Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 77
Filter
1.
Arch. argent. pediatr ; 119(3): 202-207, Junio 2021. ilus
Article in English, Spanish | LILACS, BINACIS | ID: biblio-1222985

ABSTRACT

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


Subject(s)
Humans , Male , Female , Child , Adolescent , Primary Immunodeficiency Diseases/epidemiology , Immunologic Deficiency Syndromes/epidemiology , Respiratory Tract Infections/epidemiology , Retrospective Studies , Severe Combined Immunodeficiency/epidemiology , Primary Immunodeficiency Diseases/diagnosis , Primary Immunodeficiency Diseases/therapy , Hospitals, Public , Immune System , Immunologic Deficiency Syndromes/diagnosis , Infections/epidemiology , Mexico
3.
Article in English | WPRIM | ID: wpr-785340

ABSTRACT

PURPOSE: While there is an urgent need for diagnosis and therapeutic intervention in patients with primary immunodeficiency diseases (PIDs), current genetic tests have drawbacks. We retrospectively reviewed the usefulness of flow cytometry (FCM) as a quick tool for immunophenotyping and functional assays in patients suspected to have PIDs at a single tertiary care institute.METHODS: Between January 2001 and June 2018, patients suspected of having PIDs were subjected to FCM tests, including lymphocyte subset analysis, detection of surface- or intracellular-target proteins, and functional analysis of immune cells, at Samsung Medical Center, Seoul, Korea. The genetic diagnosis was performed using Sanger or diagnostic exome sequencing.RESULTS: Of 60 patients diagnosed with definite or probable PID according to the European Society of Immune Deficiencies criteria, 24 patients were provided with useful information about immunological dysfunction after initial FCM testing. In 10 patients, the PID diagnosis was based on abnormal findings in FCM testing without genetic tests. The FCM findings provided strong evidence for the diagnosis of severe combined immunodeficiency (n = 6), X-linked chronic granulomatous diseases (CGD) (n = 6), leukocyte adhesion deficiency type 1 (n = 3), X-linked agammaglobulinemia (n = 11), autoimmune lymphoproliferative syndrome-FASLG (n = 1), and familial hemophagocytic lymphohistiocytosis type 2 (n = 1), and probable evidence for autosomal recessive-CGD (n = 2), autosomal dominant-hyper-immunoglobulin E (IgE)-syndrome (n = 1), and STAT1 gain-of-function mutation (n = 1). In PIDs derived from PIK3CD (n = 2), LRBA (n = 2), and CTLA4 mutations (n = 3), the FCM test provided useful evidence of immune abnormalities and a tool for treatment monitoring.CONCLUSIONS: The initial application of FCM, particularly with known protein targets on immune cells, would facilitate the timely diagnosis of PIDs and thus would support clinical decisions and improve the clinical outcome.


Subject(s)
Agammaglobulinemia , Diagnosis , Exome , Flow Cytometry , Genetic Testing , Granulomatous Disease, Chronic , Humans , Immunophenotyping , Korea , Leukocytes , Lymphocyte Subsets , Lymphohistiocytosis, Hemophagocytic , Phenotype , Retrospective Studies , Seoul , Severe Combined Immunodeficiency , Tertiary Healthcare
4.
Rev. chil. pediatr ; 90(6): 581-588, dic. 2019. tab
Article in Spanish | LILACS | ID: biblio-1058188

ABSTRACT

Las inmunodeficiencias primarias (IDP) son un conjunto de cerca de 350 enfermedades genéticas que afectan el funcionamiento del sistema inmunológico. Los avances en diagnóstico genético han permitido describir nuevos defectos en el sistema inmune, ampliando el espectro de manifestaciones de las IDP más allá de la susceptibilidad a infecciones. Aunque la mayoría de las IDP se presentan con infecciones recurrentes u oportunistas, un subgrupo puede presentarse por el desarrollo precoz de fenómenos autoinflamatorios, tumorales y, paradojalmente, la coexistencia de autoinmunidad e inmunodeficiencia en un mismo paciente. Al igual que sus manifestaciones clínicas, la severidad de las IDP es variable. La inmunodeficiencia combinada severa (IDCS), caracterizada por una falla en la respuesta humoral y celular, es una de las formas más graves de IDP y el único tratamiento curativo disponible en Latino-América es el trasplante de precursores hematopoyéticos. La IDCS es 100% letal durante los dos primeros años de vida si no se diagnostica y trata oportunamente. Por el contrario, si se trasplantan precozmente, estos pacientes pueden alcanzar una sobrevida normal. Pese a los avan ces en el diagnóstico de IDP que se han observado en nuestro país en los últimos años, los recursos diagnósticos no se encuentran disponibles en todas las regiones, lo que dificulta el reconocimiento temprano de la IDCS y otras IDP en grandes áreas del país. El objetivo de esta actualización es revisar conceptos generales sobre la fisiopatología de la IDCS, diagnóstico, manejo inicial y plantear la nece sidad de la implementación del tamizaje neonatal de IDCS en Chile.


Primary immunodeficiencies (PIDs) are a set of about 350 genetic disorders that affect the normal function of the immune system. Advances in genetic diagnosis have allowed the description of new defects in the immune system, broadening the clinical spectrum of PIDs' manifestations beyond susceptibility to infection. Although most PIDs present with recurrent or opportunistic infections, a subgroup of them may be recognized by the early development of auto-inflammatory events, tumors and, paradoxically, the coexistence of autoimmunity and immunodeficiency in the same patient. As their clinical manifestations, the severity of PIDs is highly variable. Severe combined immunodefi ciency (SCID), a PID that affects cellular and humoral immunity, is one of the most severe forms of PIDs and the only available curative treatment in Latin America is hematopoietic stem cells trans plantation. All patients affected by SCID die during the first two years of life if they are not diagnosed and treated opportunely. In contrast, early transplantation of patients with SCID can lead to excellent survival outcomes. Despite recent advances in the diagnosis of PIDs in Chile, diagnostic resources are not available throughout the country, making the early diagnosis of SCID and other forms of PID difficult in big areas of Chile. The objective of this article is to review general concepts on the patho physiology, diagnosis, and initial management of SCID and raise the need for the implementation of neonatal screening for SCID in Chile.


Subject(s)
Humans , Infant, Newborn , Neonatal Screening , Severe Combined Immunodeficiency/diagnosis , Early Diagnosis , Chile/epidemiology , Severe Combined Immunodeficiency/complications , Severe Combined Immunodeficiency/therapy , Severe Combined Immunodeficiency/epidemiology , Hematopoietic Stem Cell Transplantation
5.
Rev. chil. pediatr ; 90(6): 668-674, dic. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1058199

ABSTRACT

Resumen: Los pacientes con Inmunodeficiencias primarias (IDP) tienen un riesgo elevado de complicaciones severas por la vacuna BCG, incluso mortalidad. Es necesario evaluar periódicamente el riesgo versus beneficio de la vacunación universal BCG en el periodo neonatal. Chile es un país con baja incidencia de tuberculosis (TB) pero cuya epidemiología ha cambiado recientemente con un aumento de los casos. Cambios en esquemas de vacunación BCG en países con incidencias mayores o similares de TB y con coberturas de vacunación menores han sido posibles sin aumento de los casos graves de TB que son los que previene la BCG. El cambio ha evitado complicaciones graves en pacientes con IDP. Creemos que un análisis crítico de la fecha de vacunación BCG debe realizarse hoy en Chile. Más aún dada la posibilidad técnica de realizar screening neonatal de IDP.


Abstract: Patients with Primary Immunodeficiencies (PID) are at a higher risk of developing severe morbidities and mortality due to the administration of BCG vaccine. Risk-to-benefit of universal BCG vaccina tion of newborns must be assessed periodically. Chile has a low incidence of tuberculosis (TB) but the local epidemiology has recently changed with an increase of TB cases. Changes in the BCG vaccine schedule have been made in countries with similar or higher TB incidences and lower BCG vaccine coverage, with no increase in the severe TB cases, which are prevented by BCG. These changes have prevented serious complications in PID patients. We propose a critical analysis of the BCG adminis tration date in Chile due to the technical possibility of performing neonatal PID screening.


Subject(s)
Humans , Infant, Newborn , Infant , BCG Vaccine/adverse effects , Adjuvants, Immunologic/adverse effects , Primary Immunodeficiency Diseases/complications , Tuberculosis/prevention & control , Tuberculosis/epidemiology , Chile/epidemiology , Incidence , Immunization Schedule , Severe Combined Immunodeficiency/complications , Hematopoietic Stem Cell Transplantation/mortality , Contraindications, Drug
6.
Article in Chinese | WPRIM | ID: wpr-819042

ABSTRACT

Severe combined immunodeficiency disease (SCID) is a group of rare congenital diseases characterized by severe deficiencies in T lymphocyte counts and/or function. The recurrent, persistent and severe infections are its clinical manifestations. Neonatal screening and immune system reconstruction would improve the prognosis of SCID children. Newborn screening programs based on T-cell receptor excision circles (TRECs) quantitative detection have been carried out in clinical practice, however, the methods still have some limitations. Other new methods such as mass spectrometry and T lymphocyte-specific biomarker assays are still under investigation. Hematopoietic stem cell transplantation and gene therapy are the two main methods for reconstructing immune function in SCID children. Through improving the success rate of transplantation and the long-term safety and stability of viral vectors, some achievements have been made by many centers already. However, large-scale prospective studies are needed for evaluation of the long-term efficacy. In this article, the recent progress in newborn screening and immune reconstitution of SCID is reviewed.


Subject(s)
Humans , Immune Reconstitution , Infant, Newborn , Neonatal Screening , Prospective Studies , Severe Combined Immunodeficiency , Therapeutics , T-Lymphocytes
7.
Article in English | WPRIM | ID: wpr-761920

ABSTRACT

BACKGROUND: Mesenchymal stromal cells (MSCs) have potent immunomodulatory and neuroprotective properties, and have been tested in neurodegenerative diseases resulting in meaningful clinical improvements. Regulatory guidelines specify the need to perform preclinical studies prior any clinical trial, including biodistribution assays and tumourigenesis exclusion. We conducted a preclinical study of human bone marrow MSCs (hBM-MSCs) injected by intrathecal route in Non-Obese Diabetic Severe Combined Immunodeficiency mice, to explore cellular biodistribution and toxicity as a privileged administration method for cell therapy in Friedreich's Ataxia. METHODS: For this purpose, 3 × 10⁵ cells were injected by intrathecal route in 12 animals (experimental group) and the same volume of culture media in 6 animals (control group). Blood samples were collected at 24 h (n = 9) or 4 months (n = 9) to assess toxicity, and nine organs were harvested for histology and safety studies. Genomic DNA was isolated from all tissues, and mouse GAPDH and human β2M and β-actin genes were amplified by qPCR to analyze hBM-MSCs biodistribution. RESULTS: There were no deaths nor acute or chronic toxicity. Hematology, biochemistry and body weight were in the range of normal values in all groups. At 24 h hBM-MSCs were detected in 4/6 spinal cords and 1/6 hearts, and at 4 months in 3/6 hearts and 1/6 brains of transplanted mice. No tumours were found. CONCLUSION: This study demonstrated that intrathecal injection of hBM-MSCs is safe, non toxic and do not produce tumors. These results provide further evidence that hBM-MSCs might be used in a clinical trial in patients with FRDA.


Subject(s)
Animals , Biochemistry , Body Weight , Bone Marrow , Brain , Cell- and Tissue-Based Therapy , Culture Media , DNA , Friedreich Ataxia , Heart , Hematology , Humans , Injections, Spinal , Mesenchymal Stem Cells , Methods , Mice , Neurodegenerative Diseases , Neuroprotection , Reference Values , Severe Combined Immunodeficiency , Spinal Cord
9.
Laboratory Animal Research ; : 166-175, 2018.
Article in English | WPRIM | ID: wpr-719077

ABSTRACT

Recombination activating gene-2 (RAG-2) plays a crucial role in the development of lymphocytes by mediating recombination of T cell receptors and immunoglobulins, and loss of RAG-2 causes severe combined immunodeficiency (SCID) in humans. RAG-2 knockout mice created using homologous recombination in ES cells have served as a valuable immunodeficient platform, but concerns have persisted on the specificity of RAG-2-related phenotypes in these animals due to the limitations associated with the genome engineering method used. To precisely investigate the function of RAG-2, we recently established a new RAG-2 knockout FVB mouse line (RAG-2(−/−)) manifesting lymphopenia by employing a CRISPR/Cas9 system at Center for Mouse Models of Human Disease. In this study, we further characterized their phenotypes focusing on histopathological analysis of lymphoid organs. RAG-2(−/−) mice showed no abnormality in development compared to their WT littermates for 26 weeks. At necropsy, gross examination revealed significantly smaller spleens and thymuses in RAG-2(−/−) mice, while histopathological investigation revealed hypoplastic white pulps with intact red pulps in the spleen, severe atrophy of the thymic cortex and disappearance of follicles in lymph nodes. However, no perceivable change was observed in the bone marrow. Moreover, our analyses showed a specific reduction of lymphocytes with a complete loss of mature T cells and B cells in the lymphoid organs, while natural killer cells and splenic megakaryocytes were increased in RAG-2(−/−) mice. These findings indicate that our RAG-2(−/−) mice show systemic lymphopenia with the relevant histopathological changes in the lymphoid organs, suggesting them as an improved Rag-2-related immunodeficient model.


Subject(s)
Animals , Atrophy , B-Lymphocytes , Bone Marrow , Genome , Homologous Recombination , Humans , Immunoglobulins , Killer Cells, Natural , Lymph Nodes , Lymphocytes , Lymphopenia , Megakaryocytes , Methods , Mice , Mice, Knockout , Negotiating , Phenotype , Receptors, Antigen, T-Cell , Recombination, Genetic , Sensitivity and Specificity , Severe Combined Immunodeficiency , Spleen , T-Lymphocytes , Thymus Gland
10.
Rev. paul. pediatr ; 35(1): 25-32, jan.-mar. 2017. tab, graf
Article in Portuguese | LILACS | ID: biblio-845724

ABSTRACT

RESUMO Objetivo: Validar a quantificação de T-cell receptor excision circles (TRECs) e kappa-deleting recombination circles (KRECs) por reação em cadeia de polimerase (polymerase chain reaction, PCR) em tempo real (qRT-PCR), para triagem neonatal de imunodeficiências primárias que cursam com defeitos nas células T e/ou B no Brasil. Métodos: Amostras de sangue de recém-nascidos (RN) e controles foram coletadas em papel-filtro. O DNA foi extraído e os TRECs e KRECs foram quantificados por reação duplex de qRT-PCR. O valor de corte foi determinado pela análise de Receiver Operating Characteristics Curve, utilizando-se o programa Statistical Package for the Social Sciences (SSPS) (IBM®, Armonk, NY, EUA). Resultados: 6.881 amostras de RN foram analisadas quanto à concentração de TRECs e KRECs. Os valores de TRECs variaram entre 1 e 1.006 TRECs/µL, com média e mediana de 160 e 139 TRECs/µL, respectivamente. Três amostras de pacientes diagnosticados com imunodeficiência grave combinada (severe combined immunodeficiency, SCID) apresentaram valores de TRECs abaixo de 4/µL e um paciente com Síndrome de DiGeorge apresentou TRECs indetectáveis. Os valores de KRECs encontraram-se entre 10 e 1.097 KRECs/µL, com média e mediana de 130 e 108 KRECs/µL, e quatro pacientes com diagnóstico de agamaglobulinemia tiveram resultados abaixo de 4 KRECs/µL. Os valores de corte encontrados foram 15 TRECs/µL e 14 KRECs/µL, e foram estabelecidos de acordo com a análise da Receiver Operating Characteristics Curve, com sensibilidade de 100% para detecção de SCID e agamaglobulinemia, respectivamente. Conclusões: A quantificação de TRECs e KRECs foi capaz de diagnosticar crianças com linfopenias T e/ou B em nosso estudo, validando a técnica e dando o primeiro passo para a implementação da triagem neonatal em grande escala no Brasil.


ABSTRACT Objective: To validate the quantification of T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) by real-time polymerase chain reaction (qRT-PCR) for newborn screening of primary immunodeficiencies with defects in T and/or B cells in Brazil. Methods: Blood samples from newborns and controls were collected on filter paper. DNA was extracted and TRECs, and KRECs were quantified by a duplex real-time PCR. The cutoff values were determined by receiver operating characteristic curve analysis using SPSS software (IBM®, Armonk, NY, USA). Results: Around 6,881 samples from newborns were collected and TRECs and KRECs were quantified. The TRECs values ranged between 1 and 1,006 TRECs/µL, with mean and median of 160 and 139 TRECs/µL, respectively. Three samples from patients with severe combined immunodeficiency (SCID) showed TRECs below 4/µL and a patient with DiGeorge syndrome showed undetectable TRECs. KRECs values ranged from 10 to 1,097 KRECs/µL, with mean and median of 130 and 108 KRECs/µL. Four patients with agammaglobulinemia had results below 4 KRECs/µL. The cutoff values were 15 TRECs/µL and 14 KRECs/µL and were established according to the receiver operating characteristic curve analysis, with 100% sensitivity for SCID and agammaglobulinemia detection, respectively. Conclusions: Quantification of TRECs and KRECs was able to diagnose children with T- and/or B-cell lymphopenia in our study, which validated the technique in Brazil and enabled us to implement the newborn screening program for SCID and agammaglobulinemia.


Subject(s)
Humans , Infant, Newborn , Infant , Neonatal Screening/methods , Severe Combined Immunodeficiency/diagnosis , Severe Combined Immunodeficiency/blood , Brazil , DNA/analysis , Receptors, Antigen, B-Cell/genetics , Pilot Projects , Cross-Sectional Studies , Severe Combined Immunodeficiency/genetics , Real-Time Polymerase Chain Reaction
11.
Article in Korean | WPRIM | ID: wpr-211730

ABSTRACT

During the past decades, there has been a great evolution in the field of fetal therapy for congenital defects. Prenatal screening or diagnostic methods including non-invasive and invasive methods and fetal ultrasound have led to earlier and more accurate diagnosis of congenital anomalies. Recent advances in several therapeutic techniques including ultrasound-guided needle therapy, laser therapy or fetal endoscopy, have allowed some fetuses at risk with anatomical defects, to be corrected in utero but still, its clinical indications remain limited. Over the last 30 years, many researchers found usefulness of pluripotent stem cells from amniotic fluid and placenta because they are sources of diverse progenitor cell populations called mesenchymal stem cells. In some human conditions like severe combined immunodeficiency syndrome and chronic granulomatous disease, fetal therapy using stem cell replacement showed some promising results in researches but more studies are required to apply in clinical settings. The aim of this article is to summarize a current status and future perspective of stem cell therapy for treatment of congenital fetal anomalies.


Subject(s)
Amniotic Fluid , Congenital Abnormalities , Diagnosis , Endoscopy , Female , Fetal Therapies , Fetus , Granulomatous Disease, Chronic , Humans , Laser Therapy , Mesenchymal Stem Cells , Needles , Placenta , Pluripotent Stem Cells , Prenatal Diagnosis , Severe Combined Immunodeficiency , Stem Cells , Ultrasonography
12.
Article in English | WPRIM | ID: wpr-22457

ABSTRACT

PURPOSE: Severe combined immunodeficiency (SCID) is the most serious form of primary immunodeficiency. Infants with SCID are susceptible to life-threatening infections. To establish newborn screening for SCID in Korea, we performed a screening test for T-cell receptor excision circle (TREC) and κ-deleting recombination excision circle (KREC) in neonates and investigated the awareness of SCID among their parents. METHODS: Collections of dried blood spots from neonates and parent surveys were performed at the Samsung Medical Center and Cheil General Hospital & Women's Healthcare Center in Korea. The amplification crossing point (Cp) value 39.0 was defined as negative. RESULTS: For TREC/KREC screening, 141 neonates were enrolled; 63 (44.7%) were male. One hundred forty neonates (99.3%) had positive TREC/KREC results at the time of the initial test; 82.3% and 75.9% were positive and 17.0% and 23.4% were weakly positive for TREC and KREC, respectively. In one neonate (0.7%), the initial TREC/KREC test result was negative. However, repeated tests obtained and confirmed a positive result. For an awareness survey, 168 parents were engaged. Only 2% of parents (3/168) knew that the newborn screening test for SCID had been introduced and performed in other countries. Eighty-four percent of parents (141/168) replied that nationwide newborn SCID screening should be performed in Korean newborns. CONCLUSIONS: In this study, newborn SCID screening was performed along with assessment of public awareness of the SCID test in Korea. The study results showed that newborn SCID screening can be readily applied for clinical use at a relatively low cost in Korea.


Subject(s)
Delivery of Health Care , Hospitals, General , Humans , Infant , Infant, Newborn , Korea , Male , Mass Screening , Neonatal Screening , Parents , Pilot Projects , Real-Time Polymerase Chain Reaction , Receptors, Antigen, T-Cell , Recombination, Genetic , Severe Combined Immunodeficiency , Surveys and Questionnaires , T-Lymphocytes
13.
J. pediatr. (Rio J.) ; 92(4): 374-380, July-Aug. 2016. tab, graf
Article in English | LILACS | ID: lil-792575

ABSTRACT

Abstract Objective To apply, in Brazil, the T-cell receptor excision circles (TRECs) quantification technique using real-time polymerase chain reaction in newborn screening for severe combined immunodeficiency and assess the feasibility of implementing it on a large scale in Brazil. Methods 8715 newborn blood samples were collected on filter paper and, after DNA elution, TRECs were quantified by real-time polymerase chain reaction. The cutoff value to determine whether a sample was abnormal was determined by ROC curve analysis, using SSPS. Results The concentration of TRECs in 8,682 samples ranged from 2 to 2,181 TRECs/µL of blood, with mean and median of 324 and 259 TRECs/µL, respectively. Forty-nine (0.56%) samples were below the cutoff (30 TRECs/µL) and were reanalyzed. Four (0.05%) samples had abnormal results (between 16 and 29 TRECs/µL). Samples from patients previously identified as having severe combined immunodeficiency or DiGeorge syndrome were used to validate the assay and all of them showed TRECs below the cutoff. Preterm infants had lower levels of TRECs than full-term neonates. The ROC curve showed a cutoff of 26 TRECs/µL, with 100% sensitivity for detecting severe combined immunodeficiency. Using this value, retest and referral rates were 0.43% (37 samples) and 0.03% (3 samples), respectively. Conclusion The technique is reliable and can be applied on a large scale after the training of technical teams throughout Brazil.


Resumo Objetivo Aplicar no Brasil a técnica de quantificação de T-cell Receptor Excision Circles (TRECs) por PCR em tempo real para triagem neonatal de imunodeficiência combinada grave (SCID) e avaliar se é possível fazê-la em grande escala em nosso país. Métodos Foram coletadas em papel filtro 8.715 amostras de sangue de recém-nascidos e, após eluição do DNA, os TRECs foram quantificados por PCR em tempo real. O valor de corte para determinar se uma amostra é anormal foi determinado pela análise de curva ROC com o programa SSPS. Resultados A concentração de TRECs em 8.682 amostras analisadas variou entre 2 e 2.181 TRECs/µL de sangue, com média e mediana de 324 e 259 TRECs/µL, respectivamente. Das amostras, 49 (0,56%) ficaram abaixo do valor de corte (30 TRECs/µL) e foram requantificadas. Quatro (0,05%) mantiveram resultados anormais (entre 16 e 29 TRECs/µL). Amostras de pacientes com diagnóstico clínico prévio de SCID e síndrome de DiGeorge foram usadas para validar o ensaio e todas apresentaram concentração de TRECs abaixo do valor de corte. Recém-nascidos prematuros apresentaram menores níveis de TRECs comparados com os nascidos a termo. Com o uso da curva ROC em nossos dados, chegamos ao valor de corte de 26 TRECs/µL, com sensibilidade de 100% para detecção de SCID. Com o uso desse valor, as taxas de repetição e encaminhamento ficaram em 0,43% (37 amostras) e 0,03% (3 amostras), respectivamente. Conclusão A técnica é factível e pode ser implantada em grande escala, após treinamento técnico das equipes envolvidas.


Subject(s)
Humans , Male , Female , Infant, Newborn , Receptors, Antigen, T-Cell/blood , Neonatal Screening/methods , Severe Combined Immunodeficiency/diagnosis , Severe Combined Immunodeficiency/blood , Reference Values , Time Factors , Brazil , Receptors, Antigen, T-Cell/genetics , Reproducibility of Results , Sensitivity and Specificity , Age Factors , Statistics, Nonparametric , Dried Blood Spot Testing , Real-Time Polymerase Chain Reaction
14.
Article in Chinese | WPRIM | ID: wpr-287954

ABSTRACT

<p><b>OBJECTIVE</b>To explore the clinical characteristics and genetic mutations in two children with Omenn syndromes.</p><p><b>METHODS</b>Peripheral venous blood samples were collected from 2 children suspected with severe combined immunodeficiency (SCID) and their family members. The samples were subjected to RAG1 and RAG2 gene sequencing and TCR Vβ subclone analysis.</p><p><b>RESULTS</b>Both patients had recurrent infections, erythroderma rashes and alopecia baldness. One patient has fit with immunophenotype T-B-NK+, while another was consistent with typical Omenn syndrome combined with T+B-NK+ immunophenotype, IgE and eosinophil increase. Both children have carried compound heterozygous mutations of the RAG1 gene. The first patient carried c.1328 G>A (p.R443K) and c.2486-2490delGGAAA (p.R829fsX869) mutations, both were of de novel type. The second patient has carried c.1209C>T (p.R403W) and c.2892delT (p.ASN964LYSfs*14), with c.2892delT (p.ASN964LYSfs*14) being a de novel mutation. The parents of both patients were heterozygous carriers. The same mutations were not found in 100 healthy children. Both patients' 24 TCR Vβ subfamilies have presented monoclonal or oligoclonal peaks, with TCR Vβ polymorphism being severely disrupted.</p><p><b>CONCLUSION</b>Three novel mutations have been identified in two children with Omenn syndrome, which featured early onset and rapid progression. Early recognition of the disease and prompt treatment may reduce the mortality.</p>


Subject(s)
Adult , Base Sequence , DNA-Binding Proteins , Genetics , Female , Heterozygote , Homeodomain Proteins , Genetics , Humans , Infant , Male , Molecular Sequence Data , Mutation , Nuclear Proteins , Genetics , Pedigree , Severe Combined Immunodeficiency , Genetics
15.
Article in English | WPRIM | ID: wpr-107694

ABSTRACT

PURPOSE: Pneumocystis jirovecii pneumonia occurs in various immunocompromised patients. Despite the prophylaxis strategies in clinical practice, certain patients develop P. jirovecii pneumonia. This study was performed to investigate pediatric cases with P. jirovecii pneumonia in a single center. METHODS: We identified pediatric patients younger than 19 years with microbiologically confirmed P. jirovecii pneumonia from January 2000 to February 2014. A retrospective chart review was performed. RESULTS: Fifteen episodes of P. jirovecii pneumonia in 14 patients were identified with median age of 8.3 years (range, 0.4-18.6 years). Among these patients, 11 patients had hematology-oncology diseases, 2 had primary immunodeficiency disorders (one with severe combined immunodeficiency and the other with Wiskott Aldrich syndrome), 1 had systemic lupus erythematosus and 1 received kidney transplant. Four patients were transplant recipients; 1 allogeneic and 2 autologous hematopoietic cell transplant and 1 with kidney transplant. The median absolute lymphocyte count at the diagnosis of P. jirovecii pneumonia was 5,156 cells/mm³ (range, 20-5,111 cells/mm³). In 13 episodes (13 of 15, 86.7%), patients were not receiving prophylaxis at the onset of P. jirovecii pneumonia. For treatment, trimethoprim/sulfamethoxazole was given as a main therapeutic agent in all 15 episodes. Steroid was given in 9 episodes (60%). Median treatment duration was 15 days (range, 4-33 days). Overall mortality at 60 days was 35.7% (5 of 14). CONCLUSION: Majority of our patients developed P. jirovecii pneumonia while not on prophylaxis. Continuous efforts and more data are needed to identify high risk patients who may get benefit from P. jirovecii pneumonia prophylaxis.


Subject(s)
Diagnosis , Humans , Immunocompromised Host , Kidney , Lupus Erythematosus, Systemic , Lymphocyte Count , Mortality , Pediatrics , Pneumocystis carinii , Pneumocystis carinii , Pneumocystis , Pneumonia , Retrospective Studies , Severe Combined Immunodeficiency , Transplant Recipients , Transplants
16.
Annals of Dermatology ; : 257-264, 2015.
Article in English | WPRIM | ID: wpr-163404

ABSTRACT

BACKGROUND: There is no appropriate in vivo animal model that reflects the inflammatory response of human acne. OBJECTIVE: This study investigated the effect of Propionibacterium acnes on the development of inflammatory acne-like lesions in four mouse strains with different degrees of immune response for the development of an optimal mouse model of inflammatory acne. METHODS: Human P. acnes suspensions (10(8) and 10(9) colony forming unit [CFU]/microl) were injected into the backs of HR-1, BALB/c, vitamin D receptor-knockout (VDR k/o), and severe combined immunodeficiency disease mice. Inflammation levels were evaluated two weeks after injection of P. acnes suspensions. In addition, histopathological examination and immunohistochemical staining of the expressions of inflammatory biomarkers (i.e., CD4+/CD8+ T lymphocytes, neutrophils, myeloperoxidase, interleukin-1beta, matrix metalloprotease (MMP)-2, MMP-3, MMP-9, toll-like receptor (TLR)-2, LL-37, and integrin alpha6) were performed on tissue specimens. RESULTS: The HR-1 mouse strain exhibited the most remarkable inflammatory reaction with epithelial proliferation and microcomedone-like cyst formation. HR-1 mice also demonstrated aberrant integrin expression in the epidermis around both inflamed lesions and newly formed microcomedones. These findings were more prominent in the group receiving 10(9) CFU/microl P. acnes than 10(8) CFU/microl. MMP-9 expression in HR-1 mice was also upregulated around the microcomedone-like cysts. Finally, expression levels of TLR-2 and LL-37 were higher in HR-1 and BALB/c mice than the VDR k/o and SCID mice strains. CONCLUSION: P. acnes induces acneiform inflammation with small microcomedones in HR-1 mice. Therefore, the HR-1 mouse strain represents a good candidate for the development of a new inflammatory acne mouse model.


Subject(s)
Acne Vulgaris , Animals , Biomarkers , Epidermis , Humans , Inflammation , Interleukin-1beta , Mice , Mice, SCID , Models, Animal , Neutrophils , Peroxidase , Propionibacterium acnes , Severe Combined Immunodeficiency , Stem Cells , Suspensions , T-Lymphocytes , Toll-Like Receptors , Vitamin D
17.
Braz. j. allergy immunol ; 2(2): 56-65, mar.-apr.2014.
Article in Portuguese | LILACS | ID: lil-775987

ABSTRACT

A imunodeficiência combinada grave (SCID) é uma condição clínica caracterizada por marcante comprometimento da resposta imune envolvendo linfócitos T e/ou B e/ou células NK, que conduza aumento da susceptibilidade a infecções e alta taxa de mortalidade em crianças acometidas. Dificuldades na interpretação dos sintomas clínicos e na identificação de mutações genéticas, devido à ampla variedade fenotípica e genotípica da doença, representam obstáculos para o diagnóstico. Por outro lado, o tratamento é realizado de forma independente da identificação de mutação genética. O objetivo do presente trabalho foi revisar aspectos fisiopatológicos, métodos diagnósticos e tratamentos utilizados em pacientes com SCID. A revisão foi realizada com base em levantamento bibliográfico de banco de dados indexados disponíveis na Internet incluindo LILACS, MEDLINE, PubMed, SciELO Brasil, periódicos CAPES e Cochrane, e foi conduzida com os seguintes critérios de inclusão: artigos científicos publicados nos idiomas português e inglês, dentro do período de 1963 a 2014 e que possuíam as palavras-chave “Imunodeficiência Combinada Grave”, “SCID”, “Leucopenia”, “Diagnóstico”, “Tratamento” e “Transplante de medula óssea”. O levantamento bibliográfico revelou dificuldades no diagnóstico clínico, laboratorial e genético-molecular, e ressaltou a importância do diagnóstico precoce conduzindo ao tratamento adequado. O diagnóstico precoce da SCID tem papel crucial na melhora da qualidade de vida e na sobrevida dos pacientes, além de favorecer intervenções terapêuticas que previnem o surgimento de infecções e complicações clínicas subsequentes...


Severe combined immunodeficiency (SCID) is a clinical condition characterized by marked impairment of immune responses involving T and/or B lymphocytes and/or NK cells, leading to increased susceptibility to infections and a high mortality rate among affected infants. Difficulties in the interpretation of clinical symptoms and in the detection of genetic mutations make diagnosis a challenge because of the phenotypic and genotypic heterogeneity associated with the disease. Treatment is performed regardless of the detection of a genetic mutation. The objective of the present study was to review pathophysiological aspects, diagnostic methods, and therapies used in patients with SCID. The review included papers available in online databases, including LILACS, MEDLINE, PubMed, SciELO Brazil, Periódicos CAPES, and Cochrane. Papers were searched considering the following inclusion criteria: research articles published in Portuguese or English, between years 1963 and 2014, containing the keywords "Severe Combined Immunodeficiency," "SCID," "Leukopenia," "Diagnosis," "Treatment," and "Bone Marrow Transplantation." The review revealed difficulties in clinical, biochemical, and molecular genetic diagnosis, and emphasized the importance of early diagnosis leading to appropriate treatment. Early diagnosis of SCID is crucial to improve the quality of life and survival of patients, and it allows the use of therapeutic interventions that prevent the onset of infections and subsequent clinical complications...


Subject(s)
Humans , Bone Marrow Transplantation , Severe Combined Immunodeficiency/diagnosis , Leukopenia/immunology , T-Lymphocytes/immunology , Therapeutics , Diagnostic Techniques and Procedures , Methods , Patients , Quality of Life
18.
Egyptian Journal of Hospital Medicine [The]. 2014; 57 (October): 395-402
in English | IMEMR | ID: emr-160238

ABSTRACT

PD-1 expression is controlled during T-cell activation. PD-1 has an important role in regulating immune response as well as tolerance. During chronic hepatitis C virus [HCV] infection there is high level of PD-1 expression on exhausted CD8+T cells. There is also reduced expression of T-bet. T-bet is identified as a transcriptional repressor of Pdcd1. The study will attempt to find out the level of expression of PD-1 on peripheral CD8 + T-cells, associated with chronic HCV infection. Fifty patients with chronic hepatitis C virus infection [CHCV], whose age ranged between [16-59] years, were selected from the National Hepatology and Tropical Medicine Research Institute were included in this study, before Interferon and ribavirin therapy, and fifteen healthy individuals were included to serve as controls. All the patients and controls were subjected to the following: history, clinical examination, abdominal ultrasonography and collection of blood samples for routine laboratory investigations. CBCs and analysis of the expression of surface markers on CD8+T cells and PD-1. Our results suggested that increased expression of PD-1 cells was an additional inhibitory mechanism that contributed to virus-specific CD8 + T cell exhaustion in chronic hepatitis C virus [CHCV] infected patients. Our study concluded that there's significant increase in PD-1 expression of circulating HCV-specific CD8 + T cells in CHCV patients. The blockade of the inhibitory receptors [PD-1] programmed cell death is considered as a novel strategy for the treatment of chronic HCV infection


Subject(s)
Humans , Hepacivirus/pathogenicity , Severe Combined Immunodeficiency , Real-Time Polymerase Chain Reaction/statistics & numerical data , Ribavirin , Interferon-alpha , Treatment Outcome
19.
Chinese Journal of Hematology ; (12): 424-427, 2014.
Article in Chinese | WPRIM | ID: wpr-238795

ABSTRACT

<p><b>OBJECTIVE</b>To explore the risk factors, and control measures of cytomegalovirus (CMV) infection after hematopoietic stem cell transplantion (HSCT) in children with primary immunodeficiency diseases(PID).</p><p><b>METHODS</b>We retrospectively analyzed results of 26 patients with PID-Wiskott-Aldrich syndrome (WAS, n=20), severe combined immunodeficiency (SCID, n=1) , X-linked chronic granulomatous disease (XCGD, n=2) and X-linked hyper-immunoglobulin M (IgM) syndrome (XHIM, n=3)-who underwent HSCT from June 2007 to December 2012 in our center. Serologic studies (ELISA) and weekly CMV infection surveillance (quantitative PCR, qPCR) were routinely performed before and after HSCT. Ganciclovir or forcarnet was used for pre-emptive and curative therapy.</p><p><b>RESULTS</b>All 26 patients were male with the median age at HSCT of 27 months (range 7-77 months). At a median follow up of 24 months (range 5-66 months), the 5-year overall survival rate was (75.0 ± 9.0) %. CMV infection occurred in 42.3% (11 of 26) of the patients, two of them developed CMV interstitial pneumonia (CMVIP). Univariate analysis revealed that the incidence of pre-transplant CMV infection between with and without CMV activation groups after HSCT was significantly different (62.5% vs 10.0%, P=0.010). Additional variables not associated with CMV infection were stem-cell sources, donor type, HLA disparity and acute GVHD (all P values>0.05).</p><p><b>CONCLUSION</b>CMV infection was a major complication of HSCT. Sensitive monitoring, early diagnosis, timely treatment may improve the survival rate for these PID undergoing HSCT.</p>


Subject(s)
Child , Child, Preschool , Cytomegalovirus Infections , Virology , Graft vs Host Disease , Granulomatous Disease, Chronic , Therapeutics , Hematopoietic Stem Cell Transplantation , Humans , Infant , Male , Retrospective Studies , Risk Factors , Severe Combined Immunodeficiency , Therapeutics , Tissue Donors , Wiskott-Aldrich Syndrome , Therapeutics
20.
Article in English | WPRIM | ID: wpr-195961

ABSTRACT

Severe combined immunodeficiency (SCID) is a life-threatening syndrome of recurrent infections and gastrointestinal alterations due to severe compromise of T cells and B cells. Clinically, most patients present symptoms before the age of 3 months and without intervention SCID usually results in severe infections and death by the age of 2 years. Its association with intestinal anomalies as multiple intestinal atresias (MIA) is rare and worsens the prognosis, resulting lethal. We describe the case of a four year-old boy with SCID-MIA. He presented at birth with meconium peritonitis, multiple ileal atresias and underwent several intestinal resections. A targeted Sanger sequencing revealed a homozygous 4-bp deletion (c.313DeltaTATC; p.Y105fs) in tetratricopeptide repeat domain 7A (TTC7A). He experienced surgical procedures including resection and stricturoplasty. Despite parenteral nutrition-associated liver disease, the patient is surviving at the time of writing the report. Precocious immune system assessment, scrutiny of TTC7A mutations and prompt surgical procedures are crucial in the management.


Subject(s)
B-Lymphocytes , Humans , Immune System , Intestinal Atresia , Liver Diseases , Male , Meconium , Parturition , Peritonitis , Prognosis , Severe Combined Immunodeficiency , T-Lymphocytes , Writing
SELECTION OF CITATIONS
SEARCH DETAIL