The relationship between atopy and salivary IgA deficiency in infancy.

In a prospective study, infants born to atopic parents had a significantly higher prevalence of salivary IgA deficiency at all ages studied than control infants, and the mean non zero IgA level of the potentially atopic infants was significantly lower at 8 and 12 months than of control infants. Of the infants with atopic parents, the prevalence of IgA deficiency was not significantly greater in those who manifested atopic disease during the study period than in those who did not, but the levels were significantly lower at 4 months.     

Seroprevalence of enteric and nonenteric adenoviruses in Bangladesh.

Single serum samples obtained from infants between 0 and 24 months of age admitted to a diarrheal disease hospital in Bangladesh were tested for the presence of adenovirus-specific immunoglobulin G (IgG) and IgA antibodies by using enzyme immunoassay and neutralizing antibodies to adenovirus types 2, 40, and 41. IgG antibodies were more prevalent than IgA antibodies, and neutralizing activity to enteric adenovirus was found in serum samples from 50% of infants who had reached 2 years of age.     

The Variability of Immunoglobulins and Albumin in Salivary Secretions of Children

The variation of concentrations of immunoglobulins and albumin in consecutive daily collections of saliva was studied in 33 infants, aged 6 months to 5 years, for periods ranging from 16 to 26 days. The concentration and the within-child variability of IgA and albumin and the detection of IgG and IgM in saliva increased with age. Between-child variances were greater than the within-child variances by a factor of 2.8 for log (IgA) and 1.3 for log (albumin). The geometric mean IgA levels were consistently higher and IgG was detected more frequently during upper respiratory tract infections compared with periods of non-infection. There were no changes in albumin levels between infection and non-infection periods, suggesting a local immune response rather than serum leakage. There were significant within-child correlations (autocorrelations) between levels of IgA in saliva collected on consecutive days and samples collected up to 3 days apart. The autocorrelations between levels of albumin were significant for samples collected up to 2 days apart. The autocorrelation for IgA was significantly greater during infection periods compared with non-infection periods for samples collected on consecutive days.     

Total and allergen-specific immunoglobulin A levels in saliva in relation to the development of allergy in infants up to 2 years of age.

BACKGROUND: The association between salivary IgA levels and development of allergy is controversial and the employed methodology has been questioned. OBJECTIVE: The aim of the study was to relate the levels of total IgA, SIgA and allergen-specific IgA antibodies in saliva to the development of allergy in infants during the first 2 years of life. METHODS: Saliva samples from 80 infants participating in a prospective study regarding the development of allergy were collected at 3 or 6, and 12 and 24 months of age. Total IgA, SIgA and Fel d 1 and beta-lactoglobulin specific IgA levels were analysed with ELISA. RESULTS: The levels of total IgA and SIgA increased with age. The number of samples with detectable IgA to Fel d 1 tended to increase with age, whereas the opposite was observed for IgA to beta-lactoglobulin. Infants who developed allergy tended to have higher levels of total IgA, and allergen-specific IgA was more commonly detected than in non-allergic children. In contrast, non-allergic children tended to have higher levels of SIgA. Furthermore, the levels of SIgA were higher in sensitized infants with no allergic symptoms than in sensitized children with symptoms. Infants with allergic parents had lower SIgA levels than infants without. Direct exposure to cat and cow's milk did not influence the levels of allergen-specific IgA levels, nor was there any association between breast-feeding and IgA production. CONCLUSION: The kinetics of food and inhalant allergen-specific IgA in saliva during the first 2 years of life is similar to what has earlier been shown for IgG in serum. Development of allergy tended to be associated with high levels of total and allergen-specific IgA antibodies, but low levels of SIgA. Furthermore, high levels of SIgA seemed to protect sensitized children from developing allergic symptoms during the first 2 years of life, supporting a possible protective role of SIgA against development of allergy.     

Salivary antibody responses to oral and parenteral vaccines in children

Salivary IgA antibody to poliovirus and tetanus toxoid was measured in whole salivas of 151 children between 2 and 48 months of age from North America and from Scandinavia. Children from urban and suburban populations in the greater Boston, MA, area receive both oral poliovaccine and a parenteral injection with tetanus toxoid (TT), initially at approximately 2 months of age. Children from Göteborg, Sweden, initially receive parenteral injections of TT at 2 months of age and parenteral injections of killed polio vaccine initially at 9 to 10 months of age. Twenty-six percent of the Boston subjects who were less than 12 months old had detectable salivary IgA antibody to poliovirus after oral immunization. In contrast, within the first year after parenteral immunization with killed poliovirus, the Swedish group had detectable salivary antibody in 9% (1 of 13) of the subjects. Forty to 65% of the children in the older Boston-area age groups had positive salivary IgA antibody levels to this antigen. No differences were seen in salivary IgA antibody to TT among the three populations. By 36 months of age at least 50% of all populations had detectable salivary antibody to TT. The ratio of enzyme-linked immunosorbent assay (ELISA) activity using rabbit anti-human secretory component versus rabbit anti-human alpha chain was significantly higher in subjects less than 12 months of age compared with older groups. This suggested either that free secretory component was binding to tetanus toxoid or that secretory antibody of isotypes other than IgA was present in these youngest subjects.     

Comparison of immunoglobulin A (IgA), IgG, and IgM enzyme-linked immunosorbent assays, plaque reduction neutralization assay, and complement fixation in detecting seroresponses to rotavirus vaccine candidates.

In a phase 1 study to evaluate human-rhesus rotavirus reassortant vaccines, 116 infants 1 to 5 months of age received one of the following five preparations: the serotype 1 reassortant, the serotype 2 reassortant, rhesus rotavirus (serotype 3), a bivalent preparation (serotypes 1 and 3), or a placebo. Seroresponses to the different vaccines were measured by plaque reduction neutralization assay (PRNA); rotavirus-specific immunoglobulin A (IgA), IgG, and IgM enzyme-linked immunosorbent assays (ELISAs); and complement fixation (CF). The seroresponse rate, calculated by using a fourfold or greater antibody rise by any assay, was similar in the four vaccine groups (83 to 96%). When the data from all the vaccinees were pooled, IgA ELISA, IgG ELISA, and PRNA were comparable in detecting seroresponses (67, 62, and 70%, respectively) and more efficient than IgM ELISA (53%) and CF (44%). When the vaccinees were analyzed by age, the overall seroresponse rates were the same for infants 1 to 2 and 3 to 5 months old (90%). The IgA ELISA and PRNA were the most efficient for detecting antibody rises in both age groups. IgG ELISA was among the least efficient methods for detecting antibody rises in the younger age group but among the most efficient in the older age group (44 versus 78%). CF was among the least efficient methods in both age groups but was significantly better in the older age group than in the younger age group (54 versus 21%). Our findings show that ELISA, in particular rotavirus-specific IgA ELISA, is a sensitive indicator of vaccine takes in 1- to 5 month-old infants, the target population for vaccination. ELISA should also be very useful in demonstrating natural rotavirus infections in field studies in which a stool specimen from a diarrheal episode is not always available. The ELISA has the advantages of being easier and quicker and requiring less serum than PRNA, but it does not give serotype-specific information about the immune response.     

Arousal responses to somatosensory and mild hypoxic stimuli are depressed during quiet sleep in healthy term infants

STUDY OBJECTIVES: To compare arousal responses to somatosensory and hypoxic stimuli in sleeping human infants and to determine whether sleep state and postnatal age exerted similar changes in these arousal responses. DESIGN: We delivered somatosensory (nasal air-jet) stimulation and mild hypoxia (15% oxygen) to 10 healthy term infants aged 2 to 4 weeks, 2 to 3 months, and 5 to 6 months during identified sleep states. Hypoxic challenges were terminated at arousal, when the oxygen saturation fell below 85%, or at 5 minutes (failure to arouse). RESULTS: Infants failed to arouse to a greater percentage of hypoxia tests during quiet sleep (QS) than during active sleep (AS) at 2 to 3 months and 5 to 6 months of age (P < 0.01). Infants failed to arouse to a greater percentage of hypoxic challenges during QS at 2 to 3 months and 5 to 6 months than at 2 to 4 weeks of age. Arousal latency to hypoxia was significantly longer in QS than in AS at each study age; however, arousal latency was not affected by postnatal age. Arousal thresholds to somatosensory stimulation were significantly greater in QS than in AS, except at 2 to 4 weeks of age. In AS, arousability to the air-jet was greater at 2 to 3 months compared to 2 to 4 weeks of age (P < 0.05); in QS it was lower at 5 to 6 months compared to 2 to 4 weeks of age (P < 0.05). Arousal latency to hypoxia and arousal thresholds to air-jet stimulation were not correlated within infants. CONCLUSION: We conclude that arousal responses of infants to somatosensory and respiratory stimuli are similarly affected by sleep state and postnatal age. Infants are less arousable to both stimulus modalities in QS than in AS, and less arousable at 5 to 6 months of age than at 2 to 4 weeks in QS.     

Immunological sequelae of intrauterine infection.

Compared to normal children, pre-natally infected infants had significantly elevated IgM concentrations throughout the first year of life and elevated IgA levels for the first 6 months. In contrast, IgG levels dropped significantly below normal at 3 months post-partum. Infants born without overt disease but with elevated IgM were found to have precocious development of serum IgA when compared to control children. Levels of IgA and IgG in tears were markedly reduced in symptomatic children at 3 months of age. Lymphocyte response in vitro to phytohaemagglutinin and pokeweed mitogen was low in symptomatic infants. These results suggest that intratuerine infection may result in multiple immunological abnormalities.     

Energy expenditure and intake in infants born to lean and overweight mothers

We investigated the contributions of low energy expenditure and high energy intake to excessive weight gain in infants born to overweight mothers. The subjects were infants of 6 lean and 12 overweight mothers, recruited soon after birth. Total energy expenditure and metabolizable energy intake were measured with a new doubly labeled water method over a period of seven days when the infants were 3 months of age, and the postprandial metabolic rate was measured by indirect calorimetry when the infants were 0.1 and 3 months of age. The results were related to weight gain in the first year of life. No significant difference was observed between infants who became overweight by the age of one year (50 percent of infants born to overweight mothers) and those who did not, with respect to weight, length, skinfold thicknesses, metabolic rate at 0.1 and 3 months of age, and metabolizable energy intake at 3 months. However, total energy expenditure at three months of age was 20.7 percent lower in the infants who became overweight than in the other infants (means +/- SE, 256 +/- 27 and 323 +/- 12 kJ per kilogram of body weight per day; P less than 0.05). This difference could account for the mean difference in weight gain. These data suggest that reduced energy expenditure, particularly on physical activity, was an important factor in the rapid weight gain during the first year of life in infants born to overweight mothers.     

Patterns of anti-HIV IgG3, IgA and p24Ag in perinatally HIV-1 infected infants

The antibody patterns of HIV-1 IgG3, IgG and IgA and of HIV-1 p24 antigen were investigated in Thai infants born to mothers infected with HIV-1. In the 17 HIV-1 infected infants, anti-HIV antibodies were detected continuously over a period of 15-18 months and a high level of specific IgG3 subclass was observed. Anti-HIV IgA could be detected at 6 months of age whereas p24Ag was detected at 2 months. In 79 uninfected infants, maternal anti-HIV IgG gradually decreased over 9 months whilst specific IgG3 decayed rapidly during the first 6 months. Both p24Ag and anti-HIV IgA were not found in these uninfected infants. Thus, the disappearance of anti-IgG3 subclass antibodies within 6 months can predict whether infants are uninfected whereas the persistence of anti-HIV IgG and IgG3 subclass antibodies, the production of anti-HIV IgA antibody and the presence of p24Ag appear as an adjunct to the diagnosis of HIV vertical transmission. The necessary assays are relatively simple and could be performed individually.     

Subclasses of IgA antibodies in serum and saliva samples of newborns and infants immunized against rotavirus

Little is known about subclass levels of IgA in serum or saliva of infants in the perinatal period. We have previously shown that very young infants are capable of responding to an experimental rotavirus vaccine with both serum and salivary IgA, and that small amounts of IgA are already detectable in cord blood of these infants. In the present study, total IgA1 and IgA2 antibodies in serum and saliva samples of some of these infants at birth, at 6 weeks of age, and at 12 weeks of age, were determined by a quantitative ELISA. Also, subclass-specific IgA antibodies to the rotavirus group A common antigen were determined by ELISA. The ratio of average serum concentrations of IgA1 to IgA2 for 14 infants at 6 weeks of age was 19:1, while in saliva it was 5:1. Between 6 and 12 weeks of age levels of serum IgA1 increased by 25%, while levels of IgA2 did not increase perceptibly. Concentrations of IgA1 were higher in infant sera than in saliva, while concentrations of IgA2 were slightly higher in saliva than in serum. When calculated as specific ELISA units per mg IgA1, more salivary IgA1 was specific for rotavirus than serum IgA1. Further studies are needed to determine when infant IgA2 levels rise to values more characteristic of children and adults. This may be of significance for infant mucosal immunizations if secretory IgA2, more resistant to bacterial proteases than IgA1, is required for efficient defence of the respiratory and intestinal tracts.     

Campylobacter jejuni antibodies in Nigerian children.

Titers of complement-fixing (CF) antibody to Campylobacter jejuni were demonstrated in 87 (36.7%) of 237 infants 6 to 15 months old in Jos, Nigeria. Of the total number of children examined, 81 had acute diarrhea and 27 of them (33.3%) were found to have CF antibodies in their serum. The remaining 156 children were asymptomatic, and 60 (38.4%) of them had CF antibodies. In the diarrheal group, 27 of 75 children 6 to 8 months old were CF antibody positive. There was no significant difference in the incidence of CF C. jejuni antibodies in the diarrheal and nondiarrheal infants (P greater than 0.05). Also, infants 9 to 15 months old had a higher incidence of CF antibodies (46.5%) than those 6 to 8 months of age (25%). The data suggest that the infants whose sera were CF antibody positive had had an exposure to C. jejuni. All 33 infants 6 to 8 months of age who had no diarrhea were CF antibody negative.     

Lymphocyte subsets in infants: relationships to feeding, atopy, atopic heredity and infections

Numbers of T and B lymphocytes and T cell subsets were measured longitudinally in blood samples of 68 healthy infants from 1 month to 28 months of age. Monoclonal antibodies against cell surface antigens (OKT3, OKT4, OKT8, and OKIal) and antibodies to immunoglobulin heavy chains (gamma, mu, alpha and delta) were used for immunofluorescent staining. The absolute number of T lymphocytes (OKT3) was found to be highest at the age of 6-7 months, reflecting the greater numbers of both helper (OKT4) and suppressor (OKT8) cells. The percentages of OKT4 and OKT8 positive cells and hence the ratios of these cells were very stable throughout the study period. Relatively, breast-fed infants had more suppressor (OKT8) cells than infants on formula, but the difference was not apparent in absolute counts. Change to formula feeding caused an increase in B cells. The heredity for atopy did not influence the total numbers of T cells or cell numbers in the different subgroups. At the age of 4 months an altered helper/suppressor ratio was noted in infants who later developed a severe atopy. At the age of 28 months the relative number of T cells was lower in atopic than nonatopic infants. The rate of respiratory infections did not affect these numbers.     

Immunoglobulin profile of tracheal aspirate fluid in intubated children.

Pulmonary lavage immunoglobulins IgG, IgA and IgM were measured in intubated ventilated neonates during their period of intubation (range 1-64 days, mean 12). The neonates were divided into two groups based on gestational age (group 1 26-32 weeks, group 2 33-40 weeks). IgG levels were high at birth, and decreased exponentially throughout the period of intubation. There was no statistical difference in IgG levels between the two groups. IgA and IgM levels were low at birth, and increased linearly, there being a significantly greater increase with age in Group 2 (the more mature gestationally) for both immunoglobulins. Two groups of older children were also studied (2-4 year olds, and 8-10 year olds). In the 2-4 year age group, IgG levels were similar to those seen in the immediate newborn period, were quantitatively greater than IgA and IgM, and were not significantly different from levels in the 8-10 year olds. IgA and IgM levels were also not significantly different between the two groups.     

A longitudinal study of gamma-interferon production by peripheral blood mononuclear cells from breast- and bottle-fed infants.

Production of gamma-interferon (gamma-IFN) in vitro by peripheral blood mononuclear cells (PBMC) from 15 breast-fed and 15 bottle-fed infants has been studied from birth to 9 months of age and compared with production by adult cells. Using a Terasaki plate microculture system with serum-free medium, PBMC were stimulated with staphylococcal enterotoxin A (SEA) and gamma-IFN production was assessed by an immunoradiometric assay. Cord blood mononuclear cells (CBMC) and PBMC from all infants secreted large quantities of gamma-IFN. The levels secreted did not change significantly with age over the 9 months of the study, nor did they differ from the levels secreted by adult cells. Cells from the bottle-fed infants secreted slightly more gamma-IFN than cells from breast-fed infants, but this difference was not significant. These results indicate that the potential for PBMC to secrete gamma-IFN in vitro is fully developed at birth in full-term infants and cannot therefore be further influenced by subsequent breast- or bottle-feeding. In addition, the greater susceptibility of infants than adults to certain bacterial and viral infections cannot be attributed to a deficiency in the potential of infant cells to secrete gamma-IFN in vitro.     

Serum and nasal-wash immunoglobulin G and A antibody response of infants and children to respiratory syncytial virus F and G glycoproteins following primary infection.

An enzyme-linked immunosorbent assay (ELISA) with immunoaffinity-purified fusion (F) or attachment (G) glycoprotein was used to measure the serum and secretory immune responses of 18 infants and children, 4 to 21 months of age, who underwent primary infection with respiratory syncytial virus (RSV). Most of the 10 older individuals (9 to 21 months of age) developed moderate levels of serum and nasal-wash immunoglobin A (IgA) and IgG F and G antibodies. These individuals developed a moderate level of serum or nasal-wash antibodies that neutralized virus infectivity. One of the eight younger individuals (4 to 8 months of age) failed to develop an F antibody response, while three failed to develop a G antibody response. The most notable difference in the responses of the two age groups involved the titer in convalescent sera of G, F, and neutralizing antibodies which were 8- to 10-fold lower in younger individuals. Most of the younger infants failed to develop a rise in serum or nasal-wash neutralizing antibody. It is possible that the presence of maternally derived antibody in the younger infants suppressed the immune response to RSV infection, and that this accounted, in part, for the low level of postinfection antibody titer in this group. This low level and the irregular response of the infants less than 8 months of age may contribute to the severity of their initial infection and may also be responsible, in part, for their failure to develop effective resistance to subsequent reinfection by RSV.     

Age related IgG subclass response to respiratory syncytial virus fusion protein in infected infants

Respiratory syncytial virus (RSV) fusion protein was purified by immunoaffinity chromatography using a mouse monoclonal antibody coupled to Affi-gel 10. The fusion protein was homogeneous by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and free of other detectable viral or cellular protein. The purified fusion protein was used in a quantitative enzyme-linked immunosorbent assay (ELISA) to measure the age-related antibody response to this protein in infected infants. The four IgG subclasses, IgA and IgM levels were determined for infants under 6 months of age, infants aged 6 months to 1 year and infants aged 1 year and over. Most infants over 6 months of age showed marked increases in both IgG1 and IgG3 antibodies with poor or negligible response with IgG2 and IgG4. By contrast infants under 6 months failed to respond by the production of IgG antibodies, although increases in IgA and IgM levels were observed. These data may explain the failure of primary RSV infections to induce protective immunity and have implications for the strategic use of attenuated RSV vaccines.     

Response to measles vaccine in Haitian infants 6 to 12 months old. Influence of maternal antibodies, malnutrition, and concurrent illnesses

To study the factors affecting the serologic response to measles vaccination, we evaluated 595 Haitian infants from 6 through 12 months of age, and their mothers, at the beginning of an immunization program. Thirty-four per cent of the infants had preexisting serologic evidence of measles infections by 11 months of age. Among infants more than nine months of age, those who had had measles had a significantly lower nutritional status than those who had not (P less than 0.01). After vaccination, seroconversion rates increased from 45 per cent at 6 months to 100 per cent at 12 months. The lowest rate of vaccine failure compatible with acceptably low rates of natural infections could be achieved by vaccination after eight months of age. Infants born to mothers with low levels of antibody to measles (hemagglutination-inhibition antibody titers less than 1:40) were significantly more likely to have had natural measles (P less than 0.01) or to have seroconversion after vaccination (P less than 0.001) at 6 to 10 months of age than were infants born to mothers with higher of age than were infants born to mothers with higher titers. Malnutrition and acute infections did not affect seroconversion rates. These data support the World Health Organization recommendation to administer measles vaccine in under-developed countries as soon after nine months of age as possible, regardless of nutritional status or the presence of minor illnesses.     

Allergic diseases and asthma in relation to serum immunoglobulins and salivary immunoglobulin A in pre-school children: a follow-up community-based study

BACKGROUND: We have previously reported an association between low IgA and allergic manifestations in early childhood (0-2 years) and have now followed our cohort for an additional 2 years. OBJECTIVE: To evaluate in a longitudinal community-based cohort study the association between maturation of Ig production and allergic manifestations in the first 4 years of life. METHODS: A cohort of 161 randomly selected children was followed from birth to the age of 42-48 months and evaluated at 18-23 months (EV1; n = 179) and again at the age of 42-48 months (EV2; n = 161). Diagnoses were made with the help of a clinical questionnaire, physical examination and skin prick tests (SPTs) to 10 common allergens. Serum immunoglobulins were measured at EV1 and EV2, and salivary IgA (sal-IgA) at EV2. RESULTS: Serum IgA, IgE, IgG1, IgG2 and IgG4 increased from 2 to 4 years of age (P < 0.001) and their levels showed close correlations (P < or = 0.01 for most comparisons). Children with one or more positive SPTs had lower serum IgA (P = 0.004) and IgG4 (P = 0.05) at EV2 than those who did not respond, and children who developed allergic rhinitis between EV1 and EV2 had low sal-IgA (P = 0.006) and IgG3 (P < 0.05) at EV2. Atopic eczema was associated with low sal-IgA at EV2, and children who developed eczema between EV1 and EV2 had significantly lower sal-IgA than those who recovered after EV1 (P = 0.02). CONCLUSION: Allergic manifestations in predisposed children may be influenced by the rate of maturation of immunological components that counteract sensitization or inhibit effector mechanisms of allergy.     

Growth in Exclusively Breastfed and Non-exclusively Breastfed Children: Comparisons with WHO Child Growth Standards and Korean National Growth Charts

BackgroundThis study examined the relationship of infant feeding with anthropometric indices of children during their first six years of life relative to the Korean National Growth Charts (KNGC) and the World Health Organization Child Growth Standards (WHO-CGS).MethodsThe study population consisted of 547,669 Korean infants and children who were 6 months-old to 6 years-old (born in 2008–2009) and participated in the National Health Screening Program for Infants and Children. Data on height, weight, and type of feeding during the first 6 months (exclusively breastfed [BF] vs. mixed- or formula-fed [FF]) were analyzed.ResultsBF boys and girls were significantly shorter and lighter than FF counterparts from the age of 6 months to 4 years, but these differences were not significant after the age of 4 years. BF boys and girls only had significantly lower body mass index at the age of 2 years. Under the age of 2 years 6 months, and especially under the age of 1 year, BF boys and girls were significantly taller and heavier than the 50th percentile values of the 50th percentile value of the WHO-CGS.ConclusionIn this study using large-scaled national data, Korean breastfed children are shorter and lighter by 3 years 6 months–4 years 6 months, but afterward, there is no significant difference from those who had mixed- or formula-feeding. Substantial disparities in the anthropometric indices of Korean infants under the age of 1 compared to KNCG and WHO-CGS were found, regardless of their infantile feeding types. Our results emphasize the importance of constructing a nationwide reference chart based on actual measurements of BF Korean infants.