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1.
J Clin Immunol ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31749033

RESUMO

OBJECTIVES: The aim of the study was to estimate the rate of adverse reactions to live BCG Moreau vaccine, manufactured by Biomed in Poland, in severe combined immunodeficiency (SCID) patients. MATERIAL: The profiles of 52 SCID patients vaccinated at birth with BCG, hospitalized in Children's Memorial Health Institute, Warsaw (CMHI), in the years 1980-2015 were compared with those of 349 BCG-vaccinated SCID patients from other countries analyzed by Beatriz E. Marciano et al. in a retrospective study (Marciano et al. J Allergy Clin Immunol. 2014;133(4):1134-1141). RESULTS: Significantly less disseminated BCG infections (10 out of 52 SCID, 19%) occurred in comparison with Marciano study-119 out of 349, 34% (p = 0.0028), with no death in patients treated with SCID anti-TB drug, except one in lethal condition. In our study, disseminated BCG infection was observed only in SCID with T-B+NK- phenotype and significantly lower NK cell counts (p = 0.0161). NK cells do not influence on the frequency of local BCG reaction. A significantly higher number of hematopoietic stem cells transplantations (HSCT) were performed in CMHI study (p = 0.0001). Anti-TB treatment with at least two medicines was provided. CONCLUSION: The BCG Moreau vaccine produced in Poland, with well-documented genetic characteristics, seems to be safer than other BCG substrains used in other regions of the world. Importantly, NK cells seem to play a role in protecting SCID patients against disseminated BCG complications, which NK- SCID patients are more prone to. HSCT and TB therapy could be relevant due to the patients' survival and the fact that they protect against BCG infection.

2.
Front Immunol ; 10: 2322, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31611883

RESUMO

Ataxia-telangiectasia (AT) and Nijmegen breakage syndrome (NBS) belong to a group of primary immunodeficiency diseases (PI) characterized by premature aging, cerebral degeneration, immunoglobulin deficiency and higher cancer susceptibility. Despite the fact that oxidative stress has been demonstrated in vitro and in animal models of AT and NBS, the involvement of redox homeostasis disorders is still unclear in the in vivo phenotype of AT and NBS patients. Our study is the first to compare both enzymatic and non-enzymatic antioxidants as well as oxidative damage between AT and NBS subjects. Twenty two Caucasian children with AT and twelve patients with NBS were studied. Enzymatic and non-enzymatic antioxidants - glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase-1 (SOD) and uric acid (UA); redox status-total antioxidant capacity (TAC) and ferric reducing ability of plasma (FRAP); and oxidative damage products-8-hydroxy-2'-deoxyguanosine (8-OHdG), advanced glycation end products (AGE), advanced oxidation protein products (AOPP), 4-hydroxynonenal (4-HNE) protein adducts, and 8-isoprostanes (8-isop) were evaluated in serum or plasma samples. We showed that CAT, SOD and UA were significantly increased, while TAC and FRAP levels were statistically lower in the plasma of AT patients compared to controls. In NBS patients, only CAT activity was significantly elevated, while TAC was significantly decreased as compared to healthy children. We also showed higher oxidative damage to DNA (↑8-OHdG), proteins (↑AGE, ↑AOPP), and lipids (↑4-HNE, ↑8-isop) in both AT and NBS patients. Interestingly, we did not demonstrate any significant differences in the antioxidant defense and oxidative damage between AT and NBS patients. However, in AT children, we showed a positive correlation between 8-OHdG and the α-fetoprotein level as well as a negative correlation between 8-OHdG and IgA. In NBS, AGE was positively correlated with IgM and negatively with the IgG level. Summarizing, we demonstrated an imbalance in cellular redox homeostasis and higher oxidative damage in AT and NBS patients. Despite an increase in the activity/concentration of some antioxidants, the total antioxidant capacity is overwhelmed in children with AT and NBS and predisposes them to more considerable oxidative damage. Oxidative stress may play a major role in AT and NBS phenotype.

3.
Nutrients ; 10(6)2018 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-29914217

RESUMO

Whey protein concentrate (WPC) is characterized by powerful antioxidant properties, but its effect on redox homeostasis of salivary glands of aging organisms is still unknown. In this study, we are the first to evaluate the antioxidant barrier of salivary glands of 14-month Wistar rats fed WPC-80. Total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) as well as concentrations of reduced glutathione (GSH) are estimated in the submandibular and parotid glands of rats administered WPC-80 intragastrically for a period of 7 and 14 days. We demonstrate a significant increase in GSH, GPx and SOD in the salivary glands of rats fed WPC-80 for 14 days and a significant increase in TAS, GPx and SOD in the parotid glands of rats fed WPC-80 for 7 days compared to control rats. The beneficial effects of WPC-80 on salivary glands are also demonstrated by lower TOS and OSI in the parotid glands of rats fed WPC-80 compared to the submandibular glands. In summary, we demonstrate that WPC-80 improves redox homeostasis in salivary glands, particularly in the parotid glands of old rats.


Assuntos
Antioxidantes/metabolismo , Glândulas Salivares/efeitos dos fármacos , Proteínas do Soro do Leite/farmacologia , Animais , Catalase/genética , Catalase/metabolismo , Relação Dose-Resposta a Droga , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Glândulas Salivares/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Proteínas do Soro do Leite/administração & dosagem
4.
Adv Med Sci ; 63(1): 173-178, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29128760

RESUMO

PURPOSE: The objective of this study was to evaluate thevitamin D concentration in patients with recurrent respiratory infections with or without immunoglobulin G, A or M (IgG, IgA, IgM) deficiency, and to find a correlation between the vitamin D concentration and the response to hepatitis B vaccination. MATERIALS AND METHOD: The study involved 730 patients with recurrent respiratory infections. The concentration of 25-hydroxyvitamin D (25(OH)D), immunoglobulins G, A and M, anti-HBs was determined. RESULTS: The tests showed that 11% of patients presented IgG levels below the age related reference values. Children with reduced IgG concentration were also found to have significantly lower vitamin D concentrations in comparison to children with normal IgG. Vitamin D deficiency was observed in schoolchildren between 7 and 18 years of age. No correlation was found between 25(OH)D concentration and Hbs antibody levels. CONCLUSIONS: An investigation of a large group of patients who have recurrent infection found patients with IgG deficiency to whom special proceeding have to be performed: 1. Significantly lower vitamin D concentration observed in the group of children with IgG deficiency implicated in long-lasting monitoring of vitamin D level require adding to the practice guidelines for Central Europe 2013. 2. Intervention treatment with suitable doses of vitamin D to clarified metabolism of vitamin D has to be plan for children with IgG deficiency and significant lower vitamin D concentration.


Assuntos
Imunoglobulinas/deficiência , Infecções Respiratórias/complicações , Deficiência de Vitamina D/complicações , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Recidiva , Infecções Respiratórias/sangue , Estações do Ano , Vitamina D/sangue , Deficiência de Vitamina D/sangue
5.
Nutr Metab (Lond) ; 14: 57, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28824701

RESUMO

BACKGROUND: The aim of the study was to assess both patients' and their parents' knowledge of phenylketonuria (PKU) treatment and compliance with PKU diet. METHODS: The study included 173 PKU patients aged 10-19 and 110 parents of PKU children who were enrolled in the study on the basis of questionnaire data. The study also included 45 patients aged ≥20. RESULTS: Our study demonstrated that only 45% (n = 74) of PKU patients knew daily Phe intake recommendations, 27% of patients (n = 41) knew the Phe content in a minimum of three out of four researched food products. Patients' knowledge concerning Phe intake (p = 0.0181) and the knowledge of selected food products (p = 0.041819) improved with age. We did not establish such a correlation in the group of PKU children's parents. Approximately 31% of patients and 22% of parents reported helplessness, which increased with the child's age, associated with the necessity to adhere to the diet; 30% of patients reported feeling ashamed of the fact that they could not eat all food products. Regardless of age, children were more likely than parents to report helplessness (p = 0.032005). Among patients, 41.40% declared that they would wish to select products unassisted but their parents did not permit them to do so. The question of whether parents teach children self-reliance in meal preparation was answered affirmatively by 98% of parents and only 81% of children (p = 0.0001). CONCLUSION: Our data demonstrated that parents' and children's knowledge concerning treatment recommendations and food products does not have a direct impact on attitude to the PKU diet. Limiting children's independence in meal selection, growing helplessness in the face of dietary adherence and shame resulting from the necessity to follow a different diet observed in PKU families are responsible for shaping and perpetuating a consistently negative attitude to the diet. The care of PKU paediatric patients requires consistent, long-term family and individual therapy which may counteract the effects of learned helplessness. In regard to the educational effort, a good parent-child relationship as well as the teaching of behaviours motivating patients to comply with the diet are of great importance.

6.
Arch Med Sci ; 13(2): 412-417, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28261296

RESUMO

INTRODUCTION: Respiratory tract infections constitute the most frequent manifestation of X-linked agammaglobulinemia (XLA). There are not many papers elucidating gastrointestinal (GI) disorders, including inflammatory bowel disease (IBD), in such patients. The aim of the study was to evaluate the occurrence of gastrointestinal disorders and IBD compared to respiratory tract infections in XLA individuals. MATERIAL AND METHODS: Of 1563 patients with primary immunodeficiencies diagnosed in the Department of Immunology, the Children's Memorial Health Institute (CMHI), 66 boys had a provisional diagnosis of agammaglobulinemia. Forty-four subjects fulfilled definitive ESID (European Society for Immunodeficiencies) diagnostic criteria of XLA. A retrospective analysis of medical history of XLA patients was undertaken. RESULTS: Recurrent respiratory tract infections, particularly bronchitis (73%) and pneumonia (59%), were the most common symptoms of XLA. The GI disorders constituted the next main manifestation (63.6%), followed by upper respiratory tract infections. Twenty-six of 28 XLA patients with GI disorders complained of diarrhea, which was resolved generally after immunoglobulin therapy introduction. Single but prolonged episodes of Campylobacter jejuni diarrhea were reported in two individuals. Inflammatory bowel disease of mild to moderate activity was diagnosed in 1 patient, and local enteritis of mild activity in another one. CONCLUSIONS: Gastrointestinal disorders were one of the main manifestations of XLA, reported almost as often as lower respiratory tract infections. The most common GI symptom was diarrhea, which usually resolved after immunoglobulin therapy was started. Infections caused by Giardia lamblia were reported occasionally. Inflammatory bowel disease was diagnosed quite exceptionally, which presumably may be connected with normal T cell immunity.

7.
Redox Biol ; 11: 375-383, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28063379

RESUMO

Rare pleiotropic genetic disorders, Ataxia-telangiectasia (A-T), Bloom syndrome (BS) and Nijmegen breakage syndrome (NBS) are characterised by immunodeficiency, extreme radiosensitivity, higher cancer susceptibility, premature aging, neurodegeneration and insulin resistance. Some of these functional abnormalities can be explained by aberrant DNA damage response and chromosomal instability. It has been suggested that one possible common denominator of these conditions could be chronic oxidative stress caused by endogenous ROS overproduction and impairment of mitochondrial homeostasis. Recent studies indicate new, alternative sources of oxidative stress in A-T, BS and NBS cells, including NADPH oxidase 4 (NOX4), oxidised low-density lipoprotein (ox-LDL) or Poly (ADP-ribose) polymerases (PARP). Mitochondrial abnormalities such as changes in the ultrastructure and function of mitochondria, excess mROS production as well as mitochondrial damage have also been reported in A-T, BS and NBS cells. A-T, BS and NBS cells are inextricably linked to high levels of reactive oxygen species (ROS), and thereby, chronic oxidative stress may be a major phenotypic hallmark in these diseases. Due to the presence of mitochondrial disturbances, A-T, BS and NBS may be considered mitochondrial diseases. Excess activity of antioxidant enzymes and an insufficient amount of low molecular weight antioxidants indicate new pharmacological strategies for patients suffering from the aforementioned diseases. However, at the current stage of research we are unable to ascertain if antioxidants and free radical scavengers can improve the condition or prolong the survival time of A-T, BS and NBS patients. Therefore, it is necessary to conduct experimental studies in a human model.


Assuntos
Ataxia Telangiectasia/genética , Síndrome de Bloom/genética , Reparo do DNA , Mitocôndrias/metabolismo , Síndrome de Quebra de Nijmegen/genética , Estresse Oxidativo/genética , Ataxia Telangiectasia/metabolismo , Ataxia Telangiectasia/patologia , Síndrome de Bloom/metabolismo , Síndrome de Bloom/patologia , Dano ao DNA , Regulação da Expressão Gênica , Humanos , Lipoproteínas LDL/genética , Lipoproteínas LDL/metabolismo , Mitocôndrias/patologia , NADPH Oxidase 4/genética , NADPH Oxidase 4/metabolismo , Síndrome de Quebra de Nijmegen/metabolismo , Síndrome de Quebra de Nijmegen/patologia , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
8.
Oxid Med Cell Longev ; 2017: 6745840, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29456787

RESUMO

This study compared the antioxidant status and major lipophilic antioxidants in patients with ataxia-telangiectasia (AT) and Nijmegen breakage syndrome (NBS). Total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and concentrations of coenzyme Q10 (CoQ10) and vitamins A and E were estimated in the plasma of 22 patients with AT, 12 children with NBS, and the healthy controls. In AT patients, TAS (median 261.7 µmol/L) was statistically lower but TOS (496.8 µmol/L) was significantly elevated in comparison with the healthy group (312.7 µmol/L and 311.2 µmol/L, resp.). Tocopherol (0.8 µg/mL) and CoQ10 (0.1 µg/mL) were reduced in AT patients versus control (1.4 µg/mL and 0.3 µg/mL, resp.). NBS patients also displayed statistically lower TAS levels (290.3 µmol/L), while TOS (404.8 µmol/L) was comparable to the controls. We found that in NBS patients retinol concentration (0.1 µg/mL) was highly elevated and CoQ10 (0.1 µg/mL) was significantly lower in comparison with those in the healthy group. Our study confirms disturbances in redox homeostasis in AT and NBS patients and indicates a need for diagnosing oxidative stress in those cases as a potential disease biomarker. Decreased CoQ10 concentration found in NBS and AT indicates a need for possible supplementation.


Assuntos
Ataxia Telangiectasia/metabolismo , Síndrome de Quebra de Nijmegen/metabolismo , Oxirredução , Adolescente , Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas de Ciclo Celular/genética , Criança , Feminino , Homeostase , Humanos , Masculino , Síndrome de Quebra de Nijmegen/genética , Proteínas Nucleares/genética , Estresse Oxidativo , Ubiquinona/análogos & derivados , Ubiquinona/sangue , Vitamina A/sangue , Vitamina E/sangue
9.
Qual Life Res ; 25(11): 2967-2975, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27245777

RESUMO

PURPOSE: Phenylketonuria (PKU) still poses a therapeutic challenge for patients and medical professionals. The aim of the study was to assess both patients' and their parents' acceptance of the disease. METHODS: The study included 218 PKU patients and 178 parents of PKU children who were enrolled in the study on the basis of questionnaire data. RESULTS: Regarding attitude towards the disease, our study demonstrated that 63 (28.9 %) PKU patients did not accept the disease. Patients who found accepting the disease difficult, more frequently perceived themselves as inferior/different in comparison with their peers. In total, 36 % of patients did not want their friends to be aware of their condition, while only 18 % of parents believed that their children's peers should not know about their disease. In total, 42 % of parents wanted to talk to other parents of PKU children and only 13 % to a doctor. Only 20 % of patients saw the need to discuss their condition with a doctor. In total, 8 % of children, regardless of age, and 14 % of parents preferred to talk to a psychologist. CONCLUSION: Our data demonstrated that disease acceptance played an essential role in patients' social integration. The study also indicated the need to overcome communication barriers between patients and their healthy peers and for patients to find the courage to be open about the disease. The importance of support groups for PKU families and the significance of strict cooperation between patients and their families with PKU treatment teams were also revealed.


Assuntos
Pais/psicologia , Fenilcetonúrias/psicologia , Qualidade de Vida/psicologia , Adolescente , Adulto , Atitude , Criança , Feminino , Humanos , Masculino , Inquéritos e Questionários , Adulto Jovem
10.
J Clin Immunol ; 35(6): 538-49, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26271390

RESUMO

PURPOSE: Nijmegen Breakage Syndrome (NBS) is a rare inherited condition, characterized by microcephaly, chromosomal instability, immunodeficiency, and predisposition to malignancy. This retrospective study, characterizing the clinical and immunological status of patients with NBS at time of diagnosis, was designed to assess whether any parameters were useful in disease prognosis, and could help determine patients qualified for hematopoietic stem cell transplantation. METHODS: The clinical and immunological characteristics of 149 NBS patients registered in the online database of the European Society for Immune Deficiencies were analyzed. RESULTS: Of the 149 NBS patients, 91 (61%), of median age 14.3 years, remained alive at the time of analysis. These patients were clinically heterogeneous, with variable immune defects, ranging from negligible to severe dysfunction. Humoral deficiencies predisposed NBS patients to recurrent/chronic respiratory tract infections and worsened long-term clinical prognosis. Eighty malignancies, most of lymphoid origin (especially non-Hodgkin's lymphomas), were diagnosed in 42% of patients, with malignancy being the leading cause of death in this cohort. Survival probabilities at 5, 10, 20 and 30 years of age were 95, 85, 50 and 35%, respectively, and were significantly lower in patients with than without malignancies. CONCLUSIONS: The extremely high incidence of malignancies, mostly non-Hodgkin's lymphomas, was the main risk factor affecting survival probability in NBS patients. Because treatment of NBS is very difficult and frequently unsuccessful, the search for an alternative medical intervention such as hematopoietic stem cell transplantation is of great clinical importance.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndrome de Quebra de Nijmegen/diagnóstico , Fatores de Tempo , Adolescente , Adulto , Criança , Pré-Escolar , Instabilidade Cromossômica , Feminino , Humanos , Síndromes de Imunodeficiência , Lactente , Linfoma não Hodgkin , Masculino , Microcefalia , Síndrome de Quebra de Nijmegen/genética , Síndrome de Quebra de Nijmegen/terapia , Prognóstico , Estudos Retrospectivos , Adulto Jovem
11.
Acta Biochim Pol ; 60(4): 613-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24350308

RESUMO

Tetrahydrobiopterin (BH4) has been recently approved as a treatment of patients with phenylketonuria. However, as a confirmation of BH4-responsiveness, it might require a very expensive trial treatment with BH4 or prolonged BH4-loading procedures. The selection of patients eligible for BH4-therapy by means of genotyping of the PAH gene mutations may be recommended as a complementary approach. A population-wide genotyping study was carried out in 1286 Polish phenyloketonuria-patients. The aim was to estimate the BH4 demand and to cover prospectively the treatment by a National Health Fund. A total of 95 types of mutations were identified. Genetic variants corresponding with probable BH4-responsiveness were found in 28.2% of cases. However, patients with mild or classical phenylketonuria who require continuous treatment accounted for 11.4% of the studied population only. Analysis of the published data shows similar percentage of the "BH4-responsive" variants of a PAH gene in patients from other countries of Eastern Europe. Therefore, it can be concluded, that the proportion of phenylketonuria-patients who could benefit from the use of BH4 reaches approximately 10% in the entire region.


Assuntos
Biopterina/análogos & derivados , Mutação/genética , Fenilalanina Hidroxilase/genética , Fenilcetonúrias/tratamento farmacológico , Biomarcadores Farmacológicos , Biopterina/administração & dosagem , Genótipo , Humanos , Fenilalanina/deficiência , Fenilalanina/genética , Fenilcetonúrias/genética , Polônia
12.
Arthritis Res Ther ; 15(1): R30, 2013 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-23421920

RESUMO

INTRODUCTION: Mutations in the NLRP3 gene are associated with the dominantly inherited cryopyrin-associated periodic syndrome (CAPS). The significance of the V198M variant is unclear; it has been reported in association with various CAPS phenotypes and as a variant of uncertain consequence. The aim of this study was to characterize the clinical phenotypes and treatments in individuals with V198M assessed in a single UK center. METHODS: DNA samples from 830 subjects with fever syndromes or a family history of CAPS were screened for mutations in the NLRP3 gene with polymerase chain reaction (PCR) and sequencing. A detailed medical history was available in all cases. Inflammatory disease activity was monitored monthly with measurements of serum amyloid A protein (SAA) and C-reactive protein (CRP) in symptomatic individuals. RESULTS: NLRP3 V198M was identified in 19 subjects. It was found in association with CAPS in five cases, in one patient with Schnitzler syndrome, in three patients who also had a nucleotide alteration in another fever gene, and in three other patients with evidence of an autoinflammatory phenotype. Seven asymptomatic individuals were detected during screening of family members. CONCLUSIONS: The NLRP3 V198M variant shows variable expressivity and reduced penetrance. It may be associated with classical inherited or apparently sporadic CAPS and with atypical autoinflammatory disease of varying severity, intriguingly including Schnitzler syndrome. The factors that influence the pathogenic consequences of this variant remain unknown. However, the remarkable response to interleukin 1 (IL-1) blockade in all but one individual in our series confirms that their clinical features are indeed mediated by IL-1.


Assuntos
Proteínas de Transporte/genética , Doenças Hereditárias Autoinflamatórias/genética , Adulto , Criança , Pré-Escolar , Síndromes Periódicas Associadas à Criopirina/genética , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mutação , Proteína 3 que Contém Domínio de Pirina da Família NLR , Linhagem , Penetrância , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Reino Unido , Adulto Jovem
13.
Hum Immunol ; 73(11): 1091-7, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22902394

RESUMO

The aim of the current study was to examine whether a congenital lack of the spleen changes distribution, state of activation and function of peripheral lymphocyte T subsets. Seven children with congenital asplenia (CA) aged 1.5-17 years and seven age-matched controls were tested. By triple-color flow cytometry we examined: (1) the expression of CD3(+), CD4(+), CD8(+), CD19(+), and CD56(+) on lymphocytes; (2) the distribution of CD45RA(+) and CD45RO(+) in CD4(+) and CD8(+); (3) the expression of CD27(+) in the CD4(+) and CD8(+) T-cell-bearing CD45RA(+), CD45RO(+), or CD45RB(+). Lymphocyte proliferative responses and cytokines production (IFN-gamma, IL-6, TNF-alfa, and IL-10) in anti-CD3-induced peripheral blood mononuclear cells were tested. The results indicate (1) a normal distribution of the basic lymphocyte subsets, (2) low CD3(+)/CD8(+) percentage but expressing CD8(+high) and non-significantly elevated CD4(+)/CD8(+) ratio, (3) CD45RA(+high) and CD27(+high) in the CD4(+) and CD8(+) T cell, and (4) CD45RB(+high) in the CD4(+) and CD45RO(+high) in the CD8(+). The distribution of CD27(+) in the CD45RA(+) and CD45RO(+) CD4(+) T cells remained unchanged. However, the percentage of CD8(+)/CD45RO(+)/CD27(+) T cells tended to be elevated. Altogether, these data indicate that CA is connected with (1) the presence CD4(+) T cells expressing the "naive" phenotype (CD45RA(+high) RB(+high) and CD27(+high)), (2) high numbers of activated CD8(+) T cells shifted toward the memory phenotype (CD45RO(+high)) but still showing high CD27(+) expression, which may indicate failure in T CD8(+) cytotoxic effectors differentiation, and (3) a tendency to the rather pro-inflammatory status of cells, low IL-10 expression, and suboptimal lymphocytes responses to mitogenic stimulation.


Assuntos
Síndromes de Imunodeficiência/imunologia , Subpopulações de Linfócitos T/imunologia , Adolescente , Antígenos CD/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Criança , Pré-Escolar , Citocinas/biossíntese , Feminino , Humanos , Imunofenotipagem , Lactente , Antígenos Comuns de Leucócito/metabolismo , Ativação Linfocitária/imunologia , Masculino , Fenótipo , Baço/anormalidades , Baço/imunologia , Subpopulações de Linfócitos T/metabolismo , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo
14.
Antioxid Redox Signal ; 16(2): 179-82, 2012 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-21895448

RESUMO

The treatment of phenylketonuria (PKU) patients constitutes a phenylalanine (Phe) intake restriction in their diet, which is achieved by adding a special Phe-free amino acid mixture to the diet. It has been reported that this diet could have some micronutrient deficiency. Several authors have also reported an increased oxidative stress or impaired antioxidant status in human and experimental PKU. Our project assessed the concentrations of retinol, alpha-tocopherol, coenzyme Q10, and anti-oxidized low-density lipoprotein (ox-LDL) antibodies in PKU children's plasma. It was found that retinol concentration in PKU children remains within the norm despite a low intake. The lower plasma alpha-tocopherol concentration in PKU children compared with normal children was associated with the lower level of antibodies against ox-LDL. This raises the question whether higher than observed circulatory alpha-tocopherol is indeed beneficial to lower plasma ox-LDL levels. Further studies are needed to explain the genetic factor in PKU patients (e.g., CD36/FAT polymorphism gene). The open clinical question is whether daily supplementation of alpha-tocopherol changes the PKU patients' level of antibodies against ox-LDL.


Assuntos
Antioxidantes/metabolismo , Autoanticorpos/sangue , Metabolismo dos Lipídeos , Lipoproteínas LDL/imunologia , Fenilcetonúrias/sangue , Criança , Pré-Escolar , Feminino , Humanos , Masculino
15.
Immunol Invest ; 41(1): 61-74, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21877936

RESUMO

The spleen plays an important role in the granulocyte homeostasis due to such mechanisms as pooling, elimination of senescent cells and regulatory effects on granulocyte renewal in the bone marrow. The expression profile of granulocyte receptors was tested in children with congenital asplenia, and splenectomized for spherocytosis. Receptors tested included those appearing with maturation (CD16, CD11b, CD11c, TREM-1), disappearing (CD54, CD49d, CD64) and maintained during maturation (CD11a, CD45). In general, we found that the circulating granulocyte pool in the asplenic patients had phenotypical features of highly matured but not apoptotic neutrophils with a significantly elevated expression of CD16 (CD16(high)), tendency to a lower expression of CD45 (CD45(low)) and an unchanged expression of CD64 (and other markers indicating systemic inflammatory reactions). The high fluorescence intensity of CD11b,c, and TREM-1 in the congenital asplenia may indicate a potentially elevated pro-inflammatory status of granulocytes, possibly due to the low activity of vagus nerve and spleen-dependent cholinergic anti-inflammatory pathway.


Assuntos
Anemia Hemolítica Autoimune/imunologia , Síndrome de Heterotaxia/imunologia , Neutrófilos/metabolismo , Baço/imunologia , Esplenectomia , Adolescente , Antígenos CD/metabolismo , Diferenciação Celular , Sobrevivência Celular , Criança , Pré-Escolar , Feminino , Regulação da Expressão Gênica/imunologia , Síndrome de Heterotaxia/cirurgia , Humanos , Imunofenotipagem , Lactente , Mediadores da Inflamação/metabolismo , Masculino , Neutrófilos/imunologia , Neutrófilos/patologia , Baço/anormalidades
16.
DNA Repair (Amst) ; 9(4): 365-73, 2010 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-20079696

RESUMO

V(D)J rearrangement in lymphoid cells involves repair of double-strand breaks (DSBs) through non-homologous end joining (NHEJ). Defects in this process lead to increased radiosensitivity and severe combined immunodeficiency (RS-SCID). Here, a SCID patient, M3, is described with a T(-)B(+)NK(+) phenotype but without causative mutations in CD3delta, epsilon, zeta or IL7Ralpha, genes specifically involved in T cell development. Clonogenic survival of M3 fibroblasts showed an increased sensitivity to the DSB-inducing agents ionizing radiation and bleomycin, as well as the crosslinking compound, mitomycin C. We did not observe inactivating mutations in known NHEJ genes and results of various DSB-repair assays in G(1) M3 cells were indistinguishable from those obtained with normal cells. However, we found increased chromosomal radiosensitivity at the G(2) phase of the cell cycle. Checkpoint analysis indicated functional G(1)/S and intra-S checkpoints after irradiation but impaired activation of the "early" G(2)/M checkpoint. Together these results indicate a novel class of RS-SCID patients characterized by the specific absence of T lymphocytes and associated with defects in G(2)-specific DSB repair. The pronounced G(2)/M radiosensitivity of the RS-SCID patient described here, suggests a defect in a putative novel and uncharacterized factor involved in cellular DNA damage responses and T cell development.


Assuntos
Divisão Celular/efeitos da radiação , Fase G2/efeitos da radiação , Tolerância a Radiação/genética , Imunodeficiência Combinada Severa/genética , Linhagem Celular , Dano ao DNA , Rearranjo Gênico , Humanos , Linfócitos T/metabolismo , VDJ Recombinases/genética , VDJ Recombinases/metabolismo
17.
Int J Hematol ; 90(5): 571-575, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19866337

RESUMO

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by a defect of phagocyte NADPH-oxidase and characterized by severe, recurrent bacterial and fungal infections. Invasive aspergillosis (IA) is the leading cause of mortality in patients with CGD. We report the case of a 3-year-old boy with CGD, who developed IA despite antifungal prophylaxis. His treatment consisted of a 10-month-long multi-drug antifungal therapy, together with surgery, but these did not cause any substantial clinical improvement. BMT in high-risk patients with CGD remains a challenge due to both, higher risk of graft rejection and inflammatory flare in the course of immune recovery. Our patient rejected the first matched unrelated donor (MUD) allograft after RIC regimen recommended by the EBMT Inborn Errors Working Party for high-risk patients. After treosulfan-based conditioning and second MUD peripheral blood stem cell transplantation both, full reconstitution of the granulocytic series and complete recovery from IA, were achieved.


Assuntos
Aspergilose/terapia , Bussulfano/análogos & derivados , Doença Granulomatosa Crônica/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Reoperação/métodos , Condicionamento Pré-Transplante/métodos , Antineoplásicos Alquilantes/uso terapêutico , Bussulfano/uso terapêutico , Pré-Escolar , Sobrevivência de Enxerto , Doença Granulomatosa Crônica/complicações , Humanos , Masculino
18.
Med Wieku Rozwoj ; 13(1): 19-25, 2009.
Artigo em Polonês | MEDLINE | ID: mdl-19648655

RESUMO

Hyper-IgE syndrome (HIES) is a primary immunodeficiency (PID) characterized by recurrent skin abscesses (S. aureus), recurrent pneumonia with pneumatocele formation, atopic dermatitis and elevated levels of serum IgE (>2000 IU/ml). HIES is a sporadic disease, however, two distinct entities - classic HIES inherited in an autosomal dominant pattern (AD HIES), and an autosomal recessive HIES (AR HIES) have been described. Some cases of AD HIES with predominant pulmonary manifestation are caused by mutation in STAT3 gene. It is important to differentiate cases of atopic dermatitis and AD HIES where it is necessary to implement antibacterial and antifungal prophylaxis. Opportunity of performing genetic analysis in suspicion of AD HIES leads to definitive diagnosis of the disease and earlier institution of appropriate treatment. We present the case of a 22-year-old patient with typical course of autosomal dominant hyper-IgE syndrome, confirmed in the Royal Free Hospital, University College London, UK, by finding mutation in STAT3 gene.


Assuntos
Síndrome de Job/diagnóstico , Síndrome de Job/genética , Mutação , Fator de Transcrição STAT3/genética , Adulto , Humanos , Masculino
19.
Przegl Epidemiol ; 63(1): 55-60, 2009.
Artigo em Polonês | MEDLINE | ID: mdl-19522227

RESUMO

Antibody deficiency may have genetic basis or be secondary to other diseases or iatrogenic factors. Recurrent respiratory, gastrointestinal and skin infections consist on the most frequent clinical picture. Severe course of these infections, recurrences and difficulties in treatment may suggest immunodeficiency. Antibody deficiency may be associated with numerous complications. Intravenous or subcutaneous immunoglobulin substitution is the way of treating these patients. Prevention of infection in primary and secondary antibody deficiency also includes vaccinations, prophylaxis with antibiotics and education of patients, parents and caregivers.


Assuntos
Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/terapia , /imunologia , Doenças Autoimunes/imunologia , Diagnóstico Diferencial , Suscetibilidade a Doenças , Educação em Saúde/métodos , Humanos , Deficiência de IgA/imunologia , Deficiência de IgG/imunologia , Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/prevenção & controle , /terapia
20.
Int J Vitam Nutr Res ; 79(5-6): 328-36, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20533219

RESUMO

AIM: Has elimination diet applied in children with food hypersensitivity in infancy any effect on plasma levels of anti-oxidative vitamins and antibodies to oxidized low-density lipoprotein (anti-ox-LDL antibody) titer in these children at their pre-school age?" MATERIAL: The study involved 92 children (3 to 7 years of age) with food hypersensitivity treated in their infancy and early childhood with soy formula or casein hydrolysate, as a milk substitute for at least 12 months. Control group comprised 62 children, who had never been treated with an elimination diet. METHODS: The status of the anti-oxidative system was evaluated by determination of retinol, alpha-tocopherol, and coenzyme Q10 plasma levels by high-performance liquid chromatography (HPLC). The titer of antibodies to oxidized LDL lipoproteins was specified by immunoenzymatic assay. On the basis of the RESULTS, the following CONCLUSIONS have been reached: 1. It was shown that alpha-tocopherol and retinol levels in pre-school children who had received dietary treatment in their infancy, were higher than in the control group. No deficiencies in anti-oxidative vitamins within the control group were found. 2. A type of milk-substitute formula applied in the elimination diet had no effect on the status of the anti-oxidative system in the children examined.


Assuntos
Anticorpos/sangue , Hipersensibilidade Alimentar/dietoterapia , Lipoproteínas LDL/imunologia , Substitutos do Leite/administração & dosagem , Ubiquinona/análogos & derivados , Vitamina A/sangue , alfa-Tocoferol/sangue , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Distribuição Aleatória , Estudos Retrospectivos , Ubiquinona/sangue
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