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1.
Orv Hetil ; 160(38): 1487-1494, 2019 Sep.
Artigo em Húngaro | MEDLINE | ID: mdl-31537095

RESUMO

Immune status was investigated in 186 patients with chronic lymphoid leukaemia between January 2012 and March 2015. Incidences of infections and mortality were analysed in patients who did not receive prophylactic immunoglobulin therapy. Immunoglobulin G (IgG) levels were normal (7-17.8 g/L) or decreased in 62.37% and 35.48% of patients, respectively. We measured high immunoglobulin levels only in a few cases (2.15%). Immunoglobulin levels became increasingly lower in more advanced disease stages (Rai stages). The number of infections was inversely proportional to that. Hypogammaglobulinaemia proved to be more important than disease progression in terms of the development of infections. The most common infections were upper respiratory tract (33.07%) and sepsis (18.90%). Two months after chemotherapy, initially normal immunoglobulin levels decreased by an average of 21%, and at the same time the incidence of infections increased. The most common cause of death was sepsis: 30% occurred at low immunoglobulin levels, while 20% at normal immunoglobulin levels. According to literature, prophylactic immunoglobulin treatment is indicated in patients with chronic lymphoid leukaemia and immunodeficiency for decreasing both morbidity and mortality. According to recommendations in literature, replacement treatment must be administered in severe or moderately severe recurrent bacterial infections. Immunoglobulin prophylaxis may be provided as low dose (10 g), fix dose (18 g) or individually customized higher dose (300-400 mg/kg body weight) treatment. According to recommendations, higher dose immunoglobulin prophylaxis, administered every three weeks on six occasions, is more efficient when customized. With this dose, infection-free condition may be achieved in 50% of patients. Orv Hetil. 2019; 160(38): 1487-1494.


Assuntos
Agamaglobulinemia/tratamento farmacológico , Agamaglobulinemia/mortalidade , Imunoglobulinas Intravenosas/uso terapêutico , Imunoglobulinas/administração & dosagem , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Sepse/mortalidade , Agamaglobulinemia/complicações , Relação Dose-Resposta a Droga , Feminino , Humanos , Hungria/epidemiologia , Imunoglobulina G/sangue , Imunoglobulinas Intravenosas/administração & dosagem , Controle de Infecções , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Sepse/diagnóstico , Resultado do Tratamento
2.
Vet Rec ; 184(1): 17-18, 2019 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-30606855
3.
Am J Nurs ; 118(12): 72, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30461504
4.
J Clin Immunol ; 38(4): 484-493, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29744787

RESUMO

INTRODUCTION: Adenosine deaminase (ADA) deficiency is an autosomal recessive primary immunodeficiency. It results in the intracellular accumulation of toxic metabolites which have effects particularly on lymphocytes and the brain. The aim of this study was to evaluate the outcome of 13 ADA-deficient patients. We planned to evaluate their clinical and laboratory findings before and after enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (aHSCT), and hematopoietic stem cell gene therapy (HSCGT). METHODS: Measurement of ADA enzyme activity and metabolites and sequencing of the ADA gene were performed in most of the patients with ADA deficiency. One of the patients with late-onset ADA deficiency was diagnosed by the help of primary immunodeficiency panel screening. RESULTS: Ten out of 13 patients were diagnosed as SCID, while 3 out of 13 were diagnosed as delayed-/late-onset ADA deficiency. Late-onset ADA deficiency patients had clinical and laboratory findings of combined immunodeficiency (CID). Eight patients with ADA-SCID were found to have higher levels of ADA metabolite (dAXP%) (62.1% (34.6-71.9)) than 3 patients with delayed-/late-onset ADA deficiency (6.9% (2.1-8.9). All but one patient with SCID had T-B-NK- phenotype, one had T-B-NK+ phenotype. Genetic defect was documented in 11 patients. Four out of 11 patients had compound heterozygous defects. Three out of 4 patients with compound heterozygous defects had delayed-onset/late-onset ADA deficiency. Seven out of 11 patients with SCID had homozygous defects. Five out of 7 had the same homozygous indel frameshift mutation (c.955-959delGAAGA) showing a founder effect. There were two novel splice site defects: one (IVS10+2T>C) was heterozygous in a patient with late-onset ADA deficiency, and the other was homozygous (IVS2delT+2) in a SCID patient. Other defects were missense defects. Nine out of 13 patients were put on pegylated ADA ERT. Four out of six patients were transplanted without using a conditioning regimen. HSCGT was performed to one of the patients. CONCLUSION: The genetic diagnosis of SCID is utmost important. There is a chance to give ERT before the definitive therapy if the patient with SCID/CID has ADA deficiency. Although ERT was insufficient to restore a normal immune function in ADA-SCID patients, it was useful to improve and stabilize the clinical status before curative therapy (aHSCT/HSCGT). Enzyme replacement therapy was successful in patients with late-/delayed-onset ADA deficiency who presented with the features of combined immunodeficiency. Gastrointestinal polyposis in a patient with late-onset ADA deficiency may be an association or a coincidental finding. Intermittent neurodevelopmental evaluation especially for hearing impairment should be performed in most of the ADA-deficient patients. This may alleviate the speech delay and cognitive abnormalities which may be observed in the follow-up.


Assuntos
Adenosina Desaminase/deficiência , Agamaglobulinemia/diagnóstico , Estudos de Associação Genética , Imunodeficiência Combinada Severa/diagnóstico , Adenosina Desaminase/sangue , Adenosina Desaminase/genética , Agamaglobulinemia/mortalidade , Agamaglobulinemia/terapia , Idade de Início , Biomarcadores , Biópsia , Gerenciamento Clínico , Ativação Enzimática , Terapia de Reposição de Enzimas , Feminino , Testes Genéticos , Terapia Genética , Genótipo , Transplante de Células-Tronco Hematopoéticas , Homozigoto , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Fenótipo , Análise de Sequência de DNA , Imunodeficiência Combinada Severa/mortalidade , Imunodeficiência Combinada Severa/terapia , Resultado do Tratamento
5.
JAMA Netw Open ; 1(7): e184169, 2018 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-30646343

RESUMO

Importance: Rituximab is an anti-CD20 chimeric antibody used in a wide variety of clinical indications. There has not been widespread adoption of consistent immune monitoring before and after rituximab therapy. However, there is a subset of patients who develop prolonged, symptomatic hypogammaglobulinemia following rituximab, and monitoring before and after rituximab therapy could help to identify these patients and initiate measures to prevent excess morbidity and mortality. Objective: To determine the current levels of screening for hypogammaglobulinemia (specifically, low immunoglobulin G), infectious risks associated with hypogammaglobulinemia, and variables associated with an increased risk of mortality. Design, Setting, and Participants: A cohort study was conducted of 8633 patients receiving rituximab from January 1, 1997, to December 31, 2017, at a large, tertiary referral center (Partners HealthCare System). Exposures: Rituximab administration. Main Outcomes and Measures: The primary outcome measures were immunoglobulin measurements, infectious complications, and mortality. Cox regression analysis was used to examine the results of infectious complications on survival, adjusted for age, sex, and indication for rituximab use. Results: Of the 8633 patients who received rituximab in the large, academic, health care system, 4479 satisfied inclusion criteria, with a mean (SD) age of 59.8 (16.2) years; 2280 patients (50.9%) were women. Most patients (3824 [85.4%]) did not have immunoglobulin levels checked before rituximab therapy. Of those who had levels determined, hypogammaglobulinemia was noted in 313 (47.8%) patients before initiation of rituximab. Following rituximab administration, worsening hypogammaglobulinemia was noted. There was an increase in severe infections after rituximab use in the study cohort (from 17.2% to 21.7%; P < .001). In the survival analysis, increased mortality was associated with increasing age (hazard ratio [HR], 1.02; 95% CI, 1.01-1.02; P < .001), male sex (HR, 1.14; 95% CI, 1.02-1.28; P = .02), and severe infectious complications in the 6 months before (HR, 3.14; 95% CI, 2.77-3.55; P < .001) and after (HR, 4.97; 95% CI, 4.41-5.60; P < .001) the first rituximab infusion. A total of 201 patients (4.5%) received immunoglobulin replacement following rituximab, and among these patients, higher cumulative immunoglobulin replacement dose was associated with a reduced risk of serious infectious complications (HR, 0.98; 95% CI, 0.96-0.99; P = .002). Conclusions and Relevance: Many patients are not being screened or properly identified as having hypogammaglobulinemia both before and after rituximab administration. Monitoring of immunoglobulin levels both before and after rituximab therapy may allow for earlier identification of risk for developing significant infection and identify patients who may benefit from immunoglobulin replacement, which may in turn help to avoid excess morbidity and mortality.


Assuntos
Agamaglobulinemia/complicações , Causas de Morte , Imunoglobulina G/sangue , Programas de Rastreamento , Rituximab/efeitos adversos , Adulto , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/mortalidade , Idoso , Animais , Estudos de Coortes , Monitoramento de Medicamentos , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Prevalência , Modelos de Riscos Proporcionais , Fatores de Risco , Índice de Gravidade de Doença
6.
Blood ; 128(1): 45-54, 2016 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-27129325

RESUMO

Adenosine deaminase (ADA) deficiency is a rare, autosomal-recessive systemic metabolic disease characterized by severe combined immunodeficiency (SCID). The treatment of choice for ADA-deficient SCID (ADA-SCID) is hematopoietic stem cell transplant from an HLA-matched sibling donor, although <25% of patients have such a donor available. Enzyme replacement therapy (ERT) partially and temporarily relieves immunodeficiency. We investigated the medium-term outcome of gene therapy (GT) in 18 patients with ADA-SCID for whom an HLA-identical family donor was not available; most were not responding well to ERT. Patients were treated with an autologous CD34(+)-enriched cell fraction that contained CD34(+) cells transduced with a retroviral vector encoding the human ADA complementary DNA sequence (GSK2696273) as part of single-arm, open-label studies or compassionate use programs. Overall survival was 100% over 2.3 to 13.4 years (median, 6.9 years). Gene-modified cells were stably present in multiple lineages throughout follow up. GT resulted in a sustained reduction in the severe infection rate from 1.17 events per person-year to 0.17 events per person-year (n = 17, patient 1 data not available). Immune reconstitution was demonstrated by normalization of T-cell subsets (CD3(+), CD4(+), and CD8(+)), evidence of thymopoiesis, and sustained T-cell proliferative capacity. B-cell function was evidenced by immunoglobulin production, decreased intravenous immunoglobulin use, and antibody response after vaccination. All 18 patients reported infections as adverse events; infections of respiratory and gastrointestinal tracts were reported most frequently. No events indicative of leukemic transformation were reported. Trial details were registered at www.clinicaltrials.gov as #NCT00598481.


Assuntos
Adenosina Desaminase/deficiência , Agamaglobulinemia/terapia , Terapia Genética , Recuperação de Função Fisiológica , Retroviridae , Imunodeficiência Combinada Severa/terapia , Adenosina Desaminase/genética , Adenosina Desaminase/imunologia , Agamaglobulinemia/genética , Agamaglobulinemia/imunologia , Agamaglobulinemia/mortalidade , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/imunologia , Imunodeficiência Combinada Severa/mortalidade , Taxa de Sobrevida
7.
Transplant Proc ; 48(2): 479-84, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27109982

RESUMO

BACKGROUND: Severe hypogammaglobulinemia (HGG) (IgG <400 mg/dL) following intestinal transplantation is common. Although IgG replacement therapy is commonly used, clinical outcomes associated with increasing IgG levels to >400 mg/dL are not well described. METHODS: Kaplan-Meier analysis was performed to estimate survival, the log-rank test to compare survival distributions between groups, and the Fisher exact test to determine the association between HGG and rejection. RESULTS: A total of 23 intestinal transplant (IT) recipients with a median age of 2.3 years (range, 0.7-41 years) at the time of HGG diagnosis were included. The types of transplants were liver-small bowel (73.9%), liver-small bowel-kidney (8.7%), and small bowel only (17.4%). The 3-year survival after the diagnosis of HGG was 50.2% (95% confidence interval [CI] = 28.2%-68.7%). There was no difference in survival (P = .67) when patients were dichotomized based upon IgG level at last follow-up (IgG ≥400 mg/dL, n = 14; and IgG <400 mg/dL, n = 9). There was no also evidence of an association between survival and: total dose (P = .58), frequency (P = .11), and number of IgG doses administered (P = .8). There was no difference in survival between patients receiving (n = 12) or not receiving (n = 11) cytomegalovirus hyperimmunoglobulin (P = .10). CONCLUSIONS: Improved survival rates were not found in our IT recipients with severe HGG with immunoglobulin therapy to IgG levels of ≥400 mg/dL, even when cytomegalovirus hyperimmunoglobulin was administered.


Assuntos
Agamaglobulinemia/tratamento farmacológico , Imunização Passiva , Imunoglobulina G/uso terapêutico , Fatores Imunológicos/uso terapêutico , Intestinos/transplante , Complicações Pós-Operatórias/tratamento farmacológico , Adolescente , Adulto , Agamaglobulinemia/etiologia , Agamaglobulinemia/mortalidade , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulina G/sangue , Lactente , Estimativa de Kaplan-Meier , Masculino , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
8.
Clin Exp Immunol ; 184(1): 73-82, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26646609

RESUMO

Idiopathic hypogammaglobulinaemia, including common variable immune deficiency (CVID), has a heterogeneous clinical phenotype. This study used data from the national UK Primary Immune Deficiency (UKPID) registry to examine factors associated with adverse outcomes, particularly lung damage and malignancy. A total of 801 adults labelled with idiopathic hypogammaglobulinaemia and CVID aged 18-96 years from 10 UK cities were recruited using the UKPID registry database. Clinical and laboratory data (leucocyte numbers and serum immunoglobulin concentrations) were collated and analysed using uni- and multivariate statistics. Low serum immunoglobulin (Ig)G pre-immunoglobulin replacement therapy was the key factor associated with lower respiratory tract infections (LRTI) and history of LRTI was the main factor associated with bronchiectasis. History of overt LRTI was also associated with a significantly shorter delay in diagnosis and commencing immunoglobulin replacement therapy [5 (range 1-13 years) versus 9 (range 2-24) years]. Patients with bronchiectasis started immunoglobulin replacement therapy significantly later than those without this complication [7 (range 2-22) years versus 5 (range 1-13) years]. Patients with a history of LRTI had higher serum IgG concentrations on therapy and were twice as likely to be on prophylactic antibiotics. Ensuring prompt commencement of immunoglobulin therapy in patients with idiopathic hypogammaglobulinaemia is likely to help prevent LRTI and subsequent bronchiectasis. Cancer was the only factor associated with mortality. Overt cancer, both haematological and non-haematological, was associated with significantly lower absolute CD8(+) T cell but not natural killer (NK) cell numbers, raising the question as to what extent immune senescence, particularly of CD8(+) T cells, might contribute to the increased risk of cancers as individuals age.


Assuntos
Agamaglobulinemia/diagnóstico , Bronquiectasia/diagnóstico , Imunodeficiência de Variável Comum/diagnóstico , Neoplasias Pulmonares/diagnóstico , Sistema de Registros , Infecções Respiratórias/diagnóstico , Adolescente , Adulto , Agamaglobulinemia/tratamento farmacológico , Agamaglobulinemia/imunologia , Agamaglobulinemia/mortalidade , Idoso , Idoso de 80 Anos ou mais , Bronquiectasia/tratamento farmacológico , Bronquiectasia/imunologia , Bronquiectasia/mortalidade , Imunodeficiência de Variável Comum/tratamento farmacológico , Imunodeficiência de Variável Comum/imunologia , Imunodeficiência de Variável Comum/mortalidade , Feminino , Humanos , Imunoglobulinas/sangue , Imunoglobulinas Intravenosas/uso terapêutico , Contagem de Leucócitos , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Fenótipo , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/imunologia , Infecções Respiratórias/mortalidade , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo , Reino Unido
9.
Cancer ; 121(17): 2883-91, 2015 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-25931291

RESUMO

BACKGROUND: Although hypogammaglobulinemia is a well recognized complication in patients with chronic lymphocytic leukemia (CLL), its prevalence at the time of CLL diagnosis, and association with novel prognostic markers and clinical outcome is not well understood. METHODS: All patients at the Mayo Clinic between January 1999 and July 2013 who had newly diagnosed CLL and had a baseline assessment of serum immunoglobulin G (IgG) were included. The relation between hypogammaglobulinemia at diagnosis and the novel prognostic parameters time to first treatment (TFT) and overall survival (OS) were evaluated. RESULTS: Of 1485 patients who met the eligibility criteria, 382 (26%) had hypogammaglobulinemia (median IgG, 624 mg/dL), whereas the remaining 1103 patients (74%) had normal serum IgG levels (median IgG, 1040 mg/dL). Patients who had hypogammaglobulinemia at diagnosis were more likely to have advanced Rai stage (III-IV; P = .001) and higher expression of CD49d (P < .001) compared with patients who had normal IgG levels. Although the median TFT for patients who had hypogammaglobulinemia was shorter compared with that for patients who had normal IgG levels (3.8 years vs 7.4 years; P < .001), on multivariable analysis, there was no difference in OS between these 2 groups (12.8 years vs 11.3 years, respectively; P = .73). Of 1103 patients who had CLL with normal IgG levels at diagnosis and who did not receive CLL therapy, the risk of acquired hypogammaglobulinemia was 11% at 5 years and 23% at 10 years. CONCLUSIONS: Hypogammaglobulinemia is present in 25% of patients with newly diagnosed CLL. Approximately 25% of patients who have CLL with normal IgG levels at diagnosis will subsequently develop hypogammaglobulinemia on long-term follow-up. The presence of hypogammaglobulinemia does not appear to impact overall survival.


Assuntos
Agamaglobulinemia/diagnóstico , Leucemia Linfocítica Crônica de Células B/diagnóstico , Adulto , Agamaglobulinemia/mortalidade , Agamaglobulinemia/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imunoglobulina G/sangue , Estimativa de Kaplan-Meier , Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfocítica Crônica de Células B/mortalidade , Leucemia Linfocítica Crônica de Células B/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
10.
Pediatr Blood Cancer ; 62(5): 890-6, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25623620

RESUMO

BACKGROUND: Hypogammaglobulinemia (hypo-IgG) is common early post-HSCT in children, occasionally necessitating long-term immunoglobulin (Ig) G replacement therapy. IgG replacement may not reduce mortality, although infectious complications are decreased PROCEDURE: Clinical data and samples from 86 children were analyzed retrospectively with the aim to identify risk factors for developing long-term hypo-IgG (i.e., requiring ≥ 3 months IgG replacement) post-HSCT and studying the underlying biology. Laboratory studies covered serum cytokines, IGHG2 genotyping and routine laboratory investigations. Results were analyzed statistically. RESULTS: Forty-eight percent of the children developed long-term hypo-IgG. These children were younger (<5 years) and had higher acute GvHD incidence, but had better overall survival (88% vs. 69%, P = 0.036). Significantly lower Ig levels post-HSCT but equal immune cell recovery were seen in patients with long-term hypo-IgG compared with those of transient or no hypo-IgG. Pre-HSCT IL-6 and -7 and post-HSCT BAFF and APRIL levels were significantly higher in the long-term hypo-IgG group. CONCLUSIONS: Findings suggests an unfavorable cytokine milieu for graft-derived immune recovery, possibly inducing Ig isotype class switch arrest. Younger age, acute GvHD, and higher pre-HSCT IL-6 levels were identified as significant risk factors for long-term hypo-IgG. Long-term hypo-IgG post-HSCT does not need to be unfavorable and could be an effect of deteriorated cytokine signaling.


Assuntos
Agamaglobulinemia/etiologia , Citocinas/farmacologia , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Switching de Imunoglobulina/efeitos dos fármacos , Isotipos de Imunoglobulinas/efeitos dos fármacos , Adolescente , Adulto , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/mortalidade , Criança , Pré-Escolar , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
11.
Transplantation ; 99(2): 444-50, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25099705

RESUMO

BACKGROUND: After lung transplantation (LT), immunoglobulin (Ig) G plasma concentrations<6 g/L are common and correlate with an increased risk of chronic lung allograft dysfunction (CLAD) and a poorer survival. METHODS: We conducted an open substitution intervention with nonspecific intravenous Ig (IVIg), in all patients with IgG plasma less than 6 g/L post-LT in 54 of 84 consecutive recipients since 1998 who survived more than 3 months. Pre-LT and post-LT events were retrospectively analyzed. RESULTS: Both substituted and nonsubstituted groups demonstrated similar donor or recipient characteristics and events over a median follow-up of 2.8 years (Q1-Q3, 1.4-5.7], except for initial diagnosis with more chronic obstructive pulmonary disease patients and less cases of pulmonary arterial hypertension in NS group. Intravenous Ig substitution started 3.5 months (0.5-9.4) after transplantation and lasted 4.5 months after (1.0-17.7), mean cumulative dose was 52.8±47.7 g. In multivariate Cox regression model, hypogammaglobulinemic patients who were substituted with IVIg had actually a 5-year survival (hazard ratio, 0.63; 95% confidence interval, 0.26-1.49; P=0.29) and CLAD-free 5-year survival (hazard ratio, 0.51; 95% confidence interval, 0.15-1.67; P=0.27) really close to nonhypogammaglobulinemic and nonsubstituted patients. Complementary analysis using propensity score and time-dependent analysis showed that survival and CLAD-free survival were not different in both groups. CONCLUSION: Intravenous Ig post-LT achieved similar survival and CLAD-free survival in recipients with hypogammaglobulinemia as compared to those with normal IgG plasmatic rate. A randomized control trial is required to confirm benefic effects of IVIg and disentangle mechanisms, including protection from infections, acute cellular and humoral rejections in patients with hypogammaglobulinemia after LT.


Assuntos
Agamaglobulinemia/tratamento farmacológico , Imunoglobulinas Intravenosas/administração & dosagem , Transplante de Pulmão/efeitos adversos , Adulto , Agamaglobulinemia/sangue , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/imunologia , Agamaglobulinemia/mortalidade , Biomarcadores/sangue , Intervalo Livre de Doença , Esquema de Medicação , Feminino , França , Humanos , Imunoglobulina G/sangue , Estimativa de Kaplan-Meier , Transplante de Pulmão/mortalidade , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
12.
Allergol Immunopathol (Madr) ; 43(1): 62-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24485939

RESUMO

BACKGROUND: X-linked agammaglobulinaemia (XLA) is a genetic disorder characterised by a defect in the generation of mature B cells, lack of antibodies production, and susceptibility to recurrent bacterial infections. Understanding of the risk factors responsible for morbidity and mortality in these patients can help in a better management of this disorder. However, there is a lack of specific studies in the literature regarding the morbidity and mortality of XLA patients. This study is designed to evaluate morbidities and mortality and survival rates in Iranian patients with XLA diagnosis during the past 20 years. METHODS: We have registered the clinical data of the XLA patients and followed them up until 2010. At the time of diagnosis, a four-page questionnaire including complete medical information was filled out for all patients. Follow-up information was gathered either by reviewing the patients' hospital records or regularly visiting the patients. RESULTS: Among 41 patients, 26.8% died during the follow up period. All of the complications before the initiation of treatment such as pneumonia, otitis media and diarrhoea were reduced after immunoglobulin replacement, except sinusitis and conjunctivitis. There were significant associations between some immunological and clinical characteristics such as lymphocyte subsets, consanguinity marriage and mortality. CONCLUSION: Despite recent advances in the treatment of XLA, these patients still suffer from severe complications. Associations between poor prognosis and clinical and some immunological characteristics of the patients may help physicians to select poor prognoses patients at higher risk of mortality to develop prevention strategies for them.


Assuntos
Agamaglobulinemia/epidemiologia , Diarreia/epidemiologia , Doenças Genéticas Ligadas ao Cromossomo X/epidemiologia , Otite Média/epidemiologia , Pneumonia/epidemiologia , Adolescente , Adulto , Agamaglobulinemia/mortalidade , Agamaglobulinemia/terapia , Criança , Comorbidade , Consanguinidade , Seguimentos , Doenças Genéticas Ligadas ao Cromossomo X/mortalidade , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Irã (Geográfico) , Subpopulações de Linfócitos/imunologia , Masculino , Inquéritos e Questionários , Análise de Sobrevida , Adulto Jovem
13.
Clin Transplant ; 28(11): 1249-55, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25203509

RESUMO

BACKGROUND: Severe hypogammaglobulinemia (IgG < 400 mg/dL) has adverse impact on mortality during the first year post-transplantation. The aim of the study was to determine whether increasing IgG levels to ≥400 mg/dL improved outcomes. METHODS: Kaplan-Meier analyses were performed to estimate survival, log-rank test to compare survival distributions between groups, and Fisher's exact test to determine the association between hypogammaglobulinemia and rejection or graft loss. RESULTS: Thirty-seven solid organ transplant (SOT) recipients were included. Hypogammaglobulinemia was diagnosed at median of 5.6 months (range: 0-291.8 months) post-transplantation. Types of transplants: liver-small bowel (17); liver-small bowel-kidney (2); liver (5); small bowel (4); liver-kidney (1); kidney/kidney-pancreas (3); heart (3); heart-kidney (1); and heart-lung (1). The three-yr survival after the diagnosis of hypogammaglobulinemia was 49.5% (95% CI: 32.2-64.6%). Patients were dichotomized based upon IgG level at last follow-up: IgG ≥ 400 mg/dL (23 patients) and IgG < 400 mg/dL (14 patients). There was no evidence of a difference in survival (p = 0.44), rejection rate (p = 0.44), and graft loss censored for death (p = 0.99) at one yr between these two groups. There was no difference in survival between patients receiving or not immunoglobulin (p = 0.99) or cytomegalovirus hyperimmunoglobulin (p = 0.14). CONCLUSION: Severe hypogammaglobulinemia after SOT is associated with high mortality rates, but increasing IgG levels to ≥400 mg/dL did not seem to translate in better patient or graft survival in this cohort.


Assuntos
Agamaglobulinemia/mortalidade , Agamaglobulinemia/terapia , Rejeição de Enxerto/sangue , Sobrevivência de Enxerto , Imunoglobulina G/sangue , Transplante de Órgãos/mortalidade , Agamaglobulinemia/complicações , Criança , Pré-Escolar , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Estudos Retrospectivos , Resultado do Tratamento
15.
Curr Opin Allergy Clin Immunol ; 13(6): 630-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24113229

RESUMO

PURPOSE OF THE REVIEW: To review the recent advances in the understanding and management of the immune and nonimmune effects of inherited adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiencies. RECENT FINDINGS: Abnormal thymocyte development and peripheral T-cell activation in ADA-deficient and PNP-deficient patients cause increased susceptibility to infections and immune dysregulation. The impaired purine homeostasis also damages many other cell types and tissues. Animal studies suggest that defects in surfactant metabolism by alveolar macrophages cause the pulmonary alveolar proteinosis commonly seen in ADA-deficient infants, while toxicity of purine metabolites to cerebellar Purkinje cells may lead to the ataxia frequently observed in PNP deficiency. Patients' outcome with current treatments including enzyme replacement and stem cell transplantations are inferior to those achieved in most severe immunodeficiency conditions. New strategies, including intracellular enzyme replacement, gene therapy and innovative protocols for stem cell transplantations hold great promise for improved outcomes in ADA and PNP deficiency. Moreover, newborn screening and early diagnosis will allow prompt application of these novel treatment strategies, further improving survival and reducing morbidity. SUMMARY: Better understanding of the complex immune and nonimmune effects of ADA and PNP deficiency holds great promise for improved patients' outcome.


Assuntos
Adenosina Desaminase/deficiência , Agamaglobulinemia , Terapia de Reposição de Enzimas , Purina-Núcleosídeo Fosforilase/deficiência , Erros Inatos do Metabolismo da Purina-Pirimidina , Imunodeficiência Combinada Severa , Adenosina Desaminase/genética , Adenosina Desaminase/imunologia , Adenosina Desaminase/uso terapêutico , Agamaglobulinemia/tratamento farmacológico , Agamaglobulinemia/enzimologia , Agamaglobulinemia/genética , Agamaglobulinemia/imunologia , Agamaglobulinemia/mortalidade , Animais , Humanos , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Macrófagos Alveolares/enzimologia , Macrófagos Alveolares/imunologia , Purina-Núcleosídeo Fosforilase/genética , Purina-Núcleosídeo Fosforilase/imunologia , Purina-Núcleosídeo Fosforilase/uso terapêutico , Erros Inatos do Metabolismo da Purina-Pirimidina/dietoterapia , Erros Inatos do Metabolismo da Purina-Pirimidina/enzimologia , Erros Inatos do Metabolismo da Purina-Pirimidina/genética , Erros Inatos do Metabolismo da Purina-Pirimidina/imunologia , Erros Inatos do Metabolismo da Purina-Pirimidina/mortalidade , Purinas/imunologia , Purinas/metabolismo , Células de Purkinje/enzimologia , Células de Purkinje/imunologia , Imunodeficiência Combinada Severa/tratamento farmacológico , Imunodeficiência Combinada Severa/enzimologia , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/imunologia , Imunodeficiência Combinada Severa/mortalidade , Linfócitos T/enzimologia , Linfócitos T/imunologia
16.
Prague Med Rep ; 114(4): 246-57, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24485342

RESUMO

In this retrospective study we assessed the frequency of hypogammaglobulinemia in 708 patients with SIRS, severe sepsis and septic shock. We evaluated the relationship between hypogammaglobulinemia IgG, IgM and 28 day mortality. Total of 708 patients and 1,513 samples were analyzed. In the three subgroups we investigated, patients met the criteria of SIRS, severe sepsis and septic shock. IgG hypogammaglobulinemia was demonstrated in 114 patients with severe sepsis (25.2%), 11 septic shock patients (24.4%), and in 29 SIRS patients (13.9%). IgM hypogammaglobulinemia was documented in 55 patients with severe sepsis (12.2%), 6 septic shock patients (13.3%), and in 17 SIRS patients (8.1%). Mortality of patients with severe sepsis and normal IgG levels was significantly lower (111 patients; 32.8%) compared with those with IgG hypogammaglobulinemia (49 patients; 43.0%; p=0.001). Mortality of patients with septic shock and IgG hypogammaglobulinemia (n=5) was significantly higher compared with those with normal IgG levels (45.5% vs. 38.2%; p=0.001). Mortality of patients with severe sepsis and IgM hypogammaglobulinemia did not differ from that of patients with normal IgM levels (37.0 vs. 41.8%). Mortality of patients with septic shock and IgM hypogammaglobulinemia was significantly higher compared with those with normal IgM levels (50% vs. 38.5%; p=0.0001). This study documented relatively high incidence of hypogammaglobulinemia IgG and IgM in patients with severe sepsis, septic shock and SIRS respectively. The presence of IgG hypogammaglobulinemia in patients with severe sepsis is independent factor of mortality.


Assuntos
Agamaglobulinemia/etiologia , Sepse/complicações , Agamaglobulinemia/sangue , Agamaglobulinemia/mortalidade , Idoso , República Tcheca/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Sepse/mortalidade , Choque Séptico/complicações , Choque Séptico/mortalidade , Taxa de Sobrevida/tendências
17.
Blood ; 120(17): 3615-24; quiz 3626, 2012 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-22791287

RESUMO

Deficiency of the purine salvage enzyme adenosine deaminase leads to SCID (ADA-SCID). Hematopoietic cell transplantation (HCT) can lead to a permanent cure of SCID; however, little data are available on outcome of HCT for ADA-SCID in particular. In this multicenter retrospective study, we analyzed outcome of HCT in 106 patients with ADA-SCID who received a total of 119 transplants. HCT from matched sibling and family donors (MSDs, MFDs) had significantly better overall survival (86% and 81%) in comparison with HCT from matched unrelated (66%; P < .05) and haploidentical donors (43%; P < .001). Superior overall survival was also seen in patients who received unconditioned transplants in comparison with myeloablative procedures (81% vs 54%; P < .003), although in unconditioned haploidentical donor HCT, nonengraftment was a major problem. Long-term immune recovery showed that regardless of transplant type, overall T-cell numbers were similar, although a faster rate of T-cell recovery was observed after MSD/MFD HCT. Humoral immunity and donor B-cell engraftment was achieved in nearly all evaluable surviving patients and was seen even after unconditioned HCT. These data detail for the first time the outcomes of HCT for ADA-SCID and show that, if patients survive HCT, long-term cellular and humoral immune recovery is achieved.


Assuntos
Agamaglobulinemia/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas , Imunodeficiência Combinada Severa/tratamento farmacológico , Condicionamento Pré-Transplante , Adenosina Desaminase/deficiência , Adenosina Desaminase/imunologia , Agamaglobulinemia/imunologia , Agamaglobulinemia/mortalidade , Agamaglobulinemia/patologia , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Teste de Histocompatibilidade , Humanos , Imunidade Celular , Imunidade Humoral , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Contagem de Linfócitos , Masculino , Agonistas Mieloablativos/uso terapêutico , Estudos Retrospectivos , Imunodeficiência Combinada Severa/imunologia , Imunodeficiência Combinada Severa/mortalidade , Imunodeficiência Combinada Severa/patologia , Irmãos , Linfócitos T/imunologia , Resultado do Tratamento , Doadores não Relacionados
18.
J Investig Allergol Clin Immunol ; 22(3): 208-14, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22697011

RESUMO

BACKGROUND: Common variable immunodeficiency (CVID) is the most common form of symptomatic primary immunodeficiency disease. It is characterized by hypogammaglobulinemia, increased predisposition to infections, autoimmunity, and cancer. OBJECTIVES: This study was performed to evaluate the clinical and immunological features of a group of pediatric patients with CVID. METHODS: The study population comprised 69 individuals with CVID diagnosed during childhood. RESULTS: The patients were followed up for a mean (SD) period of 5.2 (4.3) years. The mean diagnostic delay was 4.4 (3.6) years, which was significantly lower in patients who were diagnosed recently. Children were classified according to 5 clinical phenotypes: infections only (n=39), polyclonal lymphocytic infiltration (n=17), autoimmunity (n=12), malignancy (n=7), and enteropathy (n=3). Postdiagnosis survival (10-year) was 71%. CONCLUSIONS: The high percentages of pediatric patients with CVID in Iran may be due to the considerable prevalence of parental consanguinity in the region and an underlying genetic background.


Assuntos
Agamaglobulinemia/imunologia , Imunodeficiência de Variável Comum/imunologia , Adolescente , Agamaglobulinemia/sangue , Agamaglobulinemia/genética , Agamaglobulinemia/mortalidade , Criança , Pré-Escolar , Imunodeficiência de Variável Comum/sangue , Imunodeficiência de Variável Comum/genética , Imunodeficiência de Variável Comum/mortalidade , Diagnóstico Tardio , Feminino , Seguimentos , Predisposição Genética para Doença , Humanos , Imunoglobulinas/sangue , Irã (Geográfico)/epidemiologia , Masculino , Fenótipo
19.
J Clin Immunol ; 31(3): 297-308, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21243521

RESUMO

Two hundred and one patients have been diagnosed with primary immunodeficiency diseases (PIDs) in our center from January 2004 to December 2009. The male-to-female ratio was 5.29:1. Spectrums of PIDs were as follows: predominantly antibody deficiency disease was the most common category (94 patients, 48.2%), followed by other well-defined immunodeficiency syndromes (40 patients, 20.5%), combined T and B cell immunodeficiencies (33 patients, 16.9%), congenital defects of phagocyte number and/or function (21 patients, 10.8%), and diseases of immune dysregulation (six patients, 3.1%). Agammaglobulinemia was the most frequent disease type. The median of diagnosis lag was 18.0 months. Pneumonia was the most common manifestation of PID patients. Some manifestations were prone to concentrate in certain diseases. As for therapy, 99 patients (50.8%) received intravenous immunoglobulin replacement therapy; 13 patients received hematopoietic stem cell transplantation and nine of them were still alive. In this study, we sought to describe and analyze the distribution, clinical features, and therapy methods of PIDs among children diagnosed in our country and to compare with reports from other countries and regions.


Assuntos
Agamaglobulinemia/imunologia , Imunodeficiência de Variável Comum/imunologia , Imunoglobulinas/farmacologia , Disfunção de Fagócito Bactericida/imunologia , Imunodeficiência Combinada Severa/imunologia , Adolescente , Agamaglobulinemia/epidemiologia , Agamaglobulinemia/mortalidade , Agamaglobulinemia/patologia , Agamaglobulinemia/terapia , Antibacterianos/farmacologia , Grupo com Ancestrais do Continente Asiático , Criança , Pré-Escolar , Imunodeficiência de Variável Comum/epidemiologia , Imunodeficiência de Variável Comum/mortalidade , Imunodeficiência de Variável Comum/patologia , Imunodeficiência de Variável Comum/terapia , Consanguinidade , Família , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Isotipos de Imunoglobulinas/análise , Imunoglobulinas/imunologia , Incidência , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Disfunção de Fagócito Bactericida/epidemiologia , Disfunção de Fagócito Bactericida/mortalidade , Disfunção de Fagócito Bactericida/patologia , Disfunção de Fagócito Bactericida/terapia , Estudos Retrospectivos , Imunodeficiência Combinada Severa/epidemiologia , Imunodeficiência Combinada Severa/mortalidade , Imunodeficiência Combinada Severa/patologia , Imunodeficiência Combinada Severa/terapia , Taxa de Sobrevida
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