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Biomedical subjects

H Scott

Publications and source records attributed to H Scott.

At least 127 records · Page 7Linked to original sources
PubMed1988

Antibodies to dietary antigens in IgA nephropathy.

It has been postulated that IgA NP is caused by mesangial deposition of IgA-containing immune complexes formed by IgA polymers (pIgA) which are overproduced in response to antigens presented at mucosal surfaces. The intestinal mucosa is one possible source of this pIgA. To test whether antibodies to dietary antigens might be involved in the pathogenesis of IgA NP, we measured IgG and IgA serum antibody activities to gluten, a gluten fraction called glyc-gli, alpha-lactalbumin, beta-lactoglobulin, casein and ovalbumin in 54 patients with IgA NP by an enzyme-linked immunosorbent assay (ELISA). The IgA activities to gluten antigens and alpha-lactalbumin were significantly increased in IgA NP compared with a group of 40 age-matched healthy controls. In a previous study we found that 4 out of 12 patients with IgA NP and gastrointestinal complaints had subtotal villous atrophy; this indicated that many patients with IgA NP have altered intestinal permeability which may lead to activation of their intestinal immune system. Taken together our results showed a relation between the intestinal humoral immune system and IgA NP and indicated that antibodies to dietary antigens in some patients may be directly involved in the pathogenesis of IgA NP.

Adult↗
PubMed1987

Expression of major histocompatibility complex class II subregion products by jejunal epithelium in patients with coeliac disease.

The MHC class II subregion products (HLA-DR), HLA-DP, and HLA-DQ) were located by immunofluorescence in serial sections of ethanol-fixed, paraffin-embedded jejunal mucosa from control subjects and patients with coeliac disease (CD). DR staining was seen in a granular luminal distribution and basolaterally on surface epithelial cells in both untreated and treated CD patients and in controls. In untreated CD the crypt epithelium was positive for DR almost to the bottom of the glands. This contrasted with virtually absent glandular DR staining in controls and weak staining including only the upper part of the crypts in 5 out of 11 treated patients. HLA-DP was present apically in the surface epithelium in all untreated patients, in 5 out of 11 treated patients, and in 4 out of 11 controls. HLA-DQ appeared only in three untreated patients and was restricted to patches of surface epithelium. The number of intraepithelial T lymphocytes per millimetre of surface epithelium was significantly higher in untreated than in treated CD patients or controls; it was also significantly higher in specimens with epithelial DP expression than in those without. This suggested that intraepithelial lymphocytes modulate epithelial class II expression.

Adult↗
PubMed1987

Production and secretion of immunoglobulins in the gastrointestinal tract.

Two decades ago it was shown that the major immunoglobulin (Ig) present in human secretions is a dimeric IgA covalently bound to an epithelial glycoprotein of about 80 kD, now called the secretory component (SC). Pentameric IgM is likewise actively enriched in most exocrine fluids and is associated with SC, although not in a covalently stabilized complex. Three findings explain the selective translocation of polymeric Ig (pIg) into exocrine fluids: (1) preferential local production; (2) J-chain-expressing capacity of pIg-producing immunocytes; and (3) SC-mediated epithelial transport. Human hepatocytes lack SC and the human liver, therefore, cannot act as an efficient "IgA pump". This is in contrast to the rat liver which shows a remarkable capacity for transport of dimeric IgA from blood into the bile. The J chain of pIg and the epithelial SC represent the "lock and key" in the glandular transport of secretory IgA (SIgA) and SIgM. It has recently been shown that SC is synthesized as a transmembrane protein of about 95 kD and constitutes the actual pIg surface receptor. Complexing between ligand and receptor in the plasma membrane is followed by endocytosis. The completed SIgA and SIgM molecules are then translocated in cytoplasmic vesicles through the epithelial cell to the gland lumen along with an excess of free SC. The main function of SIgA is to exert immune exclusion; that is, by intimate cooperation with innate nonspecific defense factors it decreases penetration of soluble antigens and inhibits epithelial colonization of bacteria and viruses. Especially in selective IgA deficiency, SIgM may exert a similar protective function since its synthesis is markedly increased in the intestinal mucosa. Leakage of IgG into exocrine fluids is enhanced by mucosal irritation. Although IgG should not be considered as a SIg, it may contribute to immune exclusion. This is seen especially in the respiratory tract where IgG is less easily subjected to proteolytic degradation than in the intestinal juice. In contrast, by activating complement, IgG antibodies may at the same time be phlogistic and accelerate mucosal penetration of antigens. IgG may thus contribute to persistent immunopathology in mucosal disease. The same is true for IgE antibodies which may be carried into mucous membranes and secretions by mast cells and cause their degranulation with local histamine release. Traces of IgD may likewise be found in the secretions but without obvious biologic significance. Regulation of secretory immunity takes place both in organized lymphoepithelial structures, such as the Peyer's patches, and adjacent to the glands in the lamina propria.(ABSTRACT TRUNCATED AT 400 WORDS)

Celiac Disease↗
PubMed1986

Serum antibodies to wheat germ agglutinin and gluten in patients with dermatitis herpetiformis.

It has been speculated that gluten may play a role in the pathogenesis of dermatitis herpetiformis (DH) because it can act as a lectin. The lectin activity of gluten preparations was recently identified as wheat germ agglutinin (WGA). IgG and IgA serum antibodies to WGA and gluten were therefore measured in patients with DH and coeliac disease (CD) by an enzyme-linked immunosorbent assay (ELISA). Compared with healthy controls, both patients categories had increased IgG and IgA activities to WGA and gluten, the CD group showing the highest antibody levels. DH patients with subtotal villous atrophy tended to have higher activities than those with no villous changes or only minor changes. No significant difference in the gluten-to-WGA ratio of IgA or IgG antibodies was found when DH patients were compared with CD patients. If WGA plays a pathogenetic role in DH, then DH patients must have dermal characteristics, as yet undefined, that explain the initiation of their skin disease.

Adult↗
PubMed1986

Antibodies to wheat germ agglutinin in coeliac disease.

Serum IgG and IgA antibodies to wheat germ agglutinin (WGA) were measured by an enzyme-linked immunosorbent assay (ELISA) with N-acetyl-D-glucosamine in all incubation steps to inhibit sugar-specific binding. Patients with coeliac disease (CD) had significantly higher antibody levels to WGA than patients with other intestinal disorders or healthy controls. Similar results were obtained for antibodies to the gluten fraction glyc-gli. The WGA antibodies did apparently not cross-react with gluten antigens, but commercial gluten powder contained traces of WGA or a similar lectin. Our findings support the proposal that WGA may be involved in the pathogenesis of CD.

Adult↗
PubMed1985

Distribution of a new myelomonocytic antigen (L1) in human peripheral blood leukocytes. Immunofluorescence and immunoperoxidase staining features in comparison with lysozyme and lactoferrin.

The L1 antigen is a highly immunogenic protein of about 36,500 daltons that can be purified from granulocytes with good yield. Immunocytochemistry with a rabbit anti-serum raised against L1 showed it to be present in the cytoplasm of virtually all resting peripheral neutrophils and monocytes. Moreover, immunofluorescence staining demonstrated variable expression of L1 on the plasma membrane of both these cell types, usually along with lysozyme. This indicated that L1 represents a secretory product like lysozyme as their coexpression on the surface of vital cells was contrasted by the absence of lactoferrin. Cytoplasmic L1 was well preserved by both precipitating and cross-linking fixatives, the latter being preferable to avoid leaching out of antigenic material and to obtain good cellular morphology. Thus, fixation for 3 minutes at room temperature in glutaraldehyde (1%)-formaldehyde (3%) afforded excellent immunoperoxidase staining, particularly when a calcium-containing buffer was used. L1 was not found in eosinophilic granulocytes or in resting B- and T-lymphocytes. Neither did blast transformation of lymphocytes seem to induce L1 expression.

Antigens, Surface↗
PubMed1985

Age-related changes of human serum antibodies to dietary and colonic bacterial antigens measured by an enzyme-linked immunosorbent assay.

IgG, IgA and IgM antibody activities in human serum to six dietary and eight gut-related microbial antigens were measured by an enzyme-linked immunosorbent assay (ELISA). IgG activities to five of the dietary antigens decreased with age; IgM activities to four of them were weaker in old people than in children. Old people showed weaker IgM but stronger IgG activities to some of the microbial antigens than children did. A decline in IgG and IgM antibody titres to most dietary antigens with increasing age is consistent with the development of systemic hyporesponsiveness due to continuous antigenic stimulation of the intestinal immune system. Persistence of microbial antigens in the gut, moreover, may lead to systemic hyporesponsiveness of IgM-producing cells. Concurrently raised IgG titres to three of the bacteria might be explained by antigenic stimulation outside the intestinal immune system.

Adolescent↗
PubMed1985

Performance testing of antigen-coated polystyrene microplates for ELISA measurements of serum antibodies to bacterial and dietary antigens.

The adsorption of dietary antigens to polystyrene microplates was influenced by pH. Coating for 5 h at 37 degrees C followed by at least 18 h at 4 degrees C gave the best result with the six dietary and nine bacterial antigens tested in this study. Unwanted background activity was mainly caused by direct binding of human immunoglobulin in the second layer. This problem was mainly observed with coats based on antigens with relatively poor binding activity and could be reduced to an acceptable level by addition of 0.5% bovine serum albumin in the diluents. Microplates from various manufacturers showed large differences in antigen adsorbing properties and there were considerable variations among batches. Careful performance testing of microplates and selection of appropriate batches are therefore necessary.

Antibodies↗
PubMed1985

Pre-excitation due to accessory sinoventricular connexions associated with coronary sinus aneurysms. A report of two cases.

Ventricular pre-excitation occurred in two cases in which the accessory pathways between the atria and the ventricles were histologically identified as being associated with aneurysmal malformations of the coronary sinus. In one case the connexions were in the posterior wall of the coronary sinus aneurysm and were not related to the atrioventricular annulus; in the other, a connexion was situated in the anterior wall of the aneurysm in close apposition to the annulus and superficially resembled a Kent fibre. These connexions were considered to be of sinus venosus origin and to represent a modification of the muscular sheath that normally surrounds the coronary sinus but does not continue along the coronary veins. One of the posterior wall connecting bundles was composed of abnormally large Purkinje-like fibres; this may have played some role in the manifestation of the pre-excitation by reducing any mismatch impedance.

Adolescent↗
PubMed1985

Changes of serum antibody activities to various dietary antigens related to gluten withdrawal or challenge in children with coeliac disease.

IgG, IgA, and IgM serum antibody activities to gluten, a gluten fraction called glyc-gli, and antigens from egg and cow's milk were monitored by an enzyme-linked immunosorbent assay (ELISA) in children with coeliac disease during treatment and gluten challenge. The IgA activity to gluten antigens showed in most patients a rapid and significant reduction after gluten withdrawal, whereas the IgG activity decreased more slowly. During gluten challenge, both these activities rose significantly, and the increases could usually be detected several months before overt clinical relapse. Such determinations, therefore, represent a valuable adjunct in the follow-up of children with coeliac disease. IgA activities to egg and cow's milk antigens likewise tended to decrease after gluten withdrawal and increase during challenge, but the changes were less consistent for individual antigens. Nevertheless, monitoring of IgA activities to a selection of dietary antigens other than gluten may be particularly valuable when it comes to evaluation of intestinal responses in patients on a gluten-free diet.

Adolescent↗
PubMed1985

The human gastrointestinal secretory immune system in health and disease.

The main function of secretory IgA is to exert immune exclusion; that is, by intimate cooperation with innate non-specific defence mechanisms, it dampens down penetration of soluble antigens and inhibits epithelial colonisation of bacteria and viruses. Secretory IgM may exert a similar protective function in the gut as its local synthesis sometimes is markedly increased, especially in selective IgA deficiency. IgG should not be considered a secretory immunoglobulin because its external translocation depends on passive intercellular diffusion. By activating complement, antibodies of this isotype may cause increased mucosal permeability and tissue damage. IgG may thus contribute to persistent immunopathology in mucosal lesions. The same is true for IgE antibodies which, in atopic individuals, may be carried into the gut mucosa by mast cells and cause their degranulation with histamine release. Secretory IgA and secretory IgM are the products of two cell types: plasma cells synthesise IgA dimers and IgM pentamers which, by non-covalent association, become complexed with the secretory component (SC) which is synthesized by serous-type glandular cells. The adsorption of the Ig polymers to the SC-expressing epithelial cells depends on J chain-determined binding sites. This fact gives biological significance to the striking J chain expression shown by mucosal immunocytes regardless of the Ig class they produce. The immunocytes populating the gut mucosa apparently belong to relatively early memory B cell clones. The obvious functional goal of J chain expression at this stage of clonal differentiation is local generation of SC-binding IgA and IgM polymers. In various gut diseases, altered immune regulation results in a disproportionately increased number of J chain-negative IgG-producing cells in the mucosa. Such altered immunological homeostasis may contribute to perpetuation of inflammatory bowel diseases.

Adult↗