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Our aim was to determine the secondary antibody deficiency (SAD) profiles of patients in a mesoregion of São Paulo state, Brazil, focusing on infectious diseases. Demographic characteristics, and clinical and laboratory data were obtained from electronic files; infections were classified as organ-specific and graded as mild, moderate, life-threatening, and fatal. Non-Hodgkin's lymphoma (NHL) accounted for 30% of patients, nephrotic syndrome (NS) 25%, chronic lymphocyte leukemia 20%, and multiple myeloma 15%. Patients with NS were younger than those in other groups, and hypo-γ-globulinemia was detected in 94.1%, IgG < 400 mg/dL in 60.0%, IgA < 40 mg/dL in 55.0%, and CD19 < 20 cells/mm3 in 30.0%. One hundred and one infections were found; 82.1% were classified as mild or moderate, 7.9% as life-threatening, and 3.0% as fatal. Respiratory tract infections were more prevalent (41.5%), and pneumonia accounted for 19.8%. Lower levels of infections were found in patients with NS compared with NHL (p = 0.0001). Most patients progressed to hypo-γ-globulinemia and SAD after treatment with immunosuppressants, and mild and moderate infections were predominant. These therapies are increasing in patients with different diseases; therefore, monitoring hypo-γ-globulinemia and infections may help to identify patients at high risk for severe complications, antibiotic prophylaxis or treatment, and immunoglobulin replacement.
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Background: Specific antibody deficiency (SAD) is an inborn error of immunity, in patients older than 2 years, characterized by normal immunoglobulin levels and IgG subclasses, but with recurrent infections and decreased antibody responses to polysaccharide antigens. Case report: A 10-year-old female, previously healthy, with no significant family history. She is known in this institution for symptoms of headache, vomiting and paresis. A CT scan of the skull was performed, where 4 brain abscesses, edema and displacement of the midline were observed, a right frontal trephine was performed and abscess drainage, antimicrobial management for infectology, blood cultures, Gram staining and cultures of negative drainage material. Assessed for allergy and immunology, for abscesses in deep focus, an approach was performed to rule out inborn error of immunity, immunoglobulins, isohemagglutinins, flow cytometry and response to normal protein antigens. Antibodies against post-vaccination polysaccharide antigens are requested, where a response to only 2 serotypes (18.1% response) is observed, with normal IgG subclasses, a diagnosis of specific antibody deficiency is integrated and management with immuno- globulin at replacement doses is started, as well as annual vaccination with 13 valent. Conclusion: SAD has been considered a problem that can be resolved over time, especially in children, but in others it can evolve into more severe forms of humoral immunodeficiency. Decisions to treat with prophylactic antibiotics and/or gamma globulin are guided by clinical judgment, small studies, and recent consensus documents, which may evolve over time.
Antecedentes: La deficiencia especifica de anticuerpos (SAD) es un error innato de la inmunidad, en pacientes de más de 2 años, caracterizada por niveles de inmunoglobulinas y subclases de IgG normales, pero con infecciones recurrentes y respuestas de anticuerpos disminuidas a antígenos polisacáridos. Reporte de caso: Femenina de 10 años, previa sana, sin antecedentes heredofamiliares de importancia. Conocida en esta institución por cuadro de cefalea, vómi- tos y paresias. Se realiza TAC de cráneo, donde se observan 4 abscesos cerebrales, edema y desplazamiento de la línea media, se realiza trepano frontal derecha y drenaje de abscesos, manejo antimicrobiano por infectología, hemocultivos, tinción de Gram y cultivos de material de drenaje negativos. Valorado por alergia e inmunología, por abscesos en foco profundo, se realizó abordaje para descartar error innato de la inmunidad, inmunoglobulinas, isohemaglutininas, citometría de flujo y respuesta a antígenos proteicos normales. Se solicitan anticuerpos contra antígenos polisacáridos post vacunación, donde se observa respuesta a solo 2 serotipos (respuesta del 18.1%), con subclases de IgG normales, se integra diagnóstico de deficiencia especifica de anticuerpos y se inicia manejo con inmuno- globulina a dosis de reemplazo, asi como vacunación anual con 13 valente. Conclusión: El SAD se ha considerado un problema que puede resolverse con el tiempo, especialmente en niños, pero en otros puede evolucionar hacia formas más severas de inmunodeficiencia humoral. Las decisiones de tratar con antibióticos profilácticos y/o gammaglobulina están guiadas por el juicio clínico, estudios pequeños y documentos de consenso recientes, que pueden evolucionar con el tiempo.
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Síndromes de Inmunodeficiencia , Enfermedades de Inmunodeficiencia Primaria , Niño , Femenino , Humanos , Inmunoglobulina G , Vacunación , Polisacáridos , Anticuerpos AntibacterianosRESUMEN
BACKGROUND: Bronchiectasis is a major respiratory complication in patients with common variable immunodeficiency (CVID) and is associated with recurrent pulmonary infections. However, it is unclear whether other infections or non-infectious respiratory conditions are related to its development. OBJECTIVE: To identify respiratory comorbidities associated with bronchiectasis in patients with CVID. METHODS: A total of 1470 CVID patients enrolled in the USIDNET registry were included in a cross-sectional analysis. The primary outcome of our study was to determine the clinical characteristics and other respiratory conditions associated with respiratory comorbidities and physician-reported bronchiectasis. RESULTS: One hundred ninety-seven CVID patients were noted to have bronchiectasis (13.4%). Affected patients were significantly older than patients without bronchiectasis (median age 54 years vs. 49 years, p = 0.0004). These patients also had lower serum IgA (13 mg/dL IQR 60 mg/dL vs. 28.4 mg/dL IQR 66 mg/dL, p = 0.000). Notably, chronic rhinosinusitis (OR = 1.69 95%CI 1.05-2.75), sinusitis (OR = 2.06 95%CI 1.38-3.09), pneumonia (OR = 2.70 95%CI 1.88-3.88), COPD (OR = 2.66 95%CI 1.51-4.67), and interstitial lung disease (OR = 2.34 95%CI 1.41-3.91) were independently associated with the development of bronchiectasis in this population. CONCLUSION: These data suggest that lower and upper respiratory infections, chronic lower airway disease, and interstitial lung diseases are independently associated with bronchiectasis in CVID patients. Further study into predisposing conditions related to the development of bronchiectasis in CVID patients may allow prediction and early intervention strategies to prevent the development of this complication.
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Bronquiectasia , Inmunodeficiencia Variable Común , Enfermedades Pulmonares Intersticiales , Neumonía , Sinusitis , Humanos , Persona de Mediana Edad , Inmunodeficiencia Variable Común/complicaciones , Inmunodeficiencia Variable Común/epidemiología , Estudios Transversales , Bronquiectasia/epidemiología , Neumonía/complicaciones , Enfermedades Pulmonares Intersticiales/etiología , Sinusitis/epidemiología , Sinusitis/complicaciones , Sistema de RegistrosRESUMEN
PURPOSE: This study aimed to investigate the correlation between calculated globulin (CG, total protein level minus albumin level) and the gamma globulin fraction (Gamma), obtained from serum protein electrophoresis with serum IgG levels in adults (≥ 18 years). METHODS: Using linear regression models, analyses of CG and Gamma levels correlation with IgG levels in adults were performed. Receiver-operator curves were created to determine cutoff values and the respective sensitivity and specificity measures. RESULTS: A total of 886 samples were analyzed. CG and Gamma were positively and statistically correlated with IgG levels (r2 = 0.4628 for CG, and = 0.7941 for Gamma, p < 0.0001 for both analyses). For the detection of hypogammaglobulinemia, i.e., IgG level below the reference value (6 g/L), a CG cutoff value of 24 g/L showed a sensitivity of 86.2% (95% CI 69.4-94.5) and a specificity of 92% (90.0-93.6). A Gamma cutoff value of 7.15 g/L yielded a sensitivity of 100% (88.3-100) and a specificity of 96.8 (95.3-97.8). CONCLUSION: Both CG and Gamma levels determined by protein electrophoresis analysis may be used to screen for antibody deficiencies in adults, enabling earlier diagnosis of antibody deficiencies in a routine clinical setting.
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Agammaglobulinemia , Enfermedades de Inmunodeficiencia Primaria , Humanos , Adulto , Electroforesis , Globinas , Inmunoglobulina GRESUMEN
Background: Inborn errors of immunity, mainly Predominantly Antibody deficiencies with normal IgG levels are unrecognized in adults with lung diseases such as bronchiectasis or recurrent pneumonia. Objective: To determine IgM, IgA, IgG2 subclass deficiencies, and Specific antibody deficiency (anti-pneumococcal polysaccharide antibodies) in adults with non-cystic fibrosis bronchiectasis or recurrent pneumonia. Methods: Cross-sectional study. Consecutive patients with non-cystic fibrosis bronchiectasis or recurrent pneumonia were recruited in Cali, Colombia. IgG, IgA, IgM, and IgE, IgG2subclass and IgG anti-pneumococcal serum levels were measured. Results: Among the 110 participants enrolled, Antibody deficiencies with normal serum IgG levels were found in 11(10%) cases. IgA deficiency (3 cases), IgM deficiency (2 cases) and IgG2 deficiency (2 cases) were the most frequent primary immunodeficiencies. In addition, IgG2+IgA deficiency, Ataxia-telangiectasia, Hyper-IgE syndrome and Specific Antibody Deficiency(anti-polysaccharides) were found in one case each. Conclusions: Predominantly antibody deficiencies with normal IgG levels are an important etiology of non-cystic fibrosis bronchiectasis and recurrent pneumonia in adults.
Antecedentes: Los Errores Innatos de la Inmunidad principalmente las Deficiencias Predominantemente de anticuerpos con niveles normales de IgG no se conocen en adultos con enfermedades pulmonares como las bronquiectasias o la neumonía recurrente. Objetivo: Determinar las deficiencias de IgM, IgA y de subclase de IgG2 y la Deficiencia Específica de Anticuerpos (anticuerpos antineumocócicos de polisacáridos) en adultos con Bronquiectasias no Fibrosis Quística (BQnoFQ) o neumonía recurrente. Métodos: Estudio observacional prospectivo. Se reclutaron 110 pacientes consecutivos con BQnoFQ o neumonía recurrente en Cali, Colombia. Se midieron los niveles séricos de IgG, IgA, IgM e IgE, subclase IgG2 y anticuerpos anti-neumococo. Resultados: Se encontraron deficiencias de anticuerpos con niveles normales de IgG en el 10% de los sujetos; Cuatro casos con IgG2 baja, incluido 1 caso de deficiencia de IgG2 + IgA, 1 caso de ataxia-telangiectasia, 3 deficiencias de IgA (IgAD), 2 deficiencias selectiva de IgM (IgMD), 1 síndrome de Hiper-IgE (HIES-AR) y 1 deficiencia específica de anticuerpos. Ocho pacientes fueron diagnosticados con enfermedades relacionadas con la hipogammaglobulinemia IgG. Conclusiones: Las deficiencias predominantemente de anticuerpos con niveles normales de IgG son una etiología importante de BQnoFQ y neumonía recurrente en adultos. Los sujetos con bronquiectasias o neumonía recurrente requieren una evaluación exhaustiva de la respuesta inmune humoral y clínica.
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Bronquiectasia , Deficiencia de IgA , Deficiencia de IgG , Síndromes de Inmunodeficiencia , Neumonía , Adulto , Humanos , Estudios Transversales , Inmunoglobulina G , Inmunoglobulina M , Inmunoglobulina A , FibrosisRESUMEN
INTRODUCTION: In recent decades, there has been a growing increase in the diagnosis of patients with inborn errors of the immune system, formerly known as primary immunodeficiency disorders (PIDs). Timely diagnosis remains a challenge due to low clinical suspicion and poor education on the subject. It is estimated that between 70% and 90% of these pathologies remain underdiagnosed in our environment. OBJECTIVE: The objective of this study is to characterize the demographic and clinical presentation of pediatric group patients with inborn errors of the immune system in a Colombian tertiary hospital. METHODS: Retrospective descriptive study of 306 patients with a diagnosis of innate errors of the immune system who consulted the PID clinic between 2011 and 2018 in a high-complexity institution in Cali, Colombia. RESULTS: Three-hundred and six patients were included. The median age was 4 years (IQR 2.3-7.7 years), and 59.5% of the patients were male. According to the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency classification for inborn errors of the immune system, the most common group was antibody deficiency in 74.8% (nË229), especially in the age group between 1 and 5 years. The least frequent in our population was complement deficiency. Of the warning signs stipulated for these pathologies, the most frequent were the (1) need for intravenous antibiotics (32%), (2) difficulty growing (15.7%), (3) four or more episodes of ear infection (10.8%), and (4) abscesses in organs or cutaneous abscesses (12.7%). No patient reported two or more episodes of pneumonia or sinusitis, and only 5.8% of the patients received a bone marrow transplant. CONCLUSIONS: Innate errors of the immune system require an early diagnosis with follow-up from an early age to ensure adequate management and follow-up in order to reduce morbidity and mortality. It is imperative to sensitize the medical population about the existence of these pathologies so that early intervention can be carried out, which improves the quality of life of patients and their families.
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Absceso , Calidad de Vida , Niño , Preescolar , Colombia/epidemiología , Femenino , Humanos , Sistema Inmunológico , Lactante , Masculino , Estudios Retrospectivos , Centros de Atención TerciariaRESUMEN
Abstract Background: Inborn errors of immunity, mainly Predominantly Antibody deficiencies with normal IgG levels are unrecognized in adults with lung diseases such as bronchiectasis or recurrent pneumonia. Objective: To determine IgM, IgA, IgG2 subclass deficiencies, and Specific antibody deficiency (anti-pneumococcal polysaccharide antibodies) in adults with non-cystic fibrosis bronchiectasis or recurrent pneumonia. Methods: Cross-sectional study. Consecutive patients with non-cystic fibrosis bronchiectasis or recurrent pneumonia were recruited in Cali, Colombia. IgG, IgA, IgM, and IgE, IgG2subclass and IgG anti-pneumococcal serum levels were measured. Results: Among the 110 participants enrolled, Antibody deficiencies with normal serum IgG levels were found in 11(10%) cases. IgA deficiency (3 cases), IgM deficiency (2 cases) and IgG2 deficiency (2 cases) were the most frequent primary immunodeficiencies. In addition, IgG2+IgA deficiency, Ataxia-telangiectasia, Hyper-IgE syndrome and Specific Antibody Deficiency(anti-polysaccharides) were found in one case each. Conclusions: Predominantly antibody deficiencies with normal IgG levels are an important etiology of non-cystic fibrosis bronchiectasis and recurrent pneumonia in adults.
Resumen Antecedentes: Los Errores Innatos de la Inmunidad principalmente las Deficiencias Predominantemente de anticuerpos con niveles normales de IgG no se conocen en adultos con enfermedades pulmonares como las bronquiectasias o la neumonía recurrente. Objetivo: Determinar las deficiencias de IgM, IgA y de subclase de IgG2 y la Deficiencia Específica de Anticuerpos (anticuerpos antineumocócicos de polisacáridos) en adultos con Bronquiectasias no Fibrosis Quística (BQnoFQ) o neumonía recurrente. Métodos: Estudio observacional prospectivo. Se reclutaron 110 pacientes consecutivos con BQnoFQ o neumonía recurrente en Cali, Colombia. Se midieron los niveles séricos de IgG, IgA, IgM e IgE, subclase IgG2 y anticuerpos anti-neumococo. Resultados: Se encontraron deficiencias de anticuerpos con niveles normales de IgG en el 10% de los sujetos; Cuatro casos con IgG2 baja, incluido 1 caso de deficiencia de IgG2 + IgA, 1 caso de ataxia-telangiectasia, 3 deficiencias de IgA (IgAD), 2 deficiencias selectiva de IgM (IgMD), 1 síndrome de Hiper-IgE (HIES-AR) y 1 deficiencia específica de anticuerpos. Ocho pacientes fueron diagnosticados con enfermedades relacionadas con la hipogammaglobulinemia IgG. Conclusiones: Las deficiencias predominantemente de anticuerpos con niveles normales de IgG son una etiología importante de BQnoFQ y neumonía recurrente en adultos. Los sujetos con bronquiectasias o neumonía recurrente requieren una evaluación exhaustiva de la respuesta inmune humoral y clínica.
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RESUMEN Introducción: Las deficiencias predominantes de anticuerpos (DPA) cursan con disminución de niveles séricos de inmunoglobulinas (hipogammaglobulinemia), infecciones recurrentes y se ha reportado su asociación con las alergias. La información sobre su frecuencia en niños alérgicos es limitada y en Paraguay no existen datos al respecto. Objetivo: Detectar DPA y establecer su frecuencia en pacientes pediátricos con enfermedades alérgicas atendidos en un hospital de referencia del país. Materiales y métodos: Fueron evaluados 64 pacientes pediátricos (1 a 17 años de edad) con diagnóstico de alergia, atendidos en la Unidad Pediátrica Ambulatoria-Especialidad Asma, Alergia e Inmunología del Hospital de Clínicas (periodo 2018-2019). Se midieron los niveles séricos de IgA, IgG e IgM por el método de inmunodifusión radial y se aplicaron criterios de diagnóstico fenotípico a los casos de hipogammaglobulinemia para definir la DPA. Resultados: La mediana de edad fue de 5 años (RIQ: 2 - 8), con predominio del sexo masculino (58%). Las alergias más frecuentes fueron asma (38%) y rinitis (34%), además predominaron las infecciones respiratorias recurrentes (80%). La frecuencia de DPA fue de 17% (11/64), detectándose 6 casos de deficiencia de inmunoglobulina A, 4 deficiencias aisladas de IgG y una inmunodeficiencia común variable. No se observaron diferencias significativas al comparar características clínico-demográficas entre pacientes alérgicos con y sin DPA. Conclusiones: La frecuencia de DPA fue elevada, por lo que se sugiere considerar el estudio de inmunoglobulinas séricas en pacientes pediátricos con enfermedades alérgicas para una detección y tratamiento oportunos.
ABSTRACT Introduction: Predominant antibody deficiencies (PAD) present with decreased serum levels of immunoglobulins (hypogammaglobulinemia), recurrent infections and their association with allergies has been reported. Information on its frequency in allergic children is limited and in Paraguay there are no data in this regard. Objective: To detect PAD and establish its frequency in pediatric patients with allergic diseases treated at a reference hospital in the country. Materials and methods: 64 pediatric patients (1 to 17 years of age) with a diagnosis of allergy, treated in the Pediatric Outpatient Unidad Pediátrica Ambulatoria-Especialidad Asma of the Hospital de Clínicas (from 2018 to 2019) were evaluated. Serum levels of IgA, IgG and IgM were measured by the radial immunodiffusion method and phenotypic diagnostic criteria were applied to hypogammaglobulinemia cases to define PAD. Results: The median age was 5 years (IQR: 2 - 8), with a predominance of males (58%). The most frequent allergies were asthma (38%) and rhinitis (34%), and recurrent respiratory infections (80%) predominated. The frequency of PAD was 17% (11/64), with 6 cases of immunoglobulin A deficiency detected, 4 isolated IgG deficiencies and a common variable immunodeficiency were also detected. No significant differences were observed when comparing clinical-demographic characteristics between allergic patients with and without PAD. Conclusions: The frequency of PAD was high, so we suggest considering serum immunoglobulins studies in pediatric patients with allergic diseases for timely detection and treatment.
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Background: Patients with antibody deficiency may experience exceptionally long diagnostic delays, increasing the risk of life-threatening infections, end-organ damage, mortality, and health costs. Objective: This study aimed to analyze serum protein electrophoresis and verify the correlation between calculated globulin (CG, total protein minus albumin levels) or electrophoretically determined serum gamma globulin fraction (Gamma) with IgG levels in children and adolescents under 18 years old (yo). Methods: We analyzed serum protein electrophoresis (GC or Gamma) and IgG levels from 1215 children and adolescents under 18 yo, classified into 5 age groups. We verified the correlation between CG or Gamma with serum IgG levels. Results: Serum IgG levels varied according to age groups (from 4.3 ± 2.3 g/l in children under 6 months old to 11.4 ± 3.2 g/l in adolescents in the 10-<18 yo group). CG sensitivity and specificity to detect IgG below the reference range for all patients were 93.1% and 81.8%, respectively, and varied according to age group. Gamma sensitivity and specificity for all patients were 100% and 87.8%, respectively, and varied according to age group as well. We found serum IgG levels below the age reference level in 29 patients (2.4% of the cases) using CG or Gamma levels. Conclusion: Both CG and Gamma levels may be of utility as a screening tool for earlier diagnosis of antibody deficiency in children and adolescents under 18 yo.
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Anticuerpos/sangre , Electroforesis de las Proteínas Sanguíneas , Disgammaglobulinemia/diagnóstico , Tamizaje Masivo/métodos , Adolescente , Factores de Edad , Área Bajo la Curva , Brasil/epidemiología , Niño , Preescolar , Disgammaglobulinemia/sangre , Disgammaglobulinemia/epidemiología , Disgammaglobulinemia/inmunología , Femenino , Humanos , Deficiencia de IgA/sangre , Deficiencia de IgA/diagnóstico , Deficiencia de IgG/sangre , Deficiencia de IgG/diagnóstico , Inmunoglobulina M/sangre , Inmunoglobulina M/deficiencia , Lactante , Recién Nacido , Masculino , Curva ROC , Seroglobulinas/análisisRESUMEN
Se presenta una serie de casos de inmunodeficiencias primarias y se describen las variables asociadas a supervivencia en pacientes ≤ 16 años. Los diagnósticos fueron acordes a los criterios de la Unión Internacional de las Sociedades de Inmunología. Se realizó un análisis de supervivencia mediante curvas de Kaplan-Meier.Entre los años 2004 y 2019, se diagnosticaron 40 pacientes con inmunodeficiencias primarias. Las más frecuentes fueron inmunodeficiencias que afectaban la inmunidad celular y humoral, el 32,5 %, y deficiencias predominantemente de anticuerpos, el 32,5 %. La mediana de edad al inicio de los síntomas y al momento del diagnóstico fue de 3,01 y 10,4 meses, respectivamente. Fallecieron el 35 % y el riesgo fue mayor en pacientes con inmunodeficiencias que afectaban la inmunidad celular y humoral y en quienes presentaron manifestaciones clínicas y tuvieron el diagnóstico en los primeros seis meses de vida.
A case series of primary immunodeficiencies is presented and outcome measures associated with survival among patients ≤ 16 years old are described. Diagnoses were made based on the criteria by the International Union of Immunological Societies. Survival was analyzed using Kaplan-Meier curves.Between 2004 and 2019, 40 patients were diagnosed with primary immunodeficiencies. The most common were immunodeficiencies affecting humoral and cell-mediated immunity (32.5 %) and predominantly antibody deficiencies (32.5 %). The median age at the onset of symptoms and at the time of diagnosis was 3.01 and 10.4 months, respectively. Thirty-five percent of patients died, and the risk was higher among those with immunodeficiencies affecting humoral and cell-mediated immunity and those who developed clinical manifestations and were diagnosed in the first 6 months of life
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Humanos , Masculino , Femenino , Niño , Adolescente , Enfermedades de Inmunodeficiencia Primaria/epidemiología , Síndromes de Inmunodeficiencia/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Estudios Retrospectivos , Inmunodeficiencia Combinada Grave/epidemiología , Enfermedades de Inmunodeficiencia Primaria/diagnóstico , Enfermedades de Inmunodeficiencia Primaria/terapia , Hospitales Públicos , Sistema Inmunológico , Síndromes de Inmunodeficiencia/diagnóstico , Infecciones/epidemiología , MéxicoRESUMEN
A case series of primary immunodeficiencies is presented and outcome measures associated with survival among patients ≤ 16 years old are described. Diagnoses were made based on the criteria by the International Union of Immunological Societies. Survival was analyzed using Kaplan-Meier curves. Between 2004 and 2019, 40 patients were diagnosed with primary immunodeficiencies. The most common were immunodeficiencies affecting humoral and cell-mediated immunity (32.5 %) and predominantly antibody deficiencies (32.5 %). The median age at the onset of symptoms and at the time of diagnosis was 3.01 and 10.4 months, respectively. Thirty-five percent of patients died, and the risk was higher among those with immunodeficiencies affecting humoral and cell-mediated immunity and those who developed clinical manifestations and were diagnosed in the first 6 months of life.
Se presenta una serie de casos de inmunodeficiencias primarias y se describen las variables asociadas a supervivencia en pacientes ≤ 16 años. Los diagnósticos fueron acordes a los criterios de la Unión Internacional de las Sociedades de Inmunología. Se realizó un análisis de supervivencia mediante curvas de Kaplan-Meier. Entre los años 2004 y 2019, se diagnosticaron 40 pacientes con inmunodeficiencias primarias. Las más frecuentes fueron inmunodeficiencias que afectaban la inmunidad celular y humoral, el 32,5 %, y deficiencias predominantemente de anticuerpos, el 32,5 %. La mediana de edad al inicio de los síntomas y al momento del diagnóstico fue de 3,01 y 10,4 meses, respectivamente. Fallecieron el 35 % y el riesgo fue mayor en pacientes con inmunodeficiencias que afectaban la inmunidad celular y humoral y en quienes presentaron manifestaciones clínicas y tuvieron el diagnóstico en los primeros seis meses de vida.
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Síndromes de Inmunodeficiencia , Enfermedades de Inmunodeficiencia Primaria , Adolescente , Niño , Hospitales Públicos , Humanos , Síndromes de Inmunodeficiencia/diagnóstico , Síndromes de Inmunodeficiencia/epidemiología , México/epidemiologíaRESUMEN
Abstract Objective: This minireview gathers the scientific foundations of the literature on genetic errors in the development of the humoral immune system to help pediatricians suspect these defects. Sources: A systemic search using the PubMed MEDLINE database was performed for all Predominantly Antibody Deficiencies (PADs) described in the 2020 IUIS Expert Committee for PID classification system, combined with terms for hypogammaglobulinemia. Search terms for PADs were based on the listed names and affected genes as classified by the IUIS 2020. Abstracts of the results were reviewed to find relevant case series, review articles of PADs associated with infection, opportunistic infection, autoimmunity, cytopenias, malignancies, inflammatory diseases, neurological and respiratory diseases. References from relevant articles were further reviewed for additional references. Relevant findings were grouped in accordance with the IUIS 2020 classification system. Clinical and genetic features, if known, were described. Data synthesis: PADs refer to impaired antibody production due to molecular defects intrinsic to B cells or a failure of interaction between B and T cells. The patients develop recurrent or chronic infection or respond to the antigens with dysregulation of the immune function, causing severe allergy, autoimmunity, inflammation, lymphoproliferation and malignancy. The diagnosis is a combined exercise of clinical and laboratory investigation similar to that performed by Bruton (1952). In the context of SARS-CoV-2 infection, the experience of XLA and CVID patients has been surprising. Variants in 39 genes were reported as causing PADs, but the clinical heterogeneity within each variant is not clear. Conclusion: Bruton (1952) used clinical expertise and protein electrophoresis to identify XLA. The IUIS (2020) committee used immunoglobulins and B lymphocyte to characterize PADs. Pediatricians should suspect it to detect it and prevent morbidities that can have an astonishing and irreversible impact on the child's life.
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Humanos , Niño , COVID-19 , Infecciones , Inmunoglobulinas , SARS-CoV-2 , InflamaciónRESUMEN
OBJECTIVE: This minireview gathers the scientific foundations of the literature on genetic errors in the development of the humoral immune system to help pediatricians suspect these defects. SOURCES: A systemic search using the PubMed MEDLINE database was performed for all Predominantly Antibody Deficiencies (PADs) described in the 2020 IUIS Expert Committee for PID classification system, combined with terms for hypogammaglobulinemia. Search terms for PADs were based on the listed names and affected genes as classified by the IUIS 2020. Abstracts of the results were reviewed to find relevant case series, review articles of PADs associated with infection, opportunistic infection, autoimmunity, cytopenias, malignancies, inflammatory diseases, neurological and respiratory diseases. References from relevant articles were further reviewed for additional references. Relevant findings were grouped in accordance with the IUIS 2020 classification system. Clinical and genetic features, if known, were described. DATA SYNTHESIS: PADs refer to impaired antibody production due to molecular defects intrinsic to B cells or a failure of interaction between B and T cells. The patients develop recurrent or chronic infection or respond to the antigens with dysregulation of the immune function, causing severe allergy, autoimmunity, inflammation, lymphoproliferation and malignancy. The diagnosis is a combined exercise of clinical and laboratory investigation similar to that performed by Bruton (1952). In the context of SARS-CoV-2 infection, the experience of XLA and CVID patients has been surprising. Variants in 39 genes were reported as causing PADs, but the clinical heterogeneity within each variant is not clear. CONCLUSION: Bruton (1952) used clinical expertise and protein electrophoresis to identify XLA. The IUIS (2020) committee used immunoglobulins and B lymphocyte to characterize PADs. Pediatricians should suspect it to detect it and prevent morbidities that can have an astonishing and irreversible impact on the child's life.
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COVID-19 , Infecciones , Niño , Humanos , Inmunoglobulinas , Inflamación , SARS-CoV-2RESUMEN
Background: Primary immunodeficiencies (PIDs) are rare genetic disorders leading to immunologic abnormalities that can affect different organs and systems. We determined the epidemiology, clinical, and geospatial characteristics of PID disorders among patients diagnosed over a 5 year period in a reference hospital covering a mesoregion in São Paulo, Brazil. Methods: A retrospective analysis of 39 patients with recognizable PIDs according to the criteria of the European Society of Primary Immunodeficiencies were enrolled. Thirty-four patients came from outpatient immunodeficiency clinics and five patients from active search. Demographic, clinical, and immunologic data were collected, and maps were constructed using a geographic information system. Results: The ratio of females to males was 1.4:1, and 48.7% of patients were younger than 17 years of age. The mean age at the onset of symptoms in children was 2.0 years [standard error of the mean (SEM), 1.7 years] and the diagnosis lag was 5.1 years (SEM, 3.1 years); the mean age at diagnosis in adults was 16.3 years (SEM, 11.8 years) and the lag was 10.8 years (SEM, 10.9 years). Antibody deficiency and common variable immunodeficiencies were the most common categories and phenotypes, respectively. The need for intravenous antibiotics and respiratory tract infections were the most prevalent warning signs, with an overall mortality rate of 15.3%. Autoimmune diseases were diagnosed in 56.4% and visceral leishmaniasis in 5.1% of patients. In the active search, 29 patients were investigated and 17.2% were diagnosed; early diagnosis, the involvement of multidisciplinary professionals, and dissemination of knowledge achieved milestone benefits. The distribution of PID networks in Brazil shows great asymmetry between regions and at a regional level; it was shown that the patients lived mainly in Presidente Prudente municipality. Conclusions: The implementation of an immunodeficiency outpatient clinic in a referral hospital covering a mesoregion with a large population has led to the generation of policies and practices to improve the diagnosis, quality of life, and care of patients with PIDs and their families. Furthermore, the search for hospitalized patients with warning signs for PIDs showed great benefits. Inequality in the distribution of PID network centers in Brazil was demonstrated.
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Síndromes de Inmunodeficiencia/epidemiología , Síndromes de Inmunodeficiencia/fisiopatología , Adolescente , Adulto , Brasil/epidemiología , Niño , Preescolar , Diagnóstico Precoz , Femenino , Geografía , Humanos , Síndromes de Inmunodeficiencia/diagnóstico , Lactante , Masculino , Persona de Mediana Edad , Calidad de Vida , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE: Poliovirus has been nearly eliminated as part of a world-wide effort to immunize and contain circulating wild-type polio. Nevertheless, poliovirus has been detected in water supplies and represents a threat to patients with humoral immunodeficiencies where infection can be fatal. To define the risk, we analyzed antibodies to poliovirus 1, 2, and 3 in serum samples collected over a year from patients with primary immunodeficiency diseases (PID) on regular intravenous immunoglobulin (IVIG) replacement. METHODS: Twenty-one patients on regular IVIG replacement therapy were evaluated: Twelve patients with common variable immune deficiency (CVID), six with X-linked agammaglobulinemia (XLA), and three with hyper IgM syndrome (HIGM). Over 1 year, four blood samples were collected from each of these patients immediately before immunoglobulin infusion. One sample of IVIG administered to each patient in the month before blood collection was also evaluated. Poliovirus antibodies were quantified by seroneutralization assay. RESULTS: All IVIG samples had detectable antibodies to the three poliovirus serotypes. Despite that, only 52.4, 61.9, and 19.0% of patients showed protective antibody titers for poliovirus 1, 2, and 3, respectively. Only two patients (9.5%) had protective antibodies for the three poliovirus serotypes on all samples. Most patients were therefore susceptible to all three poliovirus serotypes. CONCLUSIONS: This study demonstrates the need for ongoing vigilance regarding exposure of patients with PID to poliovirus in the community.
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Anticuerpos Antivirales/inmunología , Inmunoglobulinas Intravenosas/uso terapéutico , Síndromes de Inmunodeficiencia/tratamiento farmacológico , Síndromes de Inmunodeficiencia/inmunología , Poliovirus/inmunología , Adolescente , Adulto , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Niño , Preescolar , Femenino , Humanos , Síndromes de Inmunodeficiencia/sangre , Síndromes de Inmunodeficiencia/diagnóstico , Masculino , Persona de Mediana Edad , Poliovirus/clasificación , Estudios Prospectivos , Serogrupo , Resultado del Tratamiento , Adulto JovenRESUMEN
La deficiencia de anticuerpos específicos con inmunoglobulinas séricas y linfocitos B normales (SAD) es una inmunodeficiencia primaria caracterizada por una capacidad alterada de responder a antígenos específicos, especialmente polisacáridos. OBJETIVO: Describir las características clínicas de pacientes con SAD y destacar la asociación entre una inmunodeficiencia primaria y enfermedades alérgicas. Pacientes y Método: Estudio descriptivo en enfermos con SAD atendidos en un hospital público entre agosto de 2007 y julio de 2015. Se descartó otra inmunodeficiencia primaria o secundaria. El diagnóstico se basó en infecciones recurrentes y una respuesta anormal a la vacuna neumocócica polisacárida con medición de IgG específica para 10 serotipos de neumococo. RESULTADOS: Se incluyeron 12 pacientes, 4 varones, con una edad promedio de 6 años; predominaron las neumonías recurrentes (91,7%) y otras infecciones respiratorias e invasivas. Los 12 enfermos con SAD tenían asma asociada; 11, rinitis alérgica y otras alergias. Tres pacientes no respondieron a ninguno de los 10 serotipos contenidos en la vacuna neumocócica polisacárida y la mayoría de los que lo hicieron fue a títulos bajos. El tratamiento con vacuna neumocócica conjugada fue favorable en 11/12 enfermos. CONCLUSIÓN: En niños mayores de 2 años con infecciones respiratorias recurrentes o infecciones invasivas por S. pneumoniae con inmunoglobulinas normales recomendamos investigar SAD, más aún si tienen enfermedad alérgica asociada.
Specific antibody deficiency (SAD) with normal immunoglobulin and normal B cells is a primary immunodeficiency characterized by reduced ability to produce antibodies to specific antigens especially polysaccharides. OBJECTIVE: To describe the characteristics of patients diagnosed with SAD emphasizing the association between primary immunodeficiency and allergic diseases. PATIENTS AND METHOD: Descriptive study showing patients with SAD treated at a public hospital between August 2007 and July 2015. Other secondary or primary immunodeficiency was discarded. The diagnosis of SAD was based on recurrent infections and abnormal response to pneumococcal polysaccharide vaccine assessed by specific IgG to 10 pneumococcal serotypes. Results: Twelve patients were included, 4 males, mean age 6 years, recurrent pneumonia predominated (91.7%) as well as other respiratory and invasive infections. All patients with SAD had associated asthma, 11 had allergic rhinitis, and other allergies. Three patients did not respond to any of the 10 serotypes contained in pneumococcal polysaccharide vaccine, and those who responded were with low titers. Treatment with conjugate pneumococcal vaccine was favorable in 11/12 patients. CONCLUSION: In children older than 2 years with recurrent respiratory infections or invasive S. pneumoniae infections with normal immunoglobulin we recommend to investigate SAD, especially if they have a concurrent allergic disease.
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Asma/complicaciones , Rinitis Alérgica/complicaciones , Síndromes de Inmunodeficiencia/diagnóstico , Asma/inmunología , Rinitis Alérgica/inmunología , Síndromes de Inmunodeficiencia/complicaciones , Síndromes de Inmunodeficiencia/inmunologíaRESUMEN
BACKGROUND: IgA deficiency is the most common primary immunodeficiency. Early diagnosis and clinical follow-up may improve the quality of life of patients with IgA deficiency. To this end, IgA deficiency should be further studied and better understood on its clinical manifestations. OBJECTIVE: To determine IgA deficiency clinical manifestations. METHODS: Cross-sectional, retrospective, exploratory study, where the medical records of 39 patients with IgA deficiency were analyzed. RESULTS: Among the analyzed cases, 10 patients were diagnosed with total IgA deficiency and 29 patients with partial IgA deficiency. Partial and total IgA deficiency main clinical manifestations were allergic rhinoconjunctivitis and allergic asthma. In total IgA deficiency, in addition to allergic diseases, a statistically significant number (p < 0.05) of cases of infection-related rhinosinusitis, tonsillitis and conjunctivitis were also observed. CONCLUSION: This study showed that the main clinical manifestations in IgA deficiency were allergic rhinoconjunctivitis and allergic asthma. In addition, patients with total IgA deficiency showed a significant increase in infection-related rhinosinusitis, tonsillitis and conjunctivitis, when compared with patients with partial IgA deficiency.
Antecedentes: La deficiencia de inmunoglobulina A (IgA) es la inmunodeficiencia primaria más frecuente. El diagnóstico oportuno y el seguimiento clínico pueden mejorar la calidad de vida de los portadores. Para ello, deben estudiarse y entenderse las manifestaciones clínicas de este trastorno. Objetivo: Determinar las manifestaciones clínicas de la deficiencia de IgA. Métodos: Estudio transversal, retrospectivo, exploratorio, realizado mediante análisis de expedientes de 39 pacientes con deficiencia de IgA. Resultados: De los pacientes analizados, 10 fueron diagnosticados con deficiencia total de IgA y 29 con deficiencia parcial. Las principales manifestaciones clínicas fueron rinoconjuntivitis y asma alérgicas. En los pacientes con deficiencia total de IgA, además de las enfermedades alérgicas se observó un mayor número de cuadros infecciosos de rinosinusitis, amigdalitis y conjuntivitis (p < 0.05). Conclusión: En el presente estudio, las principales manifestaciones clínicas de la deficiencia de IgA fueron los cuadros alérgicos de rinoconjuntivitis y el asma; además, los pacientes portadores de deficiencia total de IgA presentaron aumento significativo de cuadros infecciosos de rinosinusitis, amigdalitis y conjuntivitis, comparados con los pacientes con deficiencia parcial de IgA.
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Deficiencia de IgA/diagnóstico , Adolescente , Adulto , Asma/etiología , Niño , Preescolar , Conjuntivitis Alérgica/etiología , Estudios Transversales , Dimerización , Diagnóstico Precoz , Femenino , Humanos , Deficiencia de IgA/complicaciones , Inmunoglobulina A/química , Masculino , Estudios Retrospectivos , Rinitis/etiología , Evaluación de Síntomas , Tonsilitis/etiología , Adulto JovenRESUMEN
BACKGROUND: This is a prospective study that assessed pneumococcal antibody levels in PID patients under intravenous immunoglobulin (IVIG) treatment using different brands. METHODS: Twenty-one patients receiving regular IVIG every 28 days were invited to participate: 12 with common variable immunodeficiency, six with X-linked agammaglobulinaemia and three with hyper-IgM syndrome. One blood sample was collected from each patient just prior to IVIG administration at a three-month time interval during one year. A questionnaire was filled in with patient's demographic data and history of infections during the study period. Streptococcus pneumoniae antibodies against six serotypes (1, 5, 6B, 9V, 14 and 19F) were assessed by ELISA both in patients' serum (trough levels) and in IVIG samples. RESULTS: Median total IgG trough serum levels were 7.91g/L (range, 4.59-12.20). All patients had antibody levels above 0.35µg/mL to the six serotypes on all four measurements. However, only 28.6% of patients had pneumococcal antibodies for the six analysed serotypes above 1.3µg/mL on all four evaluations during the one-year period. No correlation was found between IgG trough levels and pneumococcal specific antibodies. Eighteen of the 21 patients (85.7%) had infections at some point during the 12-month follow-up, 62/64 (96.9%) clinically classified in respiratory tract infections, four of which were pneumonia. CONCLUSIONS: Pneumococcal antibodies are present in a high range of concentrations in sera from PID patients and also in IVIG preparations. Even maintaining a recommended IgG trough level, these patients can be susceptible to these bacteria and that may contribute to recurrent respiratory infections.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Inmunoglobulinas Intravenosas/uso terapéutico , Síndromes de Inmunodeficiencia/inmunología , Neumonía Neumocócica/inmunología , Streptococcus pneumoniae/inmunología , Adolescente , Adulto , Brasil , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulina G/sangre , Síndromes de Inmunodeficiencia/terapia , Masculino , Neumonía Neumocócica/terapia , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: To analyse specific immune response to the 23-valent pneumococcal polysaccharide vaccine by measuring pneumococcal antibodies in children with asthma and with respiratory recurrent infection (RRI) as compared to healthy children. METHODS: The study included 60 children, divided into three groups: 20 with asthma, 20 with RRI, and 20 healthy controls. Post-vaccination specific IgG antibodies against 10 pneumococcal serotypes (S1, S3, S4, S5, S6B, S9V, S14, S18C, S19F, and S23F) contained in the 23-valent pneumococcal polysaccharide vaccine (PPV) were measured. A specific IgG concentration ≥1.3µg/mL was considered a protective response to the vaccine. For statistical analysis, levels of specific IgG antibodies against each of the 10 pneumococcal serotypes were compared across the three groups of children using the x(2) test. RESULTS: All of the children showed antipneumococcal antibody levels >1.3µg/mL for over 70% of the serotypes, considered within the normal range of response. Average IgG antibody levels and percentages of children protected were statistically comparable among the three groups studied. CONCLUSION: The asthmatic children without RRI had pneumococcal antibody levels and percentages of serotype-specific protection to PPV comparable to those of healthy children. Asthmatic children with recurrent infections should be evaluated for specific antibody deficiency (SAD). Because asthma patients are at high risk for invasive pneumococcal infections, it would be worthwhile to explore systematic administration of PPV in children over the age of two years who have not received a pneumococcal conjugate vaccine, considering the positive response to PPV reported here.
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Anticuerpos Antibacterianos/sangre , Asma/inmunología , Vacunas Neumococicas/inmunología , Infecciones del Sistema Respiratorio/inmunología , Streptococcus pneumoniae/inmunología , Adolescente , Asma/sangre , Niño , Preescolar , Chile , Femenino , Voluntarios Sanos , Humanos , Inmunoglobulina G/sangre , Síndromes de Inmunodeficiencia/diagnóstico , Masculino , Vacunas Neumococicas/administración & dosificación , Estudios Prospectivos , Infecciones del Sistema Respiratorio/sangre , VacunaciónRESUMEN
Selective IgA deficiency (SIgAD) is the most prevalent immunodeficiency worldwide, progressing to common variable immunodeficiency only in few reported cases. We report the case of a Spanish female aged 22 and diagnosed of selective IgA deficiency, a long history of bronchitis, several episodes of pneumonia, bilateral bronchiectasis, normal IgG, IgM, IgG subclasses, and detectable pre-vaccination IgG antibodies against tetanus toxoid and Streptococcus pneumoniae. She was evaluated in our clinic in order to rule out common variable immunodeficiency. We observed good antibody response to tetanus toxoid, absence of circulating switched memory B cells, decreased response to pneumococcal polysaccharide antigens and a lack of response to Salmonella typhi vaccine. Most SIgAD patients presents with upper respiratory tract infections or mild diarrhea. Those with lower tract infections, pneumonia or untreatable diarrhea should follow B-cell subpopulations' study and antibody response to vaccines. Absence of response to Salmonella typhi vaccine allowed us to expose the defective antibody production.
La deficiencia selectiva de IgA es la inmunodeficiencia con mayor prevalencia en todo el mundo, con manifestación desde asintomática hasta infecciones repetidas en las mucosas. Entre los pacientes sintomáticos, algunos muestran progresión a inmunodeficiencia común variable. Describimos el caso de una paciente española de 22 años de edad, con diagnóstico de deficiencia selectiva de IgA, con normalidad en el resto de isotipos y un largo antecedente personal de bronquitis de repetición, varios episodios de neumonía y bronquiectasias bilaterales. En el estudio realizado observamos respuesta óptima tras la vacunación contra el toxoide tetánico, respuesta disminuida a la vacuna neumocócica polisacárida de 23 serotipos y ausencia de respuesta a la vacuna polisacárida de Salmonella typhi. La administración de la vacuna contra Salmonella typhi permitió demostrar producción deficiente de anticuerpos específicos en una paciente inicialmente diagnosticada como deficiencia selectiva de IgA.