RESUMO
There is strong evidence from animal models that placental and/or breast milk-mediated transfer of maternal allergen-specific IgG prevents allergic immune responses in the progeny. Both human and animal data also point to IgA as having an important regulatory role. In contrast, little is known about maternal transfer of IgG and IgA specific for respiratory allergens in humans. Dermatophagoides pteronyssinus (Der p) is an indoor allergen that is a major cause of asthma worldwide. We analysed maternal to child Der p-specific IgG and IgA transfer in a cohort of 77 paired maternal and child samples. We found Der p-specific IgG and its IgG1, IgG2 and IgG4 subclasses in all cord blood samples. Except for IgG1, cord levels were higher in newborns from atopic mothers (n = 29) compared to non-atopic mothers (n = 48). Der p-specific IgA was found in all colostrum samples and levels were independent of maternal atopic status. Notably, anti-Der p IgG was also found in colostrum and levels were higher in atopic mothers. We believe that our work is a critical first step in the identification of early factors that may impact asthma development and should guide the development of clinical studies that assess whether Der p-specific IgG and IgA protect children from allergy as demonstrated in animal models.
Assuntos
Dermatophagoides pteronyssinus/imunologia , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Adolescente , Adulto , Animais , Colostro/imunologia , Feminino , Sangue Fetal/imunologia , Humanos , Recém-Nascido , Masculino , Adulto JovemRESUMO
Rubinstein-Taybi syndrome (RTS) is a rare developmental disorder characterized by craniofacial dysmorphisms, broad thumbs and toes, mental and growth deficiency, and recurrent respiratory infections. RTS has been associated with CREBBP gene mutations, but EP300 gene mutations have recently been reported in 6 individuals. In the present study, the humoral immune response in 16 RTS patients with recurrent respiratory infections of possible bacterial etiology was evaluated. No significant differences between patients and 16 healthy controls were detected to explain the high susceptibility to respiratory infections: normal or elevated serum immunoglobulin levels, normal salivary IgA levels, and a good antibody response to both polysaccharide and protein antigens were observed. However, most patients presented high serum IgM levels, a high number of total B cell and B subsets, and also high percentiles of apoptosis, suggesting that they could present B dysregulation. The CREBBP/p300 family gene is extremely important for B-cell regulation, and RTS may represent an interesting human model for studying the molecular mechanisms involved in B-cell development.
Assuntos
Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Adulto Jovem , Anticorpos Monoclonais/análise , Linfócitos B/imunologia , Imunidade Humoral/imunologia , Imunoglobulinas/análise , Infecções Respiratórias/imunologia , Síndrome de Rubinstein-Taybi/imunologia , Anticorpos Monoclonais/imunologia , Estudos de Casos e Controles , Proteína de Ligação a CREB/genética , Imunidade Humoral/genética , Imunoglobulinas/imunologia , RecidivaRESUMO
Rubinstein-Taybi syndrome (RTS) is a rare developmental disorder characterized by craniofacial dysmorphisms, broad thumbs and toes, mental and growth deficiency, and recurrent respiratory infections. RTS has been associated with CREBBP gene mutations, but EP300 gene mutations have recently been reported in 6 individuals. In the present study, the humoral immune response in 16 RTS patients with recurrent respiratory infections of possible bacterial etiology was evaluated. No significant differences between patients and 16 healthy controls were detected to explain the high susceptibility to respiratory infections: normal or elevated serum immunoglobulin levels, normal salivary IgA levels, and a good antibody response to both polysaccharide and protein antigens were observed. However, most patients presented high serum IgM levels, a high number of total B cell and B subsets, and also high percentiles of apoptosis, suggesting that they could present B dysregulation. The CREBBP/p300 family gene is extremely important for B-cell regulation, and RTS may represent an interesting human model for studying the molecular mechanisms involved in B-cell development.
Assuntos
Anticorpos Monoclonais/análise , Linfócitos B/imunologia , Imunidade Humoral/imunologia , Imunoglobulinas/análise , Infecções Respiratórias/imunologia , Síndrome de Rubinstein-Taybi/imunologia , Adolescente , Anticorpos Monoclonais/imunologia , Proteína de Ligação a CREB/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Imunidade Humoral/genética , Imunoglobulinas/imunologia , Masculino , Recidiva , Adulto JovemRESUMO
The pro-inflammatory cytokines play a critical role in the initiation and propagation of ocular autoimmune diseases. Regulation of these cytokines is generally mediated by the immunoregulatory cytokine such as IL-10 or TGF-beta. In this study, we investigated the immunoregulatory cytokine profile and frequency of natural regulatory T cells (nTregs) in patients with Vogt-Koyanagi-Harada (VKH). We obtained the peripheral blood mononuclear cells (PBMC) from patients with VKH and healthy controls. The cytokine profile from supernatants of PBMC cultured with or without phytohaemagglutinin (PHA) was measured by ELISA, the percentage of CD4(+) Foxp3(+) and CD25(high)Foxp3(+) T regulatory cells were analysed by flow cytometry, and the transcriptional level of Foxp3 expression was analysed by real-time quantitative PCR. The immunoregulatory cytokines, TGF-beta and IL-10, increased in patients with VKH in the inactive stage of the disease. We observed no significant difference in the CD4(+) Foxp3(+) and CD25(high)Foxp3(+) T cells as well as no reduction in FOXP3 mRNA expression in the patients with VKH when compared to healthy controls. We showed in our work, an increase in IFN-gamma secretion by PBMC of patients with VKH in the active stage of the disease when compared to healthy controls and patients in the inactive stage. Our data suggest that IL-10 and TGF-beta cytokines, rather than nTregs are associated with the resolution phase of the disease and may have a more relevant role in controlling this disease.
Assuntos
Fatores de Transcrição Forkhead/imunologia , Interleucina-10/imunologia , Linfócitos T Reguladores/imunologia , Fator de Crescimento Transformador beta/imunologia , Síndrome Uveomeningoencefálica/imunologia , Adulto , Antígenos CD4/imunologia , Feminino , Citometria de Fluxo , Fatores de Transcrição Forkhead/genética , Humanos , Subunidade alfa de Receptor de Interleucina-2/imunologia , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , RNA/química , RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto JovemRESUMO
We evaluated the ability of human anti-lipopolysaccharide (LPS) O6 immunoglobulin G (IgG) and IgM antibodies to protect mice challenged with Escherichia coli serotype O6:K2ac. Purified whole IgG, commercial gammaglobulin, whole IgM-effluent, pool of normal human serum (NHS), agammaglobulinaemic serum (test groups) or phosphate-buffered saline (control group) was injected into adult male 18 h before a challenge with viable O6 E. coli. The mortality rate was assessed over a period of 72 h. To determine the opsonic and phagocytic activity of the antibody isotypes, we incubated peritoneal macrophages from the control and test groups collected at different times after challenge with the live bacteria with acridine orange for fluorescent analysis. Tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 were quantified in serum of both the test and control groups. All mice that received commercial gammaglobulin or NHS survived. Purified whole IgG (containing 1.1 mg/l of anti-LPS O6 IgG antibodies) protected 87.5% of the animals tested in this experiment, while whole IgM-enriched effluent with 1.5 mg/l of anti-LPS O6 IgM antibodies protected only 12.5%. The agamma serum showed no protective capacity compared with PBS (serving as control). The minimal concentration of anti-LPS O6 IgG antibodies able to protect 50% of animals was 0.137 mg/l of purified whole IgG. Whole IgM-enriched effluent showed no protective capacity independently of the concentration tested (0.048-17.0 mg/l of anti-LPS O6 IgM antibodies). Fluorescent analysis of peritoneal macrophages from animals pretreated with purified whole IgG showed no bacteria at 8 h after the challenge. By contrast, whole IgM effluent showed an increasing number of live bacteria at the same time. Mice that had received whole IgM effluent (1.5 mg/l of anti-LPS O6 IgM antibodies) before the challenge with LPS O6 presented 20.5 microg/l of IL-6 and 1.5 microg/l of TNF-alpha. Serum from animals pretreated with purified IgG did not present any detectable pro-inflammatory cytokine. Our findings suggest that IgG but not IgM antibodies protect animals from a challenge with E. coli O6 serotype.
Assuntos
Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/prevenção & controle , Vacinas contra Escherichia coli/administração & dosagem , Escherichia coli/imunologia , Imunização Passiva , Imunoglobulina G/farmacologia , Imunoglobulina M/farmacologia , Animais , Formação de Anticorpos , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/farmacologia , Relação Dose-Resposta a Droga , Vacinas contra Escherichia coli/imunologia , Vacinas contra Escherichia coli/uso terapêutico , Humanos , Interleucina-6/sangue , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/imunologia , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos , Fagocitose/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
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 lysossomal granules of the phagocytes. Primary Immunodeficiencies are a diverse group of illnesses 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 lysozyme 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 age-matched healthy controls (49 children and adolescents between the ages of 3-15 and 11 adults between the ages of 22-42) were determined by the lysoplate method. RESULTS: There was no statistically significant difference between the lysozyme 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 lysozyme 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.
Assuntos
Síndromes de Imunodeficiência/enzimologia , Muramidase/análise , Saliva/enzimologia , Proteínas e Peptídeos Salivares/análise , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Síndromes de Imunodeficiência/imunologia , Masculino , Saliva/imunologiaRESUMO
A high prevalence of systemic infections caused by enterobacteria such as Escherichia coli is observed during the neonatal period. Lipopolysaccharide (LPS) is one of the major factors responsible for septic shock caused by these Gram-negative bacteria. We have recently demonstrated the presence of anti-LPS immunoglobulin (Ig)G antibodies in cord blood with a repertoire identical to that found in maternal serum. In the present study, we analyzed anti-LPS O111 antibody isotypes in maternal serum and colostrum from mothers and in cord serum from their respective full-term (n = 30) and preterm (n = 13) neonate infants. The main isotype found in serum samples from mothers of term infants was IgM (range between 28 and 54 mg/l), followed by IgA (1-2 mg/l) and IgG (2-3 mg/l). The range of IgG antibody concentrations in cord blood was between 2 and 3 mg/l, as a result of placental transfer. A novel observation in our study was that the LPS bands recognized by colostral antibodies were completely different from those recognized by IgG in serum. Colostral IgA antibodies recognized several bands not bound by serum IgG antibodies from the respective maternal serum, independently of the antibody quantity. In addition, we verified the pattern of LPS recognition by serum IgA and colostral IgA antibodies was identical, what suggested that the antibody isotype found in serum could probably be derived from differentiated IgA-positive cells which were homing to the mucosa through the mucosal homing mechanism. Identical pattern of recognition was obtained comparing the IgA and IgM isotypes in colostrum. Slight differences in the pattern of recognition were found between colostral and serum IgM antibodies. The fact that colostral antibodies recognize much more bands than serum antibodies may be important for the host to mount an effective immune response in the intestinal lumen, in order to prevent excessive absorption of LPS, reducing possible systemic effects caused by the molecule.
Assuntos
Anticorpos Antibacterianos/biossíntese , Especificidade de Anticorpos , Escherichia coli/imunologia , Recém-Nascido/imunologia , Lipopolissacarídeos/imunologia , Western Blotting , Colostro/imunologia , Feminino , Sangue Fetal/imunologia , Humanos , Imunoglobulina A/biossíntese , Imunoglobulina G/biossíntese , Imunoglobulina M/biossíntese , GravidezRESUMO
In 40 children with Haemophilus influenzae b (Hib) meningitis, we determined serum levels (mg/dl) of IgG subclasses using the radial immunodiffusion method; 67.8 per cent of these children were less than 24 months old. In 14 children of the sample we measured serum IgG and IgG2 anti-ribosyl-ribitolphosphate (anti-PRP) (by enzyme-linked immunosorbent assay, ELISA) in the acute and convalescent phases of the disease. Lower IgG2 levels than those of the control group were obtained in all age ranges: 3-12 months, 1-2 years (p < 0.01), and 2-5 years (p < 0.001). IgG4 was also present in lower levels in patients of all age ranges (p < 0.05, p < 0.001, and p < 0.01 respectively). Serum levels of IgG anti-PRP and IgG2 anti-PRP measured were very low in the acute phase of the disease in all age ranges and there was no notable increase in levels during the convalescent phase of the disease. This result indicates that children less than 24 months old do not produce sufficient levels of IgG and IgG2 anti-PRP even after Hib meningitis.
Assuntos
Imunoglobulina G/sangue , Meningite por Haemophilus/imunologia , Ribosemonofosfatos/imunologia , Doença Aguda , Distribuição por Idade , Brasil , Estudos de Casos e Controles , Pré-Escolar , Convalescença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunodifusão , Imunoglobulina G/classificação , Lactente , Masculino , Meningite por Haemophilus/sangueRESUMO
Placental transfer of antibodies to polysaccharide antigens is still a controversial subject. The incidence of invasive Haemophilus influenzae type b (Hib) infections is high in countries where the vaccine has not been included in routine immunization schedules. In the present work, we proposed to evaluate the natural immune response to Hib capsular polysaccharide in term and preterm Brazilian newborns and their respective mothers. Although the means, medians, and ranges of antibody titres in paired maternal and cord sera from preterm neonates were similar, the maternal levels were slightly higher than the cord levels and a poor correlation between these levels was verified. Term neonates showed similar antibody levels to those of their respective mothers and a very significant correlation between these levels was observed.
Assuntos
Anticorpos Antibacterianos/imunologia , Cápsulas Bacterianas/imunologia , Sangue Fetal/imunologia , Haemophilus influenzae tipo b/imunologia , Imunoglobulina G/imunologia , Recém-Nascido/sangue , Recém-Nascido Prematuro/sangue , Troca Materno-Fetal/imunologia , Gravidez/sangue , Brasil , Feminino , Humanos , Saúde da População UrbanaRESUMO
Immunological behavior (IgG, IgM, IgA) and total Complement (CH50) of newborns infants with risk factors for early onset sepsis. Comparative analysis between newborns with and without infection. Rev. Hosp. Clín. Fac. Med. S. Paulo, 53(6): 303-310, 1998. The objective of this study was to verify the immunological behavior of the newborn infant in front of an infection. We studied 60 newborn infants that had risk factors for early onset sepsis (premature rupture membranes, clinic amnionitis or tract urinary infection) from de immunological and infection point of view. They were classified into three gestational age groups: < 34 weeks, between 34 and 36 6/7 weeks and > or = 37 weeks. Sepsis diagnosis was done through clinical and laboratorial data and we also included the followings exams: Immunological types (IgG, IgM, IgA) and total complement (CH50) obtained from the newborn at birth and on the fifth day of life. We could verify that 15 newborns (25%) presented early sepsis. There was a statistical association between perinatal asfixia and infection in the group with gestational age < 34 weeks and this same group presented statistical association between infection and death. The serical levels of IgG and CH50 were directly related to the gestational age and there were significant statistical differences between levels of IgG, IgM and total Complement between infected and not infected newborns within the same group os gestional age. We observed that the infection was associated to low levels of IgG and CH50, at birth and on the fifth day, mainly in the group of infected newborns with gestional age < 34 weeks, being this group, therefore, the one that would mostly benefit from an immunological support in front of and infection.