Histopathologic Changes and the Immune Response within the Jejunal Mucosa in Infants and Children

Maffei, Helga Verena L.; Kingston, David G. I.; Hill, Ivor D.; Shiner, Margot

doi:10.1203/00006450-197906000-00002

Cited by 22 publications

(11 citation statements)

References 9 publications

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“…This did not seem to be the case in our study, as the occurrence of ACC did not correlate with histologic abnormality (Fig. 3), which has been considered to be associated with increased permeability to antigen (21). Such a situation might, however, exist in coeliac disease (19).…”

Section: Discussioncontrasting

confidence: 48%

“…This is especially so in those children with only gastrointestinal symptoms. But challenge with cow's milk often produces profound changes in the small intestinal mucosa, including villous atrophy of varying degree (9,10,12,34) and increased numbers of eosinophils (41) intra-epithelial lymphocytes (40) and plasma cells (10,21,33,34). It has not been established whether the increase in plasma cells is just part of a generalized, non-specific response of the immune system to antigenic stimulation (23, 37) or whether it represents a specific response to milk-protein antigens at the point of entry.…”

Section: A Direct Immunofluorescent Technique With Fluorescein-labeledmentioning

confidence: 99%

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Antibody Production to Milk Proteins in the Jejunal Mucosa of Children with Cow's Milk Protein Intolerance

Pearson¹,

Kingston²,

Shiner³

1983

Pediatr Res

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Summary A direct immunofluorescent technique with fluorescein-labeledantigens was used to examine the jejunal mucosa for specific antibody production in 23 children aged 2-25 months referred for diagnostic biopsy. Plasma cells containing antibodies to p-lactoglobulin (PLG) or bovine serum albumin (BSA) were present in I1 of 16 biopsies from patients with cow's milk protein intolerance (CMPI) but only one of eight controls, all on a diet containing cow's milk. Antibody-containing cells (ACC) constituted approximately 0.5-5% of the total (IgA + IgM) plasma cell population. In children with CMPI there may be gastrointestinal symptoms only, or these may be combined with other allergic manifestations such as eczema or asthma. In many CMPI children diagnostic tests for allergy-skin prick tests or RAST-are negative and the serum IgE is not raised (7, 11,20). This is especially so in those children with only gastrointestinal symptoms. But challenge with cow's milk often produces profound changes in the small intestinal mucosa, including villous atrophy of varying degree (9,10,12,34) and increased numbers of eosinophils (41) intra-epithelial lymphocytes (40) and plasma cells (10,21,33,34). It has not been established whether the increase in plasma cells is just part of a generalized, non-specific response of the immune system to antigenic stimulation (23, 37) or whether it represents a specific response to milk-protein antigens at the point of entry.In order to study the mucosal immune response to bovine milk proteins we have developed a simple direct immunofluorescent technique for the presence of plasma cells containing specific antibody to two bovine milk proteins, PLG and BSA. Brief, preliminary reports of this work have been published (16,27). MATERIALS AND METHODSPatients. Twenty-three children, aged 2-25 months, had been routinely referred to us for diagnostic jejunal biopsy. Informed consent to carry out this procedure was obtained from the parents.In 15 children a diagnosis of CMPI was made, based on a history of vomiting, diarrhoea, and weight loss (or exacerbation of eczema in atopic children) when on CM and improvement when on a CM-free diet. Details of presenting symptoms, dietary history, and results of challenges are given in Table 1. Four of these fifteen patients had additional allergies: to eggs (Nos. 6, 13, and 15), chicken, fish, and antibiotics (No. 11). Five of the fifteen had atopic symptoms such as eczema (Nos. 2, 8 and 13), asthma (NO. 13), and urticaria (No. 6). Five patients (Nos. 4, 5, 9, 10 and 11) were challenged with CM at the time of investigation, and had pre-and postchallenge biopsies as previously described (34); patient No. 4 had a second challenge at age 18 months. In this group a total of 23 biopsies were performed, 16 while the patient was taking CM and 7 while the patient was on a CM-free diet.Eight children whose symptoms could not be related to consumption of CM served as the control group. (Table 2). All were receiving CM at the time of jejunal biopsy.Biopsy specimens. Upper jej...

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Section: Discussioncontrasting

confidence: 48%

Section: A Direct Immunofluorescent Technique With Fluorescein-labeledmentioning

confidence: 99%

Antibody Production to Milk Proteins in the Jejunal Mucosa of Children with Cow's Milk Protein Intolerance

Pearson¹,

Kingston²,

Shiner³

1983

Pediatr Res

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“…Preliminary experiments with various 'fixation techniques [2,20,35] showed non-specific staining. For this reason, we used unfixed material.…”

Section: Immunofluorescent Histologymentioning

confidence: 98%

Small intestinal mucosa in coeliac disease and cow's milk protein intolerance: Morphometric and immunofluorescent studies

1982

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One hundred and twenty-five small intestinal biopsies from children with coeliac disease (CD), cow's milk protein intolerance (CMPI) and controls were compared by morphometric analysis, by counting intraepithelial lymphocytes (IEL) and by quantitative evaluation of immunoglobulin-containing cells of lamina propria. The double-stain immunofluorescent technique of Brandtzaeg and Baklien [2] was used, based on defined mucosal tissue units. A patchy enteropathy was found in 60% of CMPI, and in 14% of nonspecific changes, but never in CD. There was a significant difference in crypt depth between CD (360 +/- 80 microns) and CMPI (217 +/- 92 microns), even when lesions of equal grade were compared (P less than 0.015). IEL counts per 1000 epithelial cells showed even better discrimination between the groups (CD: 793 +/- 173, CMPI: 320 +/- 143, P less than 0.001). In CD, there was a relatively greater increase of IgM-cells (X 4.9) and of IgG-cells (X 4.2) than of IgA-cells (X 2.6). Ig-cell changes outlasted the morphological lesion in CD on a gluten-free diet. In CMPI, IgM-cells (X 2.3), IgG-cells (X 2.5), and IgA-cells (X 1.7) were proportionately increased, compared to controls. A special increase of IgE-cells in CMPI could not be substantiated. By computerized stepwise discriminant analysis based upon crypt depth, villus/crypt-ratio, IEL-count, and counts of IgM-, IgG-, IgA-containing cells of lamina propria, accurate classification of patient groups was accomplished, even when only the initial biopsy data were analysed.

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“…Os imunócitos IgA+ aparecem na Lamina Propria no período pós-natal, por volta do 12º dia de vida 22 , aumentando progressivamente até os 3-4 anos de idade. De forma semelhante, os imunócitos IgM+ aumentam até os 2 anos de idade 23 .…”

Section: Tecido Linfóide Difuso Da Lamina Propriaunclassified

Mucosal immune response development: breastfeeding and environmental influence

Machado¹

1995

J Pediatr (Rio J)

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241 ResumoA revisão das aquisições mais recentes no conhecimento sobre a ontogênese da resposta imune de mucosas indica que a migração de células linfóides para as superfícies mucosas iniciase precocemente na vida fetal. A diferenciação de estruturas linfoepiteliais organizadas no trato gastrointestinal (folículos linfói-des, placas de Peyer, amígdalas) ocorre a partir de 11-20 semanas de idade gestacional. Entretanto, essas estruturas tornam-se funcionalmente ativas somente após o nascimento, ante as primeiras exposições antigênicas. O desenvolvimento completo da imunidade secretora ocorre no período pós-natal. Em recém-nascidos e lactentes, alguns fatores ambientais, como a alimentação e a carga antigênica oral, parecem modular o desenvolvimento da resposta imune de mucosas. O aleitamento materno, por meio de propriedades anti-infecciosas, anti-inflamatórias e imunomoduladoras, além de complementar a imunidade secretora de lactentes, também estimula a maturação imunológica nas superfícies mucosas.J. pediatr. (Rio J.). 1995; 71(5):241-247: aleitamento materno, mucosas, ontogenia, resposta imune, trato gastrointestinal. AbstractA review of the current knowledge of mucosal immune response development indicates that migration of immunocytes to mucosal surfaces is an early event during fetal life. The morphologic development of gut-associated lymphoid tissues (lymphoid folicles, Peyer's patches and tonsils) occurs from 11-20 weeks' gestation upwards. But they are active only after birth, when usually antigenic challenge takes place. The complete development of secretory immunity is a postnatal achievement. In infancy, some environmental factors such as feeding and oral antigenic challenge seems to modulate immune response development. Breastfeeding, by means of antiinfectious, antiinflammatory and immunomodulating properties, besides completing infant secretory immunity, also stimulates immunological maturation on mucosal surfaces. J. pediatr. (Rio J.). 1995; 71(5):241-247:breastfeeding, gut, immune response, mucosa, ontogeny.Os fundamentos da investigação da ontogênese do tecido linfóide intestinal foram baseados inicialmente em modelos experimentais, pois há similaridade morfológica do intestino delgado de ratos e camundongos recém-nascidos com o intestino delgado humano fetal, entre 10 e 21 semanas de idade gestacional. Isso justificou o uso destes modelos na avaliação da resposta imune celular na mucosa. Contudo, na avaliação da resposta humoral, o padrão de diferenciação tardio durante a gestação, a dependência da nutriz para transferência passiva de anticorpos e a permeabilidade intestinal para absorção de macromoléculas, que nos roedores se estende até o desmame, são fatores limitantes para comparação com o desenvolvimento humano. As aquisições no conhecimento do desenvolvimento morfológico e funcional do tecido linfóide associado ao trato gastrointestinal na espécie humana são recentes e resultaram, principalmente, de estudos em biópsias aspirativas jejunais em crianças e, mais recentemente, em tecidos feta...

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Histopathologic Changes and the Immune Response within the Jejunal Mucosa in Infants and Children

Cited by 22 publications

References 9 publications

Antibody Production to Milk Proteins in the Jejunal Mucosa of Children with Cow's Milk Protein Intolerance

Antibody Production to Milk Proteins in the Jejunal Mucosa of Children with Cow's Milk Protein Intolerance

Small intestinal mucosa in coeliac disease and cow's milk protein intolerance: Morphometric and immunofluorescent studies

Mucosal immune response development: breastfeeding and environmental influence

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