RESUMO

Background: The del22q11 syndrome patients present immunological abnormalities associated to thymus alterations. Up to 75% of them present cardiopathies and thymus is frequently removed during surgery. The thymectomy per se has a deleterious effect concerning lymphocyte subpopulations, and T cell function. When compared to healthy controls, these patients have higher infections propensity of variable severity. The factors behind these variations are unknown. We compared immunological profiles of del22q11.2 Syndrome patients with and without thymectomy to establish its effect in the immune profile. Methods: Forty-six del22q11.2 syndrome patients from 1 to 16 years old, 19 of them with partial or total thymectomy were included. Heart disease type, heart surgery, infections events and thymus resection were identified. Immunoglobulin levels, flow cytometry for lymphocytes subpopulations and TREC levels were determined, and statistical analyses were performed. Results: The thymectomy group had a lower lymphocyte index, both regarding total cell count and when comparing age-adjusted Z scores. Also, CD3+, CD4+ and CD8+ lower levels were observed in this group, the lowest count in those patients who had undergone thymus resection during the first year of life. Their TREC level median was 23.6/μL vs 16.1 miL in the non-thymus group (p = 0.22). No differences were identified regarding immunoglobulin levels or infection events frequencies over the previous year. Conclusion: Patients with del22q11.2 syndrome subjected to thymus resection present lower lymphocyte and TREC indexes when compared to patients without thymectomy. This situation may be influenced by the age at the surgery and the time elapsed since the procedure


No disponible


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Linfócitos T/fisiologia , Subpopulações de Linfócitos T/fisiologia , Timectomia/métodos , Timo/cirurgia , Cromossomos Humanos Par 22/imunologia , Deleção Cromossômica , Citometria de Fluxo , Receptores de Antígenos de Linfócitos T/genética
2.
J Clin Immunol ; 39(1): 65-74, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30569262

RESUMO

PURPOSE: Immunodeficiency is one of the key features of 22q11.2 deletion syndrome (del), and it is seen in approximately 75% of the patients. The degree of immunodeficiency varies widely, from no circulating T cells to normal T cell counts. It has been hypothesized that the low number of T cells may at least in part be due to increased apoptosis of T cells. Increased spontaneous T cell apoptosis has been reported in one patient with 22q11.2del, but this has not been further investigated. METHODS: A national cohort of patients with a proven heterozygous deletion of chromosome 22q11.2 diagnosed by FISH or MLPA and a group of age and sex matched controls were studied. Spontaneous and activation-induced apoptosis, in addition to FAS expression on lymphocytes, were measured using flow cytometry. Serum levels of FASL were analyzed using ELISA. RESULTS: There was no increased spontaneous apoptosis in patients with 22q11.2del. Upon activation, anti-FAS-induced apoptosis was significantly increased in patients compared to those in controls, while there was no difference in activation induced cell death or activated cell autonomous death. We also found a significant increase in expression of FAS on freshly isolated lymphocytes from patients, while there was no difference in serum levels of FASL. Patients with congenital heart defects (CHD) had significantly higher serum levels of FASL compared to non-CHD patients. CONCLUSION: We have shown increased FAS expression on lymphocytes from patients with 22q11.2del as well as increased levels of FASL in patients with CHD. Those changes may contribute to the pathophysiology of the 22q11.2del.


Assuntos
Apoptose/imunologia , Cromossomos Humanos Par 22/genética , Síndrome de DiGeorge/genética , Síndrome de DiGeorge/imunologia , Linfócitos T/imunologia , Receptor fas/genética , Adolescente , Criança , Pré-Escolar , Cromossomos Humanos Par 22/imunologia , Feminino , Humanos , Masculino
3.
Allergol Immunopathol (Madr) ; 47(2): 141-151, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30292446

RESUMO

BACKGROUND: The del22q11 syndrome patients present immunological abnormalities associated to thymus alterations. Up to 75% of them present cardiopathies and thymus is frequently removed during surgery. The thymectomy per se has a deleterious effect concerning lymphocyte subpopulations, and T cell function. When compared to healthy controls, these patients have higher infections propensity of variable severity. The factors behind these variations are unknown. We compared immunological profiles of del22q11.2 Syndrome patients with and without thymectomy to establish its effect in the immune profile. METHODS: Forty-six del22q11.2 syndrome patients from 1 to 16 years old, 19 of them with partial or total thymectomy were included. Heart disease type, heart surgery, infections events and thymus resection were identified. Immunoglobulin levels, flow cytometry for lymphocytes subpopulations and TREC levels were determined, and statistical analyses were performed. RESULTS: The thymectomy group had a lower lymphocyte index, both regarding total cell count and when comparing age-adjusted Z scores. Also, CD3+, CD4+ and CD8+ lower levels were observed in this group, the lowest count in those patients who had undergone thymus resection during the first year of life. Their TREC level median was 23.6/µL vs 16.1µL in the non-thymus group (p=0.22). No differences were identified regarding immunoglobulin levels or infection events frequencies over the previous year. CONCLUSION: Patients with del22q11.2 syndrome subjected to thymus resection present lower lymphocyte and TREC indexes when compared to patients without thymectomy. This situation may be influenced by the age at the surgery and the time elapsed since the procedure.


Assuntos
Subpopulações de Linfócitos T/fisiologia , Linfócitos T/fisiologia , Timectomia , Timo/cirurgia , Adolescente , Criança , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 22/imunologia , Feminino , Citometria de Fluxo , Humanos , Lactente , Contagem de Linfócitos , Masculino , Receptores de Antígenos de Linfócitos T/genética
4.
Eur J Med Genet ; 61(10): 631-633, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29673649

RESUMO

22q13 deletion syndrome is a genetic disorder caused by the deletion or disruption of the segment of the long arm of chromosome 22. The characteristic clinical features of this syndrome include delayed expressive speech, autistic behavior and hypotonia, and clinically severe complications associated with autoimmunity are rarely reported. We herein report a girl with 22q13 deletion syndrome complicated with multiple inflammatory and autoimmune diseases during early childhood. We performed whole-exome sequencing to identify the genes responsible for her autoimmune diseases and identified the de novo variant p.R512W in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (PIK3CD) gene. We suspected it to be the disease-causing variant at the conserved residue in PIK(3)C p110δ. Alternatively, haplo-insufficiency of SHANK3 or other genes by 22q13 deletion and the PIK3CD variant might have synergistically contributed to the onset of the distinctive clinical manifestations in this patient.


Assuntos
Doenças Autoimunes/genética , Transtornos Cromossômicos/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Doenças Autoimunes/diagnóstico , Deleção Cromossômica , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/imunologia , Cromossomos Humanos Par 22/genética , Cromossomos Humanos Par 22/imunologia , Feminino , Humanos , Lactente , Mutação
5.
Cell Mol Life Sci ; 69(1): 17-27, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21984609

RESUMO

Chromosome 22q11 deletion is the most common chromosomal deletion syndrome and is found in the majority of patients with DiGeorge syndrome and velo-cardio-facial syndrome. Patients with CHARGE syndrome may share similar features. Cardiac malformations, speech delay, and immunodeficiency are the most common manifestations. The immunological phenotype may vary widely between patients. Severe T lymphocyte immunodeficiency is rare-thymic transplantation offers a new approach to treatment, as well as insights into thymic physiology and central tolerance. Combined partial immunodeficiency is more common, leading to recurrent sinopulmonary infection in early childhood. Autoimmunity is an increasingly recognized complication. New insights into pathophysiology are reviewed.


Assuntos
Síndrome CHARGE/imunologia , Deleção Cromossômica , Cromossomos Humanos Par 22/imunologia , Síndrome de DiGeorge , Síndromes de Imunodeficiência/imunologia , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/imunologia , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Síndrome CHARGE/genética , Tolerância Central , Cromossomos Humanos Par 22/genética , Síndrome de DiGeorge/genética , Síndrome de DiGeorge/imunologia , Humanos , Síndromes de Imunodeficiência/genética , Linfócitos T/imunologia , Linfócitos T/metabolismo , Timo/crescimento & desenvolvimento , Timo/imunologia , Timo/patologia
6.
Postepy Hig Med Dosw (Online) ; 61: 361-8, 2007 Jun 12.
Artigo em Polonês | MEDLINE | ID: mdl-17572656

RESUMO

The 22q11.2 deletion syndrome occurs in approximately 1 of 3000-5000 children. This is a congenital disorder characterized by facial dysmorphic features, cardiac defects, thymic hypoplasia, cleft palate, hypoparathyroidism, and psychiatric disorders. Patients generally exhibit a mild to moderate decrement in T-cell numbers with preservation of T-cell function. We describe advances in understanding the genetic basis of this syndrome, its clinical manifestations, and new information on immunodeficiences in this syndrome.


Assuntos
Anormalidades Múltiplas/genética , Anormalidades Múltiplas/imunologia , Deleção Cromossômica , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/imunologia , Cromossomos Humanos Par 22/genética , Síndromes de Imunodeficiência/genética , Anormalidades Múltiplas/diagnóstico , Criança , Aberrações Cromossômicas , Transtornos Cromossômicos/diagnóstico , Cromossomos Humanos Par 22/imunologia , Testes Genéticos , Humanos , Subpopulações de Linfócitos T/imunologia
7.
Clin Exp Immunol ; 144(1): 85-93, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16542369

RESUMO

Chromosome 22q11.2 deletion syndrome is a common disorder characterized by thymic hypoplasia, conotruncal cardiac defect and hypoparathyroidism. Patients have a risk of infections and autoimmunity associated with T lymphocytopenia. To assess the immunological constitution of patients, the numerical changes and cytokine profile of circulating T cells were analysed by flow cytometry and real-time polymerase chain reaction (PCR). CD3+, CD4+, T cell receptor (TCR)alphabeta+ or CD8alphaalpha+ cell counts were lower, and CD56+ cell counts were higher in patients than in controls during the period from birth to adulthood. The ageing decline of CD3+ or CD4+ cell counts was slower in patients than in controls. The proportion of CD8alphaalpha+ cells increased in controls, and the slope index was larger than in patients. On the other hand, both the number and proportion of Valpha24+ cells increased in patients, and the slope indexes tended to be larger than in controls. The positive correlation of the number of T cells with CD8alphaalpha+ cells was observed only in patients, and that with Valpha24+ cells was seen only in controls. No gene expression levels of interferon (IFN)-gamma, interleukin (IL)-10, transforming growth factor (TGF)-beta, cytotoxic T lymphocyte antigen 4 (CTLA4) or forkhead box p3 (Foxp3) in T cells differed between patients and controls. There was no significant association between the lymphocyte subsets or gene expression levels and clinical phenotype including the types of cardiac disease, hypocalcaemia and frequency of infection. These results indicated that T-lymphocytopenia in 22q11.2 deletion patients became less severe with age under the altered composition of minor subsets. The balanced cytokine profile in the limited T cell pool may represent a T cell homeostasis in thymic deficiency syndrome.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 22/genética , Citocinas/imunologia , Linfócitos T/imunologia , Adolescente , Adulto , Envelhecimento/genética , Envelhecimento/imunologia , Antígenos CD , Antígenos de Diferenciação/análise , Complexo CD3/imunologia , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos/imunologia , Antígeno CTLA-4 , Criança , Pré-Escolar , Cromossomos Humanos Par 22/imunologia , Síndrome de DiGeorge/genética , Síndrome de DiGeorge/imunologia , Feminino , Fatores de Transcrição Forkhead/análise , Expressão Gênica/genética , Expressão Gênica/imunologia , Humanos , Lactente , Interferon gama/análise , Interleucina-10/análise , Contagem de Linfócitos , Masculino , RNA Mensageiro/análise , Receptores de Antígenos de Linfócitos T/imunologia , Fator de Crescimento Transformador beta/análise
8.
Curr Opin Allergy Clin Immunol ; 4(6): 505-12, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15640691

RESUMO

PURPOSE OF REVIEW: New findings regarding the clinical manifestations and care of patients with DiGeorge syndrome or chromosome 22q11.2 deletion syndrome will be reviewed. Immunologists and primary care providers often are in a position to coordinate the complex care needs of these patients and an awareness of the clinical features is essential. RECENT FINDINGS: DiGeorge syndrome typically occurs in association with a hemizygous deletion of chromosome 22q11.2. Approximately 5-10% of patients with the clinical entity of DiGeorge syndrome do not have the deletion. Recent evidence indicates that the T cell compartment in both patients with the deletion and patients with clinical DiGeorge syndrome without the deletion is less robust than is often indicated by standard T cell enumeration. SUMMARY: This past year has seen a dramatic increase in our understanding of the clinical features of patients with the deletion. Advances in our understanding of the immunodeficiency have been particularly exciting and clinicians should be aware of the characteristics of the immunodeficiency and its changes with age.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 22/imunologia , Síndrome de DiGeorge , Cromossomos Humanos Par 22/genética , Síndrome de DiGeorge/genética , Síndrome de DiGeorge/imunologia , Humanos
9.
Curr Opin Pediatr ; 14(6): 678-83, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12436034

RESUMO

Chromosome 22q11.2 deletion syndrome occurs in approximately 1 of 3000 children. Clinicians have defined the phenotypic features associated with the syndrome and the past 5 years have seen significant progress in determining the frequency of the deletion in specific populations. As a result, caregivers now have a better appreciation of which patients are at risk for having the deletion. Once identified, patients with the deletion can receive appropriate multidisciplinary care. We describe recent advances in understanding the genetic basis for the syndrome, the clinical manifestations of the syndrome, and new information on autoimmune diseases in this syndrome.


Assuntos
Anormalidades Múltiplas/genética , Deleção Cromossômica , Cromossomos Humanos Par 22/genética , Cromossomos Humanos Par 22/imunologia , Síndrome de DiGeorge/genética , Animais , Doenças Autoimunes/genética , Criança , Síndrome de DiGeorge/diagnóstico , Ossos Faciais/anormalidades , Cardiopatias Congênitas/genética , Humanos , Hipocalcemia/genética , Recém-Nascido , Camundongos , Fenótipo , Síndrome
10.
Curr Allergy Asthma Rep ; 1(5): 438-44, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11892070

RESUMO

DiGeorge syndrome is characterized by conotruncal cardiac defects, hypocalcemia, and a hypoplastic thymus. Many, but not all, patients have a heterozygous deletion of chromosome 22q11.2. In its most severe form, it represents a devastating syndrome with high mortality. Patients with severe immunodeficiency are candidates for a thymic transplant or a fully matched bone marrow transplant. Fortunately, the majority of patients with either DiGeorge syndrome or chromosome 22q11.2 deletion syndrome have a mild to moderate immunodeficiency. These patients may develop recurrent infections or autoimmune disease.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 22 , Síndrome de DiGeorge/imunologia , Cromossomos Humanos Par 22/imunologia , Síndrome de DiGeorge/epidemiologia , Síndrome de DiGeorge/terapia , Humanos , Síndromes de Imunodeficiência/epidemiologia , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/terapia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA