RESUMO

Introduction: The World Health Organization recommends prioritizing safe and effective drugs proven by clinical or epidemiological studies. However, in population groups with little research, a drug can be used for an indication or pharmaceutical form different from that approved by the regulatory agency (off-label), extrapolating data from studies in adults and exposing pediatric patients. to develop an Adverse Drug Reaction (ADR) due to safety considerations that have not been systematically studied. Intravenous immunoglobulin (IVIg), a high-cost drug, is used with scant evidence in some low-prevalence pathologies. This paper describes and analyzes the off-label use of IVIg at the J. P. Garrahan Pediatric Hospital. Methods: Observational, descriptive, prospective study on off-label indications of IVIg. The sampling technique was non-probabilistic and for convenience during 7 months. Results: 305 IVIg infusions were studied, corresponding to 111 patients. The indication classification showed that 22% (n=67) of the infusions were off-label. In neurology there was a higher percentage of off-label indications (46%) and within them 45% corresponded to the use in neurological disorders. 81% of the doses indicated off-label were in the range 0.8-1g/kg. The off-label infusions presented 61.5% (n=8) of the ADRs. Those from the Neurology service represented 87.5%; 75% being from the "Neurological disorders" group. Conclusion: In some cases, IVIg was indicated in an off-label manner, finding a statistically significant relationship with the appearance of ADR. This finding motivates the proposition of new hypotheses to carry out more studies.

Introducción: La Organización Mundial de la Salud recomienda priorizar fármacos seguros y eficaces comprobados mediante estudios clínicos o epidemiológicos. Sin embargo, en grupos poblacionales con escasa investigación, un fármaco puede utilizarse para una indicación o, forma farmacéutica diferente a la aprobada por la agencia reguladora ("off label"), extrapolando datos provenientes de estudios en adultos y, exponiendo a los pacientes pediátricos a desarrollar una Reacción Adversa Medicamentosa (RAM) por consideraciones de seguridad no estudiadas sistemáticamente. Inmunoglobulina G endovenosa (IgG EV), medicamento de alto costo, es utilizado con escasa evidencia en algunas patologías poco prevalentes. Este trabajo describe y analiza el uso "off label" de IgG EV en el Hospital de Pediatría J. P. Garrahan. Métodos: Estudio observacional, descriptivo, prospectivo sobre indicaciones "off label" de IgG EV. La técnica de muestreo fue no probabilística y por conveniencia durante 7 meses. Resultados: Se estudiaron 305 infusiones de IgG EV que correspondieron a 111 pacientes. La clasificación de la indicación mostró que 22% (n=67) de las infusiones fueron "off label". En neurología hubo mayor porcentaje de indicaciones "off label" (46%) y dentro de ellas el 45% correspondió al uso en desórdenes neurológicos. El 81% de dosis indicadas "off label" estuvieron en rango 0,8-1g/kg. Las infusiones indicadas "off label" presentaron el 61.5% (n=8) de las RAM. Las del servicio de Neurología, representaron el 87,5 %, siendo 75% del grupo "Desórdenes neurológicos". Conclusión: En algunos casos IgG EV fue indicada en forma "off label", encontrándose una relación estadísticamente significativa con la aparición de RAM. Este hallazgo motiva al planteo de nuevas hipótesis para realizar más estudios.

Assuntos

RESUMO

Abstract This cross-sectional study evaluated the association between salivary immunoglobulins, plaque index, and gingival index in Brazilian children with and without type 1 diabetes mellitus (DM1). The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for the reporting of observational studies was followed. The DM1 group had 38 children, and an equal number of volunteers matched by sex and age were recruited as controls. Clinical examination was performed for plaque index and gingival index determination. Non-stimulated whole saliva was collected. Concentrations of IgA, IgG, and IgM were determined by ELISA test. Data were tested by the Kolmogorov-Smirnov, Mann-Whitney, and Spearman tests and a multiple linear regression model (p<0.05) was performed. Gingival index was higher in the Control (DM1: 0.16±0.17; Control: 0.24±0.23, p=0.040). In DM1, there was a correlation between IgA and age (rho=0.371, p=0.024), IgM and IgG (rho=0.459, p=0.007), and IgM and gingival index (rho=0.394, p=0.014). In DM1, multiple linear regression showed that age (p=0.041; β=0.363), gingival index (p=0.041; β=0.398), and plaque index (p=0.008; β=-0.506) were good predictors of IgA levels in saliva. Thus, IgA was the only researched immunoglobulin that was directly associated with plaque and gingival indices in Brazilian children with DM1, but not in control subjects.

RESUMO

The aim of this study was to determine effects of parity (primiparous vs. multiparous), seasonal heat stress at calving (summer vs. winter), and time postpartum on some parameters associated with colostrum quality in Holstein cows reared in the Sonoran Desert ecosystem. Forty-seven cows (11 primiparous and 36 multiparous) expected to calve during summer, and 46 cows during winter (14 primiparous and 32 multiparous) were randomly selected. Management and feeding before and after parturition were similar for cows in both seasons. After parturition, colostrum from all cows was evaluated for volume, weight, temperature, density, and content of fat, protein, solids non-fat (SNF), and immunoglobulins (IGG). Data were analyzed with a model that included effects of parity status, calving season, and time postpartum, as well as all interactions. Colostrum produced in summer was warmer (P < 0.01) by almost 6 °C than winter colostrum, while colostrum from multiparous was warmer (P = 0.02) by 1.2 °C than that produced by primiparous cows. Colostrum volume and weight were not impacted by parity, calving season or time postpartum. Density, protein, and SNF content in colostrum were higher (P < 0.01) in multiparous vs. primiparous cows, as well as at parturition (0 h postpartum) than at 12 h postpartum (P < 0.01). At calving (0 h), spring colostrum had higher fat content (P < 0.01) and lower (P < 0.01) IGG concentration than that collected in summer, and no difference (P > 0.05) between seasons was observed for these components at 12 h postpartum. Multiparous cows produced colostrum with higher (P < 0.01) IGG concentrations than primiparous cows. In conclusion, only 0-h colostrum and that from multiparous cows was categorized as "Excellent," meanwhile the colostrum produced under summer heat stress was characterized as "Good" with reduced fat content. While the lacteal secretion collected at 12 post-partum still classified as colostrum, substantially lower contents of IGG, protein, fat, and SNF decreased its classification to "Poor" from the classification of "Excellent" at 0 h postpartum.

Assuntos

RESUMO

The regulatory T (Treg) cells constitute a functionally defined subpopulation of T cells that modulate the immune system and maintain immune tolerance through suppression of the development of autoimmune responses to self-antigens and allergic reactions to external antigens. Reduction in the number or function of Treg cells has been suggested as a key immune abnormality underlying the development of autoimmune and allergic diseases. In vitro studies have demonstrated that purified polyvalent immunoglobulin G (IgG) from multiple healthy blood donors can exert immunomodulatory effects on Treg cells. Incubation of polyvalent human IgG with purified CD4+CD25high T cells increased the intracellular expression of interleukin (IL)-10. Intravenous administration of polyvalent human IgG induced significant expansions of CD4+ Foxp3+ Treg cells and clinical improvements in patients with autoimmune diseases. In human clinical trials, intramuscular administration of autologous total IgG significantly increased the percentage of IL-10-producing CD4+ Treg cells in the peripheral blood of healthy subjects and provided significant clinical improvements in patients with atopic dermatitis. These results suggest a clinical usefulness of polyvalent IgG-induced activation of Treg cells in human subjects. This review proposes a new hypothesis for immune tolerance mechanism by integrating the pre-existing "idiotypic network theory" and "Treg cell theory" into an "anti-idiotypic Treg cell theory." Based on this hypothesis, an "active anti-idiotypic therapy" for allergic and autoimmune diseases using autologous polyvalent IgG (as immunizing antigens) is suggested as follows: (1) Intramuscular or subcutaneous administration of autologous polyvalent IgG produces numerous immunogenic peptides derived from idiotypes of autologous IgG through processing of dendritic cells, and these peptides activate anti-idiotypic Treg cells in the same subject. (2) Activated anti-idiotypic Treg cells secrete IL-10 and suppress Th2 cell response to allergens and autoimmune T cell response to self-antigens. (3) These events can induce a long-term clinical improvements in patients with allergic and autoimmune diseases. Further studies are needed to evaluate the detailed molecular mechanism underlying polyvalent IgG-induced Treg cell activation and the clinical usefulness of this immunomodulatory therapy for autoimmune and allergic diseases.

Assuntos

RESUMO

The effects of supplementing the diet of sows with ßG-(1,3) derived from Euglena gracilis algae were assessed regarding quality and amount of colostrum as well as performance of piglets. A total of 120 sows (first (nulliparous) to sixth parity (multiparous)) from D85 of gestation until weaning were divided into two groups: the control diet group (n = 60) and the ßG-(1,3) diet group (n = 60). Sows receiving ßG-(1,3) exhibited an average increase of 870 g (24.9%) in colostrum production, leading to a 25.17% higher intake of colostrum by piglets. Furthermore, piglets in the ßG-(1,3) group showed significantly superior weight gain of 34 g (50%) compared to the control group 18 h after birth (p < 0.05). Sows fed with ßG-(1,3) produced colostrum with significantly higher concentrations of IgG (5.914 mg/mL, 16.16%) and IgM (0.378 mg/mL, 16.29%) than the control group (p < 0.05). Similarly, serum concentrations of IgG (13.86 mg/mL, 51.25%), IgA (17.16 mg/mL, 120.19%), and IgM (13.23 mg/mL, 144.78%) were significantly higher in sows fed with ßG-(1,3) than in the control group (p < 0.05). Supplementing sows with ßG-(1,3) derived from the Euglena gracilis algae resulted in increased colostrum production and consumption, along with greater weight gain in piglets during the first 18 h after birth. Additionally, both the colostrum produced by the sows and the blood serum of the piglets exhibited higher concentrations of immunoglobulins.

RESUMO

Birth and the first few weeks of age are critical periods of developing the immune system of puppies and kittens and adapting to an environment containing a variety of infectious agents. The survival rate during these periods depends mainly on the newborn's immune capacity to prevent and combat infections. Although most components of innate and adaptive immunity are present at birth, responses are slow and immature compared to adults. Due to immunological immaturity and the endotheliochorial placental structure, circulating concentrations of immunoglobulins in dogs and cats at birth are quite low. Thus, newborns need a prompt and immediate immune response, which is essentially provided by defense cells and maternal antibodies via colostrum. Failure to ingest colostrum is correlated with high mortality rates in the neonatal period. Concurrently, factors related to pregnant, such as pregnancy physiological immunosuppression and nutritional and health states, can directly influence newborn immunity and health. Therefore, understanding the maternal and neonatal immunological aspects, importance of colostrum, risk factors for failure to transfer passive immunity and colostrum substitute strategies are essential to ensure the survival of the litter.

Assuntos

RESUMO

This study aimed to evaluate the immunity of chickens up to 35 d subjected to posthatch fasting and supplementation with conjugated linoleic acid (CLA). A total of 320 chicks were housed in a completely randomized design with a 2 × 2 factorial arrangement (0 or 12 h of fasting × 0.000 or 0.025% CLA in a prestarter diet), totaling 4 treatments (No-F-12 h; F-12 h; No-CLA; CLA) with 8 replicates of 10 birds each. The relative weights (% body weight) of the spleen and bursa were determined 12 h posthatch (Post-12 h) and then weekly. Immunoglobulin Y (IgY) titers against Newcastle disease virus (NDV) were measured by ELISA in the yolk sac contents Post-12 h and in the serum weekly. Hypersensitivity to phytohemagglutinin (PHA) inoculation was evaluated by toe-web swelling response on d 13 and 34, 4 times a day (after 3 h, 6 h, 12 h, and 24 h inoculation, respectively, PHA-3 h, PHA-6 h, PHA-12 h, and PHA-24 h). The data were subjected to analysis of variance (P < 0.05). F-12h reduced the Post-12 h relative weight of the spleen, and CLA reduced the relative weight of the bursa at this stage and at 28 d. At 13 d, F-12 h reduced PHA-3 h, whereas PHA-12 h was increased by CLA. At 34 d, CLA reduced PHA-3 h. A greater reaction was observed in the No-F-12 h-CLA chicks, for the PHA-24 h. In the Post-12 h evaluation, F-12h reduced, whereas CLA increased NDV-specific IgY titers in the yolk sac. No-F-12 h-No-CLA chicks had the lowest serum titers. At 21 d, F-12 h-CLA chicks exhibited the highest serum titers. Titers were higher in the F-12 h-No-CLA chicks, when compared to other treatments. At 28 d, fasting reduced the titers. In conclusion, F-12 h and CLA accelerated the transfer of immunoglobulins from the yolk sac to the serum. F-12 h impairs cellular immunity, whereas CLA favors it.

Assuntos

RESUMO

El déficit selectivo de IgA se define como la ausencia parcial o total de IgA en el suero, con cifras normales en el resto de las inmunoglobulinas. Se presentó una paciente femenina de 1 año y 7 meses, de padres no consanguíneos, con antecedentes familiares negativos para enfermedades genéticas o defectos congénitos, e IgA deficiente. Los estudios inmunológicos mostraron un gran déficit de IgA, de ahí que el diagnóstico se definió como una inmunodeficiencia congénita, por déficit selectiva de IgA o inmunodeficiencia variable común (trastorno genético producto de una herencia monogénica); para lo cual se le realiza una cuantificación de la subclase de IgG y así determinar si es una mutación en un mismo gen defectuoso. La paciente evolucionó satisfactoriamente con los tratamientos recibidos; los valores de IgA permanecieron nulos, no siendo así con el resto de las inmunoglobulinas.

Selective IgA deficiency is defined as the partial or total absence of IgA in the serum, but normal levels in the rest of the immunoglobulins. We present a female patient aged 1 year and 7 months, of non-consanguineous parents, who had a negative family pathological history for genetic diseases or congenital defects and IgA deficiency. Immunological studies showed a high IgA deficiency, hence the diagnosis was defined as congenital immunodeficiency due to selective IgA deficiency or common variable immunodeficiency (genetic disorder resulting from monogenic inheritance); a quantification of the IgG subclass was also performed in order to determine if it was a mutation in the same defective gene. The patient evolved satisfactorily with the treatments received; the IgA values remained null, but this was not the case with the rest of the immunoglobulins.

Assuntos

RESUMO

Transient hypogammaglobulinemia of infancy (THI) is a primary immunodeficiency caused by a temporary decline in serum immunoglobulin G (IgG) levels greater than two standard deviations below the mean age-specific reference values in infants between 5 and 24 months of age. Preterm infants are particularly susceptible to THI, as IgG is only transferred across the placenta from mother to infant during the third trimester of pregnancy. This study aimed to conduct a systematic review of the diagnostic criteria for transient hypogammaglobulinemia of infancy. Systematic review: Three electronic databases (PubMed, MEDLINE, and Google Scholar) were manually searched from September 2021 to April 2022. Abstracts were screened to assess their fit to the inclusion criteria. Data were extracted from the selected studies using an adapted extraction tool (Cochrane). The studies were then assessed for bias using an assessment tool adapted from Cochrane. Of the 215 identified articles, 16 were eligible for examining the diagnostic criteria of THI. These studies were also assessed for bias in the six domains. A total of five studies (31%) had a low risk of bias, while four studies (25%) had a high risk of bias, and bias in the case of seven studies (44%) was unclear. We conclude that THI is only definitively diagnosed after abnormal IgG levels normalise. Hence, THI is not a benign condition, and monitoring for subsequent recurrent infections must be conducted. The diagnostic criteria should also include vaccine and isohaemagglutinin responses to differentiate THI from other immunological disorders in infants.

RESUMO

Background: More than two years after the pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) there is a great lack of information. The presence of immunoglobulin G (IgG) have been related with disease severity. Patients with comorbidities could develop more severe infection; however, the evaluation of the humoral response in pediatric population are needed especially in patients with comorbidities. Our aim was to describe the behavior of IgG in pediatric patients and to know if there is a difference between patients with comorbidities. Methods: A prospective comparative cohort study was carried out in a single center from June 2020 to January 2021, with a follow-up of 6 months. The study included all the subjects with confirmatory test for SARS-CoV-2 from 1 month to 17 years 11 months, the follow-up of the disease's evolution and measurement of IgG antibodies was collected. We obtained the clinical data, and comorbidities like arterial hypertension, diabetes, obesity, and cancer, the initial symptoms were recorded as well as the evolution regarding the severity of COVID-19 and the need for hospitalization, intensive care unit or mechanical ventilation. The follow up was carried out through medical consultation with an appointment every month that included direct interrogation, examination, and peripheral blood collection for the IgG quantification. The antibodies detection was done through peripheral blood and chemiluminescence microparticle immunoassay. Results: A total of 237 patients with positive polymerase chain reaction (PCR) for SARS-COV-2 were included, of which 147 presented IgG antibodies (62%), 112 (76%) without comorbidity and 35 (24%) with comorbidities, by the sixth month only 2.7% continue with positive antibody measurements. Patients with comorbidities reach higher IgG levels than patients without comorbidities the basal titters were: 5.17 for patients without comorbidities vs. 6.96 for the group with comorbidities (P<0.001). Conclusions: We found an association between the presence of comorbidities and high levels of IgG units in pediatric patients with COVID-19. Additionally, patients with more severe course of the disease have higher levels of IgG and by the third month less than 35% have immunity.