RESUMEN
This is the second report of the United Kingdom Primary Immunodeficiency (UKPID) registry. The registry will be a decade old in 2018 and, as of August 2017, had recruited 4758 patients encompassing 97% of immunology centres within the United Kingdom. This represents a doubling of recruitment into the registry since we reported on 2229 patients included in our first report of 2013. Minimum PID prevalence in the United Kingdom is currently 5·90/100 000 and an average incidence of PID between 1980 and 2000 of 7·6 cases per 100 000 UK live births. Data are presented on the frequency of diseases recorded, disease prevalence, diagnostic delay and treatment modality, including haematopoietic stem cell transplantation (HSCT) and gene therapy. The registry provides valuable information to clinicians, researchers, service commissioners and industry alike on PID within the United Kingdom, which may not otherwise be available without the existence of a well-established registry.
Asunto(s)
Monitoreo Epidemiológico , Síndromes de Inmunodeficiencia/epidemiología , Sistema de Registros/estadística & datos numéricos , Femenino , Humanos , Síndromes de Inmunodeficiencia/inmunología , Síndromes de Inmunodeficiencia/terapia , Masculino , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Activated phosphoinositide 3-kinase δ syndrome (APDS) is a recently described combined immunodeficiency resulting from gain-of-function mutations in PIK3CD, the gene encoding the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ). OBJECTIVE: We sought to review the clinical, immunologic, histopathologic, and radiologic features of APDS in a large genetically defined international cohort. METHODS: We applied a clinical questionnaire and performed review of medical notes, radiology, histopathology, and laboratory investigations of 53 patients with APDS. RESULTS: Recurrent sinopulmonary infections (98%) and nonneoplastic lymphoproliferation (75%) were common, often from childhood. Other significant complications included herpesvirus infections (49%), autoinflammatory disease (34%), and lymphoma (13%). Unexpectedly, neurodevelopmental delay occurred in 19% of the cohort, suggesting a role for PI3Kδ in the central nervous system; consistent with this, PI3Kδ is broadly expressed in the developing murine central nervous system. Thoracic imaging revealed high rates of mosaic attenuation (90%) and bronchiectasis (60%). Increased IgM levels (78%), IgG deficiency (43%), and CD4 lymphopenia (84%) were significant immunologic features. No immunologic marker reliably predicted clinical severity, which ranged from asymptomatic to death in early childhood. The majority of patients received immunoglobulin replacement and antibiotic prophylaxis, and 5 patients underwent hematopoietic stem cell transplantation. Five patients died from complications of APDS. CONCLUSION: APDS is a combined immunodeficiency with multiple clinical manifestations, many with incomplete penetrance and others with variable expressivity. The severity of complications in some patients supports consideration of hematopoietic stem cell transplantation for severe childhood disease. Clinical trials of selective PI3Kδ inhibitors offer new prospects for APDS treatment.
Asunto(s)
Fosfatidilinositol 3-Quinasa Clase I/genética , Síndromes de Inmunodeficiencia/genética , Trastornos Linfoproliferativos/genética , Mutación/genética , Infecciones del Sistema Respiratorio/genética , Adolescente , Adulto , Animales , Profilaxis Antibiótica , Niño , Preescolar , Fosfatidilinositol 3-Quinasa Clase I/antagonistas & inhibidores , Estudios de Cohortes , Inhibidores Enzimáticos/uso terapéutico , Femenino , Trasplante de Células Madre Hematopoyéticas , Infecciones por Herpesviridae/genética , Infecciones por Herpesviridae/mortalidad , Infecciones por Herpesviridae/terapia , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Síndromes de Inmunodeficiencia/mortalidad , Síndromes de Inmunodeficiencia/terapia , Lactante , Cooperación Internacional , Trastornos Linfoproliferativos/mortalidad , Trastornos Linfoproliferativos/terapia , Masculino , Ratones , Persona de Mediana Edad , Recurrencia , Infecciones del Sistema Respiratorio/mortalidad , Infecciones del Sistema Respiratorio/terapia , Encuestas y Cuestionarios , Análisis de Supervivencia , Adulto JovenRESUMEN
Common Variable Immunodeficiency (CVID) comprises a heterogeneous group of primary antibody deficiencies which lead to a range of complications, including infectious, neoplastic and inflammatory disorders. This report describes monozygotic twin brothers with CVID who developed cryptogenic liver disease and subsequently hepatopulmonary syndrome (HPS). This is the second report of the association of HPS and CVID. Its occurrence in two identical twins implicates a genetic basis.
Asunto(s)
Inmunodeficiencia Variable Común/diagnóstico , Síndrome Hepatopulmonar/diagnóstico , Adolescente , Inmunodeficiencia Variable Común/inmunología , Síndrome Hepatopulmonar/inmunología , Humanos , Masculino , Gemelos MonocigóticosRESUMEN
This report summarizes the establishment of the first national online registry of primary immune deficency in the United Kingdom, the United Kingdom Primary Immunodeficiency (UKPID Registry). This UKPID Registry is based on the European Society for Immune Deficiency (ESID) registry platform, hosted on servers at the Royal Free site of University College, London. It is accessible to users through the website of the United Kingdom Primary Immunodeficiency Network (www.ukpin.org.uk). Twenty-seven centres in the United Kingdom are actively contributing data, with an additional nine centres completing their ethical and governance approvals to participate. This indicates that 36 of 38 (95%) of recognized centres in the United Kingdom have engaged with this project. To date, 2229 patients have been enrolled, with a notable increasing rate of recruitment in the past 12 months. Data are presented on the range of diagnoses recorded, estimated minimum disease prevalence, geographical distribution of patients across the United Kingdom, age at presentation, diagnostic delay, treatment modalities used and evidence of their monitoring and effectiveness.
Asunto(s)
Síndromes de Inmunodeficiencia , Internet , Sistema de Registros , Femenino , Humanos , Síndromes de Inmunodeficiencia/diagnóstico , Síndromes de Inmunodeficiencia/epidemiología , Síndromes de Inmunodeficiencia/terapia , Masculino , Reino Unido/epidemiologíaRESUMEN
The molecular basis of X-linked recessive anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) has remained elusive. Here we report hypomorphic mutations in the gene IKBKG in 12 males with EDA-ID from 8 kindreds, and 2 patients with a related and hitherto unrecognized syndrome of EDA-ID with osteopetrosis and lymphoedema (OL-EDA-ID). Mutations in the coding region of IKBKG are associated with EDA-ID, and stop codon mutations, with OL-EDA-ID. IKBKG encodes NEMO, the regulatory subunit of the IKK (IkappaB kinase) complex, which is essential for NF-kappaB signaling. Germline loss-of-function mutations in IKBKG are lethal in male fetuses. We show that IKBKG mutations causing OL-EDA-ID and EDA-ID impair but do not abolish NF-kappaB signaling. We also show that the ectodysplasin receptor, DL, triggers NF-kappaB through the NEMO protein, indicating that EDA results from impaired NF-kappaB signaling. Finally, we show that abnormal immunity in OL-EDA-ID patients results from impaired cell responses to lipopolysaccharide, interleukin (IL)-1beta, IL-18, TNFalpha and CD154. We thus report for the first time that impaired but not abolished NF-kappaB signaling in humans results in two related syndromes that associate specific developmental and immunological defects.
Asunto(s)
Displasia Ectodérmica/genética , Displasia Ectodérmica/inmunología , Síndromes de Inmunodeficiencia/genética , Síndromes de Inmunodeficiencia/inmunología , FN-kappa B/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Adolescente , Niño , Preescolar , Codón de Terminación/genética , Displasia Ectodérmica/metabolismo , Ectodisplasinas , Ligamiento Genético , Humanos , Quinasa I-kappa B , Inmunidad Celular , Síndromes de Inmunodeficiencia/metabolismo , Lactante , Masculino , Proteínas de la Membrana/metabolismo , Mutación , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal , Síndrome , Cromosoma X/genéticaRESUMEN
The immunogenetic basis of severe infections caused by bacille Calmette-Guérin vaccine and environmental mycobacteria in humans remains largely unknown. We describe 18 patients from several generations of 12 unrelated families who were heterozygous for 1 to 5 overlapping IFNGR1 frameshift small deletions and a wild-type IFNGR1 allele. There were 12 independent mutation events at a single mutation site, defining a small deletion hotspot. Neighbouring sequence analysis favours a small deletion model of slipped mispairing events during replication. The mutant alleles encode cell-surface IFNgamma receptors that lack the intra-cytoplasmic domain, which, through a combination of impaired recycling, abrogated signalling and normal binding to IFNgamma exert a dominant-negative effect. We thus report a hotspot for human IFNGR1 small deletions that confer dominant susceptibility to infections caused by poorly virulent mycobacteria.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Infecciones por Mycobacterium/inmunología , Receptores de Interferón/genética , Eliminación de Secuencia , Adolescente , Adulto , Linfocitos B/efectos de los fármacos , Linfocitos B/metabolismo , Vacuna BCG/efectos adversos , Vacuna BCG/uso terapéutico , Proteínas de Unión al ADN/metabolismo , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/inmunología , Expresión Génica , Predisposición Genética a la Enfermedad/inmunología , Heterocigoto , Humanos , Interferón gamma/farmacología , Masculino , Mycobacterium/patogenicidad , Infecciones por Mycobacterium/genética , Linaje , ARN Mensajero/metabolismo , Receptores de Interferón/metabolismo , Factor de Transcripción STAT1 , Transactivadores/metabolismo , Transfección , Receptor de Interferón gammaRESUMEN
Respiratory disease is a significant cause of morbidity and mortality amongst patients with primary immunodeficiency disorders. Computed tomography (CT) plays an important role in the multidisciplinary approach to these conditions, in detecting, characterizing, and quantifying the extent of lung damage and in directing treatment. The aim of this review is to classify the primary immunodeficiency disorders and describe the thoracic complications and the associated CT findings whilst discussing the role of radiology in diagnosis and surveillance.
Asunto(s)
Inmunodeficiencia Variable Común/diagnóstico por imagen , Enfermedades Respiratorias/diagnóstico por imagen , Adulto , Inmunodeficiencia Variable Común/complicaciones , Diagnóstico Diferencial , Femenino , Humanos , Síndromes de Inmunodeficiencia/complicaciones , Síndromes de Inmunodeficiencia/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Enfermedades Respiratorias/complicaciones , Tomografía Computarizada por Rayos X/métodosRESUMEN
Genetic lack of interleukin 12 receptor beta1 (IL-12Rbeta1) surface expression predisposes to severe infections by poorly pathogenic mycobacteria or Salmonella and causes strongly decreased, but not completely abrogated, interferon (IFN)-gamma production. To study IL-12Rbeta1-independent residual IFN-gamma production, we have generated mycobacterium-specific T cell clones (TCCs) from IL-12Rbeta1-deficient individuals. All TCCs displayed a T helper type 1 phenotype and the majority responded to IL-12 by increased IFN-gamma production and proliferative responses upon activation. This response to IL-12 could be further augmented by exogenous IL-18. IL-12Rbeta2 was found to be normally expressed in the absence of IL-12Rbeta1, and could be upregulated by IFN-alpha. Expression of IL-12Rbeta2 alone, however, was insufficient to induce signal transducer and activator of transcription (Stat)4 activation in response to IL-12, whereas IFN-alpha/IFN-alphaR ligation resulted in Stat4 activation in both control and IL-12Rbeta1-deficient cells. IL-12 failed to upregulate cell surface expression of IL-18R, integrin alpha6, and IL-12Rbeta2 on IL-12Rbeta1-deficient cells, whereas this was normal on control cells. IL-12-induced IFN-gamma production in IL-12Rbeta1-deficient T cells could be inhibited by the p38 mitogen-activated protein kinase (MAP) kinase inhibitor SB203580 and the MAP kinase kinase (MEK) 1/2 inhibitor U0126, suggesting involvement of MAP kinases in this alternative, Stat4-independent, IL-12 signaling pathway.Collectively, these results indicate that IL-12 acts as a partial agonist in the absence of IL-12Rbeta1. Moreover, the results reveal the presence of a novel IL-12Rbeta1/Stat4-independent pathway of IL-12 responsiveness in activated human T cells involving MAP kinases. This pathway is likely to play a role in the residual type 1 immunity in IL-12Rbeta1 deficiency.
Asunto(s)
Interferón gamma/biosíntesis , Interleucina-12/inmunología , Infección por Mycobacterium avium-intracellulare/inmunología , Receptores de Interleucina/fisiología , Infecciones por Salmonella/inmunología , Linfocitos T/inmunología , Adolescente , Adulto , Antígenos CD/metabolismo , Butadienos/farmacología , Niño , Preescolar , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Inhibidores Enzimáticos/farmacología , Femenino , Humanos , Imidazoles/farmacología , Lactante , Integrina alfa6 , Interferón-alfa/metabolismo , Interleucina-18/metabolismo , Subunidad alfa del Receptor de Interleucina-18 , Interleucina-4/metabolismo , Masculino , Nitrilos/farmacología , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Piridinas/farmacología , Receptor de Interferón alfa y beta , Receptores de Interferón/metabolismo , Receptores de Interleucina/genética , Receptores de Interleucina/metabolismo , Receptores de Interleucina-12 , Receptores de Interleucina-18 , Factor de Transcripción STAT4 , Transducción de Señal , Células TH1/inmunología , Transactivadores/genética , Transactivadores/metabolismoRESUMEN
Interferon-gamma receptor ligand-binding chain (IFN-gammaR1) or signaling chain (IFN-gammaR2) deficiency, like interleukin 12 receptor beta1 chain (IL-12Rbeta1) deficiency, predispose to severe infections due to poorly virulent mycobacteria and salmonella. A child with bacille Calmette-Guérin and Salmonella enteritidis infection was investigated. Mutations in the genes for IFN-gammaR1, IFN-gammaR2, IL-12Rbeta1, and other molecules implicated in IL-12- or IFN-gamma-mediated immunity were sought. A large homozygous deletion within the IL-12 p40 subunit gene was found, precluding expression of functional IL-12 p70 cytokine by activated dendritic cells and phagocytes. As a result, IFN-gamma production by lymphocytes was markedly impaired. This is the first discovered human disease resulting from a cytokine gene defect. It suggests that IL-12 is essential to and appears specific for protective immunity to intracellular bacteria such as mycobacteria and salmonella.
Asunto(s)
Vacuna BCG/inmunología , Infecciones Bacterianas/genética , Interleucina-12/genética , Salmonella enteritidis/patogenicidad , Secuencia de Bases , Niño , Femenino , Prueba de Complementación Genética , Granuloma/patología , Humanos , Interferón gamma/metabolismo , Interleucina-12/deficiencia , Leucocitos , Ganglios Linfáticos/patología , Datos de Secuencia Molecular , Mycobacterium/inmunología , Mycobacterium/patogenicidad , Linaje , Salmonella enteritidis/inmunología , Análisis de Secuencia de ADN , Eliminación de Secuencia/genética , Transfección/genéticaRESUMEN
Although neonatal vaccination with bacille Calmette-Guérin (BCG) is considered to be safe, complications with disseminated disease are associated with underlying immuno-deficiency disorders. A BCG-vaccinated 4-month-old girl of Sri Lankan parentage developed progressive left axillary lymphadenopathy and severe bronchopneumonia. Lymph node biopsy demonstrated epithelioid granulomata and acid-fast bacilli. An older sibling had had a similar clinical presentation and the outcome had been fatal. Investigation for immuno-deficiency detected complete IL12RB1 deficiency. Full recovery followed a prolonged course of anti-tuberculous chemotherapy. She was put on lifelong isoniazid prophylaxis. In HIV-negative infants with unusual complications related to BCG vaccination, a primary immuno-deficiency disorder should be considered.
Asunto(s)
Vacuna BCG/efectos adversos , Síndromes de Inmunodeficiencia/complicaciones , Mycobacterium bovis/aislamiento & purificación , Receptores de Interleucina-12/deficiencia , Tuberculosis/diagnóstico , Tuberculosis/microbiología , Antituberculosos/uso terapéutico , Vacuna BCG/administración & dosificación , Biopsia , Femenino , Histocitoquímica , Humanos , Lactante , Pulmón/patología , Ganglios Linfáticos/patología , Sri Lanka , Resultado del TratamientoRESUMEN
A region 2 kb upstream of exon 1 of the P2X7 gene was sequenced using DNA from nine healthy individuals who exhibited three different ATP response phenotypes (i.e. high, low and interferon gamma-inducible). Five single nucleotide polymorphisms were identified within the nine donor promoter sequences but none were associated with a specific ATP response phenotype. A P2X7 loss of function polymorphism (1513 in exon 13) was also screened for within donor DNA but no response associations were identified. ATP response phenotype was positively associated with P2X(7) receptor expression, as assessed by flow cytometry, but not with any identified receptor or promoter gene polymorphisms.
Asunto(s)
Adenosina Trifosfato/toxicidad , Macrófagos/metabolismo , Polimorfismo de Nucleótido Simple , Receptores Purinérgicos P2/genética , Receptores Purinérgicos P2/metabolismo , Secuencia de Bases , Células Cultivadas , Humanos , Interferón gamma/farmacología , Macrófagos/efectos de los fármacos , Datos de Secuencia Molecular , Fenotipo , Regiones Promotoras Genéticas , ARN Mensajero/biosíntesis , Receptores Purinérgicos P2X7 , Alineación de Secuencia , Transcripción GenéticaRESUMEN
Patients with inherited defects in the interleukin-12 (IL-12)-dependent, 'high-output' interferon-gamma (IFN-gamma) pathway exhibit selective susceptibility to poorly pathogenic mycobacterial and salmonella infections. This review summarises the extended clinical spectrum seen in this group of patients and indicates a strategy for the identification of putative defects in the type 1 cytokine pathway.
Asunto(s)
Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/inmunología , Citocinas/deficiencia , Adulto , Infecciones Bacterianas/microbiología , Niño , Preescolar , Citocinas/genética , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Predisposición Genética a la Enfermedad , Humanos , Interferón gamma/análisis , Interferón gamma/deficiencia , Interferón gamma/genética , Interleucina-12/análisis , Interleucina-12/deficiencia , Interleucina-12/genética , Infecciones por Mycobacterium/diagnóstico , Infecciones por Mycobacterium/inmunología , Receptores de Interferón/análisis , Receptores de Interleucina/análisis , Receptores de Interleucina/fisiología , Infecciones por Salmonella/diagnóstico , Infecciones por Salmonella/inmunologíaRESUMEN
We present a scheme for routine screening of patients' sera for monoclonal immunoglobulin by isoelectric focusing in agarose gels. Using this method combined with immunofixation, we have been able to detect monoclonal immunoglobulin in the sera of patients, and to identify the isotype of the immunoglobulin when conventional techniques such as zonal and immunoelectrophoresis have yielded equivocal results.
Asunto(s)
Inmunoglobulinas/análisis , Paraproteinemias/diagnóstico , Humanos , Focalización Isoeléctrica/métodos , Tamizaje Masivo , Paraproteinemias/inmunología , Plasmacitoma/diagnóstico , Plasmacitoma/inmunologíaRESUMEN
The limits of detection of four classes of monoclonal immunoglobulin and free light chain in serum by isoelectric focusing and immunoisoelectric focusing have been determined and the sensitivity of these techniques compared with that obtained using immunoelectrophoresis and zonal electrophoresis with immunofixation. Immunoisoelectric focusing was 10-40 times more sensitive than immunoelectrophoresis and could be used to detect concentrations of monoclonal immunoglobulin that were undetectable by zonal electrophoresis with immunofixation. The relevance of this work in monitoring multiple myeloma during treatment and relapse is discussed.
Asunto(s)
Anticuerpos Monoclonales/análisis , Cadenas Ligeras de Inmunoglobulina/análisis , Mieloma Múltiple/inmunología , Proteínas de Mieloma/sangre , Humanos , Inmunoelectroforesis , Inmunoglobulina A , Inmunoglobulina D , Inmunoglobulina G , Inmunoglobulina M , Técnicas Inmunológicas , Focalización Isoeléctrica , Mieloma Múltiple/sangreRESUMEN
AIMS: To evaluate two of the recent methods of coating microtitre plates in the enzyme linked immunosorbent assay (ELISA) for detecting human antibodies against meningococcal capsular polysaccharides A and C with a view to validating a specific meningococcal antibody assay for routine clinical use. METHODS: Two four-layer ELISA protocols were standardised: one method utilised meningococcal polysaccharides conjugated to poly-L-lysine polypeptide for coating the microtitre plates; another used polysaccharides mixed with methylated human serum albumin (mHSA). Titration curves were plotted for the ELISAs and the squared Pearson correlation coefficient (R2) was used to determine the degree of accuracy of fit of the curves. Specificity tests were performed by inhibition and adsorption studies. RESULTS: Both methods gave good titration curves with a high R2 of > 0.98, indicating a high degree of accuracy in forming the curves. The titration end point after vaccination, obtained by the mHSA method, was 20 times higher, however, than that obtained by the poly-L-lysine method. Specificity tests showed that in the ELISA using polysaccharide/poly-L-lysine, antibody activity of a pre-vaccination serum sample was inhibited by 37%, and of post-vaccination serum by 50% with 1000-fold excess antigen. Antibody activity (post-vaccination) was reduced by 51% and 59%, respectively, by adsorption with antigen-coated Sepharose beads or adsorption with suspensions of killed meningococci. In contrast, antibody activity of a pre-vaccination serum was inhibited by 60% and a post-vaccination serum by 90% in ELISA employing polysaccharides mixed with mHSA. Reproducibility was better with the use of methylated human serum albumin than with poly-L-lysine; the former showed intrabatch and interbatch coefficients of variation of 4% and 2%, respectively, compared with 43% (intrabatch) and 16% (interbatch) obtained with the poly-L-lysine. CONCLUSION: It is concluded that the antibody assay using meningococcal polysaccharides groups A and C mixed with mHSA is much better than that using polysaccharides coupled with poly-L-lysine.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Ensayo de Inmunoadsorción Enzimática/métodos , Neisseria meningitidis/inmunología , Polisacáridos Bacterianos/inmunología , Especificidad de Anticuerpos , Humanos , Polilisina , Reproducibilidad de los Resultados , Albúmina SéricaRESUMEN
Microfilariae found in a breast nodule of a patient with tropical pulmonary eosinophilia were identified as Wuchereria bancrofti, confirming that the tropical pulmonary eosinophilia syndrome may be associated with infections caused by this species of filarial worm.
Asunto(s)
Enfermedades de la Mama/complicaciones , Eosinofilia/complicaciones , Filariasis/complicaciones , Adulto , Femenino , Humanos , Sri Lanka , WuchereriaRESUMEN
BACKGROUND: Common variable immune deficiency (CVID) is prone to under-diagnosis and may not reach relevant specialists until late in life. Morbidity is most commonly due to acute-on-chronic respiratory infections leading to respiratory failure. AIM: To investigate respiratory complications, lung function and high-resolution computerized tomography scan (HRCT) findings and mortality in 47 patients with CVID. SETTING: A regional immunology unit (Birmingham Heartlands Hospital). DESIGN: Retrospective observational case-note study following the introduction of shared care between immunology and respiratory medicine. RESULTS: Age at diagnosis ranged from 5 to 72 years, with a median time from development of first symptoms to diagnosis of 4.0 years. There was delay in referral between chest physicians and immunologists, (median referral time between specialities >5 years). Forty-two patients had respiratory complications, due to bronchiectasis (n=32), asthma (n=7), recurrent chest infections (n=9) without concomitant evidence of structural lung damage, and granulomatous lung disease (n=2). Spirometry was abnormal in 10/39 patients (7 obstructive, 3 restrictive). Bronchiectasis was confirmed on chest radiograph (n=9) and HRCT (n=24). Despite the high prevalence of bronchiectasis, few patients had received instruction in physiotherapy and sputum culture results were sparse. DISCUSSION: To reduce the morbidity associated with CVID, there needs to be greater awareness of respiratory complications, particularly amongst physicians caring for such patients. Emphasis has been placed on adequate dosage of immunoglobulin, but early involvement by a respiratory physician is essential to monitor lung function and initiate optimal therapy, to minimize the occurrence and progression of lung damage.
Asunto(s)
Inmunodeficiencia Variable Común/complicaciones , Pulmón/fisiopatología , Enfermedades Respiratorias/etiología , Adulto , Anciano , Anciano de 80 o más Años , Bronquiectasia/diagnóstico por imagen , Bronquiectasia/etiología , Inmunodeficiencia Variable Común/diagnóstico por imagen , Inmunodeficiencia Variable Común/fisiopatología , Femenino , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Masculino , Persona de Mediana Edad , Infecciones Oportunistas/complicaciones , Peptidil-Dipeptidasa A/sangre , Derivación y Consulta , Enfermedades Respiratorias/diagnóstico por imagen , Infecciones del Sistema Respiratorio/complicaciones , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
Mycobacterium bovis-BCG infected macrophages were exposed in vitro to PPD-stimulated T lymphocytes from tuberculin responsive donors or to a panel of mycobacterial-antigen specific CD4+ T cell clones. Both polyclonal and clonal T cells caused considerable antigen-specific lysis of autologous or MHC class II matched macrophages. However, lysis of infected macrophages did not significantly affect the number of viable mycobacteria which were released into the culture media from lysed macrophages. In tuberculosis, CD4+ cytolytic T cells may be primarily involved in tissue destruction and lack a significant role in acquired cellular immunity.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Citotoxicidad Inmunológica , Macrófagos/inmunología , Mycobacterium bovis/inmunología , Células Cultivadas , Epítopos , Antígenos de Histocompatibilidad Clase II/inmunología , Humanos , Activación de Macrófagos , Macrófagos/efectos de los fármacos , Macrófagos/microbiología , Mycobacterium bovis/crecimiento & desarrollo , Tuberculina/farmacologíaRESUMEN
It is questionable as to whether a low serum concentration of one of the IgG subclasses identifies a disease state. A low IgG(1) concentration is found in primary or secondary immunodeficiency states but does not occur in isolation. Low IgG(2) concentration is associated with an increased risk of bacterial infections but only in some individuals and not in others. Isolated IgG(3) and IgG(4) deficiency have not been convincingly demonstrated. Therefore, the isolated finding of low concentrations of one or more IgG subclass does not identify individuals at risk. In contrast, the finding of low serum concentrations of antibodies to specific bacterial antigens (Haemophilus influenzae type B, pneumococcus, tetanus and diphtheria) does identify individuals at risk and these measurements should be used in preference to IgG subclass measurement.
Asunto(s)
Deficiencia de IgG/diagnóstico , Inmunoglobulina G/análisis , Anticuerpos Antibacterianos/análisis , Anticuerpos Antibacterianos/sangre , Técnicas de Laboratorio Clínico , Humanos , Deficiencia de IgG/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/clasificación , Polisacáridos Bacterianos/inmunología , Sensibilidad y EspecificidadRESUMEN
The measurement of immunoglobulin A (IgA) endomysial antibodies is now established as an important diagnostic test in gluten-sensitive disease. Monkey oesophagus is the commonly used tissue substrate, but it has been proposed that human umbilical cord tissue may be a suitable alternative for antibody detection. In this study, we report a modified method of examining endomysial antibody reactivity with cord tissue. This involves examination of antibody reactivity with cells in Wharton's jelly, and with umbilical cord blood vessel. A total of 370 patients being investigated for coeliac disease were studied and this diagnosis was established in 42. Endomysial antibodies were found in all 42 using umbilical cord tissue, and the test results were confirmed with monkey oesophagus substrate. In three of the remaining 328 non-coeliacs, a false-positive endomysial antibody test was noted and small intestine histology was normal in these patients. All positive sera were found to react with cells in Wharton's jelly, and reticular staining of blood vessels was also present. Examination for immunofluorescence in both Wharton's jelly and blood vessel components of cord tissue greatly simplified test interpretation.