Determination of secretory IgA and albumin in saliva of newborn infants

As a first line of defence against microbial invasion, secretory IgA (sIgA) is the dominant immunoglobulin on all mucosal surfaces. In this study sIgA was determined by radial immunodiffusion in saliva samples of 63 newborn infants divided into the following age groups: (1) 1 day and younger, (2) 2-10 days. Concentrations of sIgA and albumin as well as their relation to age, postprandial time, gestational age and birth weight were analysed. sIgA could be detected in 75.0% (group 1) and 77.1% (group 2) of the saliva samples with a mean concentration of 190.2 mg/l (group 1) and 216.4 mg/l (group 2). Differences failed to reach significance. Concentration of sIgA was found to be independent of age but positively related to the concentration of albumin in the same saliva sample. In conclusion, this study provides evidence that high levels of sIgA are found in saliva of newborn infants, indicating the existence of a competent oral mucosal immune system as early as within the first 10 days of life.     

Secretory immunoglobulin A (sIgA) in parotid saliva of patients with cystic fibrosis

Investigations of immunoglobulin concentrations--especially of secretory IgA (sIgA)--were performed in isolated parotid saliva samples by means of a modified Mancini technique considering the structural specialties of sIgA. The measurement of flow rates under continuous stimulation of parotid gland secretion by citric acid allowed calculations of glandular output. Cystic fibrosis patients showed decreased secretion rates of sIgA during gland secretion stimulation. Because parotid glands and bronchial glands are parts of BALT, we can conclude, that a functional sIgA deficiency is a pathogenetic factor under others in chronic bronchopulmonary infections of cystic fibrosis patients.     

Changes in salivary and fecal secretory IgA in infants under different feeding regimens

Background:  One of the causes of food allergy in infancy is assumed to be immunological immaturity of the intestinal tract. The purpose of the present study was to examine changes in salivary and fecal secretory IgA (sIgA) levels in infants under different feeding regimens to evaluate the immunological maturity of the intestinal tract.
Methods:  Thirty-four infants were enrolled at the beginning of the study, and 28 of them were followed up to 12 months of age. sIgA was measured on enzyme-linked immunosorbent assay. Changes in the levels of salivary and fecal sIgA during the first 12 months of life were compared among formula-fed infants (F group), breast–formula-fed infants (BF group) and breast-fed infants (B group).
Results:  Salivary sIgA was detected in almost all neonates on the day of birth. Salivary sIgA was significantly higher in the F group than in the BF group at the age of 2 months ( P  < 0.05). Fecal sIgA appeared from day 2 and rapidly increased at 1 month of age in all groups. B group infants had significantly higher level of fecal sIgA than F group infants at 1 month of age ( P  < 0.05).
Conclusions:  The level of salivary sIgA hardly changed, whereas fecal sIgA was significantly influenced by intake of breast milk.     

Secretory immunoglobulin A in saliva of healthy children and children with airway diseases

Using the Elisa-Test of Dakopatts, Hamburg, described by Ishiguro et al and modified by us (Mikrotitration plates instead of tubes, blocking up free bonding capacities in the plates with 1% gel fluid, altered incubation periods) we determined secretory IgA (SIgA) in saliva samples of 376 infants and children. The probands could be divided in three groups: Group 1, serving as controls, consisted of 163 healthy children. Group 2 comprised 111 children suffering from acute infection of the respiratory tract. Group 3 consisted of 102 children with chronic airways diseases, in particular, asthma. In the healthy infants and children we found age dependent increases of SIgA until the age of 4 years. The median values amounted 16.7 (newborns), 59.2 (1st year), 118.2 (2nd year), 149.2 (3rd year), 185.5 (4th year), 159 (5th year) and 175.8 mg/l (5th-13th year). A similar age dependent increase of SIgA was evident in the saliva samples of children suffering from acute infections of the respiratory tract. In the children with chronic airways diseases there was only a slight increase of SIgA during the first 4 years (mean = 78.0-113.5 mg/l) and an abrupt (statistically significant) rise in the fifth year. The median value of SIgA was 216 mg/l in the children aged 5-13 years. Serum IgA along with salivary IgA were measured in 128 children (r = 0.40, p less than 0.001). 6 children had a complete IgA deficiency and 4 children an incomplete IgA deficiency, i.e. low secretory IgA levels in saliva (36.8-50.0 mg/l) and lacking IgA in serum (less than 14 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS)     

Slow salivary secretory IgA maturation may relate to low microbial pressure and allergic symptoms in sensitized children

It is unknown why allergic symptoms do not develop in all sensitized children. We analyzed prospectively the postnatal secretory IgA (SIgA) development and whether high SIgA levels would protect sensitized infants from developing allergic symptoms. Salivary total IgA and SIgA levels were determined by ELISA, and allergy development was investigated at 3, 6, and 12 mo and at 2 and 5 y in two birth cohorts in Estonia (n = 110) and Sweden (n = 91), two geographically adjacent countries with different living conditions and allergy incidence. Total and SIgA levels increased with age, reaching adult levels at the age of 5. Virtually, all salivary IgA in Estonian children was in the secretory form, while a major part of IgA in Swedish saliva lacked the secretory component up to 2 y of age. In Sweden, high levels of salivary IgA without secretory component correlated inversely with house dust endotoxin levels. High SIgA levels were associated with less development of allergic symptoms in sensitized Swedish children. In conclusion, postnatal maturation of the salivary SIgA system proceeds markedly slower in Swedish than Estonian children, possibly as a consequence of low microbial pressure. SIgA may limit allergy-mediated tissue damage at mucosal surfaces in sensitized individuals.     

Daily Ingestion of Immunologic Components in Human Milk during the. First Four Months of Life

ABSTRACT. The amounts of lactoferrin, lysozyme, SIgA and SIgA antibodies to E. coli somatic antigens in human milk ingested per day and per kg per day by breast-fed infants were determined during the first four months of life. A gradual decline in the amounts of lactoferrin, SIgA, and SIgA antibodies ingested per day or per kg per day was found, whereas the quantities of lysozyme ingested by the infants rose during that period. These data suggest that the production and secretion of these immunologic factors by the mammary gland may be linked to the ontogeny of the production or catabolism of those components at mucosal tissues of the recipient infant.     

Daily Ingestion of Immunologic Components in Human Milk during the. First Four Months of Life

ABSTRACT. The amounts of lactoferrin, lysozyme, SIgA and SIgA antibodies to E. coli somatic antigens in human milk ingested per day and per kg per day by breast-fed infants were determined during the first four months of life. A gradual decline in the amounts of lactoferrin, SIgA, and SIgA antibodies ingested per day or per kg per day was found, whereas the quantities of lysozyme ingested by the infants rose during that period. These data suggest that the production and secretion of these immunologic factors by the mammary gland may be linked to the ontogeny of the production or catabolism of those components at mucosal tissues of the recipient infant.     

Congenital pernicious anemia: report of seven patients, with studies of the extended family

Unstimulated whole saliva was collected from 203 uninfected individuals at various ages from birth until adulthood. Levels of specific antibodies against Escherichia coli O antigens of secretory IgA, secretory IgM and IgG, as well as total amounts of SIgA, were determined using ELISA. Levels of SIgA antibodies found in adults were approached by the age of 12 months, but high levels could be attained earlier, presumably in response to antigenic exposure at the mucosal level. During the first few months of life, secretory IgM antibodies appeared in the saliva, possibly compensating for the relative lack of IgA.     

Secretory IgA antibody responses in Venezuelan children infected with Giardia duodenalis

We standardized and evaluated an ELISA technique for the detection of total and specific anti-Giardia duodenalis secretory IgA antibodies (sIgA). Samples of saliva and serum of 161 Venezuelan schoolchildren were analysed. After stool examination, 66 children were diagnosed to be infected with Giardia duodenalis, 22 with other protozoa, and 73 non-parasitized. The mean (+ 2 SD) values of secretory IgA in the non-parasitized group was considered as the criterion of positivity. The levels of total and specific anti-Giardia sIgA were significantly higher in children with Giardia compared with the group with other protozoa (p < 0.01) and the non-parasitized group (p < 0.001). The ELISA technique developed showed values of sensitivity and specificity of 74 and 94 per cent, respectively, a predictive value of 92 per cent for positive samples and 80 per cent for negative samples. Specific anti-Giardia IgA serum levels showed a low sensitivity (57 per cent) and a predictive value for negative samples (53 per cent). Our results suggest that secretory anti-Giardia IgA levels measured in saliva samples may reflect local intestinal IgA responses elicited by these parasites. Thus, determinations of the levels of sIgA anti-Giardia could be a useful diagnostic tool for giardiasis in children.     

Comparison of serum and salivary antibodies in children vaccinated with oral live or parenteral inactivated poliovirus vaccines of different antigen concentrations.

A new antigen-rich inactivated poliovirus vaccine (IPV) in ordinary (IPV1), double (IPV2) and quadruple (IPV4) antigen concentrations was given in 2 doses to 6 and 18 week old Pakistani infants. The immune responses to poliovirus types 1 and 3 were compared to those in infants given three doses of oral poliovirus vaccine (OPV) at 6, 12 and 18 weeks of age. Enzyme-linked immunosorbent assay, ELISA, was used to estimate IgG and IgA in serum and secretory IgA (SIgA) in saliva. Two to three years later, a follow-up of the serum antibody response was carried out in the same infants using a microneutralization test. Serum IgG antibody responses to poliovirus type 1 antigen after two doses of IPV1, IPV2 and IPV4 were not significantly higher than the response after three doses of OPV at 21 weeks of age (p greater than 0.05). The serum IgG responses to poliovirus type 3 were similar to those against type 1 in all the groups. Mean neutralizing antibody titres to poliovirus type 1 was significantly higher in the IPV2 group than the rest of the groups (p less than 0.01). For type 3, these titres were highest but not significantly, in the IPV4 group (p greater than 0.05). This study shows that two doses of a new antigen-rich IPV can give similar immediate serum antibody responses as OPV but higher late responses. SIgA antibodies in saliva were more efficiently induced by OPV after three doses than after 2 doses of IPV (p less than 0.05).     

Comparison of Serum and Salivary Antibodies in Children Vaccinated with Oral Live or Parenteral Inactivated Poliovirus Vaccines of Different Antigen Concentrations

ABSTRACT. A new antigen-rich inactivated poliovirus vaccine (IPV) in ordinary (IPV1), double (IPV2) and quadruple (IPV4) antigen concentrations was given in 2 doses to 6 and 18 week old Pakistani infants. The immune responses to poliovirus types 1 and 3 were compared to those in infants given three doses of oral poliovirus vaccine (OPV) at 6, 12 and 18 weeks of age. Enzyme-linked immunosorbent assay, ELISA, was used to estimate IgC and IgA in serum and secretory IgA (SIgA) in saliva. Two to three years later, a follow-up of the serum antibody response was carried out in the same infants using a microneutralization test. Serum IgG antibody responses to poliovirus type 1 antigen after two doses of IPV1, IPV2 and IPV4 were not significantly higher than the response after three doses of OPV at 21 weeks of age ( p > 0.05). The serum IgC responses to poliovirus type 3 were similar to those against type 1 in all the groups. Mean neutralizing antibody titres to poliovirus type 1 was significantly higher in the IPV2 group than the rest of the groups ( p <0.01). For type 3, these titres were highest but not significantly, in the IPV4 group ( p > 0.05). This study shows that two doses of a new antigen-rich IPV can give similar immediate serum antibody responses as OPV but higher late responses. SIgA antibodies in saliva were more efficiently induced by OPV after three doses than after 2 doses of IPV ( p <0.05).     

Local antibodies to alpha-casein and beta-lactoglobulin in the saliva of infants

Salivary antibodies were studied in 112 infants between 1 day and 8 yr of life. SIgA anticasein was present from birth in breast-fed and bottle-fed infants. Bottle-feeding resulted in significantly higher concentrations of SIgA anticasein at 3 wk to 3 months of life as compared to breast-feeding. Salivary anticasein declined toward the end of the 1st yr and was present in less than half of the children older than 1 yr. Salivary anti-beta-lactoglobulin was also present at birth in some infants. Levels increased slightly over the following 3 months but remained low. Only a minority of older children had this antibody in their saliva.     

Hiv-specific secretory IgA in breast milk of HIV-positive mothers is not associated with protection against HIV transmission among breast-fed infants

OBJECTIVES: To test whether secretory immunoglobulin A (sIgA) to human immunodeficiency virus (HIV) antigens in breast milk of HIV-positive women is associated with protection against HIV transmission among breast-fed infants. STUDY DESIGN: Nested, case-control design in which HIV-specific sIgA was measured in breast milk collected from 90 HIV-positive women enrolled in a study in Lusaka, Zambia. Milk samples were selected to include 26 HIV-positive mothers with infected infants (transmitters) and 64 mothers with uninfected infants (nontransmitters). RESULTS: HIV-specific sIgA was detected more often in breast milk of transmitting mothers (76.9%) than in breast milk of nontransmitting mothers (46.9%, P = .009). There were no significant associations between HIV-specific sIgA in breast milk and other maternal factors, including HIV RNA quantities in breast milk, CD4 count, and plasma RNA quantities. CONCLUSIONS: HIV-specific sIgA in breast milk does not appear to be a protective factor against HIV transmission among breast-fed infants.     

Faecal SIgA secretion in infants fed on pre- or probiotic infant formula

Secretory immunoglobulin A (SIgA) plays an important role in the defence of the gastrointestinal tract. The level of faecal SIgA antibody is associated with increased neutralization and clearance of viruses. Formula-fed infants who lack the transfer of protective maternal SIgA from breast milk may benefit from strategies to support maturation of humoral immunity and endogenous production of SIgA. We aimed at studying the effects of standard, prebiotic and probiotic infant formulas on the faecal SIgA levels. At birth, infants of whom the mother had decided not to breastfeed were allocated to one of three formula groups in a randomized, double-blind fashion. Nineteen infants received standard infant formula; 19 received prebiotic formula containing a specific mixture of 0.6 g galacto-oligosaccharides (GOS)/fructo-oligosaccharides (FOS)/100 ml formula and 19 received probiotic formula containing 6.0 × 10⁹ cfu Bifidobacterium animalis /100 ml formula. Faecal samples were taken on postnatal day 5, day 10, wk 4 and every 4 wk thereafter until wk 32. SIgA in faeces was determined by an enzyme-linked immunosorbent assay. During the intervention, infants fed on prebiotic formula showed a trend towards higher faecal SIgA levels compared with the standard formula-fed infants reaching statistical significance at the age of 16 wk. In contrast, infants fed on the probiotic formula showed a highly variable faecal SIgA concentration with no statistically significant differences compared with the standard formula group. Formula-fed infants may benefit from infant formulas containing a prebiotic mixture of GOS and FOS because of the observed clear tendency to increase faecal SIgA secretion. Adding viable B. animalis strain Bb-12 to infant formula did not reveal any sign for such a trend.     

Presence of secretory IgA antibodies to an enteric bacterial pathogen in human milk and saliva.

The concept of a common mucosal immune system in man was tested by examining the concurrent presence of specific-secretory IgA (SIgA) antibodies in human milk and saliva from three groups of subjects: 64 Sri Lankan women living in Sri Lanka; 20 immigrant Asian women living in Birmingham (median duration of residence in the United Kingdom five years); and 75 Caucasian women living in Birmingham (controls). Enzyme linked immunosorbent assays (ELISA) were developed to detect enterotoxigenic Escherichia coli (ETEC) colonisation factor/1 (CFA/1) specific SIgA antibodies in milk and saliva. ETEC CFA/1 specific SIgA antibody activity was detectable in milk (37.5% and 25%) and saliva (42.1% and 35%) of Sri Lankan and immigrant Asian women, respectively, but not in any of the Caucasian controls. Eighty five point two per cent of subjects who were positive had specific antibodies detectable in both milk and saliva; 5% of all Sri Lankan women and 10% of all immigrant Asian women had detectable antibody only in saliva. These observations lend further strong support to the idea that a common mucosal immune system exists in man. The continuing presence of specific SIgA antibodies in Asian immigrants to previously encountered antigens suggests that there may be an ''immunological memory'' in the human secretory immune system.     

Ontogeny of the intestinal immune system in the premature infant

A variety of variables influence the development of secretory immunity and oral tolerance, two immune mechanisms that are of paramount importance for the mucosal barrier function. Epithelial permeability is likely a significant primary or secondary event in the pathogenesis of several intestinal diseases, including adverse immune reactions to foods. This variable is determined by the individual's age (e.g., preterm versus term infant), concurrent infections, and the shielding effect of secretory IgA (SIgA) antibodies provided by breast milk. The clinical consequences will depend on how fast “closure” of the epithelial barrier can be attained or re-established, which is influenced both by the age of the infant and by its successful mounting of adaptive intestinal SIgA responses as well as generation of oral tolerance towards innocuous antigens from the diet and from the normal indigenous microbiota. SIgA is the best defined effector component of the mucosal immune system; its enhancement, and the homeostatic mucosal immune regulation in general, induced by probiotic commensal bacteria is of considerable clinical interest. Importantly, the feeding and treatment regimen (e.g., antibiotics) to which the newborn is subjected, may disturb the balance of the developing mucosal immune system.     

Salivary anti-RSV IgA antibodies and respiratory infections during the first year of life in atopic and non-atopic infants

Salivary SIgA antibodies against RS virus were studied in 105 children during the first year of life. The infants were divided into groups according to their risk of atopy. At birth 13 neonates showed measurable amounts of SIgA to RS virus. In another 26 children specific antibodies were detected but in concentrations too low for quantitative analysis. During the first year of life this increased to 29 antibody-positive samples with measurable amounts of antibody and 39 with concentrations too low for quantitative determination. At this time 8 children of the high risk group had developed symptoms of allergy. None of these children had measurable amounts of SIgA anti-RSV in their saliva. In comparison, 10 of the remaining 26 high risk infants without symptoms of allergy did have such antibodies. Atopic infants had significantly more respiratory infections during the first year of life than nonatopic infants. The avidity of SIgA anti-RSV in neonatal samples was significantly higher than avidity determined in breast milk SIgA but comparable to the avidity of serum IgG. During the first year of life a continuing decrease of salivary SIgA avidity was observed.     

Enhanced fecal excretion of selected immune factors in very low birth weight infants fed fortified human milk

The amounts of lactoferrin, lysozyme, total IgA, secretory IgA (SIgA), and specific SIgA antibodies to a pool of Escherichia coli O antigens were measured in 96-h collections of feces obtained from 28 very low birth weight infants, 28-30 wk of gestation, studied at 2.5 and 6 wk of age. Eighteen of these infants were fed their mothers' milk fortified with fractions of skim and cream derived from pasteurized, lyophilized, mature human milk (FM) and 10 infants were fed commercial cow's milk-based formula. The concentrations of these selected immune factors in the FM and formula also were measured. Specific SIgA antibodies to E. coli O antigens were detected in the feces of 90% of the FM-fed infants, but in none of the feces of the formula-fed infants. The feces obtained from FM-fed infants had markedly greater quantities of lactoferrin (p less than 0.001), lysozyme (p = 0.006), and IgA (p less than 0.001) than those of cow's milk formula-fed infants. The concentrations of total and secretory IgA were correlated significantly (r = 0.88, p less than 0.001) and 95% of total IgA was SIgA. The fecal concentration of specific SIgA antibodies to E. coli O antigens in FM-fed infants correlated with the concentration of these antibodies in their milk (p less than 0.001). However, there were no direct relationships between the milk concentrations or the infant's intakes of the other selected immune factors and the excretion of these factors in the feces.(ABSTRACT TRUNCATED AT 250 WORDS)     

CIRCULATORY ADAPTATION IN THE THERMOREGULATION OF FULLTERM AND PREMATURE NEWBORN INFANTS

Blood flow measurements by venous occlusion plethysmography were performed on 131 sleeping healthy fullterm newborns at various external temperature conditions. The peripheral circulation varies among different individuals, but a definite relationship between ambient temperature and the rate of peripheral circulation could, nevertheless, be established. Different series of observations on exposure to acute changes of temperature conditions on a further 46 newborn infants allow the following conclusions: The control of peripheral circulation in relation to the temperature of the surroundings is reflex in nature and independent of the local effects of a cold stimulus. Circulatory changes are quantitatively prominent and do not support the view that thermolability in the newborn is due to a deficient thermocontrol of the cutaneous circulation. The circulatory thermoreflex operates even during the first day of life and is as prominent in premature infants as in fullterm infants. The importance of these observations in relation to other mechanisms deciding heat loss and thermogenesis in the newborn is briefly discussed.     

Pulsatile and sexually dimorphic secretion of luteinizing hormone in the human infant on the day of birth.

Experimental evidence indicates that the hypothalamic-pituitary-gonadal axis is operational and sexually dimorphic in the mammalian fetus and newborn. We examined the dynamics of human luteinizing hormone (LH) secretion in five male and three female infants on the day of birth, after 34-41 wk of gestation. The infants were polycythemic, and blood samples were obtained every 20 min for 160 to 360 min during a therapeutic, standardized, isovolumetric, partial exchange transfusion. Serum LH was measured by an immunoradiometric assay that does not cross-react with human chorionic gonadotropin. The serum profiles of LH presented a striking sex dimorphism with elevated LH levels in male compared with female newborns. Deconvolution analysis of all male LH profiles was consistent with a high-frequency, pulsatile secretory pattern. Testosterone, measured in a pooled serum sample of each infant, was 10-fold higher in male than in female newborns. These results document pulsatile and sexually dimorphic secretion of LH in the human infant as early as the first day of postnatal life. It is possible that the augmented LH secretion in the male newborn participates in the neonatal rise of the serum testosterone concentration.