Assessment of vitamin D status in common variable immunodeficiency or ataxia-telangiectasia patients

Introduction and objectives: Vitamin D plays a role in the immune system, however studies regarding this are scarce. This study aimed to evaluate the nutritional status of vitamin D in patients with Common Variable Immunodeficiency (CVID) or Ataxia-Telangiectasia (A-T) and to relate it to body composition, inflammatory and bone metabolism markers. Patients and methods: This is a cross-sectional and controlled study involving 24 patients of both sexes (59.3% male), aged 8-56 years, with CVID (n = 15) or A-T (n = 9). The following variables were evaluated: body mass index (BMI), 25-hydroxyvitamin D (25 (OH) D), hepatic profile, parathormone, calcium, phosphorus, alkaline phosphatase, interleukin 6 and high-sensitivity C-reactive protein. Results: The median age was 26.0 years. A deficiency of 25 (OH) D was found in four A-T patients (44%) and two CVID patients (13%). Nine patients with CVI (60%) and six with A-T (66.7%) were overweight and underweight, respectively. There was a negative correlation between vitamin D and fat mass in the CVID group, and vitamin D and BMI in the A-T group. Vitamin D was negatively associated with the percentage of total fat among the patients (β - 0.842, 95% CI: -1.5-0.17, p = 0.015), R2 = 0.21, after adjusting for sex and age. Conclusion: Vitamin D deficiency occurred in a quarter of the patients although there was no difference between the patient and the control group; without association with bone and inflammation biomarkers. The percentage of fat and BMI were negatively associated with the concentrations of 25 (OH) D

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B-cell subsets imbalance and reduced expression of CD40 in ataxia-telangiectasia patients

BACKGROUND: Ataxia-telangiectasia (AT) is a well-known primary immunodeficiency with recurrent sinopulmonary infections and variable abnormalities in both the humoral and cellular immune system. Dysfunctions in immunoglobulin production, reduced number of B cells, and B-cell receptor excision circles copies have been reported. We aimed to understand the immunological mechanisms involving the humoral compartment in AT patients by analysing peripheral blood B cells subsets, B-T lymphocyte cooperation through the expression of CD40 and CD40 ligand (CD40L), and cytokines involved in class-switch recombination production. METHODS: We compared the proportion of B-cell subsets, the expression of CD40/CD40L, and the plasma levels of IL-6 and IFN-gamma of 18 AT patients and 15 healthy age-sex-matched controls using flow cytometry. RESULTS: We found that some steps in peripheral B cell development were altered in AT with a pronounced reduction of cell-surface CD40 expression. The proportions of transitional and naïve-mature B cells were reduced, whereas CD21-low, natural effector memory, IgM-only memory, and IgG atypical memory B cells were present in a higher proportion. CONCLUSIONS: These findings revealed a disturbed B-cell homeostasis with unconventional maturation of B lymphocyte memory cells, which can explain the consequent impairment of humoral immunity

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Prospective evaluation of Streptococcus pneumoniae serum antibodies in patients with primary immunodeficiency on regular intravenous immunoglobulin treatment

BACKGROUND: This is a prospective study that assessed pneumococcal antibody levels in PID patients under intravenous immunoglobulin (IVIG) treatment using different brands. METHODS: Twenty-one patients receiving regular IVIG every 28 days were invited to participate: 12 with common variable immunodeficiency, six with X-linked agammaglobulinaemia and three with hyper-IgM syndrome. One blood sample was collected from each patient just prior to IVIG administration at a threemonth time interval during one year. A questionnaire was filled in with patient's demographic data and history of infections during the study period. Streptococcus pneumoniae antibodies against six serotypes (1, 5, 6B, 9V, 14 and 19F) were assessed by ELISA both in patients' serum (trough levels) and in IVIG samples. RESULTS: Median total IgG trough serum levels were 7.91 g/L (range, 4.59-12.20). All patients had antibody levels above 0.35 g/mL to the six serotypes on all four measurements. However, only 28.6% of patients had pneumococcal antibodies for the six analysed serotypes above 1.3 g/mL on all four evaluations during the one-year period. No correlation was found between IgG trough levels and pneumococcal specific antibodies. Eighteen of the 21 patients (85.7%) had infections at some point during the 12-month follow-up, 62/64 (96.9%) clinically classified in respiratory tract infections, four of which were pneumonia. CONCLUSIONS: Pneumococcal antibodies are present in a high range of concentrations in sera from PID patients and also in IVIG preparations. Even maintaining a recommended IgG trough level, these patients can be susceptible to these bacteria and that may contribute to recurrent respiratory infections

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Tuberculosis in an autosomal recessive case of chronic granulomatous disease due to mutation of the NCF1 gene

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Doctors’ awareness concerning primary immunodeficiencies in Brazil

BACKGROUND: PIDs are a heterogeneous group of genetic illnesses, and delay in their diagnosis is thought to be caused by a lack of awareness among physicians concerning PIDs. The latter is what we aimed to evaluate in Brazil. METHODS: Physicians working at general hospitals all over the country were asked to complete a 14-item questionnaire. One of the questions described 25 clinical situations that could be associated with PIDs and a score was created based on percentages of appropriate answers. RESULTS: A total of 4026 physicians participated in the study: 1628 paediatricians (40.4%), 1436 clinicians (35.7%), and 962 surgeons (23.9%). About 67% of the physicians had learned about PIDs in medical school or residency training, 84.6% evaluated patients who frequently took antibiotics, but only 40.3% of them participated in the immunological evaluation of these patients. Seventy-seven percent of the participating physicians were not familiar with the warning signs for PIDs. The mean score of correct answers for the 25 clinical situations was 48.08% (±16.06). Only 18.3% of the paediatricians, 7.4% of the clinicians, and 5.8% of the surgeons answered at least 2/3 of these situations appropriately. CONCLUSIONS: There is a lack of medical awareness concerning PIDs, even among paediatricians, who have been targeted with PID educational programmes in recent years in Brazil. An increase in awareness with regard to these disorders within the medical community is an important step towards improving recognition and treatment of PIDs

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The relationship between nutritional status, vitamin A and zinc levels and oxidative stress in patients with ataxia-telangiectasia

BACKGROUND: Ataxia-telangiectasia (A-T) is a rare and degenerative disease that leads to varying degrees of immunodeficiency, oxidative stress, and malnutrition. Vitamin A and zinc are essential for immune function and antioxidant defence. OBJECTIVE: To compare levels of retinol, beta carotene, and zinc in patients with ataxia-telangiectasia and healthy controls. METHODS: We performed a cross-sectional study with 14 AT patients and 14 healthy controls matched for age and gender. All participants underwent a nutritional and laboratory evaluation comprising concentrations of retinol, beta carotene, serum and erythrocyte zinc, malondialdehyde (MDA), T lymphocyte numbers (CD4+ and CD8+) and immunoglobulin (IgA). RESULTS: The AT patients showed high rates of malnutrition with reduced lean body mass when compared to the control group. However, the concentrations of MDA, retinol, beta carotene, and serum and erythrocyte zinc in AT patients were similar to those of the control group. The retinol levels presented a negative correlation with MDA and positive correlation with IgA serum level. CONCLUSIONS: The AT patients assessed showed no change in nutritional status for vitamin A and zinc; however, they presented severe impairment in overall nutritional status observed and correlation between retinol with MDA and IgA

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Guidelines for the use of human immunoglobulin therapy in patients with primary immunodeficiencies in Latin America

Antibodies are an essential component of the adaptative immune response and hold long-term memory of the immunological experiences throughout life. Antibody defects represent approximately half of the well-known primary immunodeficiencies requiring immunoglobulin replacement therapy. In this article, the authors review the current indications and therapeutic protocols in the Latin American environment. Immunoglobulin replacement therapy has been a safe procedure that induces dramatic positive changes in the clinical outcome of patients who carry antibody defects

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Severe combined immunodeficiency in Brazil: management, prognosis, and BCG-associated complications

Background: Severe combined immunodeficiency (SCID) is one of the most severe forms of primary immunodeficiency. The objectives of this study were to analyze the diagnosis, treatment, and prognosis of SCID in Brazil and to document the impact of BCG vaccine. Methods: We actively searched for cases by contacting all Brazilian referral centers. Results: We contacted 23 centers and 70 patients from 65 families. Patients were born between 1996 and 2011, and 49 (70%) were male. More than half (39) of the diagnoses were made after 2006. Mean age at diagnosis declined from 9.7 to 6.1 months ( P= .058) before and after 2000, respectively, and mean delay in diagnosis decreased from 7.9 to 4.2 months ( P= .009). Most patients (60/70) were vaccinated with BCG before the diagnosis, 39 of 60 (65%) had complications related to BCG vaccine, and the complication was disseminated in 29 of 39 (74.3%). Less than half of the patients (30, 42.9%) underwent hematopoietic stem cell transplantation (HSCT). Half of the patients died (35, 50%), and 23 of these patients had not undergone HSCT. Disseminated BCG was the cause of death, either alone or in association with other causes, in 9 of 31 cases (29%, no data for 4 cases). Conclusions: In Brazil, diagnosis of SCID has improved over the last decade, both in terms of the number of cases and age at diagnosis, although a much higher number of cases had been expected. Mortality is higher than in developed countries. Complications of BCG vaccine are an important warning sign for the presence of SCID and account for significant morbidity during disease progression (AU)

Antecedentes: La inmunodeficiencia severa combinada (IDSC) es una de las formas más graves de la inmunodeficiencia primaria. El objetivo de este estudio fue analizar el estado del diagnóstico, tratamiento y pronóstico de esta enfermedad en Brasil y documentar el impacto de la vacunación con BCG (bacillus Calmette-Guérin). Métodos: Los casos fueron seleccionados tras contactar con los centros de referencia de Brasil. Resultados: Se contactaron 23 centros en total, que permitieron recopilar a 70 pacientes entre los años 1996 y 2011 procedentes de 65 familias, 49 de ellos (70%) varones. En más de la mitad de ellos (39), el diagnóstico fue realizado con posteriridad al año 2006. La edad media en el diagnóstico varió entre los 9,7 a los 6,1 meses (p=0.058), antes y después del año 2000, respectivamente, y el tiempo en que se realizó el diagnóstico disminuyó de los 7,9 a los 4,2 meses (p=0.009). La mayoría de ellos (60/70) se habían vacunado con BCG antes del diagnóstico, 39/60 (65%) tuvieron complicaciones con la BCG y en 29/39 (74.3%) la enfermedad se diseminó. En menos de la mitad de los pacientes (30/70, 42,9%) se realizó un trasplate de células madre (HSCT). La mitad de los pacientes (35/70, 50%) murieron; 23/35 de ellos sin HSCT. La diseminación del BCG fue la causa de la muerte, sola o asociada con otras causas, en 9/31 casos (29%, en 4 casos sin datos). Conclusiones: En conclusión, el diagnóstico de IDSC en Brasil ha mejorado en la última década, tanto en términos numéricos, cómo respecto a la edad de detección de la enfermedad. La mortalidad es alta en comparación con los países desarrollados. La vacuna con BCG provoca complicaciones importantes en estos pacientes, lo cual alerta sobre el posible diagnóstico y progresión de esta enfermedad (AU)

Food allergy in an exclusively breast-fed infant with Hyper-IgE syndrome

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Salivary lysozyme levels in patients with primary

Background: Lysozyme is a muramidase that acts on the peptideoglycan wall of Gram positive bacteria, causing cell death. It plays part in innate immunity and is present in blood, external fluid, as well in Iysossomal granules of the phagocytes. Primary Immunodeficiencies are a diverse group of iIInesses that, as a result of abnormalities of the immune system, increase susceptibility to infection. Among the examples of impaired natural immunity are defects in phagocytes and in the complement system. Innate immunity could be important in protecting mucosas against infections in patients with different forms of primary immunodeficiencies. The aim of this study was to investigate Iysozyme concentrations in saliva from patients with primary immunodeficiencies. Methods: Lysozyme levels in saliva samples from 34 patients with primary immunodeficiency (30 children and adolescents between the age of 3-13 years and 4 adults between the age of 20-33) and 60 agematched healthy controls (49 children and adolescents between the ages of 3-15 and 11 adults between the ages of 22-42) were determined by theIysoplate method. Results: There was no statistically significant difference between the Iysozyme concentrations in the saliva of the immunodeficient subjects and those of the healthy controls. Conclusion: The results in the present work clearly show that salivary Iysozyme levels in primary immunodeficient patients are equivalent to those found in healthy controls, suggesting that this enzyme still represents a remaining (but not a compensatory mechanism), contributing to the protection of there patients against infections

Introducción: La lisozima es una muramidasa que actua sobre la pared de peptidoglicano de las bacterias Gram-positivas, provocando la muerte celular. Desempeña un papel en la inmunidad innata y está presente en la sangre, secreciones externas y en los gránulos de los fagocitos. Las inmunodeficiencias primarias constituyen un grupo diverso de enfermedades que, como consecuencia de las anormalidades en el sistema inmune, presentan un aumento de susceptibilidad a las infecciones. Ejemplos de deficiencias de la inmunidad natural son los defectos de los fagocitos y del sistema de complemento. La inmunidadinnata puede ser importante para la protección contra las infecciones de las mucosas en los pacientes con diferentes tipos de inmunodeficiencia primaria. El objetivo de este estudio es investigar la concentración de lisozima en la saliva en pacientes con inmunodeficiencia primaria. Métodos: Los niveles de lisozima en las muestras de saliva de 34 pacientes con inmunodeficiencia primaria (30 niños y adolecentes con edad entre 3-13 años y 4 adultos con edad entre 20-33 años) y 60 controles sanos de la misma edad (49 niños y adolescentes con edad entre 3-15 años y 11 adultos conedad entre 22-42 años) fueron determinados por el método Iysoplate. Resultados: No se observó una diferencia estadística significativa entre las concentraciones de lisozima en la saliva de los individuos inmunodeficientesy de los controles sanos. Conclusión: Los resultados del presente trabajo claramente indican que los niveles de lisozima en la saliva de los pacientes con inmunodeficiencias primarias son equivalentes a los de los controles sanos, sugiriendo que este enzima representa un mecanismo remanescente, pero no compensador, que contribuye a la protección contra las infecciones en estos pacientes