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Biomedical subjects

S P Fällström

Publications and source records attributed to S P Fällström.

At least 19 recordsLinked to original sources

Avidity progression of dietary antibodies in healthy and coeliac children.

In most individuals minute amounts of food proteins pass undegraded across the intestinal mucosa and trigger antibody formation. Children with coeliac disease have enhanced antibody production against gliadin as well as other dietary antigens, e.g. beta-lactoglobulin, in cow's milk. Antibody avidity, i.e. the binding strength between antibody and antigen, often increases during antibody responses and may be related to the biological effectiveness of antibodies. The aim of the present study was to determine the avidity of serum IgG antibodies against beta-lactoglobulin and gliadin in healthy children during early childhood and compare these avidities to those found in children with coeliac disease. The average antibody avidity was analysed using a thiocyanate elution assay, whereas the antibody activity of the corresponding sera was assayed by ELISA. The avidity of serum IgG antibodies against beta-lactoglobulin as well as gliadin increased with age in healthy children, even in the face of falling antibody titres to the same antigens. Children with untreated coeliac disease had IgG anti-beta-lactoglobulin antibodies of significantly higher avidity than healthy children of the same age, and the same trend was observed for IgG antigliadin antibodies. The present data suggest that the avidities of antibodies against dietary antigens increase progressively during early childhood, and that this process seems to be accelerated during active coeliac disease.

Aging↗

IgG subclass profile of serum antigliadin antibodies and antibody-dependent cell-mediated cytotoxicity in young children with coeliac disease.

Recently, sera from children with active coeliac disease were found to efficiently induce antibody-dependent cell-mediated cytotoxicity (ADCC) of gliadin-coated cells. In the present study, the subclass profile of immunoglobulin (Ig)G antigliadin antibodies in sera from young children, with or without coeliac disease, was determined and related to the ADCC-mediating capacity of the same sera. In addition, IgG subclasses were selectively depleted from sera and the effect on ADCC-mediating was studied. Children with untreated coeliac disease had high antigliadin antibody activities of all four IgG subclasses. However, they had a particularly high proportion of IgG1 antigliadin antibodies (ratio IgG1/IgG) compared with healthy references or coeliac children in remission. In contrast, children who had high serum antigliadin antibody activity but no histological signs of enteropathy (disease references), showed significantly lower proportions of antigliadin antibodies of the IgG1 as well as the IgG3 subclass compared with healthy references or untreated coeliac children. Regression analysis showed that IgG1 and IgG3 antigliadin antibody activity correlated positively to ADCC-mediating capacity, and depletion of IgG1 from sera profoundly diminished ADCC. The results suggest that gliadin-specific antibodies of predominantly the IgG1 subclass mediate tissue-damaging immune reactions like ADCC, and may, thus, contribute to the disease process of coeliac disease.

Antibody Specificity↗

Antibody-dependent cell-mediated cytotoxicity to gliadin-coated cells with sera from children with coeliac disease.

Antibody-dependent cell-mediated cytotoxicity (ADCC) has been suggested as a contributing immunological mechanism in the disease process of coeliac disease. In the present study, sera from coeliac children were examined for their capacity to mediate ADCC against gliadin-coated target cells. The ADCC-mediating efficacy of sera were tested using monocytes from healthy adults as effector cells and gliadin-coated erythrocytes from the same donor as targets. Using monocytes as effector cells, sera from children with active coeliac disease (untreated or challenged), demonstrated significantly higher ADCC-mediating capacity than sera from healthy and disease references as well as children with treated coeliac disease. A positive correlation was found between the ADCC-mediating capacity and serum IgG as well as IgA anti-gliadin antibody levels. The results suggest that an antibody-dependent monocyte/macrophage-induced cytotoxic reaction might be involved in the disease process of coeliac disease.

Adult↗

High incidence of urinary tract infection in patients with coeliac disease.

The concomitant occurrence of urinary tract infection (UTI) and coeliac disease was studied retrospectively among children with coeliac disease. There was a significantly higher risk of first time UTI in children with coeliac disease than in an unselected population of children. In the majority of cases UTI was associated with untreated, active coeliac disease.

Adolescent↗

ADCC-mediating capacity in children with cow's milk protein intolerance in relation to IgG subclass profile of serum antibodies to beta-lactoglobulin.

In a previous study sera from children with cow's milk protein intolerance (CMPI) exhibiting gastrointestinal symptoms were found to efficiently induce antibody-dependent cell-mediated cytotoxicity (ADCC) to beta-lactoglobulin-coated cells. In contrast, sera from children with coeliac disease showed a low ADCC-mediating capacity, despite high levels of IgG anti-beta-lactoglobulin antibodies. The study described here was undertaken to evaluate whether differences in IgG subclass profile of anti-beta-lactoglobulin antibodies could explain the observed variations in the ADCC-mediating capacity. Forty-eight sera from the following groups of children were investigated: CMPI with predominantly gastrointestinal symptoms, CMPI with skin symptoms of immediate-onset, children with untreated coeliac disease and healthy references. Absorption experiments indicated that primarily IgG1 antibodies were responsible for the ADCC-mediating capacity of the sera. Accordingly, the ADCC reactivity of individual sera correlated with their IgG1 antibody levels. Sera from CMPI children with gastrointestinal symptoms, most of which had a high ADCC reactivity, also demonstrated a distinctive subclass pattern of their anti-beta-lactoglobulin antibodies with higher relative proportions of IgG1 (ratios: IgG1/IgG, IgG1/IgG3 and IgG1/IgG4) than those from the other diagnostic groups. Using logistic regression analysis, the diagnostic potential of ADCC as well as of different IgG subclass variables for the recognition of gastrointestinal symptoms caused by CMPI was evaluated. The ADCC reactivity of sera was found to be the best predictor in this model.

Antibody-Dependent Cell Cytotoxicity↗

Duplication in the hypoxanthine phosphoribosyl-transferase gene caused by Alu-Alu recombination in a patient with Lesch Nyhan syndrome.

We have determined the structure, at the nucleotide sequence level, of a duplication in the hprt gene in a patient with Lesch-Nyhan syndrome (LN). The duplication extends over exons 7 and 8 and approximately 1.8 kb of the surrounding hprt sequence. The duplication junction is localized within two Alu sequences and has apparently been generated by unequal homologous recombination. This is the second reported case of a partial duplication of the hprt gene in an LN patient, and the first that involves an Alu-Alu recombination.

Base Sequence↗

Antibody-dependent cell-mediated cytotoxicity to beta-lactoglobulin-coated cells with sera from children with intolerance of cow's milk protein.

The capacity of serum antibodies against beta-lactoglobulin to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) was analysed in sera from children with cow's milk protein intolerance (CMPI). The children with CMPI were divided into three groups according to clinical features: delayed-onset CMPI with gastrointestinal symptoms (n = 8); immediate-onset CMPI with gastrointestinal and skin symptoms (n = 8); and immediate-onset CMPI with skin symptoms only (n = 8). The CMPI groups were compared with children with untreated (n = 9) or treated (n = 8) coeliac disease and a control group (n = 22). Sera from the children were examined for cytotoxic effects using lymphocytes from healthy adults as effector cells and radiolabelled beta-lactoglobulin-coated erythrocytes from the same donor as target cells. In addition, IgG and IgA serum antibodies against beta-lactoglobulin were determined with ELISA. Sera from children with CMPI and gastrointestinal symptomatology showed a significantly increased capacity to induce ADCC reactivity as compared with controls. This increased capacity was seen in sera from those with immediate as well as delayed onset of the gastrointestinal symptoms. In contrast, sera from children who had an immediate-onset CMPI with only skin symptoms mediated no such increase in ADCC reactivity. Moreover, children with coeliac disease with a few exceptions, demonstrated low ADCC reactivity, despite the fact that they had high levels of antibodies against beta-lactoglobulin. ADCC may be an immunopathogenic mechanism in certain cases of CMPI with gastrointestinal symptoms.

Antibodies↗

Clinical disease activity and inflammatory activity in the rectum in relation to mucosal inflammation assessed by colonoscopy. A study of children and adolescents with chronic inflammatory bowel disease.

The relationship between clinical disease activity, rectal inflammatory activity and mucosal inflammation established at total colonoscopy has been studied in 36 young patients with ulcerative colitis (UC) and 24 with Crohn's colitis (CC). Semiformed stools, diarrhea and frequent bowel movements seem to be better indicators of extensive mucosal inflammation of a moderate or severe degree than blood in faeces. There were, however, several patients with a discrepancy between the degree of clinical disease activity and the extent and degree of mucosal inflammation at endoscopic and histologic assessment. In about one-third of the patients with UC and in about half of the patients with CC, who had mucosal inflammatory activity of a moderate or severe degree, the rectal inflammatory activity was of a lower degree. Total colonoscopy seems to be necessary in order to establish the extent and degree of mucosal inflammation.

Adolescent↗

Relationship between results of laboratory tests and inflammatory activity assessed by colonoscopy in children and adolescents with ulcerative colitis and Crohn's colitis.

The relationship between the results of nine laboratory tests and inflammatory activity in the colon assessed macroscopically (macro) and histologically (hist) has been studied in 60 children and adolescents, 36 with ulcerative colitis (UC), and 24 with Crohn's colitis (CC). The mean duration of disease was 38 months. Eleven patients were newly diagnosed and not treated. Special attention was paid to severe and extensive colitis (SEC), in other words, moderate or severe inflammation in at least six of eight colon segments. A significant correlation was found between some laboratory parameters and the inflammatory activity of colonic mucosa. In UC, the following abnormal laboratory test results only occurred in SEC/macro: thrombocytosis, low serum albumin, and high serum orosomucoid. The combination of low serum iron and low or normal total iron binding capacity (TIBC) occurred in seven cases, six of whom had SEC/macro. Eleven of the 17 patients with SEC/macro had at least one of these four test results. SEC/hist was indicated only by thrombocytosis and high orosomucoid. In CC, a combination of low serum iron and low TIBC only occurred in SEC/macro. Thirteen of 36 patients with UC (36%) and four of 24 with CC (17%) had no abnormal test results.

Adolescent↗

The diagnostic value of colonoscopy compared with rectosigmoidoscopy in children and adolescents with symptoms of chronic inflammatory bowel disease of the colon.

Seventy-eight young patients with symptoms of chronic inflammatory bowel disease (IBD) of the colon have been investigated to determine to what degree colonoscopy adds important information for the diagnosis of IBD in addition to results of the routine procedures, including rectosigmoidoscopy carried out at the same time. After colonoscopy IBD was established in 4 of 12 patients classified as non-IBD after the routine procedures. Eleven of 18 patients with the routine diagnosis indeterminate colitis (IC) could after colonoscopy be differentiated into UC or probable CC. In 30 of 31 cases classified as UC the routine diagnosis was confirmed by colonoscopy. Routine diagnosis as probable CC was changed to definite CC in 3 of 10 cases. In all cases but one with previously established IBD it was possible to confirm the diagnosis. Thirty-seven of 70 patients with established IBD of the colon had no radiologic evidence of colitis.

Adolescent↗

Growth at the age of 4 years subsequent to early failure to thrive.

Fifty-five children previously investigated for failure to thrive (a rate of weight gain below -2 SD) during at least 6 weeks at 4-18 months of age were followed up and reinvestigated at the age of 4 years. The children were studied in two groups: children with organic causes (OFTT) (n = 21); and children for whom no organic cause was found (nonorganic failure to thrive, NFTT) (n = 34). In children with OFTT, normalization of growth was found for both weight and height attained, as most of the diseases were either amenable to treatment or spontaneously subsided. The only exception was a child with severe encephalopathy. In children with NFTT, much lower values were found, particularly for weight, p less than .01 for both weight and height. Children with a low psychosocial score (less than or equal to 3 adverse factors) showed partial catch-up growth, although significantly lower than that of children with OFFT. Among 13 children with high psychosocial scores (greater than or equal to 4), 6 children had been subjected to strong social and/or psychological intervention. These children showed a more favorable growth pattern compared to children with comparable psychosocial scores where no intervention had been undertaken. The children with NFTT continued to grow slowly, remained meager and seemed to maintain a suboptimal growth pattern, particularly those with higher numbers of risk factors.

Body Height↗

Coeliac disease in children of short stature without gastrointestinal symptoms.

Eighty-seven children with short stature (height more than 2 SD below the mean for age and sex) were investigated by small intestinal biopsy. There was no obvious reason for their growth retardation found by routine examination and they had no gastrointestinal symptoms. Coeliac disease was found in two children and probable coeliac disease in two children. Although the prevalence of coeliac disease was comparatively low in this study of Swedish children with short stature, it emphasizes the fact that coeliac disease must be considered in a child with short stature even in the absence of gastrointestinal symptoms.

Adolescent↗

Serum antibodies against native, processed and digested cow's milk proteins in children with cow's milk protein intolerance.

Children with or without cow's milk protein intolerance were investigated for serum antibodies to native cow's milk proteins, processed cow's milk proteins and native- and pepsin-digested beta-lactoglobulin. Antibodies of IgG and IgA isotypes were determined with ELISA and those of IgE isotype with RAST. Children who exhibited slowly appearing untoward reactions to cow's milk feeding had significantly higher titres of IgG antibodies against both native and digested beta-lactoglobulin than children with an immediate type of reaction or no intolerance. The IgG antibodies to pepsin-digested beta-lactoglobulin were efficiently inhibited by native beta-lactoglobulin even at low concentrations, which suggests that there were no antibodies specific for the degraded proteins. The children with slow reactions to cow's milk also tended to have higher antibody levels of the IgG and IgA isotypes to both native and processed cow's milk. Antibodies to this mix of antigens discriminated less well, however, than the antibodies to isolated beta-lactoglobulin between the groups of children with slowly appearing reactions, with immediate reactions and the controls. Seven out of nine children with an immediate type of reaction to cow's milk protein had IgE antibodies against cow's milk protein determined with the RAST, while this type of antibodies could not be demonstrated in any child in the two other groups. Using processed or digested protein as antigen did not increase the sensitivity of the antibody determinations.

Animals↗

Bile acid malabsorption in children and adolescents with chronic colitis.

Bile acid malabsorption was measured as the fecal excretion of 14C after intravenous administration of carboxyl-14C-cholic acid and was studied in 31 patients, 8-17 years old, with chronic colitis. There were 15 patients with proven or probable Crohn's disease and 16 patients with ulcerative colitis. The mean excretion was 14.7% and 19.9%, respectively. The patients with moderate or severe inflammatory activity in the ascending colon, assessed by colonoscopy, had a significantly higher 14C excretion than the patients with no or mild inflammatory activity, 24.1% and 6.6%, respectively. These findings suggest that the ascending colon is more important in the preservation of bile acids than has usually been postulated. When the inflammation in this part of the colon is pronounced, the 14C excretion is high, independent of the type of colitis and the clinical disease activity.

Adolescent↗

Serum IgA and IgG gliadin antibodies and small intestinal mucosal damage in children.

Serum immunoglobulin (Ig) A and IgG gliadin antibodies were determined with a simple, rapid, and inexpensive method--diffusion-in-gel enzyme-linked immunosorbent assay (DIG-ELISA)--and the results were related to small intestinal mucosal morphology in 234 children suspected of having malabsorption. Fifty-six of 58 children with flat intestinal mucosa had increased IgA and/or IgG gliadin antibody levels (sensitivity 97%). Fifty-four of the 58 children had celiac disease (CD) (n = 25) or probable CD (n = 29). Four children with flat mucosa had cow's milk protein and/or soy protein intolerance and three of these had increased gliadin antibody levels. Seventeen percent of 132 children with normal intestinal mucosa had increased IgA and/or IgG gliadin antibody levels. IgA and IgG gliadin antibody levels decreased significantly in the celiac children on a gluten-free diet and increased significantly after gluten challenge. Determination of serum IgA and IgG gliadin antibodies by means of DIG-ELISA is a sensitive test for small intestinal mucosal damage in children. When malabsorption is suspected, we suggest that this assay be used to select children for a small intestinal biopsy. It is also very useful for the follow-up of adherence to a gluten-free diet and to determine the effect of gluten challenge in celiac children.

Adolescent↗

Detection of soy protein in soy lecithin, margarine and, occasionally, soy oil.

Samples of soy lecithin, soy oil and margarine were tested for the presence of soy proteins by an inhibition technique using ELISA. All but one of the soy lecithin samples contained soy protein, as did some of the soy oil and margarine samples. The positive margarines contained only about 25% as much soy protein as the soy lecithin preparations. The presence of soy proteins in these soy products might account for hitherto unrecognized exposure to soy proteins in various foods.

Animals↗

Protective factors in milk and the development of the immune system.

The neonate is immature in certain immunologic functions. The slow development of secretory immunoglobin A (IgA) seems to be compensated by selective transfer of secretory IgM into exocrine secretions on mucous membranes during the first few months of life. Secretory IgA and secretory IgM antibodies against Escherichia coli and poliovirus are already found in the neonate, possibly in response to the maternal anti-idiotypic IgG antibodies transplacentally exposing the fetus. Via such a mechanism, food antibodies could occur before direct food exposure in the infant. Human milk provides large amounts of antibodies (as a crude comparison, about 50 times the amount of antibodies given to a patient with hypogammaglobulinemia). The milk antibodies, dominated by secretory IgA, protect especially against intestinal infections. The milk also contains oligosaccharide analogues to epithelial receptors for bacteria. They, as well as a number of milk components such as lactoferrin and lysozyme, may contribute to host defense. The food antibodies in human milk may influence the infant's immune response to foreign food proteins introduced during weaning.

Animals↗

Influence of breast feeding on the development of cow's milk protein antibodies and the IgE level.

In 48 infants unselected with regard to atopic heredity, the levels of serum IgG, IgA and IgM antibodies against native cow's milk proteins and IgG antibodies against beta-lactoglobulin were measured with ELISA and the total serum IgE concentration with Phadebas PRIST. Using multiple regression analysis the level of each type of antibody was related to the age at weaning, at first exposure to cow's milk and at sampling. The longer the infants were exposed to cow's milk protein without concomitant breast feeding and the younger they were at the introduction of cow's milk formula, the higher were the IgG antibody levels against native cow's milk proteins. The investigated variables explained only 17% of the variation of the antibody level, however. The IgG antibodies against beta-lactoglobulin showed significant negative correlations to the age at weaning and the age at first cow's milk exposure, explaining 8% of the variation. Specific IgA and IgM antibody levels an those of total serum IgE did not show any significant relation to the investigated independent variables.

Animals↗