Regional deficiency of secretory IgA in a patient with combined immunodeficiency of the ADA deficient type.

The IgA system in a patient with SCID and ADA deficiency showed heterogeneity. Serum IgA and stool secretory IgA (SIgA) levels were normal, but with altered kappa/lambda and A1/A2 subclass ratios; IgA in saliva and urine was deficient. Amounts of secretory component were normal. Jejunal and rectal biopsies showed prominent lymphonodular hyperplasia, but no cells containing IgA. A normal serum IgA level therefore does not always predict an intact secretory IgA system.     

Persistence of Human Milk Proteins in the Breast-Fed Infant

Several proteins in human milk are postulated to have physiological functions in the breastfed infant. Therefore, survival of human milk proteins after passage through the gastrointestinal tract of the breast-fed infant was investigated. Fecal samples were collected from exclusively breast-fed term infants and milk samples from their mothers. Soluble proteins in the feces were extracted and analyzed for total protein, nitrogen, lactoferrin, secretory IgA, serum albumin and lysozyme. Significant amounts of lactoferrin and secretory IgA were excreted by the infants and this excretion decreased throughout the study period in a trend similar to the decreasing milk concentrations of these proteins. Gel filtration demonstrated excreted lactoferrin and secretory IgA to be intact. No serum albumin or lysozyme was detected in the fecal extracts. Crossed Immunoelectrophoresis showed three human milk proteins to be present in the feces—the third was identified as α₁-antitrypsin. Excretion of these proteins indicates the total protein content of human milk is an over-estimation of the protein nutritionally available to the infant.     

COURSE OF RENAL FUNCTION IN IgA GLOMERULONEPHRITIS IN CHILDREN AND ADOLESCENTS

ABSTRACT. The pathophysiology of IgA GN was investigated in different stages of the disease. Seventeen patients who were between 3.5 and 16.5 years of age at the onset were included in the study. Clearance studies were performed repeatedly in 6 patients (in 5 of them over a period extending from the onset to 5-9.5 years) and only once in 9 patients (10-23 years after the onset). Two patients (one with uremia) were only evaluated clinically. C_In, C_PAH and U_NaV were studied during hydropenia (HP) and 3% isotonic saline volume expansion (VE). Shortly after the onset C_In, C_PAH and U_NaV were depressed. Renal function was essentially normal 1 and 2 years after the onset in spite of signs of active disease. A supernormal GFR was found in 7 patients after they had had the condition between 5 and 17 years. After a duration of IgA GN for >9 years 3 of 12 patients had developed hypertension and uremia and 2 had hypertension or labile BP. Three of 10 patients had a normal GFR and BP, but had increased natriuresis during VE. Only 2 of 10 patients were normotensive and had normal renal function. Disturbancies in the renal function are thus frequent in all stages of IgA GN and the changes seem to be related to the duration of the disease. Exaggerated natriuresis may indicate progressive disease.     

Serum immunogiobulin G subclasses and serum immunogiobulin A in healthy Norwegian children and adults

IgG subclass concentrations were determined by a capture ELISA antibody assay using monoclonal antibodies to IgG₁, IgG₂, IgG₃, and IgG₄. All the antibodies had been tested for specificity in an IUIS/WHO collaborative study, and this was confirmed by us by testing against purified myeloma proteins representing the 4 subclasses. The sera to be tested were diluted to obtain optimal sensitivity in the lower normal range for each subclass. With these serum dilutions, the lower limit of reading was 1. 2 g/l for IgG₁, 0. 25 g/l for IgG₂, 0.04 g/l for IgG₃ and for IgG₄. Age specific reference limits of the IgG subclass concentrations were determined in serum samples from 138 healthy infants and children under 14 years of age and 66 adults. The reference limits for each age group were determined by calculating the mean ± 2 SD of the logarithms to the values and then taking the antilog of the results. IgA was determined by a turbidimetric method with a reading limit of 0. 1 g/l, and the reference limits were calculated from serum samples from the 138 children under 14 years of age and from 31 healthy adults. The age specific reference limits of the IgG subclasses and IgA are given. Several infants and children had IgG₄ levels below the lower reading limit. To determine lower reference limits of IgG₄ below the age of 7 years was therefore of little clinical significance.     

Parathyroid hormone resistance and B cell lymphopenia in propionic acidemia

The mechanisms of hypocalcemia, recurrent infections and hypogammaglobulinemia associated with metabolic decompensation of propionic acidemia due to propionyl-CoA carboxylase deficiency have not been defined. A 7-week-old infant with this disorder presented with severe hypocalcemia and B cell lymphopenia during an episode of metabolic acidosis and hyperammonemia. Hypocalcemia (1.1 mmoll ¹) was associated with elevated serum intact parathyroid hormone (122 ng 1 ¹), hyperphosphatemia, hypophosphaturia and hypercalcuria, indicating parathyroid hormone resistance. B cell lymphopenia (20 cells μl^-1) was associated with transient neutropenia, anemia and subsequent hypogammaglobulinemia (IgG < 294mgdl^-1, IgM < 8mgdl^-1, IgA < 8mgdl ¹), while T cells were normal. Parathyroid hormone resistance and B cell lymphopenia resolved following treatment with hemodialysis, diet and carnitine. These complications may be due to interference with parathyroid hormone renal tubular action and B cell maturation/proliferation by accumulated organic acids.     

THE ROLE OF ACTIVE SODIUM AND POTASSIUM TRANSPORT IN HYPONATREMIC STATES IN INFANCY AND CHILDHOOD

ABSTRACT. Sigström, L. (Department of Paediatrics I, University of Goteborg, östra Sjukhuset, Göteborg, Sweden). The role of active sodium and potassium transport in hyponatremia states in infancy and childhood. Acta Psediatr Scand, 70:353, 1981.–Erythrocytes from 14 infants and children with serum sodium concentrations of 125 mmol/1 or less were analyzed for total and Na⁺, K⁺-ATPase, sodium and potassium content and ATP concentrations to evaluate the role of active Na⁺-K⁺ transport in hyponatremia. In six out of nine patients, with a duration of hyponatremia of more than 48 hours low Na⁺, K -ATPase activities and high erythrocyte sodium concentrations and Na⁺-K⁺ ratios were found indicating that a decreased Na⁺, K⁺-ATPase activity leading to an increased intracellular accumulation of sodium ions may have reduced the extracellular sodium concentration. Three subjects with large sodium losses had high Na⁺, K⁺-ATPase activities and normal erythrocyte sodium concentrations. In five cases of hyponatremia with a duration of less than 24 hours the variables indicating active Na⁺-K⁺ transport were normal. The therapeutic implications with sodium substitution and the use of drugs affecting active Na⁺-K⁺ transport are discussed.     

EFFECT OF LONG-TERM GH ADMINISTRATION ON PITUITARY-THYROID FUNCTION IN IDIOPATHIC HYPOPITUITARISM

Abstract. Twenty-four euthyroid children with idiopathic pituitary dwarfism were studied. The euthyroid state for seven of these patients was determined by negative physical examinations, normal plasma T₄ assays and normal ¹³¹I uptakes. For the other children, thyroid function was evaluated with T₃ and T₄assays and on the basis of the TRH test. Each of the children was treated with HGH in one of three different ways. The first group (five cases) was given a HGH dose, ranging from 12.4 to 17.2 IU/m²/week. The second and third groups (nine and ten cases, respectively) were treated with 10 and 20 IU/m²/week, respectively. Treatment was carried out for periods ranging from 6 months to 6 years. After no less than 6 months of treatment, and at intervals of 6 months (or some multiple of 6 months) plasma T₃ and T₄ assays, as well as a TRH test were performed in each patient. In some patients one of the indices was once beyond the upper or lower limit of the normal range (none of the children presented simultaneous abnormal levels of more than one index during the controls). This value, however, returned to within normal limits at the following control. There was no correlation between T₃, T₄ and TSH with the duration of HGH therapy. There was no significant difference between the groups of children treated with the different HGH doses. These data seem to demonstrate that the risk of inducing an alteration in thyroid function in hypopituitary patients during HGH treatment is very slight, and that the irregularly abnormal thyroid indices observed in some of the children during one of the controls might be an expression of their metabolic status at that moment.     

Nasal IgA response in wheezy infants

It is unknown why some infants wheeze during upper respiratory tract infections. One possibility is that secretory IgA, which has a major role in mucosal defence against viral infection, might be deficient in wheezy infants. The nasal IgA response to upper respiratory tract infection in 32 wheezy infants (median age 5.8 months) was compared with nine siblings (median age 2.6 years) who had nasal symptoms only. Nasal lavage was performed during infections and on follow up when free from symptoms, using inulin as a marker of dilution to determine absolute concentrations of IgA in the nasal secretions. The two groups showed a similar increase in total IgA and total protein levels during infection, but secretory IgA concentrations were unchanged. This study shows that wheezy infants have a normal nasal IgA response to infection and that the increase in total IgA during early infection is due to plasma exudation rather than increased production of secretory IgA.     

Nasal IgA response in wheezy infants.

It is unknown why some infants wheeze during upper respiratory tract infections. One possibility is that secretory IgA, which has a major role in mucosal defence against viral infection, might be deficient in wheezy infants. The nasal IgA response to upper respiratory tract infection in 32 wheezy infants (median age 5.8 months) was compared with nine siblings (median age 2.6 years) who had nasal symptoms only. Nasal lavage was performed during infections and on follow up when free from symptoms, using inulin as a marker of dilution to determine absolute concentrations of IgA in the nasal secretions. The two groups showed a similar increase in total IgA and total protein levels during infection, but secretory IgA concentrations were unchanged. This study shows that wheezy infants have a normal nasal IgA response to infection and that the increase in total IgA during early infection is due to plasma exudation rather than increased production of secretory IgA.     

ASSESSMENT OF LUNG FUNCTION ON HEALTHY CHILDREN USING AN ELECTRONIC SPIROMETER AND AN AIR-FLOWMETER BEFORE AND AFTER INHALATION OF AN ADRENERGIC RECEPTOR STIMULANT

Abstract. VC measured with a Monaghan electronic spirometer equipped with a backflow valve is significantly lower (about 4%) than when measured with the same spirometer without such a valve. The measurements of FEV_1.0 were not influenced by the valve. 73 healthy children were investigated with the Monaghan spirometer equipped with the backflow valve and normal reference data were established. The results were very similar to those obtained in an investigation of healthy children with the same spirometer about one year earlier. Reference data on children for a simple flow meter, Airflometer (Glaxo Ltd.), are given. The data correlated very highly to the FEV_1.0 values obtained by the Monaghan spirometer. After inhalation of salbutamol healthy children had a small and significant increase of FEV_1.0 and of the Airflometer value but not of VC. The deviations of the differences were small. A 6% increase of VC and 10% increase of FEV_1.0 were taken as normal upper limits after inhalation of salbutamol. Corresponding increase of the Airflometer values was 15 arbitrary units for children with body heights 116–145 cm and 21 units for children with body heights 146–175 cm.     

Humoral immunity in children with proven bronchiectasis, bronchial deformations and chronic bronchitis

In 70 children with defined chronic chest disease, immunoglobulins, IgG subclass levels and antibody concentrations specific for Haemophilus influenzae b (Hib), and pneumococcal antigen, were related to disease severity. Bronchological examinations revealed 30 children with chronic bronchitis, 21 with bronchial deformations and 19 with bronchiectasis. Of the 70 children 12 (17.1%) showed an underlying immunodeficiency. The commonest finding was an IgG subclass deficiency, 7 were IgG₂ and 1 IgG₃ deficient, followed by IgA deficiency in 3 patients. All patients had normal IgG and IgM levels except one who had immunodeficiency with elevated IgM. Pneumococcal antibody levels were found to increase between patient groups in the order healthy children < chronic bronchitis < bronchiectasis < bronchial deformations (p < 0.01), but this was not the case for Hib antibodies. We found no selective deficiency of pneumococcal and Hib antibodies in our patients. Pathogens were detected in bronchial cultures from 10% of patients with chronic bronchitis, 33% of those with bronchial deformations and in 63% with bronchiectasis. This increase (p < 0.01) reflects a more severe inflammation of the respiratory tract in such patients. However, immunodeficiencies were equally distributed between patient groups. We conclude that only a subgroup of children with chronic chest disease have an underlying immunodefiency, but most patients (83%) do synthesize normal or even high antibodies in the presence of a bacterial load.     

Both allergen-specific CD4 and CD8 Type 2 T cells decreased in asthmatic children with immunotherapy

Allergen-specific immunotherapy (IT) has been used for the treatment of atopic diseases since the turn of this century. The precise working mechanisms, however, remain to be clarified. The aim of this study was to investigate the role of particular subsets of allergen-specific T cells in the non-atopic individuals, untreated asthmatic children and the asthmatic children receiving immunotherapy. We collected peripheral blood from 16 untreated asthmatic children and 17 asthmatic children receiving immunotherapy over one and half years. All the patients were sensitive to mite allergen. Peripheral blood mononuclear cells (PBMC) were isolated and, in vitro , stimulated with crude mite extract to enrich the mite-specific T-cell population. After 14 days, the enriched mite-specific T cells were stimulated with phorbol-12-myristate-13-acetate (PMA) and ionomycin for intracellular detection of cytokines such as IFN-γ, IL-4 in CD4⁺ and CD8⁺ T lymphocytes. The data here demonstrated that the levels of mite-specific IgG4 and IgA increased significantly in asthmatic children after immunotherapy. In addition, both IL-4 expressing CD4⁺ and CD8⁺ T cells were significantly lower in asthmatic children after immunotherapy compared with those of before treatment and the normal control (p < 0.05). In contrast, the frequency of IFN-γ expressing CD4⁺ and CD8⁺ T cells did not significantly differ between untreated and SIT-treated groups. All these data suggested that decreased Type 2 CD4⁺ and CD8⁺ T cells might be closely correlated with the regulatory mechanisms of immunotherapy.     

Working Capacity and Pulmonary Gas Exchange in Children with Exercise-Induced Asthma

ABSTRACT. Sixteen children aged 10.1-14.3 years with a history of exercise-induced asthma (EIA) were evaluated as to their working capacity both during a maximal exercise test and during sub-maximal exercise. During submaximal exercise ventilation and alveolar gas exchange were measured. Working capacity was normal with respect to the oxygen uptake and to the maximal load. Arterial blood gases were normal before exercise but PaO₂ decreased ( p <0.01) during the submaximal exercise test. The values were, however, still within the normal limits in all but two of the children. The flow-volume data showed bronchial obstruction in the resting state, before exercise, with lower values of MEF₅₀ and MEF₂₅ ( p <0.01) than in healthy children. Following exercise, 14 of the 16 children developed clinical symptoms of asthma with increased impairment of the flow-volume curves. Most of them recovered from asthmatic symptoms within 30 min. Flow-volume curves were found to be a sensitive measurement of bronchial obstruction during the symptom-free phase and during EIA although with larger individual variations than FEV₁.     

CHARACTERISTICS OF ACTIVE SODIUM AND POTASSIUM TRANSPORT IN ERYTHROCYTES OF HEALTHY INFANTS AND CHILDREN

ABSTRACT. Sigström, L. Waldenström, J. and Karlberg, P. (Departments of Paediatrics I and Clinical Chemistry, University of Göteborg, Göteborg, Sweden). Characteristics of active sodium and potassium transport in erythrocytes of healthy infants and children. Acta Paediatr Scand, 70:347, 1981.–Erythrocytes were analysed for adenosine triphosphatase (total and sodium-potassium activated) activities, concentrations of sodium and potassium ions and ATP in normal individuals from birth to adulthood age. A decrease of Na, K⁺-ATPase activity and an increase of the sodium concentration was seen in infants aged 1–3 and 4–8 months. A decrease of Na⁺, K⁺-ATPase was seen during puberty. A correlation was seen between the Na⁺, K⁺-ATPase activity and the Na⁺-K+ ratio. Different influences which might lead to the observed changes in Na⁺, K⁺-ATPase activity and erythrocyte sodium concentration are discussed.     

ELECTRICAL POLARIZATION OF RECTAL MUCOSA and EXCRETION OF TETRAHYDROALDOSTERONE IN PATIENTS WITH CYSTIC FIBROSIS OF PANCREAS and IN NORMAL SUBJECTS

Abstract. Rask-Madsen, J., Schiøtz, P. O., Bartels, U., Nielsen, M. D. and Becher-Christensen, F. Medical Department F and the Department of Clinical Physiology, Glostrup Hospital, Glostrup, and the Department of Pediatrics TG, Rigshospitalet, Copenhagen, Denmark). Electrical polarization of rectal mucosa and excretion of tetrahydro-aldosterone in patients with cystic fibrosis of pancreas and in normal subjects. Acta Paediatr Scand, 64:81, 1975.–The electrical potential difference (PD) across the rectal wall was measured in 26 patients with cystic fibrosis of pancreas (CFP) and in 18 healthy subjects. The PDs obtained in normal children were identical to those previously obtained in normal adults. A significantly greater dispersion of the values was observed in CFP. When the patients were divided into groups according to metachromasia in fibroblast cultures, the mean PD was increased only in the ametachromatic group. True enough, this observation suggests a difference between various forms of CFP, distinguished by metachromasia, and thus is a further indication of the heterogeneity of the disease. The greater abnormalities in metachromasia negative patients may, however, be due solely to the fact that these patients are more severely affected by the disease. The urinary excretion of tetrahydroaldosterone in patients was within the ranges obtained in controls, which excludes the possibility of secondary hyperaldosteronism as the source of increased PD. No evidence was provided in favour of a basic defect in the intestinal transport of Na⁺ or CI⁻, but K⁺ concentrations in faecal fluids of patients were significantly lower than in controls. The equilibrium concentration of K⁺ could be accounted for by simple passive diffusion, suggesting that the epithelium behaved inertly with respect to this ion in CFP.     

Clinical Manifestations in Selective IgA Deficiency in Childhood; A Follow-up Report

ABSTRACT. Clinical manifestations in 40 children with selective IgA deficiency were studied during a follow-up period of 2-10 years. The patients were divided into two groups: group I consisted of 25 children with "sporadic" IgA deficiency and group II of 15 children with "familial" IgA deficiency. Respiratory tract infections including otitis media were frequent in both groups. Concomitant IgG,-IgG, deficiency was found in two patients in group I. Longitudinal serum IgG levels were elevated significantly in both groups. Atopic complaints were observed in 10 children of the "sporadic" group, but only in two of the "familial" group. However, elevated serum IgE levels were more often found in group II. Two children of group I were mentally retarded and chromosomal examination showed abnormalities in both. Anti-IgA antibodies were detected in one child in group I and three children in group II. These three patients had an IgA deficient mother with class-specific anti-IgA antibodies. Concomitant IgG₄-IgE deficiency was found in all four.     

Reduced levels of IgG subclasses and IgA in young children with asthma

Serum immunoglobulins including IgG subclasses were measured in 73 unselected children with asthma. The results showed that 22 (30%) had partial IgA and/or IgG₄ subclass deficiency. Clinical assessment showed that 21 children were infection-prone, and 52 were not. Further analysis showed that infection-prone children were significantly different from non-infection-prone children with regard to familial history of allergy (29% vs 60%, p = 0.015), elevated IgE (62% vs 33%, p = 0.021), IgA deficiency (38% vs 15%, p = 0.38) and IgG subclass deficiency (24% vs 4%, p = 0.018). These results suggest that there may be subgroups of children with asthma who are also immunodeficient.     

Transforming growth factor-β1 is elevated in unpasteurized cow's milk

Unpasteurized milk consumption was associated with less atopy prevalence. Not only microbial load but also fatty acids and cytokines such as transforming growth factor-β₁ (TGF-β₁) may play a role on the effect of unpasteurized milk. Levels of TGF-β₁ in different cow's milk samples were evaluated: we consider raw unpasteurized milk before and after boiling, commercial pasteurized and micro-filtrated cow's milk and different commercially available cow's milk formulas. TGF-β₁ concentration in raw unpasteurized cow's milk was 642.0 ± 52.9 pg/ml before boiling and decreased significantly after boiling (302.7 ± 50.59 pg/ml) (p < 0.05). TGF-β₁ concentrations were also significantly lower in commercial pasteurized milk (246.2 ± 43.15 pg/ml) and in commercial micro-filtrated milk (213.0 ± 31.6 pg/ml) in comparison to unpasteurized unboiled milk (p = 0.002). The levels of TGF-β₁ in all formula samples were below the threshold of detectability for the assays. As TGF-β₁ in the milk may contribute to the development of the immature gastrointestinal tract by influencing IgA production and oral tolerance induction, we suggest to consider not only the microbial compounds but also the cytokine patterns to explain the protective effect of unpasteurized cow's milk on allergic disorders.     

Partial Splenic Embolization in Hypersplenism

ABSTRACT. Four patients with portal hypertension, oesophageal varices and severe hypersplenism were treated by partial splenic embolization. All showed improvement of blood and platelet counts early in the postoperative period. Three months after embolization IgA and C₃ levels increased significantly. All patients had a decrease in the incidence of variceai bleeding and this procedure provides an acceptable alternative to splenectomy.     

Secretory IgA in protein-calorie malnutrition

The secretory IgA system was investigated in children with protein-calorie malnutrition (PCM). The results of the study indicated that in children suffering from kwashiorkor and marasmus the concentration of IgA in duodenal fluid, saliva, nasal secretions, and tears was significantly reduced on admission and returned to normal 4 weeks after treatment. However, the concentration of secretory IgA in children with mild to moderate PCM was similar to that of normal children. Secretory IgA deficiency may be an important factor in promoting bacterial growth and this may account for the increased incidence and severity of mucosal infections in children with severe PCM.