Application of the diagnostic criteria for Common Variable Immunodeficiency in resource-limited settings.

INTRODUCTION: Common variable immunodeficiency (CVID) is the most prevalent symptomatic humoral deficiency; however, its heterogeneous presentation makes the diagnosis difficult. The present study is aimed to verify the CVID diagnostic criteria as established by the European Society for Immunodeficiencies in 42 CVID patients from our outpatient clinic. METHODS: Information was collected from their medical records and when needed, lymphocyte subpopulations in peripheral blood (PB) were performed by flow cytometry. RESULTS: All the patients fulfilled the clinical working definition for CVID and showed decreased serum IgG and IgA at diagnosis. Over two-thirds of the patients had decreased memory B cell percentages. However, the remaining patients exhibited other quantitative B cell defects in PB. Evaluation of vaccination responses was only found in 13 records and 69% were not responsive. None of the patients were subjected to vaccination studies to both, T-cell dependent and independent antigens. The two required tests to evaluate T cell responses were performed in 84.2% of the patients and reported normal. Without the support of third-party payers, only 34.2% of our patients would have completed the required evaluations. CONCLUSIONS: Further efforts are needed to speed up CVID diagnosis in low-resourced settings, increasing the availability of the required resources and optimizing the healthcare supply chain.

Tosferina: una mirada epidemiológica, clínica y del laboratorio / Pertussis: an epidemiological, clinical and laboratory view

Resumen: la tosferina es una enfermedad aguda bacteriana, causada por Bordetellapertussis, que afecta el tracto respiratorio superior, produciendo fuertes accesos de tos, asfixia y cianosis. Otros microorganismos pueden producir un cuadro similar a la tosferina, conocido como síndrome coqueluchoide, el cual es su principal diagnóstico diferencial. La enfermedad se presenta en su mayoría en lactantes menores, especialmente los que no están adecuadamente inmunizadosy están en contacto con adolescentes y adultos, potenciales reservorios de la enfermedad. Actualmente se realiza el diagnóstico mediante criterios clínicos y microbiológicos, que permiten clasificar al paciente en caso probable o confirmado.En cuanto al tratamiento el manejo estándar de la enfermedad incluye antibióticostipo macrólidos. Dependiendo de la severidad del cuadro se implementa tratamiento de soporte con oxígeno, corticoides, vasodilatadores pulmonares y sedantes. La mejor forma de prevención es una alta cobertura de vacunación cumpliendo los esquemas propuestos. La protección inducida por la vacuna alcanzaentre 70%-85% de los títulos de anticuerpos, los cuales disminuyen entre los 4-7 años posvacunación, lo que hace imprescindible la implementación de una dosis de refuerzo a los 18 meses y 5 años. En Colombia todavía falta el establecimiento de otras opciones a edades más avanzadas, previniendo que la persona joven y adulta sea el reservorio de la enfermedad. En general, los hallazgos y avances en el estudio de la tosferina evidencian que es una entidad clínica con un aumento significativo en su incidencia en la población pediátrica, a pesar de que se cree que está totalmente controlada.

Abstract: pertussis is an acute bacterial disease caused by Bordetella pertussis that affects the upper respiratory tract, producing severe cough, asphyxia, and cyanosis. Other microorganisms can cause a similar clinical picture to pertussis, known as coqueluchoide syndrome, which is the main differential diagnosis. The disease occurs mainly in infants, especially those who are not adequately immunizedand are exposed to adolescents and adults, the potential reservoirs of the disease. Currently the diagnosis is by clinical and microbiological criteria for classifying the patient as probable or confirmed case. The treatment standard management is with antibiotic, especially macrolides. Depending on the severity of case, support treatment including oxygen, steroids, sedatives, and pulmonary vasodilators is implemented. The best prevention of disease is high vaccination coverage, fulfilling with the schemes proposed. The induced protection by the vaccine reaches between 70%-85% of antibody titers, which decrease between 4-7 years post vaccination, which make essential to implement a strategy of booster shot at 18 months and 5 years-old. However, Colombia has not developedother options at older ages, that prevent the young and adults become the reservoir of the disease. Overall findings and advances in the whooping cough study shows that is a clinical entity with a significant increase of its incidence in the pediatric population, although it is believed that is fully controlled.

[Variation in NK cell number and function in individuals with recurrent or severe infections]. / Variaciones en el número y función de los linfocitos asesinos naturales durante infecciones recurrentes o graves.

INTRODUCTION: The information about defects affecting natural killer cell (NK) development and activity in patients with an abnormal increase of recurrent infections is scarce. OBJECTIVE: To perform a systematic analysis of NK abnormalities in patients with recurrent infections. MATERIALS AND METHODS: Our study enrolled twenty patients with severe or recurrent viral infections. Natural killer cell subsets, surface receptors expression and cytotoxicity were analyzed. Results were compared with those from age- and sex-matched healthy controls. RESULTS: Transient alterations were observed in the percentages and absolute numbers of NK cells in patients with infection active episodes. We also described five patients with stable disturbances in the distribution of NK cell subpopulations. These defects are mainly due to a decrease in the CD56 dim CD16 bright cells in peripheral blood. In addition, NK cell function abnormalities were observed in some patients, however, those were always transient and mainly associated to active disease. CONCLUSIONS: These findings demonstrate transient alterations in the percentages and absolute numbers of NK cells in patients with recurrent or severe infection. Also, stable disturbances in CD56 dim CD16 bright NK cells are observed in these patients. Nevertheless, these parameters must be thoroughly studied to determine the mechanisms that entail these immune abnormalities and investigate how they alter the immune response.

Variaciones en el número y función de los linfocitos asesinos naturales durante infecciones recurrentes o graves / Variation in NK cell number and function in individuals with recurrent or severe infections

Introducción. Existen pocos datos sobre los defectos que afectan el desarrollo y función de los linfocitos asesinos naturales ( natural killers, NK) en pacientes con un incremento anormal en la recurrencia de infecciones. Objetivo. Realizar una evaluación sistemática de las diferentes subpoblaciones y la función de estas células en pacientes con infecciones recurrentes. Materiales y métodos. Se incluyeron 20 pacientes con infecciones graves o recurrentes y se analizaron las subpoblaciones y la respuesta citotóxica de los linfocitos NK en sangre periférica. Los resultados de los pacientes se compararon con controles sanos pareados por edad y sexo. Resultados. Los pacientes con episodios infecciosos activos presentaron anormalidades transitorias en el porcentaje o el número absoluto de linfocitos NK. Se caracterizaron, además, cinco pacientes con alteraciones persistentes en la distribución de las subpoblaciones de linfocitos NK. Estas alteraciones se debieron principalmente a la disminución de células CD56 dim CD16 bright . Se evidenciaron, también, defectos en la función de los linfocitos NK en algunos de nuestros pacientes; sin embargo, estas alteraciones fueron transitorias y se asociaron principalmente a la fase activa de la enfermedad. Conclusiones. Nuestros resultados evidencian defectos transitorios en el número y función de los linfocitos NK en pacientes con infecciones recurrentes o graves, además de alteraciones persistentes en los LNK CD56 dim CD16 bright en algunos individuos. Es necesario profundizar en los mecanismos que conllevan al desarrollo de estos defectos inmunes y estudiar cómo estas alteraciones influyen en la respuesta inmune.

Introduction: The information about defects affecting natural killer cell (NK) development and activity in patients with an abnormal increase of recurrent infections is scarce. Objective: To perform a systematic analysis of NK abnormalities in patients with recurrent infections. Materials and methods: Our study enrolled twenty patients with severe or recurrent viral infections. Natural killer cell subsets, surface receptors expression and cytotoxicity were analyzed. Results were compared with those from age- and sex-matched healthy controls. Results: Transient alterations were observed in the percentages and absolute numbers of NK cells in patients with infection active episodes. We also described five patients with stable disturbances in the distribution of NK cell subpopulations. These defects are mainly due to a decrease in the CD56 dim CD16 bright cells in peripheral blood. In addition, NK cell function abnormalities were observed in some patients, however, those were always transient and mainly associated to active disease. Conclusions: These findings demonstrate transient alterations in the percentages and absolute numbers of NK cells in patients with recurrent or severe infection. Also, stable disturbances in CD56 dim CD16 bright NK cells are observed in these patients. Nevertheless, these parameters must be thoroughly studied to determine the mechanisms that entail these immune abnormalities and investigate how they alter the immune response.

Analyses of the PRF1 gene in individuals with hemophagocytic lymphohystiocytosis reveal the common haplotype R54C/A91V in Colombian unrelated families associated with late onset disease.

Familial hemophagocytic lymphohistiocytosis (FHL), is a rare autosomal recessive disorder characterized by an impairment of cytotoxic cells and uncontrolled activation of macrophages. This study presents the first description of four patients with FHL type 2 in Latin America. Patient 1 fulfilled the disease diagnostic criteria since 2 months of age, whereas patients 2, 3 and 4 exhibited the typical manifestations of the disease only later in their childhood. The PRF1 genetic analysis in these patients revealed two previously reported mutations: L17fsx50 and R54C. Interestingly, seven out of the 8 alleles evaluated here in patients carried the haplotype R54C/A91V, suggesting that this is a highly frequent FHL type 2 allele in Colombia. This haplotype confers residual cytotoxic function leading to late onset disease. Therefore, this report highlights the remarkable complexity of FHL diagnostic, emphasizing the importance of the genetic characterization of the disease.