Dietary insulin as an immunogen and tolerogen

We have shown that exposure to bovine insulin (BI) in cow's milk (CM) formula induces an insulin-specific immune response in infants. Here we studied the role of human insulin (HI) in breast milk as a modulator of the immune response to insulin. In a group of 128 children participating in the TRIGR pilot study, maternal breast milk samples were collected 3-7 days and/or 3 months after delivery. After exclusive breast-feeding, the children received either CM formula or casein hydrolysate during the first 6-8 months of life. Insulin concentration in breast milk and immunoglobulin G (IgG) antibodies to BI in plasma samples were measured by EIA. The levels of insulin in breast milk samples were higher in mothers affected by type 1 diabetes than in non-diabetic mothers (p = 0.007 and p < 0.001). The concentration of insulin in breast milk correlated inversely with the plasma levels of IgG antibodies to BI at 6 months of age in children who received CM formula (r = -0.39, p = 0.013), and at 12 months of age in all children (r = -0.25, p = 0.029). The levels of breast milk insulin were higher in the mothers of nine children who developed beta-cell autoimmunity when compared with autoantibody-negative children (p = 0.030); this holds true also when only children of diabetic mothers were included (p = 0.045). BI in CM induces higher levels of IgG to insulin in infants than does HI in breast-fed children. Instead, HI in breast milk seems to be tolerogenic and may downregulate the IgG response to dietary BI. However, our results in infants who developed beta-cell autoimmunity suggest that in this subgroup of children breast milk insulin does not promote tolerance.     

Maternal consumption of dairy products during pregnancy and lactation, and the development of cow's milk antibodies in the offspring

OBJECTIVE: To assess whether the maternal consumption of milk and milk products affects development of cow's milk (CM) antibodies in infants. DESIGN: A randomized pilot trial using food frequency questionnaires (mothers) and food records (infants). SETTING: Families with a newborn infant with increased HLA-DQB1-conferred risk of type 1 diabetes and at least one first-degree relative affected by type 1 diabetes from 16 hospitals in Finland between April 1995 and November 1997. Subjects and intervention: Infants randomized to receive a hydrolysed formula when breast milk was not available during their first 6-8 mo (n=112). Of these, 13 dropped out by the age of 3 mo and two were excluded due to incomplete CM antibody data. RESULTS: Maternal milk protein intake from cheese during pregnancy was inversely related to IgA-class antibody titres to beta-lactoglobulin (BLG) and casein (CAS) at 3 mo, and to IgA antibody titres to BLG at 6 mo. Maternal consumption of raw milk products during lactation was positively related to the development of IgA antibody titres to CAS at 6 mo, and inversely correlated to IgG antibody titres to bovine serum albumin (BSA) and IgA antibody titres to CAS at 2 y. Maternal cheese consumption was inversely related to the IgG antibody titres to CM formula and CAS and to the IgA antibody titres to CAS in early infancy. CONCLUSIONS: Few associations were established between maternal CM protein intake and CM protein antibody levels in the infants. The milk and milk products taken by the mother differed in their impact on the emerging CM antibody response in the offspring.     

Plasma Antibodies to Cow's Milk Are Increased by Early Weaning and Consumption of Unmodified Milk, but Production of Plasma IgA and IgM Cow's Milk Antibodies Is Stimulated Even during Exclusive Breast-Feeding

ABSTRACT. We measured levels of cow's milk-specific (CM) antibodies of immunoglobulin classes G, A and M by enzyme-linked immunosorbent assay in plasma of 198 healthy infants; a variable number of samples taken at birth and at ages of 2, 4, 6, 9, 12 and 28 months were available (altogether 765 samples). The rise in the level of IgG CM antibodies was highest and most rapid in infants exposed to CM formula before the age of 1 month. The level fell by 9 months, but rose again by 12 months. This second rise was attributed to the introduction of dairy milk. Partially breast-fed and fully weaned infants had similar levels of IgG CM antibodies. The levels of IgG CM antibodies were unaffected by the infants' own atopy, their heredity for atopy, and the umbilical serum level of IgG CM antibodies. IgA and IgM CM antibodies were absent at birth. Their levels increased similarly in exclusively breast-fed infants and infants fed CM formula. We conclude that plasma IgG antibodies to cow's milk are increased by early weaning and by consumption of unmodified cow's milk. Production of plasma IgA and IgM antibodies to cow's milk is stimulated even during exclusive breast-feeding.     

Serum immunoglobulin E,IgA, and IgG antibodies to different cow's milk proteins in children with cow's milk allergy: Association with prognosis and clinical manifestations

Diverse pathogenic mechanisms elicit different clinical manifestations in cow's milk allergy (CMA). Our aim was to determine the concentration of serum immunoglobulin levels to different cow's milk proteins in patients with CMA and to determine how these values were related to clinical symptoms and prognosis. Fifty children (mean age 10.9 months, range: 1–34 months) with previously confirmed CMA were enrolled in this study. All had various clinical manifestations of CMA, including gastrointestinal, skin, and respiratory symptoms. At the diagnosis of CMA the serum total and the milk‐specific immunoglobulin (Ig)E values were measured by enzyme immunoassay and fluoroimmunoassay, respectively, while the relative levels of serum IgA and IgG antibodies against different cow's milk proteins were determined by a sensitive enzyme‐linked immunosorbent assay (ELISA). The results were compared to those of 30 non‐atopic age‐matched control children. On average, after 9.2 months (range 2–31 months) on a milk‐free diet, a repeated challenge was performed in 38 children. At the re‐challenge, 12 patients had clinical symptoms while the remaining 26 children were symptom‐free. The IgG antibody level to bovine serum albumin (BSA) was significantly lower in the patients than in the controls (median: 0.36 vs. 2.94, p < 0.01). There was a close correlation among all individual IgA and IgG antibodies to different cow's milk proteins. The anti‐α‐casein IgG level (of 2.10) in children with a positive reaction at the re‐challenge was significantly higher than in those with a negative reaction (0.89) (p < 0.05). The total IgE serum concentration was also significantly higher in those who had symptoms at the re‐challenge compared to those who did not have any reaction at this time (22.9 vs. 6.8 kU/l, geometric mean, p < 0.02). There was no association between the clinical manifestations and the IgG and IgA antibody levels to the cow's milk proteins studied, except for the anti‐BSA IgA level, which was higher in patients with gastrointestinal symptoms. The serum total IgE and anti‐α‐casein IgG levels could have prognostic values; their increase at the beginning of the disease may indicate the development of tolerance to cow's milk only at a later age and after a longer duration of CMA. However, as there is considerable overlap among the values observed in different groups of patients, there is a limitation of these tests for predicting the prognosis.     

An exploration of Glo‐3A antibody levels in children at increased risk for type 1 diabetes mellitus

Aims: To determine whether Glo‐3A, (formerly referred to as homologue of Glb1 or Glb1) antibodies are associated with islet autoimmunity (IA) in children at increased risk for type 1 diabetes (T1D) and to investigate their relation with environmental correlates of T1D. Methods: We selected a sample from the Diabetes Autoimmunity Study in the Young (DAISY), a prospective study of children at increased risk for T1D. Cases were positive for insulin, glutamic acid decarboxylase (GAD), or insulinoma‐associated antigen‐2 (IA‐2) autoantibodies on two consecutive visits and either diagnosed with diabetes mellitus or still autoantibody positive when selected. Controls were from the same increased risk group, of similar age as the cases but negative for autoantibodies. Sera from 91 IA cases and 82 controls were analyzed in a blinded manner for immunoglobulin G (IgG) antibodies to Glo‐3A by ELISA. Results: Adjusting for family history of T1D and human leukocyte antigen (HLA)‐DR4 positivity, Glo‐3A antibodies were not associated with IA case status (OR: 1.01, 95% CI: 0.99–1.03). Adjusting for age, family history of T1D, and HLA‐DR4 positivity, Glo‐3A antibody levels were inversely associated with breast‐feeding duration (beta = ?0.08, p = 0.001) and directly associated with current intake of foods containing gluten (beta = 0.24, p = 0.007) in IA cases but not in controls. Zonulin, a biomarker of gut permeability, was directly associated with Glo‐3A antibody levels in cases (beta = 0.73, p = 0.003) but not in controls. Conclusion: Differing correlates of Glo‐3A antibodies in IA cases and controls suggest an underlying difference in mucosal immune response.     

Cow's milk and ovalbumin-specific IgG and IgA in children with eczema: low β-lactoglobulin-specific IgG4 levels are associated with cow's milk allergy

To cite this article: Savilahti EM, Viljanen M, Kuitunen M, Savilahti E. Cow's milk and ovalbumin-specific IgG and IgA in children with eczema: low β-lactoglobulin-specific IgG4 levels are associated with cow's milk allergy. Pediatric Allergy Immunology 2012: 23: 590-596. ABSTRACT: Tolerance to allergens may partly depend on allergen-specific IgG and IgG subclasses and IgA antibodies. We investigated whether specific IgG and IgG subclasses and IgA antibodies to β-lactoglobulin, α-casein, and ovalbumin differed between infants who had verified cow's milk allergy (CMA) and infants with cow's milk (CM)-associated eczema, but negative CM oral challenge. The study population comprised 95 infants with clinical eczema that was by history associated with the consumption of CM. After an elimination period, a double-blind, placebo-controlled (DBPC) CM oral challenge confirmed CMA in 45 infants. Skin prick tests (SPT) were performed with CM and hen's egg. Serum levels of IgE antibodies to CM and hen's egg were measured with UniCAP (Phadia, Uppsala, Sweden), and levels of IgA, IgG, IgG1, and IgG4 antibodies to β-lactoglobulin, α-casein, and ovalbumin were measured with enzyme-linked immunosorbent assay. We observed that infants with CMA had lower IgG4 levels to β-lactoglobulin than infants with negative DBPC CM challenge (p?=?0.004). Positive CM SPT was associated with lower IgG4 levels to α-casein (p?=?0.04). The relation of CM IgE to β-lactoglobulin and α-casein IgG4 was higher in CMA than in infants with negative challenge (p?相似文献   

CLINICAL AND IMMUNOLOGICAL ASPECTS OF FOOD ALLERGY IN CHILDHOOD

ABSTRACT. 36 children of atopic mothers (group I) and 17 children of healthy mothers (Group II) were selected for a study of the relationship between the onset of atopic symptoms and the occurrence of IgE-, IgG- and IgA-antibodies, with special regard to the development of antibodies to β-lactoglobulin (BLG) and ovomucoid (OM). Atopic symptoms developed in 50 % of the children in group I and in no one of group II. The cord serum IgE concentrations were shown to be predictive of subsequent development of atopic symptoms, and the levels remained higher in group I than in group II. The serum IgA concentrations were low and within normal limits in both groups and bore no relationship to atopic heredity or to later development of atopic symptoms. However, at six months of age the serum IgA levels were lower in the children of atopic mothers (p<0.1). Low titers of IgE antibodies to BLG and OM occurred in several children of Group I but seemed to have clinical significance in only a few children. IgG antibodies to BLG and OM were shown to occur frequently and in equivalent titers in cord sera and maternal sera indicating a transport across the placental barrier. High cord titers were found in children of group I who remained asymptomatic, indicating a possible protective function by these antibodies. The titers to BLG were higher in group I than in group II. Most titers decreased during the first months of life and then a rise occurred.     

Study design of the Trial to Reduce IDDM in the Genetically at Risk (TRIGR)

Abstract:  The hypothesis for this study is that weaning to an extensively hydrolyzed infant formula will decrease the incidence of type 1 diabetes (T1D), as it does in all relevant animal models for the disease. This will be tested in children who carry risk-associated human leukocyte antigen genotypes and have a first-degree relative with T1D. The trial will use a double-blind, prospective, placebo-controlled intervention protocol, comparing casein hydrolysate with a conventional cow's milk (CM)-based formula. A secondary aim is to determine relationships between CM antibodies, a measure of CM exposure, and diabetes-associated autoantibodies. To achieve an 80% power for the detection of a 40% intervention-induced difference in the development of autoantibodies and subsequent diabetes, the study requires 2032 subjects. A multicenter, international, collaborative effort is necessary to achieve recruitment targets. A collaborative international study group of 78 clinical centers in 15 countries has therefore been assembled for this purpose.     

Characteristics of the development of immunity in healthy children during the first year of life

Studies of the levels of serum IgA, IgG, and IgM, of B and T lymphocyte function in 20 neonates of days 7-8 of life (funic blood) and their mothers, in children aged 1,3,6,9 and 12 months made it possible to define the characteristic features of the establishment of humoral and cellular immunity during the first year of the child's life. The children placed under observation were normal as regards their physical and psychomotor development and had no infectious or inflammatory diseases. The neonates were characterized by high activity of T lymphocytes, the lack of IgA and traces of IgM, and the high level of IgG in blood serum. The least IgG concentration was seen at an age of 1 month. The data obtained will permit a proper assessment of the changes occurring in the child's immune status during different diseases. The changes should be taken into consideration in carrying out preventive and treatment measures during the first year of the child's life.     

Antibodies to human immunodeficiency virus in the breast milk of healthy, seropositive women

Reports of rare cases of suspected transmission of the human immunodeficiency virus (HIV) from mother to children by breast milk have been recently published. To study the factors that possibly limit HIV transmission through breast-feeding, milk samples obtained from 15 healthy, seropositive mothers and 4 seronegative control subjects were studied for the presence of anti-HIV antibodies. All samples from seropositive women contained IgG antibody against envelope glycoproteins gp160 and/or gp120, and 11 of 15 samples contained IgA antibodies against gp160. IgA antibodies against other viral antigens were more rarely recovered, except against the internal proteins of the virus, p18 and p25. The finding of IgA antibodies to HIV-1 in breast milk establishes that the virus elicits a local immune response in heterosexual, seropositive women. The role of local antibodies in the postnatal transmission of HIV remains to be determined.     

Serodiagnosis of Helicobacter pylori infection is not accurate for children aged below 10

BACKGROUND: In order to investigate the immune response to Helicobacter pylori in childhood, we compared anti-H. pylori IgG and IgA antibodies with H. pylori antigen in the stool and examined the clinical usefulness of the anti-H. pylori IgG and IgA antibodies. METHODS: This study included 157 children who were seen at our hospital. Serum and stool samples were obtained for these children. Antibodies to H. pylori were examined using an H. pylori IgG enzyme-linked immunosorbent assays (ELISA) and an H. pylori IgA ELISA. Analysis of stool samples was carried out by the H. pylori stool antigen (HpSA) enzyme immunoassay. RESULTS: Of the 157 children, 45 children were HpSA positive, 110 were negative and two were undetermined. Out of 45 HpSA positive patients, 25 children were both IgG and IgA positive and seven were negative for both IgG and IgA antibodies. Of the 110 patients who were HpSA negative, 97 were negative for both antibodies. All HpSA positive children older than 10 years were positive for IgG and IgA antibodies, but of the HpSA positive children under the age of 10, only 18 out of 35 (51.4%) were positive for IgG antibodies or IgA antibody. CONCLUSION: These facts suggested that an immature immune response or tolerance to H. pylori exists in childhood and serodiagnosis of H. pylori infection is less useful in children aged below 10.     

Feasibility and compliance in a nutritional primary prevention trial in infants at increased risk for type 1 diabetes

Aim: The international Trial to Reduce IDDM in the Genetically at Risk (TRIGR) was launched to determine whether weaning to a highly hydrolysed formula in infancy reduces the incidence of type 1 diabetes in children at increased genetic disease susceptibility. We describe here the findings on feasibility and compliance from the pilot study. Methods: The protocol was tested in 240 children. The diet of the participating children was assessed by self‐administered dietary forms, a structured questionnaire and a food record. Blood samples were taken and weight and height measured at birth and at 3, 6, 9, 12, 18 and 24 months. Results: A majority of the subjects (84%) were exposed to the study formula at least for 2 months. Linear growth or weight gain over the first 2 years of life was similar in the two study groups. The levels of IgA and IgG antibodies to cow’s milk and casein were higher in the cow’s milk–based formula group than in the hydrolysed formula group during the intervention period (p < 0.05), reflecting the difference in the intake of cow’s milk protein. Conclusion: This randomized trial on infant feeding turned out to be feasible, and dietary compliance was acceptable. Valuable experience was gained for the planning and sample size estimation of the study proper.     

Local production of total IgE and specific antibodies to the house dust mite in adenoid tissue

Adenoids are known as immunosecretory organs and those in atopic children present cellular and cytokine profiles different from those of non‐atopic children. We hypothesized that locally produced total IgE and allergen‐specific antibodies could be involved in the inflammatory responses in adenoid tissue. Local productions of total IgE and Dermatophagoides pteronyssinus (DP)‐specific IgE, IgA, IgG1, and IgG4 antibodies were evaluated, as well as their relationships with the markers of allergic inflammation within adenoid tissue. Eighteen atopic subjects, who were sensitized to more than one common aeroallergen, and 22 non‐atopic subjects undergoing adenotonsillectomy, were recruited. Immunoassays using adenoid tissue homogenate were performed to quantify the levels of total IgE, eosinophil cationic protein (ECP), and mast cell tryptase. DP‐specific IgE, IgA, IgG1, and IgG4 antibodies, soluble IL‐2 receptors (sIL‐2R), soluble CD23 (sCD23), and IL‐6 were measured by ELISA. All parameters measured in adenoid tissue homogenate were presented as a ratio to the albumin level found in the adenoid. Median level of total IgE in adenoid tissue homogenate was significantly higher in atopic individuals than in non‐atopic individuals. Median values of DP‐specific IgE and IgA antibodies were significantly higher in atopics than in non‐atopics (p = 0.001, p = 0.006, respectively), while no differences were seen in DP‐specific IgG1 and IgG4 antibodies. ECP and sCD23 levels in adenoid homogenate were significantly higher in atopics than in non‐atopics (p = 0.026, p = 0.048, respectively), while no significant differences were noted in tryptase, sIL‐2R, and IL‐6 levels. The levels of DP‐specific IgE, IgA, IgG1, and IgG4 antibodies in adenoid homogenate correlated significantly with ECP levels, but not with those of sIL‐2R, sCD23, and IL‐6. The presence of total IgE and DP‐specific antibodies in adenoid tissue was confirmed to be more prominent in atopics. In conclusion, locally‐produced total IgE and DP‐specific antibodies may contribute to eosinophilic inflammation in adenoid tissue in atopic children.     

病毒性心肌炎患儿免疫状况的研究

目的：探讨病毒性心肌炎 (VMC)患儿在细胞免疫、体液免疫和自身免疫方面的改变,从而指导免疫治疗。方法：用流式细胞技术分别测定 30例急性期、2 2例迁延期VMC患儿及30例对照的血清CD2 3,CD3/HLA DR,用比浊法测IgG,IgA和IgM。 结果：VMC患儿急性期、迁延期的CD2 3,IgG ,IgA ,IgM及CD3+ /HLA -DR+,CD3-/HLA -DR+ 细胞比例均高于正常对照组 (P均 <0 .0 1)。VMC患儿CD2 3和IgG ,IgA ,IgM呈正相关 (r分别=0.30,0.17,0.40,P<0.0 5),而急性期、迁延期VMC患儿的CD3+ /HLA DR-细胞表达率与正常对照组相比均无明显差异 (P均 >0 .0 5 )。迁延期患儿的各项指标和急性期相比无明显差异(P均>0.05)。结论：病毒性心肌炎患儿急性期、迁延期的细胞免疫、体液免疫均处于增强状态,提示细胞免疫、体液免疫可能参与了VMC患儿的心肌损伤。     

Selective IgA deficiency

Of 140 patients referred to the Pediatric Immunology Clinic during of 12-month period with the symptoms of recurrent infections or allergic respiratory illness, 21 (75%) were found to have selective IgA deficiency defined as serum concentration ≤ 5 mg. with normal levels of IgG and IgM. T lymphocyte number was reduced in the patients where as B cells with surface membrane IgA were increased. Autoantibodies and circulatory immune complexes were found more often in IgA-deficient subjects than in controls. Follow-up beyond the age of 9 years showed a spontaneous increase in serum IgA in 6, whereas 15 continued to have IgA deficiency. The latter group of children were characterized by more frequent infections, a higher prevalence of atopic disease, lower T cell count and serum IgG concentration, higher serum IgE level and a higher prevalence of food antibodies and immune complexes. These observations highlight the natural history and immunologic features of selective IgA deficiency.     

Serum and salivary anti-capsular antibodies in infants and children immunized with the heptavalent pneumococcal conjugate vaccine

AIM: To study the ability of seven-valent experimental pneumococcal polysaccharide CRM197 protein conjugate vaccine (PncCRM) to induce antibodies in serum and saliva of infants. METHODS: Sixty Finnish infants received Pnc-CRM vaccine at 2, 4 and 6 months of age and were boosted with PncCRM (n = 30) or pneumococcal polysaccharide (PncPS) (n = 29) vaccine at the age of 15 months. Serum IgG antibody concentrations to vaccine serotypes 4, 6B, 9V, 14, 18C, 19F and 23F were measured by enzyme immunoassay at 2, 4, 6, 7, 15, 16 and 24 months of age. Salivary IgA, IgG and secretory Ig antibody titers at 7 and 16 months of ages were analyzed by enzyme immunoassay against the same serotypes, except 23F. RESULTS: PncCRM induced systemic immune responses and immunologic memory. At 7 months of age 69 to 100% of children, depending on the serotype, had serum IgG antibody concentrations exceeding the value of 1.0 microg/ml. At 15 months the titers were still higher than before the vaccinations. Booster doses of either PncPS or PncCRM induced an increase in antibody concentrations. The titers were still elevated at 24 months of age. Salivary IgA and IgG antibodies were found rarely at 7 months of age, but in up to 80% of samples taken at 16 months of age, depending on the serotype and nature of the booster vaccine. Salivary IgG correlated with IgG in serum, supporting the theory that salivary IgG is derived from serum. Salivary IgA and secretory Ig correlated positively, which indicates that IgA was locally produced. CONCLUSIONS: PncCRM induces both systemic and mucosal immune responses in infants.     

Cow milk-specific humoral and cellular immune response in infants with high risk of atopy under feeding a whey hydrolysate infant formula

BACKGROUND: Hypoallergenic infant formulas (HAF) were developed for atopy prevention in infants with high risk of atopy if these cannot be breastfed. HAF mount an antigen-specific immune response in infants. The aim of the study was to analyse the immune response in infants fed with a new infant formula based on a whey hydrolysate (HAF) and to compare it with that of exclusively breastfed controls. PATIENTS AND METHODS: Plasma concentrations of cow milk-specific IgE were analysed in 94 infants with high risk of atopy, 44 were exclusively breastfed, 50 were fed with HAF. In addition, cow milk-specific IgG antibodies (26 breastfed, 30 fed with HAF) as well as proliferation of periph-eral blood mononuclear cells to bovine beta-lactoglobulin (BLG) (41 breastfed, 47 fed with HAF) were tested. Specific IgE and IgG antibodies were determined using enzymoimmunometric assay (Alastat). Cellular proliferation was measured using tritiated thymidine incorporation assay after 6 day stimulation with BLG. RESULTS: Elevated IgE to cow milk antibodies (> 0.35 kU/L) were detected in two infants from the breastfed group and in one from the HAF-fed group. The plasma concentrations of milk specific IgG antibodies in HAF-fed infants were insignificantly higher than those in breastfed ones. No significant difference was found in bovine BLG-specific cell proliferation between both groups. CONCLUSION: Concerning the properties investigated like antigenicity, allergenicity and immunogenicity, the extensively hydrolysed whey based hypoallergenic formula does not significantly differ from mother milk in 6 month-old infants with an increased atopy risk.     

Immune complexes and Pseudomonas aeruginosa antibodies in cystic fibrosis.

Serum samples from 57 patients with cystic fibrosis were tested for the presence of IgG, IgA, IgM, IgE, and circulating immune complexes containing IgG, IgA, and IgM. Titres of class specific antibodies to Pseudomonas aeruginosa, and class specific antibodies to Ps aeruginosa in circulating immune complexes, were also measured. According to the Shwachman score the patients were divided into three clinical groups: group 1-moderate and severe disease, group 2-mild disease, and group 3-well. The results of the immunological investigations were correlated with the clinical state of the patients as assessed by the Shwachman score. Serum concentrations of IgG, IgA, and IgM were inversely correlated with the Shwachman score, but the differences between the groups were only significant for IgG and IgA. The same correlations were found for circulating immune complexes containing IgG and IgA. Antibodies to Ps aeruginosa could be detected in most of the patients'' serum samples. IgA antibody specific to Ps aeruginosa was the most often raised, even in patients in group 3. It is therefore suggested that IgA antibody specific to Ps aeruginosa could be an early marker of colonisation by Ps aeruginosa and a sensitive measurement of infection with Ps aeruginosa in young children with cystic fibrosis. Moreover, in the circulating immune complexes, class specific antibodies to Ps aeruginosa were found in nearly half the patients. The highest titres of IgG and IgA antibodies specific to Ps aeruginosa in the circulating immune complexes were detected in the patients with the worst clinical state (group 1).     

Immunological evaluation in the early diagnosis of prenatal or perinatal HIV infection.

A longitudinal evaluation was carried out of the clinical, infective, and immunological progress of 34 children (who were aged 6 to 68 months--mean 25 months at the time of writing) born to 31 mothers infected with human immunodeficiency virus (HIV), over a mean observation period of 13.4 months. Clinical symptoms, not always clearly related to HIV became apparent in 11 children, and preceding immune abnormalities were documented in two of them. In eight children culture for HIV was positive, and six of these were symptomatic. No cancers were diagnosed and none of the children died. Immune abnormalities including hypergammaglobulinaemia, IgG subclass deficiency, low serum IgA concentration, antibody deficiency, a decrease in the number of CD4+(T helper) cells, and defective cellular responses to antigens, were found in seven of the children in whom culture for HIV was positive; in two of four who had symptoms and in all four who were symptom free and in whom culture was negative for HIV but in whom HIV antibodies persisted and who were older than 15 months; and in three of nine who were symptom free and in whom culture was negative with loss of HIV antibodies. We conclude that serological diagnosis alone may be misleading and that additional immunological assessment may help to identify affected children. Analysis of humoral and cellular responses to antigens used for vaccination such as tetanus toxoid by measurement of specific antibodies and skin testing are simple and helpful in clinical practice.     

IgG subclass specific antibody response in recurrent bronchitis.

The IgG subclass specific immune response against pneumococcal type 3 polysaccharide antigen before and after immunisation in healthy children and children with recurrent bronchitis was studied. Recurrent bronchitis was defined as three or more episodes a year, during at least two consecutive years, of bronchopulmonary infection, productive cough with or without fever, and/or diffuse rales by physical examination. Twenty five patients and 15 healthy children were selected. The patient group had lower concentrations of IgG1 and IgG2 specific pneumococcal antibodies compared with healthy children, regardless of whether or not the total IgG2 concentration was low. The children with recurrent bronchitis showed a greater increase in IgG1 and IgG2 antibodies after immunisation than the controls. It is concluded that children with recurrent bronchitis show a decreased humoral immune response to pneumococcal type 3 polysaccharide antigen. This finding suggests that a defect in the humoral immune response against polysaccharide antigens is an important cause of recurrent bronchitis in childhood.