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1.
Blood ; 123(6): 863-74, 2014 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-24345756

RESUMO

Constitutive heterozygous GATA2 mutation is associated with deafness, lymphedema, mononuclear cytopenias, infection, myelodysplasia (MDS), and acute myeloid leukemia. In this study, we describe a cross-sectional analysis of 24 patients and 6 relatives with 14 different frameshift or substitution mutations of GATA2. A pattern of dendritic cell, monocyte, B, and natural killer (NK) lymphoid deficiency (DCML deficiency) with elevated Fms-like tyrosine kinase 3 ligand (Flt3L) was observed in all 20 patients phenotyped, including patients with Emberger syndrome, monocytopenia with Mycobacterium avium complex (MonoMAC), and MDS. Four unaffected relatives had a normal phenotype indicating that cellular deficiency may evolve over time or is incompletely penetrant, while 2 developed subclinical cytopenias or elevated Flt3L. Patients with GATA2 mutation maintained higher hemoglobin, neutrophils, and platelets and were younger than controls with acquired MDS and wild-type GATA2. Frameshift mutations were associated with earlier age of clinical presentation than substitution mutations. Elevated Flt3L, loss of bone marrow progenitors, and clonal myelopoiesis were early signs of disease evolution. Clinical progression was associated with increasingly elevated Flt3L, depletion of transitional B cells, CD56(bright) NK cells, naïve T cells, and accumulation of terminally differentiated NK and CD8(+) memory T cells. These studies provide a framework for clinical and laboratory monitoring of patients with GATA2 mutation and may inform therapeutic decision-making.


Assuntos
Linfócitos B/patologia , Células Dendríticas/patologia , Fator de Transcrição GATA2/genética , Células Matadoras Naturais/patologia , Monócitos/patologia , Mutação/genética , Síndromes Mielodisplásicas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/imunologia , Linfócitos B/metabolismo , Biomarcadores , Estudos de Casos e Controles , Criança , Pré-Escolar , Evolução Clonal , Estudos Transversais , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Estudos de Associação Genética , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/metabolismo , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/genética , Linhagem , Prognóstico , Adulto Jovem , Tirosina Quinase 3 Semelhante a fms/metabolismo
2.
J Allergy Clin Immunol ; 134(1): 116-26, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24582312

RESUMO

BACKGROUND: Common variable immunodeficiency (CVID) is an antibody deficiency with an equal sex distribution and a high variability in clinical presentation. The main features include respiratory tract infections and their associated complications, enteropathy, autoimmunity, and lymphoproliferative disorders. OBJECTIVE: This study analyzes the clinical presentation, association between clinical features, and differences and effects of immunoglobulin treatment in Europe. METHODS: Data on 2212 patients with CVID from 28 medical centers contributing to the European Society for Immunodeficiencies Database were analyzed retrospectively. RESULTS: Early disease onset (<10 years) was very frequent in our cohort (33.7%), especially in male subjects (39.8%). Male subjects with early-onset CVID were more prone to pneumonia and less prone to other complications suggesting a distinct disease entity. The diagnostic delay of CVID ranges between 4 and 5 years in many countries and is particularly high in subjects with early-onset CVID. Enteropathy, autoimmunity, granulomas, and splenomegaly formed a set of interrelated features, whereas bronchiectasis was not associated with any other clinical feature. Patient survival in this cohort was associated with age at onset and age at diagnosis only. There were different treatment strategies in Europe, with considerable differences in immunoglobulin dosing, ranging from 130 up to 750 mg/kg/mo. Patients with very low trough levels of less than 4 g/L had poor clinical outcomes, whereas higher trough levels were associated with a reduced frequency of serious bacterial infections. CONCLUSION: Patients with CVID are being managed differently throughout Europe, affecting various outcome measures. Clinically, CVID is a truly variable antibody deficiency syndrome.


Assuntos
Imunodeficiência de Variável Comum/complicações , Transtornos Linfoproliferativos/complicações , Pneumonia/complicações , Adolescente , Adulto , Idade de Início , Autoimunidade , Bronquiectasia/patologia , Criança , Pré-Escolar , Imunodeficiência de Variável Comum/tratamento farmacológico , Imunodeficiência de Variável Comum/imunologia , Imunodeficiência de Variável Comum/mortalidade , Diagnóstico Tardio , Europa (Continente) , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/mortalidade , Masculino , Pneumonia/tratamento farmacológico , Pneumonia/imunologia , Pneumonia/mortalidade , Estudos Retrospectivos , Esplenomegalia/patologia , Análise de Sobrevida
3.
Ann Rheum Dis ; 72(2): 229-34, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22532633

RESUMO

INTRODUCTION: Anti-tumour necrosis factor (TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). In 2001, BSRBR was established to evaluate the safety of these agents. This paper addresses the safety of anti-TNF therapy in RA with specific reference to serious skin and soft tissue infections (SSSI) and shingles. METHODS: A cohort of anti-TNF-treated patients was recruited alongside a comparator group with active RA treated with non-biological disease-modifying antirheumatic drugs (nbDMARD). 11 881 anti-TNF and 3673 nbDMARD patients were analysed. Follow-up was by 6-monthly questionnaires to patients and clinicians. Analyses considered SSSI and shingles separately. Incidence rates (IR) were calculated and then compared using survival analyses. RESULTS: The crude IR for SSSI were: anti-TNF 1.6/100 patient-years (95% CI 1.4 to 1.8); nbDMARD 0.7/100 patient-years (95% CI 0.5 to 1.0) and shingles: anti-TNF 1.6/100 patient-years (95% CI 1.3 to 2.0); nbDMARD 0.8/100 patient-years (95% CI 0.6 to 1.1). Adjusted HR were SSSI 1.4 (95% CI 0.9 to 2.4), shingles 1.8 (95% CI 1.2 to 2.8). For SSSI, no significant differences were seen between anti-TNF agents. For shingles, the lowest risk was observed for adalimumab (adjusted HR vs nbDMARD) 1.5 (95% CI 1.1 to 2.0) and highest for infliximab (HR 2.2; 95% CI 1.4 to 3.4)). CONCLUSION: A significantly increased risk of shingles was observed in the anti-TNF-treated cohort. The risk of SSSI tended towards being greater with anti-TNF treatment but was not statistically significant. As with any observational dataset cause and effect cannot be established with certainty as residual confounding may remain. This finding would support the evaluation of zoster vaccination in this population.


Assuntos
Antirreumáticos/efeitos adversos , Herpes Zoster/epidemiologia , Dermatopatias Infecciosas/epidemiologia , Infecções dos Tecidos Moles/epidemiologia , Adalimumab , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Etanercepte , Humanos , Imunoglobulina G/efeitos adversos , Incidência , Infliximab , Pessoa de Meia-Idade , Receptores do Fator de Necrose Tumoral , Fatores de Risco , Fator de Necrose Tumoral alfa/antagonistas & inibidores
4.
Rheumatol Int ; 32(11): 3373-82, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22045517

RESUMO

This study is an audit and a comparison of major infective complications in patients with granulomatosis with polyangiitis (GPA) and systemic lupus erythematosis (SLE). Data were collected on consecutive patients attending a single treatment approach, multidisciplinary vasculitis centre who met diagnostic criteria for GPA and SLE from 01/01/2006 to 30/06/2006. Immunosuppressive treatment is used in this clinic with guidelines targeting avoidance of neutropenia. For each patient, documentation was made of disease presentation, organ involvement and therapy used. A history of major infections requiring hospital admission and intravenous antimicrobials pre- and post-diagnosis was recorded. Patients with GPA received a higher cumulative dose of cyclophosphamide, had a higher median age, shorter period of follow-up and had lower mean and nadir absolute lymphocyte counts and nadir neutrophil counts. GPA patients had more major infections per patient years (P = 0.0027) and respiratory tract infections (P = 0.0031) per patient years. Relative risk (RR) of major infection was significantly increased with methylprednisolone, RR 11.1 (P = <0.0001), cyclophosphamide, RR 2.0 (P = 0.0246) and the intensive phase of treatment, RR 13.3 (P = <0.0001). Marked lymphopenia was common in both groups during follow-up and was associated with an increased risk of major infection (P = 0.0020). Major infections, in particular respiratory tract infections, are more common in those treated for GPA than SLE. This may be due to a combination of factors including greater doses and duration of methyprednisolone and cyclophosphamide. We recommend treatment strategies that aim not only to avoid neutropenia but that also identify lymphopenia as a risk factor for major infection.


Assuntos
Granulomatose com Poliangiite/complicações , Infecções/complicações , Lúpus Eritematoso Sistêmico/complicações , Adulto , Idoso , Anti-Infecciosos/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Feminino , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Infecções/tratamento farmacológico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Fatores de Risco
6.
Clin Endocrinol (Oxf) ; 73(4): 425-31, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20039902

RESUMO

Hypopituitarism is not currently considered as a potential cause of immune disruption in humans. Accumulating data from in vitro and animal models support a role for the pituitary gland in immune regulation. Furthermore, the increased mortality risk noted in patients with adult hypopituitarism remains poorly explained and immune dysfunction could conceivably contribute to this observation. In a recent issue of Clinical & Experimental Immunology, we presented new data relating to immune status in adults with treated, severe hypopituitarism. We observed humoral immune deficiency in a significant proportion, despite stable pituitary replacement, including growth hormone (GH). This was especially evident in those with low pretreatment IGF-I levels and appeared independent of anticonvulsant use or corticosteroid replacement. These observations require substantiation with future studies. In this short review, we summarize existing data relating to the effects of pituitary hormones on immune function and discuss potential clinical implications surrounding the hypothesis of immune dysregulation in severe hypopituitarism.


Assuntos
Hipopituitarismo/imunologia , Sistema Imunitário/fisiologia , Animais , Glucocorticoides/farmacologia , Hormônio do Crescimento/fisiologia , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Imunidade Inata , Fator de Crescimento Insulin-Like I/fisiologia , Modelos Animais , Sistemas Neurossecretores/fisiologia , Prolactina/fisiologia
7.
Hum Vaccin ; 5(2): 85-91, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18758242

RESUMO

Asplenic individuals are at increased risk of infection with Streptococcus pneumoniae. The immune response to pneumococcal conjugate vaccine has not been investigated in this clinical risk group. We investigated immune responses to pneumococcal vaccination in asplenic individuals. Eligible subjects aged > or =4 years received one dose 7-valent pneumococcal conjugate vaccine (PCV7) and, if no prior 23-valent polysaccharide vaccine (PPV23) had been received within previous 5 years, one dose was given 6 months following PCV7. Pre- and post-vaccination blood samples were taken. Pneumococcal serotype-specific IgG levels were determined for 9 serotypes; the 7 in PCV7 plus serotypes1 and by standardized ELISA. One hundred and eleven asplenic individuals were recruited [median age 54.8 years, (18.1-81.8)]. Median age at splenectomy was 29.6 years (3.6-78.3); 108 (97.3%) individuals had previously received PPV23. Compliance with UK recommendations on immunization and prophylaxis in this group was poor, 91 (82%) subjects had received Haemophilus influenzae type b conjugate vaccine and only 68 (62%) had received meningococcal serogroup C conjugate vaccine. In total 61 (55%) subjects were taking antibiotic prophylaxis and 12 subjects had reported previous invasive pneumococcal disease, five episodes of which occurred post-splenectomy. High serotype-specific IgG concentrations were observed pre-PCV7, with significant increases (p < 0.01) in geometric mean concentrations pre- to post-PCV7 for the PCV7 serotypes. Post-PCV7, between 27% (serotype 14) and 69% (serotype 23F) of subjects had a > or =2-fold rise in IgG. Pre-PCV7, the percentage of individuals with levels > or =0.35 microg/mL ranged between 77% (serotype 4) and 97% (serotypes 14, 19F), whilst post-PCV7 this was 90% (serotype 6B) and 99% (serotype 14). No significant increases were observed post-PPV23. Asplenic individuals responded well to PCV7, though protective levels were demonstrated pre-PCV7 in majority of participants due to prior PPV23. Although immunogenic, there is insufficient evidence here to recommend routine PCV7 immunization over PPV23 immunization in adult asplenic individuals.


Assuntos
Vacinas Pneumocócicas/imunologia , Esplenectomia/efeitos adversos , Streptococcus pneumoniae/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Vacina Pneumocócica Conjugada Heptavalente , Humanos , Imunização Secundária , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Reino Unido , Adulto Jovem
8.
Infect Immun ; 76(11): 5305-9, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18779338

RESUMO

Following the introduction of the pneumococcal 7-valent conjugate vaccine (PCV7) into the routine infant immunization schedule in England, Wales, and Northern Ireland, pneumococcal serotype-specific immunoglobulin G (IgG) antibody testing was offered as a clinical service to all children within the program with invasive pneumococcal disease (IPD) to confirm an adequate antibody response to PCV7. As of March 2008, serum samples taken within 14 to 90 days of vaccination had been submitted from 107 children who had received one or more doses in the second year of life. Sera were assayed by a multiplexed microsphere assay incorporating both cell wall polysaccharide and serotype 22F adsorption. A protective serotype-specific antibody level was defined as a concentration of > or = 0.35 microg/ml. Eight children failed to develop a response to their infecting serotype (6B [n = 4], 18C [n = 2], 4 [n = 1], and 14 [n = 1]), despite receiving at least three doses of PCV7 in the second year of life or two doses in the second and two or three in the first year of life. A further two children were nonresponsive to a serotype (6B) different than that causing disease. None of the 10 children had a clinical risk factor for IPD. Two had marginally low levels of total serum IgG but mounted adequate responses to the other six PCV serotypes. This serotype-specific unresponsiveness may reflect immune paralysis due to large pneumococcal polysaccharide antigen loads and/or a potential genetic basis for nonresponse to individual pneumococcal serotypes.


Assuntos
Anticorpos Antibacterianos/sangue , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/imunologia , Anticorpos Antibacterianos/imunologia , Pré-Escolar , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Lactente , Polissacarídeos Bacterianos/imunologia , Sorotipagem
9.
Clin Infect Dis ; 38(1): e10-4, 2004 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-14679469

RESUMO

We evaluated a patient with disseminated Mycobacterium tuberculosis and Mycobacterium chelonae infection, of which he died. He also developed autoimmune (type I) diabetes and primary hypothyroidism. His serum contained a high titer of immunoglobulin G autoantibody to interferon-gamma (IFN-gamma) capable of blocking in vitro responses to this cytokine by peripheral blood mononuclear cells from normal donors. These results suggest that autoantibodies to IFN-gamma can induce susceptibility to disseminated mycobacterial infection, which may be refractory to chemotherapy.


Assuntos
Autoanticorpos/sangue , Imunoglobulina G/sangue , Interferon gama/imunologia , Infecções por Mycobacterium não Tuberculosas/imunologia , Tuberculose/imunologia , Autoimunidade , Diabetes Mellitus Tipo 1/etiologia , Suscetibilidade a Doenças , Humanos , Hipotireoidismo/etiologia , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/complicações , Mycobacterium chelonae/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose/complicações
10.
J Behav Ther Exp Psychiatry ; 34(3-4): 219-24, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14972669

RESUMO

This study concerns a woman with a very specific phobia of free-flying wasps. Her underlying and disabling belief was that she was allergic to wasp venom and, if stung, would certainly die. A behavioural approach, such as systematic desensitization and exposure, was not thought suitable because of the patient's pattern of fear. Instead, the treatment of choice was an allergy test to directly challenge her belief. The allergy test was negative and led to a dramatic improvement which was maintained 1 year after treatment.


Assuntos
Transtornos Fóbicos , Vespas , Adulto , Alergia e Imunologia , Animais , Dessensibilização Imunológica , Feminino , Seguimentos , Humanos , Imunoterapia , Transtornos Fóbicos/fisiopatologia , Transtornos Fóbicos/psicologia , Transtornos Fóbicos/terapia , Escala de Ansiedade Frente a Teste , Venenos de Vespas/efeitos adversos
11.
Int J STD AIDS ; 25(3): 228-30, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23970648

RESUMO

We report a case in which an HIV-positive man developed general malaise, skin rash and biochemical hepatitis within days of starting a nevirapine-based antiretroviral treatment regimen. At the same time, his syphilis serology proved positive. We discuss the diagnostic dilemma: was this a nevirapine hypersensitivity reaction, secondary syphilis or both?


Assuntos
Fármacos Anti-HIV/efeitos adversos , Exantema/induzido quimicamente , Infecções por HIV/tratamento farmacológico , Nevirapina/efeitos adversos , Sífilis/diagnóstico , Adulto , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Diagnóstico Diferencial , Hepatite/complicações , Hepatite/tratamento farmacológico , Humanos , Hipersensibilidade/complicações , Hipersensibilidade/tratamento farmacológico , Quênia , Nevirapina/uso terapêutico , Sífilis/tratamento farmacológico , Resultado do Tratamento
12.
Cytometry B Clin Cytom ; 84(4): 248-54, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23788473

RESUMO

UK NEQAS for Leucocyte Immunophenotyping, an ILAC G13:2000 accredited External Quality Assessment (EQA) organization, with over 3000 international laboratories participating in 14 programmes, issues 2 proficiency testing samples of stabilized whole blood to 824 participants in the Immune Monitoring (lymphocyte subset) programme every two months. We have undertaken a study of 58,626 flow cytometric absolute CD4⁺ T lymphocyte count data sets from these laboratories over a 12-year-period (2001-2012) to determine counting method variation in data measurement limits and how this could influence the clinical management of HIV patients. Comparison of relative error and 99.9% confidence limits for absolute CD4⁺ T lymphocyte values was undertaken using dual platform (DP) and single platform (SP) data and showed that the SP consistently outperformed DP, giving lower relative errors and confidence limits at clinically significant absolute CD4⁺ T lymphocyte counts. Our data shows that absolute CD4⁺ T lymphocyte counts should be obtained using single platform technology to reduce the variability at clinically relevant levels. On data where results (irrespective of platform) were below the international treatment threshold of 350 cells/µl, there was no significant misclassification between either SP or DP techniques meaning most patients would receive the correct treatment at the correct time. However, results that were above the treatment level of 350 cells/µl had a significant difference (P = 0.04) between DP and SP platforms, suggesting patients monitored using DP technology were 20% more likely to start therapy prematurely than those monitored with SP technology.


Assuntos
Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/patologia , Citometria de Fluxo/métodos , Infecções por HIV/diagnóstico , Adulto , Infecções por HIV/imunologia , Infecções por HIV/patologia , Infecções por HIV/virologia , Soropositividade para HIV , HIV-1/imunologia , HIV-1/patogenicidade , Humanos , Imunofenotipagem , Padrões de Referência
13.
Hum Fertil (Camb) ; 16(2): 128-31, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23751111

RESUMO

Hypersensitivity to human semen (HHS) is an increasingly reported condition with symptoms manifested locally and systemically, which in some cases may result in anaphylaxis. This report describes four cases of HHS all with positive allergy skin prick tests to partner's whole semen. None of the patients elicited a response to seminal fluid-free washed spermatozoa. In cases of high risk of anaphylaxis, we recommend avoiding exposure to semen. By carrying out an allergy skin prick test on seminal fluid-free washed spermatozoa, the risk of immunogenic reaction to the spermatozoa could be eliminated.


Assuntos
Hipersensibilidade/diagnóstico , Sêmen/imunologia , Testes Cutâneos , Espermatozoides/imunologia , Adulto , Feminino , Humanos , Hipersensibilidade/imunologia , Masculino , Adulto Jovem
15.
BMJ Case Rep ; 20112011 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-22675085

RESUMO

Anaphylaxis can occur secondary to breastfeeding. The authors present a case of a 30-year-old woman who complained of chest tightness, shortness of breath and a rash on the third day postpartum. She was treated for anaphylaxis and her symptoms resolved. Because she had taken tramadol prior to this event, a drug reaction was initially suspected. However, she experienced further episodes related to breastfeeding, despite stopping tramadol. Effective control of her symptoms was achieved with regular antihistamines, enabling her to continue breastfeeding. Antihistamines were interrupted after 8 weeks at which point lactation (in hospital) was once again associated with anaphylaxis. The diagnosis of breastfeeding induced anaphylaxis was made. There are six previously reported cases of breastfeeding induced anaphylaxis. The authors describe the second case of breastfeeding anaphylaxis extending beyond the neonatal period, controlled with antihistamines.


Assuntos
Anafilaxia/etiologia , Aleitamento Materno/efeitos adversos , Adulto , Anafilaxia/tratamento farmacológico , Feminino , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Leite Humano , Período Pós-Parto
16.
Pediatr Infect Dis J ; 30(6): 462-5, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21487328

RESUMO

BACKGROUND: This study aimed to determine whether nonprotective, convalescent pneumococcal serotype-specific immunoglobulin G (IgG) concentrations in children with invasive pneumococcal disease (IPD) might be associated with an underlying IgG deficiency. METHODS: The first 200 convalescent blood samples from children with IPD that were submitted for pneumococcal antibody testing also had total serum IgG concentrations measured. Pneumococcal IgG testing was performed for 12 serotypes (1, 3, 5, 7, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F); serotype-specific pneumococcal IgG concentrations <0.35 µg/mL were considered nonprotective. IgG deficiency was defined as total serum IgG ≥2 standard deviations below the mean for age. RESULTS: Nineteen of 172 children (11.0%) with sufficient serum had IgG deficiency although serum IgG concentrations were only marginally below the lower limit for age and all 19 had IgG concentrations >2.0 g/L. IgG deficiency was associated with younger age at disease (median, 5.2 [interquartile range, 2.3-13.5] vs. 12.5 [7.4-17.0] months; P = 0.005) and nonprotective convalescent antibody concentrations against the infecting serotype (10/13 [77%] vs. 51/105 [49%]; P = 0.05). There was a correlation between IgG deficiency and the number of serotypes against which children had nonprotective pneumococcal antibody concentrations, particularly among vaccinated cases (P < 0.05). Vaccine failure was also twice as common among those with IgG deficiency (3/19 [16%] vs. 11/53 [7%], P = 0.20), although this association was not statistically significant. Three children with IgG deficiency who were retested 3 to 5 months later had normal serum IgG concentrations. CONCLUSIONS: Although 11% of children with IPD had IgG deficiency, total serum IgG concentrations were reassuringly only marginally below the reference range and were within the normal range in those who were retested, suggesting a transient deficiency rather than a serious underlying primary immunodeficiency.


Assuntos
Deficiência de IgG/complicações , Deficiência de IgG/epidemiologia , Imunoglobulina G/sangue , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/etiologia , Anticorpos Antibacterianos/sangue , Feminino , Humanos , Lactente , Masculino , Reino Unido/epidemiologia
17.
Hum Immunol ; 71(4): 372-6, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20096740

RESUMO

Toll-like receptors (TLRs) are important in the initiation of immune responses in both health and disease. How TLR activity alters with age, gender, and also with immunosuppressive agents is still largely unexplored. We studied TLR activity in 49 healthy individuals as well as in 26 patients receiving immunosuppressive drugs. TLR activity did not alter significantly between the ages of 2 and 67 years. However, females had twice the TLR7 ligand-induced interferon-I response of males (OR [95% CI] 2.7 [1.4-5.1]), whereas TLR3 and four activities were not significantly different between the sexes. The T-cell immunosuppressant agents cyclosporine, tacrolimus, and azathioprine, as well as low dose glucocorticosteroids did not significantly alter TLR pathway responses. In contrast, high dose glucocorticosteroids reduced in vivo TLR responses by 70%-90%. We suggest that gender differences in TLR responses may help to explain the female preponderance of some autoimmune disorders. Furthermore, an understanding the effects of immunosuppressive agents on TLR-pathway activity should allow more focused therapy for autoimmune disorders.


Assuntos
Células Sanguíneas/efeitos dos fármacos , Hospedeiro Imunocomprometido/imunologia , Transdução de Sinais/efeitos dos fármacos , Receptores Toll-Like/metabolismo , Adolescente , Adulto , Fatores Etários , Idoso , Células Sanguíneas/imunologia , Células Sanguíneas/metabolismo , Células Sanguíneas/patologia , Células Cultivadas , Criança , Pré-Escolar , Citocinas/metabolismo , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Transdução de Sinais/imunologia , Receptores Toll-Like/imunologia
18.
Br J Hosp Med (Lond) ; 68(4): 206-10, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17465102

RESUMO

This article provides an overview on the management of primary immunodeficiency, and discusses the pharmacokinetics of subcutaneous and intravenous immunoglobulin and the relationship between blood levels and therapeutic effects in both treatments. The article will further highlight both treatments' efficacy in preventing infections and the risk of systemic side effects with each treatment.


Assuntos
Anticorpos/imunologia , Imunoglobulinas/administração & dosagem , Síndromes de Imunodeficiência/terapia , Administração Cutânea , Anticorpos/economia , Custos e Análise de Custo , Humanos , Imunoglobulinas/economia , Síndromes de Imunodeficiência/economia
19.
Br J Haematol ; 116(2): 497-9, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11841458

RESUMO

Early bone marrow transplant is now standard treatment for infants with severe immunodeficiencies such as Wiskott-Aldrich Syndrome (WAS), but results in older children and adults are poor. Non-myeloablative transplant has shown promise in the treatment of older children, who are likely to have active infections and organ damage. We describe a non-myeloablative transplant of a 26-year-old man with WAS, undertaken because of severe infections and vasculitis. Partial engraftment and immunorestoration were achieved. The patient is well 1 year post transplantation.


Assuntos
Transplante de Medula Óssea/métodos , Síndrome de Wiskott-Aldrich/terapia , Adulto , Alemtuzumab , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Anticorpos Antineoplásicos/uso terapêutico , Ciclofosfamida/uso terapêutico , Humanos , Imunoglobulinas Intravenosas , Imunossupressores/uso terapêutico , Masculino , Penicilina V/administração & dosagem , Quimeras de Transplante , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico
20.
Mem. Inst. Oswaldo Cruz ; 91(3): 359-362, May-Jun. 1996.
Artigo em Inglês | LILACS | ID: lil-319862

RESUMO

Immunological monitoring of disease progression following HIV infection and seroconversion illness, latency and AIDS, not only helps in the basic investigation of the natural history of the viral infection in man, but also can assist in prognosis and treatment of AIDS-defining illnesses. However, outside clinical trials, these tests should be selected and used in clinical practice only if they are validated as relevant and effective. The absolute CD4+ T-helper lymphocyte count, measured by flow cytometry, has emerged as the best available investigation, but needs care in sampling due to diurnal and circadian rhythms, effects of age, pregnancy, therapy, intercurrent infections and technique. Sampling should provide a baseline and trends-monthly intervals initially, then quarterly in uncomplicated cases. Thresholds may be given for counts (e.g. 200/microliter) below which prophylaxis against pneumocystis pneumonia should be administered, and repeating persistently low counts (e.g. below 50/microliter) is seldom helpful in practice. Serum levels of beta-2 microglobulin, neopterin and immunoglobulins rarely add information. Physicians and laboratories should have testing guidelines based on clinical audit of best practice, based in turn on scientific understanding of the immunological processes involved.


Assuntos
Humanos , Monitorização Imunológica , Síndrome da Imunodeficiência Adquirida/imunologia , Microglobulina beta-2 , Citometria de Fluxo , Biomarcadores/sangue , Microscopia de Fluorescência , Síndrome da Imunodeficiência Adquirida/sangue
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