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K Baklien

Publications and source records attributed to K Baklien.

33 records · Page 2Linked to original sources

Complement system studies in adult coeliac disease.

Detailed complement system studies were performed in 22 patients with adult coeliac disease. Activation products of C3 were observed in the fresh sera of all untreated patients, while only 4 had activation products of factor B of the alternate pathway. Levels of C4 and C3 were lower than normal mean, but only the depression of C4 reached a level of statistical significance. The amounts of circulating C3 activation products were significantly reduced when the patients were on a gluten-free diet. There is thus evidence that activation of the classical pathway of the complement system takes place in adult coeliac disease, and there is an association between gluten ingestion and the complement activity. We suggest that a possible mechanism of tissue injury in this disease is activation of complement factors by a humoral immune reaction to dietary gluten in the intestinal wall.

Adult↗

Immunoglobulins in jejunal mucosa and serum from patients with adult coeliac disease.

Immunoglobulin (Ig)-containing cells were quantitated immunohistochemically in biopsy specimens from the proximal jejunal mucosa. The numbers of IgA, IgM, and IgG immunocytes in a defined "mucosal tissue unit" were, on the average, raised 2.4, 4.6, and 6.5 times, respectively, when 13 adult patients with untreated coeliac disease (CD) were compared with 15 patients who had a histologically normal mucosa. The IgA-:IgM-:IgG-cell ratios averaged 66:28:6 in untreated CD and 79:18:2.6 in the controls. Similar quantitative data in 10 patients with treated CD were intermediate. IgD- and IgE-containing cells were rare in all patient groups. Most patients in a heterogeneous malabsorption group showed a jejunal Ig-containing cell population similar to that seen in CD, indicating that the local immunocyte pattern may not be specific for the latter disease. The only significant alteration in serum Ig levels related to CD was a raised concentration of IgA compared with normal. This was consistent with the increased amounts of extracellular IgA revealed in the mucosa. However, there was no indication of a defect in the transport of dimeric IgA and IgM through SC-producing cells, which in the CD mucosa were present in both crypt and surface epithelium.

Adolescent↗

Immunoglobulins in jejunal mucosa and serum from patients with dermatitis herpetiformis.

The quantitative distribution of immunoglobulin-(Ig)-producing cells of the major classes was determined by paired immunohistochemistry in the proximal jejunal mucosa of 29 patients with dermatitis herpetiformis (DH). The specimens were categorized stereomicroscopically in three groups. Compared with controls, the total number of Ig-producing cells in a defined "mucosal tissue unit" was for group I (normal or minor abnormality) found to be raised by a factor of 1.4, but the class ratios remained normal. In group II (major abnormality) the total immunocyte number was raised 2.6 times; IgA, IgM, and IgG cells showed a 2.4-, 3.5-, and 5.1-fold increase, respectively. Group II (intermediate abnormality) fell between the two other groups with regard to changes in the immunocyte population. Altogether the local immunocyte pattern was very similar to that previously found in coeliac disease (CD) specimens of comparable mucosal abnormalities. IgD cells were few, and showed no increase compared with controls. Also IgE cells were few, but were encountered more frequently than in controls. As in CD, staining for extracellular Ig in the lamina propria tended to be more intense than in controls. Normal or increased staining for SC, IgA and IgM in the crypt epithelium indicated a normal external transfer of these components. DH differed from DC in showing no significant rise in the level of serum IgA. Serum IgM was reduced in group III, and IgG was increased in group I.

Adolescent↗

Characterization of the IgA immunocyte population and its product in a patient with excessive intestinal formation of IgA.

An 11-year-old Norwegian boy presented with clinico-pathological features indicative of coeliac or alpha-chain disease. However, his major serum component (about 50 mg/ml) was found to be a polyclonal, polymeric (about 80% dimeric) IgA consisting mainly of the subclass IgA1 and showing a kappa:lambda ratio of 67:33. Also the serum concentration of IgA monomers was increased (about 9 mg/ml). The polymers were heterogeneous with regard to J-chain content--varying on a molar basis from 1.9 for the more basic fraction to at least 2.4 for the more acidic one. Both fractions showed non-covalent affinity for secretory component (SC) in vitro. Most of the serum IgA seemed to originate from the small intestine, which contained a five-times-increased population of IgA immunocytes. These cells were heterogeneous with regard to production of polymeric IgA; many of them showed definitely more J-chain synthesis than normal intestinal IgA immunocytes. The cell population had apparently not spread to the bone marrow, but the polymeric IgA product permeated the connective tissue throughout the body and appeared also in the urine, partly associated with SC. The possibility that such an excessively proliferating intestinal B-cell population may bear some relation to alpha-chain disease is discussed.

B-Lymphocytes↗

Immunohistochemical characterization of local immunoglobulin formation in Crohn's disease of the ileum.

Paired direct immunofluorescence was used to localize and differentially enumerate immunocytes containing the various immunoglobulin (Ig) classes in ileal bowel walls of patients with Crohn's disease. In slightly inflamed mucosa the total number of Ig-containing cells of an average "tissue unit" increased threefold compared with normal controls, but only minor changes occurred in class ratios. In severely inflamed mucosa with persisting glands, the total immunocyte number was increased by a factor of 12.2 compared with the control unit. For IgA, IgM, and IgG cells this increase was 9.0, 12.0, and 60.9, respectively. The immunocyte ratios for these three major Ig classes were 57.5:14.7:27.7 in the inflamed mucosa, and 83.1:11.4:5.4 in the histologically normal control mucosa. When severely inflamed specimens from the ileum and from the colon were compared, there was no statistically significant difference in absolute immunocyte counts or class distributions. IgD and IgE immunocytes were extremely rare, and no consistent increase was found in the inflamed mucosae. In both the ileum and the colon fairly dense immunocyte populations with a marked IgG-cell predominance were encountered in the deeper layers of the inflamed bowel wall. The possible pathogenetic consequences of the pronounced local "over-production" of IgG in inflammatory bowel disease are discussed.

Adolescent↗

Comparative mapping of the local distribution of immunoglobulin-containing cells in ulcerative colitis and Crohn's disease of the colon.

The local response pattern of immunoglobulin-containing cells was compared in Crohn's disease and ulcerative colitis by paired immunohistochemistry on specimens of the large bowel wall. In the "Crohn mucosa" with persisting glands the total cell count was on the average raised more than three times compared with controls. The numbers of IgA, IgM and IgG immunocytes were increased 2.0, 4.8 and 28.6 times, respectively. Only 0-2 IgD- and IgE-containing cells were generally found per section. No consistent differences in the mucosal response pattern were revealed when Crohn's disease was compared with ulcerative colitis. The deeper layers of the bowel wall were in both diseases more or less densely infiltrated by immunocytes-IgG cells compromising about 80%. Immunoglobulin-containing cells in the muscularis propria and subserosa were characteristically found in Crohn's disease. There was no indication of a primary defect in the secretory immunoglobulin system which appeared to be normal in areas with intact glands. The pronounced local humoral immune response, particularly that involving IgG, might be of pathogenetic importance by aggravating and perpetuating in the inflammatory bowel disease.

Adolescent↗

Intestinal secretion of IgA and IgM: a hypothetical model.

The secretory component (SC) has recently been found to be associated with IgM in external secretions, although in a less stable complex than secretory IgA. Moreover, SC combines spontaneously in vitro with both IgA and IgM. A prerequisite is that the immunoglobulins contain the J chain, which is present only in dimers and polymers. This polypeptide is essential for the formation of an SC-binding site which appears already at the cytoplasmic level in IgA- and IgM-producing immunocytes. Locally formed J-chain-containing immunoglobulins are therefore readily available for complexing with SC present in the membranes of columnar secretory epithelial cells of glandular sites. This complexing initiates pinocytosis and external transport. Immunohistochemically the gland cells are shown to contain SC, IgA and IgM in identical locations, except that SC alone appears in the Golgi zone. Locally formed IgA and IgM antibodies are thus efficiently transferred to the mucosal surface where they exert an immunological exclusion of antigens. Conversely, IgG antibodies, which are not actively drained away from the lamina propria, may rather become engaged in complement activation and cell-mediated cytotoxicity with potentially deleterious effects on the tissue. Secondary to severe inflammatory reactions, secretory epithelium may show decreased production of SC; the selective external transport of SC-stabilized secretory IgA and IgM is thus jeopardized, and a vicious circle may be set up in the mucosa.

Animals↗