RESUMO
CD40 ligand (CD40L) deficiency is a rare inborn error of immunity presenting with heterogeneous clinical manifestations. While a detailed characterization of patients affected by CD40L deficiency is essential to an accurate diagnosis and management, information about this disorder in Latin American patients is limited. We retrospectively analyzed data from 50 patients collected by the Latin American Society for Immunodeficiencies registry or provided by affiliated physicians to characterize the clinical, laboratory, and molecular features of Latin American patients with CD40L deficiency. The median age at disease onset and diagnosis was 7 months and 17 months, respectively, with a median diagnosis delay of 1 year. Forty-seven patients were genetically characterized revealing 6 novel mutations in the CD40LG gene. Pneumonia was the most common first symptom reported (66%). Initial immunoglobulin levels were variable among patients. Pneumonia (86%), upper respiratory tract infections (70%), neutropenia (70%), and gastrointestinal manifestations (60%) were the most prevalent clinical symptoms throughout life. Thirty-five infectious agents were reported, five of which were not previously described in CD40L deficient patients, representing the largest number of pathogens reported to date in a cohort of CD40L deficient patients. The characterization of the largest cohort of Latin American patients with CD40L deficiency adds novel insights to the recognition of this disorder, helping to fulfill unmet needs and gaps in the diagnosis and management of patients with CD40L deficiency.
Assuntos
Ligante de CD40 , Síndromes de Imunodeficiência , Ligante de CD40/genética , Estudos de Coortes , Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/terapia , América Latina/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Severe combined immunodeficiency (SCID) is a syndrome characterized by profound T-cell deficiency. BCG vaccine is contraindicated in patients with SCID. Because most countries encourage BCG vaccination at birth, a high percentage of patients with SCID are vaccinated before their immune defect is detected. OBJECTIVES: We sought to describe the complications and risks associated with BCG vaccination in patients with SCID. METHODS: An extensive standardized questionnaire evaluating complications, therapeutics, and outcomes regarding BCG vaccination in patients given a diagnosis of SCID was widely distributed. Summary statistics and association analysis was performed. RESULTS: Data on 349 BCG-vaccinated patients with SCID from 28 centers in 17 countries were analyzed. Fifty-one percent of the patients had BCG-associated complications, 34% disseminated and 17% localized (a 33,000- and 400-fold increase, respectively, over the general population). Patients receiving early vaccination (≤1 month) showed an increased prevalence of complications (P = .006) and death caused by BCG-associated complications (P < .0001). The odds of experiencing complications among patients with T-cell numbers of 250/µL or less at diagnosis was 2.1 times higher (95% CI, 1.4-3.4 times higher; P = .001) than among those with T-cell numbers of greater than 250/µL. BCG-associated complications were reported in 2 of 78 patients who received antimycobacterial therapy while asymptomatic, and no deaths caused by BCG-associated complications occurred in this group. In contrast, 46 BCG-associated deaths were reported among 160 patients treated with antimycobacterial therapy for a symptomatic BCG infection (P < .0001). CONCLUSIONS: BCG vaccine has a very high rate of complications in patients with SCID, which increase morbidity and mortality rates. Until safer and more efficient antituberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications.
Assuntos
Vacina BCG/efeitos adversos , Imunodeficiência Combinada Severa/epidemiologia , Vacina BCG/imunologia , Pré-Escolar , Comorbidade , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Prevalência , Estudos Retrospectivos , Risco , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/terapia , Vacinação/efeitos adversos , Vacinação/legislação & jurisprudênciaRESUMO
Down syndrome, or trisomy 21, has a higher mortality than the general population, mainly due to respiratory tract infections. The objective of this study was to describe immune compromise in a series of cases of patients with Down syndrome referred to the Pediatric Immunology Section due to recurrent infections or pathological laboratory findings between 6/1/2016 and 5/31/2022. Here we describe immune compromise in 24 patients. Twelve patients failed to develop a polysaccharide response and received antibiotic chemoprophylaxis, or gamma globulin replacement therapy. Three patients developed agammaglobulinemia with presence of B cells and gamma globulin replacement therapy was indicated. Nine patients had T-cell lymphopenia and 1 patient, combined immune compromise.
El síndrome de Down, o trisomía 21, tiene una mortalidad mayor que la población general, debido principalmente a infecciones respiratorias. El objetivo de este trabajo es describir el compromiso inmunológico en una serie de casos de pacientes con síndrome de Down derivados a Inmunología por infecciones recurrentes o por hallazgo patológico de laboratorio, entre el 1 de junio de 2016 y el 31 de mayo de 2022. Se describe el compromiso de la inmunidad en 24 pacientes. Doce pacientes presentaron falla de respuesta a polisacáridos y recibieron quimioprofilaxis antibiótica y/o gammaglobulina sustitutiva. En 3 pacientes, se observó agammaglobulinemia con linfocitos B presentes y se indicó gammaglobulina sustitutiva. En 9 pacientes, se observó linfopenia T y en 1 paciente, compromiso inmune combinado.
Assuntos
Síndrome de Down , Infecções Respiratórias , Criança , Humanos , Síndrome de Down/complicações , Imunoglobulinas Intravenosas/uso terapêutico , Antibacterianos/uso terapêutico , gama-GlobulinasRESUMO
BACKGROUND AND OBJECTIVE: IgG replacement therapy (IgG-RT) has radically changed the clinical evolution of primary immunodeficiencies, yet the information regarding secondary hypogammaglobulinemia (SHG) is insufficient or conflicting. We aim to describe clinical features, evolution and treatment of SHG patients in our center. METHODS: Dynamic retrospective cohort between January 2001 and July 2021 of adults with gamma globulin fraction <0.6g/dL in a serum protein electrophoresis and a coincident decrease of IgG levels - with a disease-related SHG or treatment that reduces serum immunoglobulins. RESULTS: We included 1012 patients with SHG with a median follow-up of 5 years (IQR 2-8). Hematological diseases were identified in 95% of the patients and 61% received drugs related to SHG. Sixty five percent had more than one etiological factor associated with SHG. Infectious diseases were present in 69% of the patients, 48% had respiratory infections and 17% had severe infections. There was statistical association between respiratory and severe infections with multiple myeloma (MM), lymphoma and rituximab. MGUS had less infections and death compared with other etiologies. IgG-RT was indicated in 18.7% of the patients and 4.6% received it for more than 6 months with variable intervals. Among the latter group, there was a significant reduction of all-type infections and respiratory infections with IgG-RT (p<0.001), and it was consistent with similar findings in lymphoma, MM and all IgG levels subgroups. CONCLUSION: SHG was associated with more than one etiological factor and a high frequency of infections. IgG-RT indication was irregular yet still effective. It is relevant to consider IgG levels screening, monitoring and accurate indication of IgG-RT.
Assuntos
Agamaglobulinemia , Imunodeficiência de Variável Comum , Linfoma , Infecções Respiratórias , Adulto , Humanos , Imunoglobulina G , Estudos Retrospectivos , Agamaglobulinemia/complicações , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/epidemiologia , Imunodeficiência de Variável Comum/complicações , Infecções Respiratórias/complicações , Infecções Respiratórias/epidemiologia , Linfoma/tratamento farmacológicoRESUMO
Inborn errors of immunity (IEI) are a heterogeneous group of hereditary disorders that affect in number and/or function different components of the immune system, resulting in an increased risk and severity of infections, autoimmune diseases, allergic manifestations, autoinflammation and malignancy. Inactivated vaccines are generally safe in these patients, but may be ineffective in some cases, due to difference in immunogenicity. However, live viral and bacterial vaccines may lead to disease, with high morbidity and mortality, so it is essential a previous immunological work-out. In this document, the Pediatric Immunology Work Group of the Sociedad Argentina de Pediatría summarizes recommendations about immunizations in patients with IEI, their household contacts, as well as in patients under immunosuppressive treatment and hematopoietic stem cell transplant recipients.
Los errores innatos de la inmunidad (EII) constituyen un grupo heterogéneo de enfermedades hereditarias que afectan el número y/o la función de los distintos componentes del sistema inmune, lo que predispone a un incremento de la tasa y gravedad de infecciones, enfermedades autoinmunes, manifestaciones alérgicas, autoinflamación y malignidad. En estos pacientes, la inmunización con vacunas inactivadas es generalmente segura, pero puede no ser efectiva en determinados grupos de EII, sin generar el efecto protector deseado. La aplicación de vacunas vivas atenuadas (virales y bacterianas) puede llevar al desarrollo de enfermedad asociada a la inmunización, con elevada morbimortalidad, por lo que amerita previamente consultar al especialista. El presente informe resume las conclusiones del Grupo de Trabajo de Inmunología de la Sociedad Argentina de Pediatría respecto a la vacunación en pacientes con EII y sus convivientes, en pacientes bajo inmunosupresión farmacológica y en receptores de trasplante de células precursoras hematopoyéticas.
RESUMO
Inborn errors of immunity, previously named primary immunodeficiency are a heterogeneous group of genetic defects of different components of the immune system. Patients present high susceptibility to an only or several microorganisms, developing recurrent infections; the severity is related to the specific genetic type of immunity defect. The main strategy on the management of these illness is the prevention of infections. These consensus guidelines made by the Pediatric Immunology Work Group of Sociedad Argentina de Pediatría, givese main approaches of infection prevention in order to provide a useful tool for all practitioners who are involved in the management of these patients, based on scientific evidence and broad consensus of a specialized panel expert..
Los errores innatos de la inmunidad (EII), antes llamados inmunodeficiencias primarias (IDP), son un grupo heterogéneo de trastornos genéticos con defectos en uno o más componentes del sistema inmune. Los pacientes afectados por EII presentan aumentada susceptibilidad a microorganismos únicos o múltiples que se manifestará con infecciones recurrentes de diferente tipo y gravedad dependiendo del tipo de la localización del defecto. La prevención de infecciones es uno de los pilares fundamentales en el abordaje integral de los pacientes con EII. En este trabajo se resumen las conclusiones consensuadas en el Grupo de Trabajo de Inmunología Pediátrica de la Sociedad Argentina de Pediatría, sobre la base de la revisión de la evidencia disponible, respecto a los principios esenciales para el cuidado, la prevención de infecciones y la quimioprofilaxis en los errores innatos de la inmunidad para la orientación del pediatra y especialista dedicados al seguimiento de estas enfermedades.
Assuntos
Quimioprevenção , Criança , Humanos , ArgentinaRESUMO
El síndrome de Down, o trisomía 21, tiene una mortalidad mayor que la población general, debido principalmente a infecciones respiratorias. El objetivo de este trabajo es describir el compromiso inmunológico en una serie de casos de pacientes con síndrome de Down derivados a Inmunología por infecciones recurrentes o por hallazgo patológico de laboratorio, entre el 1 de junio de 2016 y el 31 de mayo de 2022. Se describe el compromiso de la inmunidad en 24 pacientes. Doce pacientes presentaron falla de respuesta a polisacáridos y recibieron quimioprofilaxis antibiótica y/o gammaglobulina sustitutiva. En 3 pacientes, se observó agammaglobulinemia con linfocitos B presentes y se indicó gammaglobulina sustitutiva. En 9 pacientes, se observó linfopenia T y en 1 paciente, compromiso inmune combinado.
Down syndrome, or trisomy 21, has a higher mortality than the general population, mainly due to respiratory tract infections. The objective of this study was to describe immune compromise in a series of cases of patients with Down syndrome referred to the Pediatric Immunology Section due to recurrent infections or pathological laboratory findings between 6/1/2016 and 5/31/2022. Here we describe immune compromise in 24 patients. Twelve patients failed to develop a polysaccharide response and received antibiotic chemoprophylaxis, or gamma globulin replacement therapy. Three patientsdeveloped agammaglobulinemia with presence of B cells and gamma globulin replacement therapy was indicated. Nine patients had T-cell lymphopenia and 1 patient, combined immune compromise.
Assuntos
Humanos , Lactente , Pré-Escolar , Criança , Adolescente , Infecções Respiratórias , Síndrome de Down/complicações , gama-Globulinas , Imunoglobulinas Intravenosas/uso terapêutico , Antibacterianos/uso terapêuticoRESUMO
Los errores innatos de la inmunidad (EII), antes llamados inmunodeficiencias primarias (IDP), son un grupo heterogéneo de trastornos genéticos con defectos en uno o más componentes del sistema inmune. Los pacientes afectados por EII presentan aumentada susceptibilidad a microorganismos únicos o múltiples que se manifestará con infecciones recurrentes de diferente tipo y gravedad dependiendo del tipo de la localización del defecto. La prevención de infecciones es uno de los pilares fundamentales en el abordaje integral de los pacientes con EII. En este trabajo se resumen las conclusiones consensuadas en el Grupo de Trabajo de Inmunología Pediátrica de la Sociedad Argentina de Pediatría, sobre la base de la revisión de la evidencia disponible, respecto a los principios esenciales para el cuidado, la prevención de infecciones y la quimioprofilaxis en los errores innatos de la inmunidad para la orientación del pediatra y especialista dedicados al seguimiento de estas enfermedades.
Inborn errors of immunity, previously named primary immunodeficiency are a heterogeneous group of genetic defects of different components of the immune system. Patients present high susceptibility to an only or several microorganisms, developing recurrent infections; the severity is related to the specific genetic type of immunity defect. The main strategy on the management of these illness is the prevention of infections. These consensus guidelines made by the Pediatric Immunology Work Group of Sociedad Argentina de Pediatría, givese main approaches of infection prevention in order to provide a useful tool for all practitioners who are involved in the management of these patients, based on scientific evidence and broad consensus of a specialized panel expert.
Assuntos
Humanos , Criança , Quimioprevenção , Doenças do Sistema Imunitário/congênitoRESUMO
The block in differentiation from pro-B to pre-B cells results in a selective defect in the humoral immune response characteristic of human X-linked agammaglobulinemia (XLA). Mutations of Bruton tyrosine kinase (BTK) gene have been identified as the cause of XLA. Mutation detection is the most reliable method for making a definitive diagnosis, except when clinical and laboratory findings are distinctive and coupled with history of X-linked inheritance. To provide a definitive diagnosis to 40 families incorporated in the Argentinian Primary Immunodeficiencies Registry we analysed the BTK gene by SSCP analysis as screening method for XLA, followed by direct sequencing. The molecular defect was localized in 45 patients from 34 unrelated families. From the 34 independent mutations identified, 16 were previously undescribed, 31 were unique mutations, 22 were exonic single nucleotide changes (16 missense and 6 nonsense) and four intronic mutations. Because five families had clinical, immunological and inheritance data sufficient for a definitive diagnosis, our study allowed 37 patients from 29 families previously categorized probable/ possible XLA, have now definitive diagnosis leading to appropriate genetic counseling.
Assuntos
Agamaglobulinemia/enzimologia , Agamaglobulinemia/genética , Mutação , Proteínas Tirosina Quinases/genética , Tirosina Quinase da Agamaglobulinemia , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/epidemiologia , Argentina/epidemiologia , Triagem de Portadores Genéticos/métodos , Testes Genéticos/métodos , Humanos , Masculino , Polimorfismo Conformacional de Fita SimplesRESUMO
PFAPA is a periodic fever syndrome characterized by: fever, aphthous stomatitis, pharyngitis and cervical adenitis. It is one of the autoinflammatory syndromes, but yet of unknown etiology. Our aim is to report our experience, describe clinical manifestations, laboratory findings, relapses occurrence and response to treatment. We present 12 PFAPA patients. Median age at onset: 1.15 years, mean duration of febrile episodes: 4 days, and relapses at regular intervals. All children received prednisone (1-2 mg/kg/dose) one to two doses, 9 patients responded immediately after the first dose and all experienced a lower periodicity of attacks. PFAPA is the most frequent periodic fever syndrome. To our knowledge, there are no other local series of PFAPA patients published. Recognizing this syndrome will prevent from ordering unnecessary studies and will favor family coping.
Assuntos
Febre , Linfadenite , Faringite , Estomatite Aftosa , Pré-Escolar , Feminino , Febre/diagnóstico , Febre/tratamento farmacológico , Humanos , Linfadenite/diagnóstico , Linfadenite/tratamento farmacológico , Masculino , Pescoço , Faringite/diagnóstico , Faringite/tratamento farmacológico , Estudos Retrospectivos , Estomatite Aftosa/diagnóstico , Estomatite Aftosa/tratamento farmacológico , SíndromeRESUMO
El síndrome de fiebre periódica se caracteriza por: fiebre, estomatitisaftosa, faringitis y adenitis cervical. Pertenece al grupo de los síndromes autoinflamatorios, pero su causa es aúndesconocida.Describimos una serie de doce pacientes con fiebre periódica para caracterizar sus manifestaciones clínicas, de laboratorio, aparición de recurrencias y respuesta al tratamiento.La mediana de edad de comienzo fue 1,15 años, con una media de duración de los episodios febriles de 4 días y brotes a intervalos regulares. Todos los niños recibieron meprednisona(1-2 mg/kg/dosis) una o dos dosis, nueve pacientes tuvieron una respuesta inmediata a la primera dosis y en todos hubo prolongación de los intervalos entre las crisis.El reconocimiento de este síndrome podrá limitar la realizaciónde estudios y calmar la preocupación de estas familias.
PFAPA is a periodic fever syndrome characterized by: fever, aphthous stomatitis, pharyngitis and cervical adenitis. It is one of the autoinflammatory syndromes, but yet of unknown etiology. Our aim is to report our experience, describe clinical manifestations, laboratory findings, relapses occurrence and responseto treatment. We present 12 PFAPA patients. Median age at onset: 1.15 years, mean duration of febrile episodes: 4 days, and relapses at regular intervals. All children received prednisone (1-2 mg/kg/dose) one to two doses, 9 patients responded immediately afterthe first dose and all experienced a lower periodicity of attacks. PFAPA is the most frequent periodic fever syndrome. To ourknowledge, there are no other local series of PFAPA patients published. Recognizing this syndrome will prevent from ordering unnecessary studies and will favor family coping.
Assuntos
Humanos , Masculino , Feminino , Lactente , Diagnóstico Diferencial , Febre , Linfadenite , Faringite , Estomatite Aftosa , Estudos RetrospectivosRESUMO
This study evaluated the success of a national program for the prevention of mother-to-child transmission (MTCT) of HIV-1 in 874 mother-infant pairs from Buenos Aires and surroundings. This population was referred to the National Reference Center for AIDS for diagnosis of neonatal infection during 1993-2000. The data revealed an increase in the use of antiretroviral therapy during pregnancy from 3.2% in 1993-1994 to 73.1% in 1999-2000 and in the use of cesarean delivery (reaching 54.8% in 1999-2000). However, the proportion of HIV-infected women who continued to breast-feed their children remained steady (around 12%). General improvement of the conditions for decreasing MTCT resulted in a significant decrease in the proportion of infected infants from 37.3% before 1995 to 10.7% in 1999-2000 and even 6.5% during 2001. Data on the time of diagnosis indicated that only 42.7% of the women knew about their HIV status before pregnancy, 44.8 knew during pregnancy, and 12.3% knew after the birth of their child. The main risk factor for HIV infection in the mothers was heterosexual contact (73%), and in the fathers, it was injection drug use (67%). These results point out the urgent need to develop additional strategies for prevention of MTCT of HIV-1 to generalize education, counseling, and testing of young women.
Assuntos
Infecções por HIV/complicações , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez , Adulto , Fármacos Anti-HIV/uso terapêutico , Argentina , Aleitamento Materno/efeitos adversos , Feminino , Infecções por HIV/diagnóstico , HIV-1 , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Fatores de Risco , Assunção de Riscos , Comportamento Sexual , Abuso de Substâncias por Via Intravenosa/complicaçõesRESUMO
La introducción de la vacuna antipoliomielítica a virus inactivados en 1955 (IPV)y la vacuna antipoliomielítica oral(OPV)en 1961 llevó a una disminución notable de la incidencia de poliomielitis por virus salvaje en todo el mundo.Sin embargo,una desventaja con el uso de la OPV,es la rara ocurrencia de poliomielitis paralítica vaccinal asociada a la vacuna.Se describe un niño de 9 meses de edad que desarrolló una parálisis fláccida de miembros inferiores a los 60 días de haber recibido su tercera dosis de vacuna oral sabin.El cultivo de la materia fecal fue positivo para poliovirus tipo 2.La evaluación inmunológica confirmó el diagnóstico de agammaglobulinemia