RESUMEN
The clinical outcomes of primary immunodeficiencies (PIDs) are greatly improved by accurate diagnosis early in life. However, it is not common to consider PIDs before the manifestation of severe clinical symptoms. Including PIDs in the nation-wide newborn screening programs will potentially improve survival and provide better disease management and preventive care in PID patients. This calls for the detection of disease biomarkers in blood and the use of dried blood spot samples, which is a part of routine newborn screening programs worldwide. Here, we developed a newborn screening method based on multiplex protein profiling for parallel diagnosis of 22 innate immunodeficiencies affecting the complement system and respiratory burst function in phagocytosis. The proposed method uses a small fraction of eluted blood from dried blood spots and is applicable for population-scale performance. The diagnosis method is validated through a retrospective screening of immunodeficient patient samples. This diagnostic approach can pave the way for an earlier, more comprehensive and accurate diagnosis of complement and phagocytic disorders, which ultimately lead to a healthy and active life for the PID patients.
Asunto(s)
Enfermedades por Deficiencia de Complemento Hereditario/diagnóstico , Síndromes de Inmunodeficiencia/diagnóstico , Tamizaje Neonatal/métodos , Disfunción de Fagocito Bactericida/diagnóstico , Fagocitos/fisiología , Diagnóstico Precoz , Humanos , Recién Nacido , Fagocitosis , Estudios RetrospectivosRESUMEN
The Swiss National Registry for Primary Immunodeficiency Disorders (PID) was established in 2008, constituting a nationwide network of paediatric and adult departments involved in the care of patients with PID at university medical centres, affiliated teaching hospitals and medical institutions. The registry collects anonymized clinical and genetic information on PID patients and is set up within the framework of the European database for PID, run by the European Society of Immunodeficiency Diseases. To date, a total of 348 patients are registered in Switzerland, indicating an estimated minimal prevalence of 4·2 patients per 100 000 inhabitants. Distribution of different PID categories, age and gender are similar to the European cohort of currently 19 091 registered patients: 'predominantly antibody disorders' are the most common diseases observed (n = 217/348, 62%), followed by 'phagocytic disorders' (n = 31/348, 9%). As expected, 'predominantly antibody disorders' are more prevalent in adults than in children (78 versus 31%). Within this category, 'common variable immunodeficiency disorder' (CVID) is the most prevalent PID (n = 98/217, 45%), followed by 'other hypogammaglobulinaemias' (i.e. a group of non-classified hypogammaglobulinaemias) (n = 54/217, 25%). Among 'phagocytic disorders', 'chronic granulomatous disease' is the most prevalent PID (n = 27/31, 87%). The diagnostic delay between onset of symptoms and diagnosis is high, with a median of 6 years for CVID and more than 3 years for 'other hypogammaglobulinaemias'.
Asunto(s)
Agammaglobulinemia/epidemiología , Inmunodeficiencia Variable Común/epidemiología , Bases de Datos Factuales/estadística & datos numéricos , Disfunción de Fagocito Bactericida/epidemiología , Sistema de Registros/estadística & datos numéricos , Adulto , Agammaglobulinemia/diagnóstico , Agammaglobulinemia/genética , Niño , Inmunodeficiencia Variable Común/diagnóstico , Inmunodeficiencia Variable Común/genética , Diagnóstico Tardío/estadística & datos numéricos , Femenino , Humanos , Masculino , Disfunción de Fagocito Bactericida/diagnóstico , Disfunción de Fagocito Bactericida/genética , Suiza/epidemiologíaRESUMEN
There are few reports about congenital indifference to pain or Hereditary and Sensory Autonomic Neuropathy (HSAN). Several investigations for pathophysiology of this syndrome have been performed and different classifications about it. In this report we present a case of HSAN type II with general absence of pain and self amputations and leprosy-like damage of extremities which was suspected to be phagocytic immunodeficiency due to past history of repeated ulcer and abscess formation.
Asunto(s)
Diagnóstico Diferencial , Neuropatías Hereditarias Sensoriales y Autónomas/diagnóstico , Disfunción de Fagocito Bactericida/diagnóstico , Preescolar , Neuropatías Hereditarias Sensoriales y Autónomas/patología , Humanos , Masculino , Disfunción de Fagocito Bactericida/patologíaAsunto(s)
Síndromes de Inmunodeficiencia/diagnóstico , Síndromes de Inmunodeficiencia/terapia , Atención Primaria de Salud , Agammaglobulinemia/diagnóstico , Agammaglobulinemia/terapia , Algoritmos , Formación de Anticuerpos/genética , Formación de Anticuerpos/inmunología , Enfermedades Autoinmunes/inmunología , Inmunodeficiencia Variable Común/diagnóstico , Inmunodeficiencia Variable Común/terapia , Proteínas del Sistema Complemento/deficiencia , Humanos , Inmunidad Celular/genética , Inmunidad Celular/inmunología , Síndromes de Inmunodeficiencia/clasificación , Síndromes de Inmunodeficiencia/genética , Linfopenia/diagnóstico , Linfopenia/terapia , Disfunción de Fagocito Bactericida/diagnóstico , Disfunción de Fagocito Bactericida/terapia , Inmunodeficiencia Combinada Grave/diagnóstico , Inmunodeficiencia Combinada Grave/terapiaRESUMEN
Se realiza una revisión sobre los defectos presentes en la función de los fagocitos que provocan trastornos inmunitarios. Se exponen las características clínicas, moleculares e inmunológicas que caracterizan a cada desorden fagocítico, así como los métodos de laboratorio utilizados para el diagnóstico de estos. Se hace referencia a los tratamientos terapéuticos efectivos que eliminan o atenúan las manifestaciones clínicas de cada defecto de la fagocitosis estudiado.(AU)
Asunto(s)
Humanos , Fagocitosis/genética , Fagocitosis/inmunología , Disfunción de Fagocito Bactericida/diagnóstico , Disfunción de Fagocito Bactericida/genética , Disfunción de Fagocito Bactericida/inmunologíaRESUMEN
Se realiza una revisión sobre los defectos presentes en la función de los fagocitos que provocan trastornos inmunitarios. Se exponen las características clínicas, moleculares e inmunológicas que caracterizan a cada desorden fagocítico, así como los métodos de laboratorio utilizados para el diagnóstico de estos. Se hace referencia a los tratamientos terapéuticos efectivos que eliminan o atenúan las manifestaciones clínicas de cada defecto de la fagocitosis estudiado.
Asunto(s)
Humanos , Disfunción de Fagocito Bactericida/diagnóstico , Disfunción de Fagocito Bactericida/genética , Disfunción de Fagocito Bactericida/inmunología , FagocitosisRESUMEN
The field of phagocytic disorders has attained major biologic and clinical significance in the past 40 years. The development of exciting new techniques in molecular biology and the cellular physiology of signal transduction have made it possible to identify the genetic defects involved in many of these disorders. Moreover through immunopharmacologic intervention, bone marrow or peripheral or cord blood stem cell transplantation along with the prospect of gene therapy, we have begun attempts to at least partially correct genetic defects in cell development and activation pathways in the entire spectrum of phagocyte disorders. Carrier detection and prenatal diagnosis employing with chain reaction techniques or direct nucleotide sequencing in fetal blood have made these diseases potentially preventable or treatable in utero or shortly after birth.
Asunto(s)
Agranulocitosis/genética , Granulocitos/fisiología , Disfunción de Fagocito Bactericida/genética , Disfunción de Fagocito Bactericida/terapia , Fagocitosis/genética , Agranulocitosis/congénito , Agranulocitosis/fisiopatología , Niño , Preescolar , Enfermedad Crónica , Femenino , Terapia Genética/métodos , Humanos , Lactante , Recién Nacido , Masculino , Biología Molecular , Disfunción de Fagocito Bactericida/diagnóstico , PronósticoRESUMEN
Neutrophils have a crucial function in the defense against bacteria and fungi. Indeed, during chronic, severe neutropenia and in case of severe neutrophil dysfunctions, the patients may suffer recurrent and sometimes life-threatening infections. This article describes the clinical symptoms, the theory behind the antimicrobial systems of neutrophils, the methods to diagnose the various aberrations, and the possibilities for treating these patients. A few of the most common causes of neutropenia and neutrophil dysfunctions are described in detail, including recent genetic information regarding the cause of these diseases.
Asunto(s)
Neutropenia/diagnóstico , Neutrófilos/patología , Disfunción de Fagocito Bactericida/diagnóstico , Animales , Pruebas Diagnósticas de Rutina/métodos , Humanos , Sistema Inmunológico/inmunología , Sistema Inmunológico/patología , Neutropenia/sangre , Neutropenia/inmunología , Neutropenia/patología , Neutrófilos/inmunología , Disfunción de Fagocito Bactericida/sangre , Disfunción de Fagocito Bactericida/patologíaRESUMEN
The evaluation of phagocytic and microbicidal activities of the blood neutrophils has been recognized as one of the important tools for investigating phagocytic dysfunctions in patients with recurrent infections. In the present study, these activities were examined in neutrophils and monocytes from healthy adults and patients affected by primary phagocytic dysfunctions by using a modified fluorochromic microbicidal assay, discriminating simultaneously the extracellular adherence, ingestion and intracellular killing of Staphylococcus aureus Cowan I. The assay employs acridine orange staining, as described in Bellinati-Pires et al. (1989) (AO assay), but was modified by the addition of an alternative leukocyte treatment with 0.5 U/ml of lysostaphin (LS) for 5 min at 37 degrees C, after phagocytosis (AO-LS assay). The LS treatment was standardized to eliminate staphylococci adhered to the outer surface of the phagocytes without affecting the determination of intracellular live or dead bacteria, as demonstrated in normal neutrophils and monocytes. Our purpose in this study was to compare AO and AO-LS assays in order to evaluate the effect of LS on the determination of actually ingested staphylococci and to provide a means for improving the fluorochromic assay for detecting phagocytic defects, as well as bactericidal disturbances. By using the AO-LS assay, decreased ingestion of staphylococci by neutrophils in Chediak-Higashi Syndrome (CHS) was demonstrated. However, increased staphylococci adherence, as well as ingestion, was observed in neutrophils or monocytes from chronic granulomatous disease (CGD) patients, comparing AO and AO-LS assays. Bactericidal defect, which is a common feature in CHS and CGD, was detected in neutrophils or monocytes in both assays. We emphasize that such alterations were deduced by comparing the patients' results with those obtained from their respective normal controls and with the normal range of values previously established for 160 healthy adults. No alteration was observed in hyper IgE syndrome phagocytes. Despite the possible penetration of LS into the leukocytes, as stated in other studies, we concluded that a short period of phagocyte incubation with this enzyme increased the sensitivity of the fluorochromic assay to detect phagocytic defect without affecting the determination of the bactericidal activity. Moreover, comparations between AO and AO-LS assays may be important in the study of the initial pathways of staphylococci phagocyte interaction, including adherence by non-phagocytic receptors.
Asunto(s)
Actividad Bactericida de la Sangre , Lisostafina , Monocitos/inmunología , Neutrófilos/inmunología , Disfunción de Fagocito Bactericida/sangre , Disfunción de Fagocito Bactericida/diagnóstico , Disfunción de Fagocito Bactericida/etiología , Adulto , Niño , Preescolar , Estudios de Evaluación como Asunto , Femenino , Colorantes Fluorescentes , Humanos , Inmunoglobulina E/sangre , Masculino , Monocitos/microbiología , Neutrófilos/microbiología , Staphylococcus aureus/inmunologíaAsunto(s)
Humanos , Neutropenia/fisiopatología , Disfunción de Fagocito Bactericida/etiología , Síndrome de Deficiencia de Adhesión del Leucocito/fisiopatología , Quimiotaxis/fisiología , Neutropenia/clasificación , Neutropenia/etiología , Disfunción de Fagocito Bactericida/diagnóstico , Síndrome de Chediak-Higashi/cirugía , Síndrome de Chediak-Higashi/diagnóstico , Síndrome de Chediak-Higashi/tratamiento farmacológico , Síndrome de Deficiencia de Adhesión del Leucocito/diagnóstico , Síndrome de Job/fisiopatología , Síndrome de Job/inmunologíaAsunto(s)
Humanos , Disfunción de Fagocito Bactericida/etiología , Neutropenia/fisiopatología , Síndrome de Deficiencia de Adhesión del Leucocito/fisiopatología , Neutropenia/clasificación , Neutropenia/etiología , Quimiotaxis/fisiología , Disfunción de Fagocito Bactericida/diagnóstico , Síndrome de Deficiencia de Adhesión del Leucocito/diagnóstico , Síndrome de Chediak-Higashi/cirugía , Síndrome de Chediak-Higashi/diagnóstico , Síndrome de Chediak-Higashi/tratamiento farmacológico , Síndrome de Job/fisiopatología , Síndrome de Job/inmunologíaRESUMEN
The functional activity of polymorphonuclear leukocytes (PMNL) was studied in the test of biochemical luminescence (BCL) in 43 patients including 31 patients with systemic lupus erythematosus (SLE) and 12 with nodular periarteritis (NP). Generation of the active forms of oxygen depended on the activity of the pathological process and the level of the circulating immune complexes (CIC). As established, under the conditions of hyperproductions IC PMNL in patients with SLE and NP preserve a rather high capacity to generate active forms of oxygen into intracellular space that allows one to speak about the role of oxygen radicals in the development of vascular lesions in patients with rheumatic diseases.
Asunto(s)
Lupus Eritematoso Sistémico/inmunología , Neutrófilos/inmunología , Disfunción de Fagocito Bactericida/etiología , Fagocitosis/inmunología , Poliarteritis Nudosa/inmunología , Adolescente , Adulto , Femenino , Humanos , Técnicas In Vitro , Lupus Eritematoso Sistémico/complicaciones , Masculino , Persona de Mediana Edad , Disfunción de Fagocito Bactericida/diagnóstico , Poliarteritis Nudosa/complicacionesAsunto(s)
Fibronectinas/deficiencia , Macrófagos del Hígado/inmunología , Hígado/inmunología , Macrófagos/inmunología , Peritonitis/inmunología , Disfunción de Fagocito Bactericida/etiología , Fagocitosis/inmunología , Adyuvantes Inmunológicos/uso terapéutico , Fibronectinas/administración & dosificación , Humanos , Macrófagos del Hígado/efectos de los fármacos , Hígado/patología , Macrófagos/efectos de los fármacos , Disfunción de Fagocito Bactericida/diagnóstico , Disfunción de Fagocito Bactericida/tratamiento farmacológico , Fagocitosis/efectos de los fármacosAsunto(s)
Colelitiasis/cirugía , Hepatopatías/etiología , Pancreatitis/etiología , Complicaciones Posoperatorias/etiología , Adulto , Anciano , Colelitiasis/fisiopatología , Femenino , Humanos , Hígado/fisiopatología , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Neutrófilos/inmunología , Nitroazul de Tetrazolio , Páncreas/fisiopatología , Pruebas de Función Pancreática , Disfunción de Fagocito Bactericida/complicaciones , Disfunción de Fagocito Bactericida/diagnóstico , Pronóstico , Infección de la Herida Quirúrgica/etiologíaRESUMEN
This article presents an outline of a rational approach to the patient with recurrent infections. The different categories of phagocytic defects are reviewed, and a brief discussion of the various tests of phagocyte function is presented.
Asunto(s)
Disfunción de Fagocito Bactericida/diagnóstico , Quimiotaxis , Proteínas del Sistema Complemento/deficiencia , Humanos , Linfocitos/inmunología , Neutrófilos/fisiología , Disfunción de Fagocito Bactericida/sangre , FagocitosisRESUMEN
CD11/CD18 leukocyte glycoprotein deficiency is a rare, inherited disorder of leukocyte function, manifested by recurrent severe bacterial infections. A deficiency in the expression of a family of leukocyte membrane glycoproteins (the CD11/CD18 glycoproteins) represents the molecular basis for this disease.
Asunto(s)
Leucocitos/inmunología , Glicoproteínas de Membrana/deficiencia , Disfunción de Fagocito Bactericida/inmunología , Quimiotaxis , Humanos , Leucocitos/metabolismo , Linfocitos/inmunología , Glicoproteínas de Membrana/genética , Disfunción de Fagocito Bactericida/diagnóstico , Disfunción de Fagocito Bactericida/genética , Disfunción de Fagocito Bactericida/terapia , Fagocitosis , PronósticoRESUMEN
Os autores apresentam os principais achados clínicos e laboratoriais de 16 crianças portadoras de distúrbios de fagócitos atendidas no Ambulatório de Imunopatologia do Instituto da Criança "Prof. Pedro de Alcantara". Os diagnósticos verificados foram Doença Granulomatosa Crônica da Infância (B), Síndrome de Chediak-Higashi (3), Neutropenia Persistente (3), Síndrome de Job (1) e Defeito de Quimiotaxia (1). Estes pacientes constituem 20% dos casos de Imunodeficiências Primárias de nossa casuística e as principais manifestaçöes clínicas foram de infecçöes piogênicas recorrentes, acometendo pele, mucosa oral e trato respiratório, com a formçäo de abcessos. Acompanham o quadro clínico, hepatoesplenomegalia e adenomegalia supurativa. O presente trabalho destaca a importância da pesquisa destes distúrbios da imunidade para que o tratamento seja instituído precocemente
Asunto(s)
Lactante , Preescolar , Niño , Humanos , Masculino , Femenino , Disfunción de Fagocito Bactericida/diagnóstico , Fagocitos/fisiologíaRESUMEN
When patients suffer from recurrent infections with bacteria or fungi that react poorly with the commonly prescribed antibiotics, phagocyte dysfunctions should be considered. In this article, a survey is given of the mechanism of action of these cells, the dysfunctions that may occur, the resulting clinical symptoms, the laboratory diagnostics and some therapeutical approaches.