RESUMEN
Polymorphic variants of the IL2RA gene, which encodes high-affinity alpha subunit (CD25) of the interleukin-2 receptor, were recently found to affect the risk of several autoimmune disorders. This study was aimed to investigate the association of selected IL2RA polymorphisms (rs11594656, rs3118470, rs2104286 and rs7093069) with type 1 diabetes (T1D) in a Polish cohort comprising 445 patients and 671 healthy control subjects. The minor A allele at rs11594656 was found significantly less frequently among T1D subjects, compared with the control group [P = 0.011; odds ratio (OR) = 0.77; 95% confidence interval (CI) = 0.629-0.942]. In contrast, the minor C allele at rs3118470 appeared to be significantly associated with the occurrence of T1D (P = 0.003; OR = 1.30; 95% CI = 1.094-1.550). Two other IL2RA single nucleotide polymorphisms (SNPs) did not show significant differences among investigated groups. In conclusion, the study confirms the association of the IL2RA locus with T1D in the Polish population.
Asunto(s)
Diabetes Mellitus Tipo 1/genética , Predisposición Genética a la Enfermedad , Variación Genética , Subunidad alfa del Receptor de Interleucina-2/genética , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Edad de Inicio , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Polonia , Reacción en Cadena de la PolimerasaRESUMEN
Susceptibility to multiple sclerosis (MS) is most likely affected by a number of genes, including HLA and T-cell receptor (TCR) genes. T cells expressing gamma/delta receptors seem to contribute to autoagression in MS, as evidenced by their localization in the MS plaques in the brain. The aim of this study was to analyse the TCRdelta chain gene rearrangement at the RNA (cDNA) level and compare to the DNA pattern rearrangement. TCRdelta gene rearrangement was analysed in MS patients and healthy individuals with the use of primers specific for Vdelta1-6 and Jdelta1 genes (at the DNA level) and specific for Vdelta1-6 and Cdelta1 genes (at the cDNA level). The size of PCR products was analysed on agarose gel and by ALF-Express (Pharmacia). Additionally, the lymphocyte surface immunophenotype was studied with specific monoclonal antibodies. At the DNA level a restricted pattern of Vdelta3-Jdelta1 and Vdelta5-Jdelta1 was found only in MS patients. Contrary to DNA, mono-, oligoclonal RNA (cDNA) rearrangements were limited to Vdelta1-Cdelta1, Vdelta2-Cdelta1 and Vdelta3-Cdelta1 only in MS patients as well. Surface immunophenotype analysis revealed in MS a much higher frequency of activated gamma/delta T lymphocytes, i.e. expressing HLA-DR and CD25. An elevated level of CD56 positive cells in MS was recorded. Mono-oligoclonal pattern of TCRdelta gene rearrangement at the RNA level, along with increase in activated gamma/delta T cells, strongly argue for a significant role of gamma/delta T lymphocytes in the pathogenesis of MS.
RESUMEN
The object of the study is a comparison of intrathecal IgG synthesis and gamma/delta TCR genes rearrangement in multiple sclerosis. The subgroup of 13 cases with intrathecal IgG synthesis and positive oligoclonal bands was compared with 8 cases with IgG index below 0.75 and with undetectable oligoclonal bands. TCR gene rearrangement was studied in peripheral blood lymphocytes by PCR analysis. In majority of cases of the first group the V delta-J delta junctional repertoire was restricted as evidenced by oligoclonal rearrangement. Monoclonal pattern of rearrangement was also established in some cases concerning V delta 1-J delta 1 and V delta 5-J delta 1. In all cases with one exception, demonstrating IgG index < 0.75 and with negative oligoclonal bands in CSF the oligo- or polyclonal pattern of V delta-J delta gene rearrangement was noticed. It is therefore suggested that subset T and B lymphocytes may undergo clonal expansion in MS as evidenced by restricted pattern of V delta-J delta rearrangement and intrathecal oligoclonal IgG synthesis, respectively. Oligoclonal expansion at certain B and T cells may occur due to stimulation by an antigen related to MS pathogen.
Asunto(s)
Plaquetas/inmunología , Reordenamiento Génico de la Cadena beta de los Receptores de Antígenos de los Linfocitos T , Inmunoglobulina G/biosíntesis , Linfocitos Infiltrantes de Tumor/inmunología , Esclerosis Múltiple/genética , Médula Espinal/inmunología , Anticuerpos Monoclonales/inmunología , Femenino , Humanos , Masculino , RecurrenciaRESUMEN
UNLABELLED: Infections by hepatotropic viruses belong to the most common complications of chemotherapy in children suffering from neoplastic diseases. The rate of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and the effectiveness of passive immunization against HBV were studied in 285 children; 148/285 with lymphoproliferative diseases and 137/285 with solid tumours. HBV infection was observed in 10.2% children receiving hepatitis B immune globulin as compared to 36.8% without passive immunization against HBV. Anti-HCV antibodies were similar in both groups amounting 38.7% and 32.6% respectively. CONCLUSION: The results show that hepatitis B immune globulin administration is effective and that HCV might become the main cause of hepatitis among immunosuppressed patients in the future.
Asunto(s)
Antineoplásicos/efectos adversos , Hepatitis B/prevención & control , Hepatitis C/epidemiología , Huésped Inmunocomprometido , Neoplasias/complicaciones , Adolescente , Niño , Preescolar , Hepatitis B/epidemiología , Vacunas contra Hepatitis B/uso terapéutico , Humanos , Inmunización Pasiva , Lactante , Neoplasias/tratamiento farmacológico , Neoplasias/mortalidad , Polonia/epidemiología , Prevalencia , Estudios Prospectivos , VacunaciónRESUMEN
T-cell receptor (TCR) delta gene repertoire, as assessed by V delta-J delta rearrangements, has been analyzed in nine multiple sclerosis (MS) cases and in 30 healthy individuals by seminested PCR technique. Among the V delta-J delta junctional diversities studied, the most striking result has been observed in V delta 5-J delta 1 rearrangement. The detection of repeated V delta 5-J delta 1 nucleotide sequences in all analyzed clones from seven out of nine patients studied proved the monoclonal nature of gamma delta T-cells with V delta 5-J delta 1 rearrangement. The clonal nature of this rearrangement proved by PAGE and sequencing analysis may suggest an antigen-driven expansion of gamma delta T cells and argues for a significant role of gamma delta T-cells with V delta 5-J delta 1 rearrangement in MS pathogenesis. However, it cannot be excluded that clonal expansion of these lymphocytes may represent secondary change to central nervous system damage.
Asunto(s)
Reordenamiento Génico de la Cadena delta de los Receptores de Antígenos de los Linfocitos T , Linfocitos/inmunología , Esclerosis Múltiple/genética , Esclerosis Múltiple/inmunología , Adulto , Secuencia de Bases , Cartilla de ADN , Variación Genética , Humanos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , Valores de ReferenciaRESUMEN
Central nervous system (CNS) involvement in children with newly diagnosed acute lymphoblastic leukemia (ALL) would have profound implication for the prognosis and accurate stratification of CNS prophylactic therapy. Using PCR technique with specific primers for V, D and J segments of TCRD gene, the pattern of TCRD gene rearrangements in bone marrow lymphoblasts and in cells from cerebrospinal fluid (CSF) have been investigated. The study involved 21 children at the time of diagnosis with B-lineage ALL. In nine of 21 patients incomplete TCRDVD gene rearrangement has been found in CSF cells, which was identical to that observed in bone marrow of the same children. It can be concluded that at least in 43 per cent of all analysed cases, there were signs of CNS involvement in newly diagnosed ALL patients.
Asunto(s)
Sistema Nervioso Central/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/análisis , Adolescente , Secuencia de Bases , Médula Ósea/inmunología , Médula Ósea/metabolismo , Niño , Preescolar , Reordenamiento Génico , Humanos , Lactante , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Leucemia-Linfoma Linfoblástico de Células Precursoras/líquido cefalorraquídeo , Receptores de Antígenos de Linfocitos T gamma-delta/genéticaRESUMEN
The authors of this paper presented a case of a baby with full-symptomatic WAGR syndrome (Wilms tumor, aniridia, genital tract malformation and mental retardation) treated in the I Department of Pediatrics, Institute of Pediatrics, Medical Academy Poznan. The etiology of this syndrome was discussed (deletion of the 13th band of the 11th chromosome short arm). The reason for treatment failure was analysed.
Asunto(s)
Síndrome WAGR/genética , Terapia Combinada , Femenino , Humanos , Lactante , Fenotipo , Insuficiencia del Tratamiento , Síndrome WAGR/terapiaRESUMEN
DNA-based PCR with various sets of primers for TCR gamma/delta, and Ig heavy chain (IgH) genes were used to study clonality in childhood B-lineage acute lymphoblastic leukemia. Amplification of the IgH CDR-III was observed in 75 of 120 analyzed cases (62.5%). From all analyzed groups, the IgH gene rearrangement was most often observed in pre-B ALL (85.7%) and was rather rare in null-ALL (34.5%). TCR delta gene rearrangement was the most common, and was observed in 77 patients (64.2%). The typical pattern of rearrangements was defined as an incomplete V delta 2 to D delta 3, V delta 2 to D delta 2, or D delta 3 to D delta 2 recombination product. Rearrangements of TCR gamma gene we observed in 61 cases (50.8%). TCR gamma gene rearrangements were detected predominantly in null-ALL and early B-ALL (55.2% and 60%, respectively) and were rather rare in other groups. Of all eight V segments of V gamma I group, the most frequent gene usage concerns regions V gamma 2, V gamma 4, and psi V gamma 7. We have confirmed that IgH gene amplification, together with TCR gamma and delta gene amplification, provides a rapid, sensitive approach to assessing clonality in ALL almost in 100% of cases.
Asunto(s)
Linfoma de Burkitt/genética , Reordenamiento Génico , Reacción en Cadena de la Polimerasa , Adolescente , Preescolar , Células Clonales , Femenino , Reordenamiento Génico de Cadena Pesada de Linfocito B , Reordenamiento Génico de la Cadena delta de los Receptores de Antígenos de los Linfocitos T , Reordenamiento Génico de la Cadena gamma de los Receptores de Antígenos de los Linfocitos T , Humanos , Lactante , Recién Nacido , MasculinoRESUMEN
DNA-based PCR with various sets of primers for T-cell receptor gamma/delta (TCR gamma/delta) chain genes was used to study clonality in childhood B-lineage acute lymphoblastic leukaemia. TCR delta genes rearrangements were the most common and were observed in 77 patients (64.2%). The typical pattern of rearrangements was defined as an incomplete V delta 2 to D delta 3 or to D delta 2 recombination product. Rearrangements of TCR gamma genes were observed in 61 cases (50.8%). Predominantly, TCR gamma genes rearrangements were detected in null-ALL and the early B-ALL (55.2% and 60%, respectively) and were rather rare in other groups. From all eight V segments of V gamma l group rearrangements concerned mostly regions V gamma 2, V gamma 4 and V gamma 7. We have confirmed that TCR gamma and delta genes amplification provides a rapid, sensitive method for assessing clonality in ALL almost in 100%.
Asunto(s)
Leucemia de Células B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Adolescente , Niño , Preescolar , Células Clonales , ADN de Neoplasias/genética , Femenino , Amplificación de Genes , Reordenamiento Génico de la Cadena delta de los Receptores de Antígenos de los Linfocitos T/genética , Humanos , Lactante , Masculino , Reacción en Cadena de la PolimerasaRESUMEN
A rare case of the generalized of histiocytosis X is described. Due to pulmonary involvement the disease was complicated by three episodes of spontaneous pneumothorax.
Asunto(s)
Histiocitosis de Células de Langerhans/complicaciones , Neumotórax/etiología , Terapia Combinada , Histiocitosis de Células de Langerhans/diagnóstico , Histiocitosis de Células de Langerhans/terapia , Humanos , Lactante , Masculino , Neumotórax/diagnóstico , Neumotórax/terapia , RecurrenciaAsunto(s)
Carboxilesterasa , Deleción Cromosómica , Cromosomas Humanos Par 13 , Neoplasias del Ojo/congénito , Retinoblastoma/congénito , Hidrolasas de Éster Carboxílico/genética , Hidrolasas de Éster Carboxílico/metabolismo , Neoplasias del Ojo/genética , Neoplasias del Ojo/terapia , Humanos , Recién Nacido , Masculino , Retinoblastoma/genética , Retinoblastoma/terapia , SíndromeRESUMEN
The results of the treatment of 26 patients with histiocytosis hospitalized in the years 1970-1990 were evaluated. The age of the children at the time of diagnosis was from 4 months to 14 years, mean 32 months. In 4 cases the changes were restricted to the skeletal system, in the remaining 22 patients generalized histiocytosis was present with involvement of the skeleton and/or internal organs, and/or bone marrow. In the group with generalized histiocytosis 3 children had respiratory failure, 5 had hepatic failure, and 6 bone marrow failure. Full remission was obtained in 19 cases. Another 4 ones had persistent focal changes in the bones. Three children died of disease progression. Thus the probability of 10-year survival was for the whole group 0.86 +/- 0.13.
Asunto(s)
Histiocitosis de Células de Langerhans/tratamiento farmacológico , Adolescente , Niño , Preescolar , Ciclofosfamida/administración & dosificación , Esquema de Medicación , Quimioterapia Combinada , Femenino , Histiocitosis de Células de Langerhans/mortalidad , Humanos , Lactante , Masculino , Metotrexato/administración & dosificación , Prednisona/administración & dosificación , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Factores de Tiempo , Vinblastina/administración & dosificaciónRESUMEN
Results of treatment of 46 children within 6 months-16 years limits of age, with neuroblastoma hospitalized at the I-st Clinic of Children Diseases in Poznan, are presented. In 44 of patients the III-rd or IV-th stage of clinical advancement has been diagnosed, hence the analysis is concerned mainly with advanced forms of disease. 3 year survival of patients treated since 1985 with application of an intensive GPO-NBL programme appeared to be higher (p = 0.37 +/- 0.15) as compared with a group of children treated earlier (p = 0.17 +/- 0.07). The difference appeared however is not significant. Among analysed prognostic factors only age has been of importance. The probability of survival of younger children-below 2 years of a age (p = 64 +/- 0.23) is significantly higher as compared with older age group (p = 0.03 +/- 0.04).