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1.
J Clin Immunol ; 44(6): 138, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38805138

RESUMO

BACKGROUND: Inborn Errors of Immunity (IEI) comprise several genetic anomalies that affect different components of the innate and adaptive responses, predisposing to infectious diseases, autoimmunity and malignancy. Different studies, mostly in adults, have reported a higher prevalence of cancer in IEI patients. However, in part due to the rarity of most of these IEI subtypes (classified in ten categories by the Primary Immunodeficiency Committee of the International Union of Immunological Societies), it is difficult to assess the risk in a large number of patients, especially during childhood. OBJECTIVE: To document the cancer prevalence in a pediatric cohort from a single referral institution, assessing their risk, together with the type of neoplasia within each IEI subgroup. METHOD: An extensive review of clinical records from 1989 to 2022 of IEI patients who at some point developed cancer before the age of sixteen. RESULTS: Of a total of 1642 patients with IEI diagnosis, 34 developed cancer before 16 years of age, showing a prevalence (2.1%) significantly higher than that of the general age matched population (0.22). Hematologic neoplasms (mostly lymphomas) were the most frequent malignancies. CONCLUSION: This study represents one of the few reports focused exclusively in pediatric IEI cases, describing not only the increased risk of developing malignancy compared with the age matched general population (a fact that must be taken into account by immunologists during follow-up) but also the association of the different neoplasms with particular IEI subtypes, thus disclosing the possible mechanisms involved.


Assuntos
Neoplasias , Humanos , Criança , Prevalência , Neoplasias/epidemiologia , Neoplasias/imunologia , Neoplasias/etiologia , Masculino , Feminino , Pré-Escolar , Adolescente , Lactente , Síndromes de Imunodeficiência/epidemiologia , Síndromes de Imunodeficiência/imunologia , Recém-Nascido
2.
J Clin Immunol ; 44(4): 86, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578389

RESUMO

BACKGROUND: The CDC and ACIP recommend COVID-19 vaccination for patients with inborn errors of immunity (IEI). Not much is known about vaccine safety in IEI, and whether vaccination attenuates infection severity in IEI. OBJECTIVE: To estimate COVID-19 vaccination safety and examine effect on outcomes in patients with IEI. METHODS: We built a secure registry database in conjunction with the US Immunodeficiency Network to examine vaccination frequency and indicators of safety and effectiveness in IEI patients. The registry opened on January 1, 2022, and closed on August 19, 2022. RESULTS: Physicians entered data on 1245 patients from 24 countries. The most common diagnoses were antibody deficiencies (63.7%). At least one COVID-19 vaccine was administered to 806 patients (64.7%), and 216 patients received vaccination prior to the development of COVID-19. The most common vaccines administered were mRNA-based (84.0%). Seventeen patients were reported to seek outpatient clinic or emergency room care for a vaccine-related complication, and one patient was hospitalized for symptomatic anemia. Eight hundred twenty-three patients (66.1%) experienced COVID-19 infection. Of these, 156 patients required hospitalization (19.0%), 47 required ICU care (5.7%), and 28 died (3.4%). Rates of hospitalization (9.3% versus 24.4%, p < 0.001), ICU admission (2.8% versus 7.6%, p = 0.013), and death (2.3% versus 4.3%, p = 0.202) in patients who had COVID-19 were lower in patients who received vaccination prior to infection. In adjusted logistic regression analysis, not having at least one COVID-19 vaccine significantly increased the odds of hospitalization and ICU admission. CONCLUSION: Vaccination for COVID-19 in the IEI population appears safe and attenuates COVID-19 severity.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Vacinas contra COVID-19/efeitos adversos , Vacinação , Hospitalização , Cuidados Críticos
3.
J Pediatr Endocrinol Metab ; 37(4): 380-386, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38436354

RESUMO

OBJECTIVES: Transcobalamin II (TC) promotes the cellular uptake of cobalamin (Cbl) through receptor-mediated endocytosis of the TC-cbl complex in peripheral tissues. TC deficiency is a rare disorder that causes intracellular Cbl depletion. It presents in early infancy with a failure to thrive, diarrhea, anemia, agammaglobulinemia, and pancytopenia. Data from five TC-deficient patients including clinical, biochemical, and molecular findings, as well as long-term outcomes, were collected. CASE PRESENTATION: Mutation analysis revealed one unreported pathogenic variant in the TCN2 gene. One patient had exocrine pancreatic insufficiency. We conducted a retrospective analysis of C3 and C3/C2 from dried blood samples, as this is implemented for newborn screening (NBS). We detected a marked increase in the C3/C2 ratio in two samples. Treatment was based on parenteral Cbl. Three patients treated before six months of age had an initial favorable outcome, whereas the two treated later or inadequately had neurological impairment. CONCLUSIONS: This is the first report of Argentinean patients with TC deficiency that detected a new variant in TCN2. NBS may be a tool for the early detection of TC deficiency. This data emphasizes that TC deficiency is a severe disorder that requires early detection and long-term, aggressive therapy. Accurate diagnosis is imperative, because early detection and treatment can be life-saving.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Anemia Macrocítica , Deficiência de Vitamina B 12 , Recém-Nascido , Humanos , Vitamina B 12/uso terapêutico , Transcobalaminas/genética , Estudos Retrospectivos , Deficiência de Vitamina B 12/diagnóstico , Deficiência de Vitamina B 12/tratamento farmacológico , Deficiência de Vitamina B 12/genética , Erros Inatos do Metabolismo dos Aminoácidos/tratamento farmacológico , Diagnóstico Precoce
4.
Arch Argent Pediatr ; : e202310308, 2024 Aug 29.
Artigo em Espanhol | MEDLINE | ID: mdl-39178179

RESUMO

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.

5.
Front Immunol ; 13: 1020927, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405754

RESUMO

CARD11-associated diseases are monogenic inborn errors of immunity involving immunodeficiency, predisposition to malignancy and immune dysregulation such as lymphoproliferation, inflammation, atopic and autoimmune manifestations. Defects in CARD11 can present as mutations that confer a complete or a partial loss of function (LOF) or contrarily, a gain of function (GOF) of the affected gene product. We report clinical characteristics, immunophenotypes and genotypes of 15 patients from our center presenting with CARD11-associated diseases. Index cases are pediatric patients followed in our immunology division who had access to next generation sequencing studies. Variant significance was defined by functional analysis in cultured cells transfected with a wild type and/or with mutated hCARD11 constructs. Cytoplasmic aggregation of CARD11 products was evaluated by immunofluorescence. Nine index patients with 9 unique heterozygous CARD11 variants were identified. At the time of the identification, 7 variants previously unreported required functional validation. Altogether, four variants showed a GOF effect as well a spontaneous aggregation in the cytoplasm, leading to B cell expansion with NF-κB and T cell anergy (BENTA) diagnosis. Additional four variants showing a LOF activity were considered as causative of CARD11-associated atopy with dominant interference of NF-kB signaling (CADINS). The remaining variant exhibited a neutral functional assay excluding its carrier from further analysis. Family segregation studies expanded to 15 individuals the number of patients presenting CARD11-associated disease. A thorough clinical, immunophenotypical, and therapeutic management evaluation was performed on these patients (5 BENTA and 10 CADINS). A remarkable variability of disease expression was clearly noted among BENTA as well as in CADINS patients, even within multiplex families. Identification of novel CARD11 variants required functional studies to validate their pathogenic activity. In our cohort BENTA phenotype exhibited a more severe and expanded clinical spectrum than previously reported, e.g., severe hematological and extra hematological autoimmunity and 3 fatal outcomes. The growing number of patients with dysmorphic facial features strengthen the inclusion of extra-immune characteristics as part of the CADINS spectrum. CARD11-associated diseases represent a challenging group of disorders from the diagnostic and therapeutic standpoint, especially BENTA cases that can undergo a more severe progression than previously described.


Assuntos
Proteínas Adaptadoras de Sinalização CARD , Síndromes de Imunodeficiência , Humanos , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Guanilato Ciclase/metabolismo , Heterozigoto , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/terapia , NF-kappa B/metabolismo
6.
Artigo em Inglês | MEDLINE | ID: mdl-32944031

RESUMO

Interferon-stimulated gene 15 (ISG15) was the first ubiquitin-like modifier protein identified that acts by protein conjugation (ISGylation) and is thought to modulate IFN-induced inflammation. Here, we report a new patient from a non-consanguineous Argentinian family, who was followed for recurrent ulcerative skin lesions, cerebral calcifications and lung disease. Whole Exome Sequencing (WES) revealed two novel compound heterozygous variants (c.285del and c.299_312del, NM_005101.4 GRCh37(hg19), both classified as pathogenic according to ACMG criteria) in the ISG15 gene, resulting in a complete deficiency due to disruption of the second ubiquitin domain of the corresponding protein. The clinical phenotype of this patient is unique given the presence of recurrent pulmonary manifestations and the absence of mycobacterial infections, thus resulting in a phenotype distinct from that previously described in patients with biallelic loss-of-function (LOF) ISG15 variants. This case highlights the role of ISG15 as an immunomodulating factor whose LOF variants result in heterogeneous clinical presentations.

8.
Med. infant ; 24(4): 325-328, dic. 2017. tab, ilus
Artigo em Espanhol | LILACS | ID: biblio-878279

RESUMO

Introducción: El pie plano flexible es una de las entidades ortopédicas más frecuentes en Pediatría. Algunos autores lo consideran una variante anatómica. La incertidumbre en cuanto a su evolución y pronóstico, sumado a la preocupación y demanda por parte de los padres, hace que en muchas ocasiones se indique tratamiento ortésico. Metodología: se realizó una búsqueda sistemática en Medline, Lilacs, Cochrane y Google académico, usando los términos therapy, flatfoot, flatfeet, pie plano y pes planus; población hasta los 18 años, publicaciones hasta abril 2017 y restringiendo por idiomas español e inglés. Para el aná- lisis de los artículos se utilizaron la guía de lectura crítica del Hospital Garrahan y la escala de calidad metodológica JADAD. Resultados: de 778 artículos encontrados, 421 correspondían a pacientes con enfermedad de base, 194 evaluaban corrección quirúrgica, 144 eran descriptivos, 7 comparaban diferentes ortesis entre sí y 7 eran revisiones de trabajos. Finalmente fueron analizados 5 trabajos (cuatro ECCAs y un estudio de cohorte). De los 5 artículos, 2 poseían aceptable y muy buena calidad metodológica según la escala JADAD, ninguno demostrando diferencias significativas con el tratamiento ortésico. De los 3 restantes, sólo uno halló mejores resultados en cuanto al alivio del dolor y de la marcha combinando ortesis con ejercicios (RR 0.33 y 0.29 respectivamente). Conclusión: en base a esta revisión no hay evidencia científica que demuestre la eficacia del uso de ortesis para la corrección del pie plano flexible en la población pediátrica sana.(AU)


Introduction: Flexible flatfoot is one of the most common orthopedic findings in children. Some authors consider the entity to be a normal anatomical variant. Uncertainty regarding outcome and prognosis added to the worries and demands of the parents often results in the indication of orthotic treatment. Methods: A systematic search was conducted in Medline, Lilacs, Cochrane, and Google academics using the terms therapy, flatfoot, flatfeet, and pes planus; population up to 18 years of age, publications until April 2017, in Spanish and English. For the analysis of the articles the critical reading guidelines of Hospital Garrahan and the JADAD scale for methodological quality were used. Results: Of 778 articles found, 421 were related to patients with an underlying disease, 194 evaluated surgical correction, 144 were descriptive studies, 7 compared different orthosis, and 7 were review studies. Finally, 5 studies were analyzed (four randomized controlled trials (RCT) and one cohort study). Of the five studies, two were considered acceptable and of good quality on the JADAD scale. None of the studies showed significant differences with orthotic treatment. Of the three remaining studies, only one found better results regarding pain relief and gait improvement with orthosis combined with exercise (RR 0.33 and 0.29, respectively). Conclusion: Based on this review, there is no scientific evidence that shows efficacy of the use of orthosis for the correction of flatfoot in healthy children. (AU)


Assuntos
Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Pé Chato/terapia , Órtoses do Pé , Resultado do Tratamento
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