Nonresponse to recombinant hepatitis B surface antigen may be a sign of undiagnosed celiac disease. However, there is a good vaccine response in adequately treated patients. Human leukocyte antigen DQ alleles do not seem to have a primary role. Revaccination is recommended during a controlled gluten-free diet.
The incidence of pediatric IBD in Hungary was among the higher range reported. This is the first large, nationwide incident cohort analyzed according to the Paris classification, which is a useful tool to determine the characteristic pediatric CD phenotype.
The multifunctional, protein cross-linking transglutaminase 2 (TG2) is the main autoantigen in celiac disease, an autoimmune disorder with defined etiology. Glutamine-rich gliadin peptides from ingested cereals, after their deamidation by TG2, induce T-lymphocyte activation accompanied by autoantibody production against TG2 in 1-2% of the population. The pathogenic role and exact binding properties of these antibodies to TG2 are still unclear. Here we show that antibodies from different celiac patients target the same conformational TG2 epitope formed by spatially close amino acids of adjacent domains. Glu153 and 154 on the first alpha-helix of the core domain and Arg19 on first alpha-helix of the N-terminal domain determine the celiac epitope that is accessible both in the closed and open conformation of TG2 and dependent on the relative position of these helices. Met659 on the C-terminal domain also can cooperate in antibody binding. This composite epitope is diseasespecific, recognized by antibodies derived from celiac tissues and associated with biological effects when passively transferred from celiac mothers into their newborns. These findings suggest that celiac antibodies are produced in a surface-specific way for which certain homology of the central glutamic acid residues of the TG2 epitope with deamidated gliadin peptides could be a structural basis. Monoclonal mouse antibodies with partially overlapping epitope specificity released celiac antibodies from patient tissues and antagonized their harmful effects in cell culture experiments. Such antibodies or similar specific competitors will be useful in further functional studies and in exploring whether interference with celiac antibody actions leads to therapeutic benefits.conformational epitope | endomysial antibodies | immunotherapy
Phagocytic and killing capacities of resident and cytokine-activated human macrophages against group B Streptococcus (GBS) type III were studied. Evidence is presented that monocyte-derived macrophages from cord and adults ingest serum-opsonized GBS but that killing of bacteria was negligible in resident cells. Treatment of adult macrophages with recombinant human gamma interferon (rhIFN-␥; 100 U/ml) or recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 200 U/ml) resulted in significant increases of killing of GBS (P < 0.01 for each). The killing capacity of cord macrophages treated with rhGM-CSF was also enhanced compared to that of untreated cells (P < 0.01). However, treatment with rhIFN-␥ resulted in only a moderate increase in the capacity of cord macrophages to kill GBS (P > 0.1). These results mirrored the effect of rhIFN-␥ on candidacidal capacities of cord and adult macrophages, reported earlier from our laboratory. These data indicate differential modulation of neonatal macrophages by rhGM-CSF and rhIFN-␥. We suggest that administration of rhGM-CSF to neonates with invasive GBS disease may enhance host resistance to these bacteria.Group B streptococci (GBS) are the most common cause of deep-seated bacterial infection and sepsis in neonates (4,20). Over the last decade, the burden of invasive GBS disease in immunocompromised children and adults has also been increasing (24). In adults, common predisposing conditions for severe GBS infection and sepsis include malignant neoplasms, diabetes mellitus, human immunodeficiency virus type 1 infection, trauma, and older age (6,8,18). The mortality of invasive GBS disease in both newborns and adults remains high despite advances in intensive care and the susceptibility of the pathogen to penicillin (4,18,20).The propensity of GBS to cause invasive neonatal infections might be related to inappropriate opsonization due to the lack of maternally derived, type-specific antibodies (20). Polymorphonuclear neutrophil granulocytes play a key role in phagocytosis and eventual killing of streptococci and other extracellular pathogens. We reported earlier that a clinical isolate of GBS type III was rapidly ingested and killed by cord and adult granulocytes in the presence of serum opsonins (13). In contrast to what is found for granulocytes, the capacity of cord monocytes to kill GBS was decreased compared to that of adult blood monocytes (13). To gain more insight into the newborn's ability to resist infection by GBS, we studied various interactions between these bacteria and monocyte-derived macrophages isolated from the cord. Experiments were performed to study the effect of recombinant human gamma interferon (rhIFN-␥) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on phagocytosis and the bactericidal capacities of cord and adult macrophages. We show here that cord macrophages efficiently phagocytose serum-opsonized GBS but that the ingested bacteria survive inside the cells. Bacterial killing was augmented b...
There was a high frequency of UGI involvement in children with CD and UC. One third of CD patients showed significant lesions at upper endoscopy and one patient out of ten had real diagnostic help from EGD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.