B-cell development in lamina propria of the large intestine: influence of age and t-cell densities.

The development of B-cells and immunoglobulin-isotype and IgA subclass-positive cells in the lamina propria of the large intestine during infancy was investigated. Biopsy specimens from 36 infants, taken for diagnostic purposes, were available. All samples showed normal morphology. Monoclonal antibodies to CD22, IgA, IgA1, IgA2, IgM and IgG and a peroxidase method were used to demonstrate positive cells in the cryostat sections. Cell densities were counted from a known area. T-cells had been measured in a previous study using the same specimens. The density of CD22+ cells was already high in infants below the age of 1 month and increased little with age. Four specimens from infants below the age of 40 days lacked IgA-, IgA1- and IgA2-positive cells. The densities of these cells increased with age; the correlation coefficient between the age and the density of the cells was for IgA: R=0.47, p=0.04; for IgA1: R=0.57, p=0.001, and for IgA2: R=0.34, p=0.04. The densities of IgG- and IgM-positive cells remained unchanged with age. The negative correlation between density of IgG+cells and CD8+ cells in the lamina propria (R= -0.43, p=0.01) was significant. Strong local stimulation results in early accumulation of CD22+, IgM+ and IgG+ cells in the large intestine, but little change takes place after the first few days of life. The terminal differentiation to IgA-positive cells is slowest, and this population showed significant developmental change.

Immunohistochemical findings in the jejunal mucosa of patients with coeliac disease.

In the pathogenesis of coeliac disease, disturbed immunological processes play a basic role. This is also proved by immunohistochemical findings in the jejunal mucosa of patients with this disorder, which are discussed in this review. Intraepithelial lymphocytes are increased in number in active coeliac disease, most being of the CD8 subpopulation. The counts of lamina propria lymphocytes and the relative numbers of their subsets are comparable to those in healthy controls, but several studies have indicated that the densities of IgA, IgM and IgG immunoglobulin-containing cells in the lamina propria are increased in untreated coeliac disease. Activated T cells can also be found in the lamina propria of patients on gluten-containing diets. In the crypt epithelial cells of coeliac patients on normal diets, strong expression of HLA Class II antigens can be observed. All of these changes are normalized on a gluten-free diet. It was recently discovered by the authors and others that one of the hallmarks of coeliac disease, both active and treated, is an increase in number and proportion of gamma/delta intraepithelial T lymphocytes. The permanent increase of gamma/delta T cells may facilitate identification of a coeliac patient also when an intestinal biopsy is taken on a gluten-free diet and other morphologic signs are normalized. The detection of elevated numbers of intraepithelial gamma/delta T cells is also an indispensable help in the diagnosis of latent coeliac disease.

Density of gamma/delta+ T cells in the jejunal epithelium of patients with coeliac disease and dermatitis herpetiformis is increased with age.

Increased density of gamma/delta T cell receptor (TCR)+ intraepithelial lymphocytes is the only characteristic in the jejunum of patients with coeliac disease and dermatitis herpetiformis which is not normalized on a gluten-free diet. We explored the age-dependent changes in intraepithelial gamma/delta and alpha/beta TCR+ cells from 137 biopsies from patients with coeliac disease and dermatitis herpetiformis and from controls. Biopsy specimens from 100 patients with coeliac disease and dermatitis herpetiformis and from 37 controls were studied with an immunohistochemical method using MoAbs to T cell receptors and peroxidase staining. An increase in the density of intraepithelial gamma/delta T cells above the mean +2 s.d. of the density in controls was present in 97 of 100 specimens from patients with coeliac disease and dermatitis herpetiformis. The density of gamma/delta+ cells of patients with coeliac disease and dermatitis herpetiformis on a normal gluten-containing diet showed a positive correlation with age (r = 0.45, P < 0.0001). In controls, the density of gamma/delta+ cells remained low throughout the age-range studies, from age 0.6-57 years. In controls, alpha/beta+ cells increased with age (r = 0.57, P < 0.001). The increase in density of intraepithelial lymphocytes with age is in agreement with their thymus-independent character and local proliferation.

Increase in density of jejunal IgA2 cells during infancy without change in IgA1 cells.

To determine any association between densities of cells containing IgA, IgA1, IgA2, IgG, and IgM in the lamina propria of the jejunum and the age of the individual, we restudied 65 specimens from 65 patients in the age range 66 days to 4 years. Indications for jejunal biopsy were minor symptoms; none of the patients had any gastrointestinal disease, and the specimens showed normal morphology. We used murine anti-human monoclonal antibodies to IgA, IgA1, IgA2, IgG, and IgM and an indirect immunoperoxidase method and found a significant increase with advancing age in the densities of cells containing IgA, IgA2, and IgG, whereas the densities of IgA1- and IgM-positive cells did not change with age. Densities of IgA2 and IgG cells in children over 1 year were significantly greater than in infants under 9 months (upper vs. lower quartile of the study group, p < 0.05 in both comparisons). In the jejunum, an increase in IgA2 cells was responsible for the increase in total IgA production for the age range studied.

[Characteristics of HLA II antigen expression in the rectal mucosa of children suffering form ulcerative colitis and Crohn disease]. / A HLA II. antigén expresszió sajátosságai colitis ulcerosában és Crohn-betegségben szenvedö gyermekek rektum nyálkahártyájában.

The staining of HLA class II. antigens was studied with monoclonal antibodies using sensitive immunohistochemical methods in the rectal biopsy specimens taken from 4 children with Crohn's disease and 9 with ulcerative colitis as well as from 10 controls. HLA class II. antigen expression was not seen in the surface and crypt epithelium of controls. The majority of patients showed epithelial HLA-DR, and HLA-DP expression, fewer had HLA-DQ expression. In patients who had more severe clinical and histological symptoms the epithelial HLA-DR and HLA-DP expression was more intense, than in those with milder presentation (p < 0.05). We conclude that the activity of ulcerative colitis may be infered from the intensity of HLA class II. antigen expression.

Different cholesterol fractions, LCAT activity and lipid peroxides in the serum of children whose parents had early coronary heart disease.

Children whose parents had early coronary heart disease were investigated for lipid abnormalities. In order to assess high risk parameters and the efficacy of the applied care, serum total cholesterol (TC), total triglyceride (TT), total free cholesterol (FC) high density lipoprotein cholesterol (HDLC), high density lipoprotein free cholesterol (HDLFC), lipid peroxide (LP) levels, and lecithin: cholesterol acyl transferase (LCAT) activity were measured. Compared to a group of control children, the offspring of high risk subjects had increased TC, FC, and LP levels and decreased HDLC levels. After one year of preventative care all parameters normalized except the high FC level and elevated LCAT activity. The measurement of serum FC and LP levels seems to be a useful method for the determination of true high risk. The LCAT activity may show the efficacy of the dietary treatment.