muramidase and Celiac-Disease

The mucosa of the esophagus, the stomach, the small intestine, the large intestine and rectum are unremittingly challenged by adverse micro-environmental factors, such as ingested pathogenic and non-pathogenic bacteria, and harsh secretions with digestive properties with disparate pH, as well as bacteria and secretions from upstream GI organs. Despite the apparently inauspicious mixture of secretions and bacteria, the normal GI mucosa retains a healthy state of cell renewal. To by-pass the tough microenvironment, the epithelia of the GI react by speeding-up cell exfoliation, by increasing peristalsis, eliminating bacteria through secretion of plasma cell-immunoglobulins and by increasing production of natural antibacterial enzymes (lysozyme) and host defense peptides (defensin-5). Lysozyme was recently found up-regulated in Barrett's esophagitis, in chronic gastritis, in gluten-induced atrophic duodenitis (celiac disease), in collagenous colitis, in lymphocytic colitis and in Crohn's colitis. This up-regulation is a response directed towards the special types of bacteria thriving in the microenvironment in each of the aforementioned clinical inflammatory maladies. The purpose of that up-regulation is to protect the mucosa affected by the ongoing chronic inflammation. Bacterial antibiotic resistance continues to exhaust our supply of effective antibiotics. The future challenge is how to solve the increasing menace of bacterial resistance to anti-bacterial drugs. Further research on natural anti-bacterial enzymes such as lysozyme, appears mandatory.

Topics: Barrett Esophagus; Celiac Disease; Colitis, Collagenous; Colitis, Lymphocytic; Colitis, Ulcerative; Crohn Disease; Gastritis; Gastrointestinal Diseases; Humans; Inflammation; Muramidase

Enzymological alterations in functional disturbances and in diseases of the intestine are reviewed. Examples are given for diagnostic significance (e.g. in Hirschsprung's and Crohn's diseases), for pathogenetic considerations (e.g. in hypolactasia and in celiac disease), and for secondary involvement of the liver (e.g. in intestinal tumors and after bypass surgery) and are discussed in more detail.

Topics: Acetylcholinesterase; Adult; Alcoholism; Animals; Antineoplastic Agents; Black People; Celiac Disease; Child; Child, Preschool; Colonic Neoplasms; Diarrhea; Enteritis; Enteropeptidase; Humans; Infant; Intestinal Diseases; Isoenzymes; Jejunum; L-Lactate Dehydrogenase; Lactose; Malabsorption Syndromes; Megacolon; Microbial Collagenase; Microvilli; Muramidase; Rats; Rectum; White People

The protective effect of breastfeeding on celiac disease (CD) onset is controversial. We studied a wide range of milk components in milk produced by celiac mothers following long-term gluten-free diet (GFD) in comparison to milk produced by healthy mothers.. Breast-milk samples from celiac (n = 33) and healthy (n = 41) mothers were obtained during the first year of lactation. A panel of bioactive components was analyzed by enzyme-linked immunosorbent assay in the aqueous fraction. We studied molecules involved in defenses, immunoregulation, and strengthening of the gut-epithelial barrier.. During late lactation (from 6 to 12 months after delivery), the content of total immunoglobulin A (IgA) and IgM was significantly lower in the milk produced by celiac patients. Nevertheless, gliadin (GFD)-specific IgA relative contribution was higher in this group, in contrast to tetanus toxoid-specific antibodies. The balance between pro-inflammatory and anti-inflammatory molecules was different. While interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 were most frequently found in samples from celiac mothers, soluble Toll-like receptor-2 prevalence was lower.. We describe differences between the innate and adaptive immune profile of milk produced by celiac and healthy mothers. These results might explain previous controversial reports about breastfeeding and CD protection.. In spite of a long-term adherence to GFD, the milk produced by mothers with CD exhibit a different immune profile, in relation with some immunoregulatory factors and antibody content. This work shows a more comprehensive characterization of milk from celiac mothers, including macronutrients, lysozymes, growth factors, and immunoregulatory components that had not been studied before. The present study widens the available data regarding the characteristics of human milk of celiac mothers following GFD. Further follow-up studies of the health of children who were breastfed by celiac mothers will be necessary in order to also estimate the impact of the present results therein.

Topics: Adult; Antibodies, Bacterial; Autoantibodies; Breast Feeding; Celiac Disease; Cytokines; Diet, Gluten-Free; Female; Gliadin; Humans; Immunoglobulin A; Immunoglobulin M; Milk, Human; Muramidase; Tetanus Toxoid; Toll-Like Receptor 2

Lysozyme is as an innate enzyme with potent antibacterial properties found in Paneth cells in normal duodenal crypts. Since celiac disease concurs with an abnormal duodenal microbiota we explored the expression of lysozyme in this disease. Fifty-three duodenal biopsies were stained with anti-lysozyme: 15 had normal duodenal mucosa (NDM), 7 chronic active duodenitis (CAD), 3 borderline (BL), 17 subtotal villous atrophy (SVA) and 11 total villous atrophy (TVA). NDM showed lysozyme-positive Paneth cells arranged in "Indian file" in 93.3%. In contrast, lysozyme-positive mucus metaplasia in crypts (LPMMC) replacing Paneth cells was found in 71.5% in CAD, in 96.4% in SVA/TVA, and in 2 cases with B. In 19.3% cases with BL/SVA/TVA, LPMMC replaced all Paneth cells in all crypts in entire sections. In crypts and villi, lysozyme-positive goblet cells (LPGC) were found in 92.8%. Changes were more frequent in the duodenal bulb than in pars descendens. In normal duodenal mucosa, absorptive enterocytes and goblet cells migrate from stem cells upwards, while Paneth cells migrate downwards, towards the base of the crypts. In celiac disease stem cells seem to have been re-programmed, as the normal production of Paneth cells in the crypts was replaced by lysozyme-producing mucus cells. LPMMC and LPGC in celiac disease might mirror an antimicrobial adaptation of stem cells to signals generated by pathogenic duodenal bacteria. The molecular mechanism(s) behind the abrogation of Paneth cells in duodenal crypts and its substitution by LPMMC in celiac disease remains to be elucidated.

Topics: Celiac Disease; Child; Child, Preschool; Chronic Disease; Duodenitis; Duodenum; Female; Goblet Cells; Humans; Intestinal Mucosa; Male; Metaplasia; Microvilli; Muramidase; Paneth Cells; Staining and Labeling

One major expectation from the transcriptome in humans is to characterize the biological basis of associations identified by genome-wide association studies. So far, few cis expression quantitative trait loci (eQTLs) have been reliably related to disease susceptibility. Trans-regulating mechanisms may play a more prominent role in disease susceptibility. We analyzed 12,808 genes detected in at least 5% of circulating monocyte samples from a population-based sample of 1,490 European unrelated subjects. We applied a method of extraction of expression patterns-independent component analysis-to identify sets of co-regulated genes. These patterns were then related to 675,350 SNPs to identify major trans-acting regulators. We detected three genomic regions significantly associated with co-regulated gene modules. Association of these loci with multiple expression traits was replicated in Cardiogenics, an independent study in which expression profiles of monocytes were available in 758 subjects. The locus 12q13 (lead SNP rs11171739), previously identified as a type 1 diabetes locus, was associated with a pattern including two cis eQTLs, RPS26 and SUOX, and 5 trans eQTLs, one of which (MADCAM1) is a potential candidate for mediating T1D susceptibility. The locus 12q24 (lead SNP rs653178), which has demonstrated extensive disease pleiotropy, including type 1 diabetes, hypertension, and celiac disease, was associated to a pattern strongly correlating to blood pressure level. The strongest trans eQTL in this pattern was CRIP1, a known marker of cellular proliferation in cancer. The locus 12q15 (lead SNP rs11177644) was associated with a pattern driven by two cis eQTLs, LYZ and YEATS4, and including 34 trans eQTLs, several of them tumor-related genes. This study shows that a method exploiting the structure of co-expressions among genes can help identify genomic regions involved in trans regulation of sets of genes and can provide clues for understanding the mechanisms linking genome-wide association loci to disease.

Topics: Adaptor Proteins, Signal Transducing; Adult; Aged; Celiac Disease; Diabetes Mellitus, Type 1; Female; Gene Expression Profiling; Gene Expression Regulation; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Genome, Human; Humans; Hypertension; Intracellular Signaling Peptides and Proteins; Male; Middle Aged; Monocytes; Muramidase; Polymorphism, Single Nucleotide; Proteins; Quantitative Trait Loci; Ribosomal Proteins; Transcription Factors

Topics: Animals; Antigens; CD4-Positive T-Lymphocytes; Celiac Disease; Chick Embryo; Cyclooxygenase Inhibitors; Dinoprostone; Disease Models, Animal; Egg White; Humans; Indomethacin; Mice; Mice, Inbred Strains; Mice, Transgenic; Muramidase; Receptors, Antigen, T-Cell

Histological material was studied in five unselected cases of intestinal large-cell non-Hodgkin's lymphoma, occurring in patients either with previously diagnosed coeliac disease, or with atrophic mucosa at the time of diagnosis. The morphological diagnosis in each case was centroblastic lymphoma: these tumours were composed of large cells with pale nuclei and prominent nucleoli. No phagocytosis was evident, but some cells showed considerable pleomorphism. Polykaryotic giant cells were infrequent. Immunohistochemical staining for lysozyme, alpha-1-anti-trypsin and alpha-1-anti-chymotrypsin failed to demonstrate any of these proteins in the tumour cells, although they were identified in accompanying reactive macrophages. There is thus no evidence for a histiocytic nature in these five cases. The tumours were immunoglobulin-negative. Again, polyclonal immunoglobulin could be demonstrated in reactive (plasma) cells in and near the tumour. The relevance of these immunological markers is discussed. We suggest that these tumours, and possibly some of those reported in a similar situation by other investigators, are in fact lymphocytic in origin. They are probably examples of centroblastic lymphoma, although T-cell lymphoma, rare in the gastrointestinal tract, cannot be ruled out by our immunohistological studies.

Topics: Adult; Aged; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Celiac Disease; Cell Nucleolus; Cell Nucleus; Chymotrypsin; Histocytochemistry; Humans; Intestinal Neoplasms; Lymphocytes; Lymphoma; Macrophages; Male; Middle Aged; Muramidase; Plasma Cells

Using a sequential method for the simultaneous demonstration of lysozyme and mucins, the possible existence of a transitional cell intermediate in form between Paneth and goblet cells has been investigated in childhood coeliac disease. Mixed staining for both mucins and lysozyme has not been encountered within intestinal cells of affected mucosae and controls.

Topics: Adolescent; Celiac Disease; Child; Child, Preschool; Duodenum; Humans; Infant; Jejunum; Mucins; Muramidase

Topics: Celiac Disease; Female; Humans; Intestinal Neoplasms; Lymphoma; Male; Muramidase

By conventional light microscopy, a reduced number of Paneth cells per intestinal crypt was found in the jejunal mucosa of patients with untreated or gluten-challenged coeliac disease as compared with histologically normal control specimens. A much better detection sensitivity was obtained when Paneth cells were counted by fluorescence microscopy after immunostaining for lysozyme with a rhodamine-labelled rabbit IgG conjugate. This method showed that there was no numerical reduction of Paneth cells in coeliac disease, but that the proportion of cells with a low lysozyme content was increased. Most of these cells were probably missed by conventional microscopy in which identification of Paneth cells is principally based on a substantial cellular complement of acidophilic granules. A reduced number of lysozyme-containing granules in coeliac disease may reflect increased discharge enhanced secretory activity, or a raised turnover of the Paneth cells.

Topics: Adolescent; Adult; Aged; Celiac Disease; Cell Count; Child; Child, Preschool; Female; Fluorescent Antibody Technique; Humans; Intestinal Mucosa; Jejunum; Male; Middle Aged; Muramidase

Serum lysozyme activities were measured in 34 control subjects, 13 untreated adult coeliac patients, 21 adult coeliac patients on gluten-free diet, and eight coeliac patients with a histiocytic lymphoma. Serum lysozyme activities were raised in three untreated patients, three patients treated with a gluten-free diet, and in only two patients with coeliac disease and lymphoma. Serum lysozyme estimations cannot be recommended as an aid to the diagnosis of lymphoma in patients with coeliac disease.

Topics: Adult; Celiac Disease; Female; Humans; Lymphoma; Male; Muramidase

Serum lysozyme levels were significantly raised in a group of eight patients with malabsorption associated with gastrointestinal lymphomas of a type recently characterised as malignant histiocytosis of the intestine. In four of the cases, levels were markedly raised. In contrast there was no significant difference between groups of patients with uncomplicated adult coeliac disease and healthy controls. The estimation of serum lysozyme is a simple test to perform and may be valuable in the diagnosis of malignant histiocytosis of the intestine, in particular differentiating it from uncomplicated adult coeliac disease.

Topics: Adolescent; Adult; Aged; Celiac Disease; Female; Humans; Intestinal Neoplasms; Lymphatic Diseases; Male; Middle Aged; Muramidase

The jejunal mucosa of patients with coeliac disease contains significantly fewer Paneth cells (PCC) per crypt (p less than 0.001) and tissue lysozyme activity (JLA) P less than 0.001) when compared with a group of subjects with normal jejunal mucosa. Neither PCC nor JLA return to normal with complete clinical recovery and otherwise complete histological recovery on a gluten free diet. There is a significant linear correlation between JLA and PCC suggesting that the Paneth cell is the principal source of jejunal lysozyme.

Topics: Adult; Celiac Disease; Dietary Proteins; Female; Glutens; Humans; Intestinal Mucosa; Jejunum; Male; Muramidase

Serum lysozyme levels were determined by a turbidometric method using egg white lysozyme as standard in 100 patients with Crohn's disease, 86 with ulcerative colitis, 31 with coeliac disease, and in 38 normal control subjects. Though the levels in Crohn's disease were significantly higher than those in ulcerative colitis and in coeliac disease, there was marked overlap between the disorders and control subjects, and so they were of no value in differential diagnosis. There was some evidence that serum lysozyme levels reflected disease activity in Crohn's disease but not in ulcerative colitis.

Topics: Celiac Disease; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Humans; Muramidase

Topics: Adult; Aged; Biopsy; Celiac Disease; Child; Enteritis; Female; Humans; Intestinal Secretions; Jejunum; Malabsorption Syndromes; Male; Middle Aged; Mitosis; Muramidase; Whipple Disease