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1.
J Investig Allergol Clin Immunol ; 25(3): 205-13, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26182687

RESUMEN

BACKGROUND: X-linked lymphoproliferative syndrome type 2 is a rare hereditary immunodeficiency caused by mutations in the XIAP gene. This immunodeficiency frequently results in hemophagocytic lymphohistiocytosis, although hypogammaglobulinemia and dysgammaglobulinemia are also common. OBJECTIVE: We identified 17 patients from 12 Japanese families with mutations in XIAP. The Glu349del mutation was observed in 3 patients, each from a different family. Interestingly, these patients exhibited dysgammaglobulinemia but not hemophagocytic lymphohistiocytosis. We conducted an immunological study of patients carrying Glu349del and other mutations to elucidate the pathogenic mechanisms of dysgammaglobulinemia in patients with mutations in the XIAP gene. PATIENTS AND METHODS: We performed an immunological study of 2 patients carrying the Glu349del mutation and 8 patients with other mutations. RESULTS: Flow cytometry showed that the percentage of memory B cells in patients with a mutation in XIAP was lower than that observed in the healthy controls. The patients with the Glu349del mutation had a lower percentage of memory B cells than those with other mutations. Ig production was reduced in patients with the Glu349del mutation. Increased susceptibility to apoptosis was observed in the patients with other mutations. Susceptibility to apoptosis was normal in patients with Glu349del. Microarray analysis indicated that expression of Ig-related genes was reduced in patients with the Glu349del mutation and that the pattern was different from that observed in the healthy controls or patients with other mutations in XIAP. CONCLUSIONS: Patients carrying the Glu349del mutation in the XIAP gene may have a clinically and immunologically distinct phenotype from patients with other XIAP mutations. The Glu349del mutation may be associated with dysgammaglobulinemia.


Asunto(s)
Disgammaglobulinemia/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Trastornos Linfoproliferativos/genética , Mutación , Proteína Inhibidora de la Apoptosis Ligada a X/genética , Adolescente , Apoptosis , Pueblo Asiatico/genética , Linfocitos B/inmunología , Estudios de Casos y Controles , Células Cultivadas , Niño , Preescolar , Análisis Mutacional de ADN , Disgammaglobulinemia/diagnóstico , Disgammaglobulinemia/etnología , Disgammaglobulinemia/inmunología , Femenino , Citometría de Flujo , Perfilación de la Expresión Génica/métodos , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/etnología , Enfermedades Genéticas Ligadas al Cromosoma X/inmunología , Predisposición Genética a la Enfermedad , Humanos , Memoria Inmunológica , Inmunofenotipificación/métodos , Lactante , Japón , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/etnología , Trastornos Linfoproliferativos/inmunología , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Linaje , Fenotipo , Linfocitos T/inmunología , Linfocitos T/patología
2.
J. investig. allergol. clin. immunol ; 25(3): 205-213, 2015. tab, ilus
Artículo en Inglés | IBECS | ID: ibc-136426

RESUMEN

Antecedentes: El síndrome linfoproliferativo ligado al cromosoma X (XLP) tipo 2, está causado por la mutación del gen XIAP. Se trata de una inmunodeficiencia hereditaria rara. Frecuentemente, los pacientes con XLP2 padecen linfohistiocitosis hemofagocítica (HLH) y disgammaglobulinemia. Objetivo: Se han evaluado diecisiete pacientes japoneses, provenientes de doce familias con mutaciones XIAP y tres pacientes con la mutación Glu349del. Curiosamente, estos últimos pacientes desarrollaron una disgammaglobulinemia pero no HLH. Para dilucidar el fondo patogénico de la disgammaglobulinemia en pacientes con mutación del gen XIAP , se llevó a cabo un estudio inmunológico de estos pacientes. Pacientes y métodos: Pudieron concluir el estudio inmunológico dos pacientes con la mutación Glu349del y ocho pacientes con otras mutaciones. Resultados: Mediante análisis de citometría de flujo se observó que la proporción de linfocitos B de memoria en los pacientes con la mutación XIAP fue menor que la observada en los controles. Los pacientes con la mutación Glu349del tuvieron una menor proporción de linfocitos B de memoria que aquellos con otras mutaciones. Los pacientes con la mutación Glu349del presentaron menor producción de inmunoglobulinas. Los pacientes con la mutación Glu349del mostraron una susceptibilidad normal a la apoptosis, mientras que en los portadores de otras mutaciones se observó una mayor susceptibilidad a la muerte celular. El análisis de microarray indicó que los pacientes con la mutación Glu349del tenían disminuida la expresión de genes relacionados con las inmunoglobulinas y un patrón diferente de la observada en los controles normales o en pacientes con otras mutaciones de genes de XIAP. Conclusiones: Los pacientes portadores de la mutación en el gen Glu349 del XIAP pueden tener un fenotipo clínicamente e inmunológicamente diferente que los pacientes con otras mutaciones XIAP . La mutación Glu349del puede estar asociada con disgammaglobulinemia (AU)


Background: X-linked lymphoproliferative syndrome type 2 is a rare hereditary immunodeficiency caused by mutations in the XIAP gene. This immunodeficiency frequently results in hemophagocytic lymphohistiocytosis, although hypogammaglobulinemia and dysgammaglobulinemia are also common. Objective: We identified 17 patients from 12 Japanese families with mutations in XIAP . The Glu349del mutation was observed in 3 patients, each from a different family. Interestingly, these patients exhibited dysgammaglobulinemia but not hemophagocytic lymphohistiocytosis. We conducted an immunological study of patients carrying Glu349del and other mutations to elucidate the pathogenic mechanisms of dysgammaglobulinemia in patients with mutations in the XIAP gene. Patients and Methods: We performed an immunological study of 2 patients carrying the Glu349del mutation and 8 patients with other mutations. Results: Flow cytometry showed that the percentage of memory B cells in patients with a mutation in XIAP was lower than that observed in the healthy controls. The patients with the Glu349del mutation had a lower percentage of memory B cells than those with other mutations. Ig production was reduced in patients with the Glu349del mutation. Increased susceptibility to apoptosis was observed in the patients with other mutations. Susceptibility to apoptosis was normal in patients with Glu349del. Microarray analysis indicated that expression of Ig-related genes was reduced in patients with the Glu349del mutation and that the pattern was different from that observed in the healthy controls or patients with other mutations in XIAP. Conclusions: Patients carrying the Glu349del mutation in the XIAP gene may have a clinically and immunologically distinct phenotype from patients with other XIAP mutations. The Glu349del mutation may be associated with dysgammaglobulinemia (AU)


Asunto(s)
Humanos , Masculino , Femenino , Trastornos Linfoproliferativos/inmunología , Síndrome Linfoproliferativo Autoinmune/genética , Síndrome Linfoproliferativo Autoinmune/inmunología , Linfohistiocitosis Hemofagocítica/genética , Linfohistiocitosis Hemofagocítica/inmunología , Anticuerpos Monoclonales/análisis , Mutación/genética , Disgammaglobulinemia/genética , Disgammaglobulinemia/inmunología , Citometría de Flujo/instrumentación , Citometría de Flujo , Inmunoglobulinas/análisis , Inmunoglobulinas/inmunología
3.
Anaesthesia ; 69(7): 752-6, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24800903

RESUMEN

We hypothesised that an in-vivo adjustment method and/or a newer sensor would increase the accuracy of non-invasive and continuous haemoglobin monitoring (SpHb) measurements. Two sensors, the R1-25 and R2-25a (the newer version), were used with laboratory total haemoglobin concentration (tHb) values simultaneously recorded. In-vivo adjusted SpHb (AdHb) was calculated by a simple formula: AdHb = SpHb - (1(st) SpHb - 1(st) tHb). The correlation coefficients between SpHb (or AdHb) and tHb were compared: SpHb in both sensors correlated strongly with tHb (p < 0.0001). In-vivo adjustment improved the correlation coefficient between SpHb and tHb from 0.86 to 0.95 for the R1-25 and from 0.83 to 0.93 for the R2-25a. There was no difference between the R1-25 and R2-25a sensors. The in vivo adjustment method improved the accuracy of SpHb measurements in both sensors.


Asunto(s)
Hemoglobinometría/instrumentación , Hemoglobinometría/métodos , Monitoreo Intraoperatorio/instrumentación , Monitoreo Intraoperatorio/métodos , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oximetría/instrumentación , Oximetría/métodos , Reproducibilidad de los Resultados
4.
Pharmacogenomics J ; 13(1): 52-9, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21987091

RESUMEN

Functional single-nucleotide polymorphisms (SNPs) in inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) (rs28493229) and caspase-3 (CASP3) (rs113420705; formerly rs72689236) are associated with susceptibility to Kawasaki's disease (KD). To evaluate the involvement of these 2 SNPs in the risk for intravenous immunoglobulin (IVIG) unresponsiveness, we investigated 204 Japanese KD patients who received a single IVIG dose of 2 g kg(-1) (n=70) or 1 g kg(-1) daily for 2 days (n=134). The susceptibility allele of both SNPs showed a trend of overrepresentation in IVIG non-responders and, in combined analysis of these SNPs, patients with at least 1 susceptible allele at both loci had a higher risk for IVIG unresponsiveness (P=0.0014). In 335 prospectively collected KD patients who were treated with IVIG (2 g kg(-1)), this 2-locus model showed a more significant association with resistance to initial and additional IVIG (P=0.011) compared with individual SNPs. We observed a significant association when all KD patients with coronary artery lesions were analyzed with the 2-locus model (P=0.0031). Our findings strongly suggest the existence of genetic factors affecting patients' responses to treatment and the risk for cardiac complications, and provide clues toward understanding the pathophysiology of KD inflammation.


Asunto(s)
Caspasa 3/genética , Vasos Coronarios/patología , Inmunoglobulinas Intravenosas/administración & dosificación , Síndrome Mucocutáneo Linfonodular/genética , Síndrome Mucocutáneo Linfonodular/patología , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Alelos , Pueblo Asiatico/genética , Niño , Vasos Coronarios/enzimología , Resistencia a Medicamentos , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Lactante , Recién Nacido , Masculino , Síndrome Mucocutáneo Linfonodular/enzimología , Polimorfismo de Nucleótido Simple , Estudios Prospectivos
5.
Genes Immun ; 9(3): 214-23, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18273033

RESUMEN

Leukocyte immunoglobulin-like receptors (LILRs) are inhibitory, stimulatory or soluble receptors encoded within the leukocyte receptor complex. Some LILRs are extensively polymorphic, and exhibit evidence for balancing selection and association with disease susceptibility. LILRA2 (LIR7/ILT1) is an activating receptor highly expressed in inflammatory tissues, and is involved in granulocyte and macrophage activation. In this study, we examined the association of LILRA2 and adjacently located LILRA1 with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and microscopic polyangiitis (MPA). Polymorphism screening detected a LILRA2 SNP (rs2241524 G>A) that disrupts splice acceptor site of intron 6. Case-control association studies on 273 Japanese SLE, 296 RA, 50 MPA and 284 healthy individuals revealed increase of genotype A/A in SLE (12.1%, odds ratio (OR) 1.82, 95% confidence interval (CI) 1.02-3.24, P=0.041) and in MPA (16.0%, OR 2.52, 95% CI 1.07-5.96, P=0.049) compared with healthy individuals (7.0%). The risk allele caused an activation of a cryptic splice acceptor site that would lead to a novel LILRA2 isoform lacking three amino acids in the linker region (Delta 419-421). Flow cytometry indicated that this isoform was expressed on the surface of monocytes. These findings suggested that LILRA2 Delta 419-421 isoform encoded by the splice site SNP may play a role in SLE and MPA.


Asunto(s)
Empalme Alternativo/genética , Pueblo Asiatico/genética , Predisposición Genética a la Enfermedad/genética , Lupus Eritematoso Sistémico/genética , Receptores Inmunológicos/genética , Vasculitis/genética , Secuencia de Bases , Cartilla de ADN/genética , Citometría de Flujo , Genotipo , Humanos , Datos de Secuencia Molecular , Monocitos/metabolismo , Oportunidad Relativa , Polimorfismo de Nucleótido Simple/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADN
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