Autoimmunity of Gastrointestinal Tract

Gastrointestinal tract diseases are recognised as autoimmune based on typical histopathology, presence of autoantibodies in serum and clinical response to immunosuppressive therapy. Like in other autoimmune diseases, the inducing factor is unknown; however, accumulating data suggests an increasing role of microbiota homeostasis and relation between the immune system (mucous-associated lymphoid tissue) and microbiota in intestinal lumen. The inflammation process is now described as autoinflammation with inflammasome formation or autoimmune chronic inflammation with overproduction of pro-inflammatory cytokines. Diagnostic procedures include autoantibodies assay, histology of biopsy from intestinal mucous, genetic background (especially in celiac disease) and clinical symptoms. Therapy is adjusted to pathomechanism including regulation of microbiota homeostasis with pre-biotics and probiotics, inhibition of inflammatory process with steroids, classical immunosuppression and anti-cytokine monoclonal antibodies and haematopoietic stem cells transplantation in severe cases with therapy resistance, progression and life-threatening course. The aim of this chapter is to review mechanisms of autoinflammation and autoimmunity, diagnosis and therapy of gastrointestinal tract

Occurrence of autoantibodies for gastrointestinal autoimmune diseases in children with common variable immune deficiency and selected IgA deficiency

Introduction: Selected IgA deficiency (IgAD) and common variable immune deficiency (CVID) are humoral immunity deficiencies frequent in children. In both these types of immunodeficiency, autoimmune diseases are present in 20-30% of patients, but the disease profiles are different between adults and children. Autoimmune diseases of the gastrointestinal tract (IBD) and celiac disease are typical for children with IgAD and CVID. Diagnosis is based on clinical symptoms, histology of jejunum and antibodies often preceding the onset of disease. However, the diagnosis of IBD and celiac disease is difficult in immune deficiency patients due to weaker or absent production of antibodies, and different jejunum histology, particular in CVID patients. Aim: Detection of antibodies for autoimmune diseases in children with diagnosis of CVID and IgAD. Material and methods: The study included 43 children with CVID and 63 children with IgAD diagnosis. Antibodies typical for celiac disease (for endomysium, tissue transglutaminase and gliadin) were tested in IgA class (CVID patients), IgG class (IgAD, CVID patients) and found in 16 patients (3 - CVID, 13 - IgAD). Results: Antibodies for IBD (for Saccharomyces cerevisiae antigen - ASCA, goblet cells - Gab, neutrophil’s cytoplasm - ANCA, pancreatic cells - Pab) were noted in 17 patients (7 - CVID, 10 - IgAD). Celiac disease was diagnosed in two children with mild and unspecific clinical symptoms followed by introduction of a gluten-free diet. The remaining children with present antibodies but without clinical symptoms involving the gastrointestinal tract are under careful clinical observation with antibody assay every 6 months. Conclusions: The antibodies are produced despite impaired humoral immunity but the level might be low so the lower limit of positive results is postulated

Expression of proteins associated with therapy resistance in rhabdomyosarcoma and neuroblastoma tumour cells

The activity of multidrug resistance (MDR) proteins in tumour cells is associated with an increased resistance to therapy and in consequence with a decreased effectiveness of chemotherapy. The majority of MDR molecules belong to a family of ABC (ATP binding cassette) transporters. Neuroblastoma (NBL) and rhabdomyosarcoma (RMS) are common solid tumours of childhood. The response to therapy is better in NBL, worse in RMS, but still unsatisfactory despite surgery and aggressive chemotherapy. The immunohistochemical staining for p-gp (p-glycoprotein), MRP1 (multidrug resistance associated protein 1), BCRP (breast cancer resistance protein) and LRP (lung resistance protein) expression was performed in primary tumour sections of NBL (10 cases) and RMS (10 cases). A different pattern of MDR expression in NBL and RMS were noted. In NBL, MRP1 was expressed in all studied tumours, p-gp, BCRP only in 3 out of 10 tumours, LRP, in 4 cases. The combination of more than one protein was noted in the majority of NBL tumours. In RMS, the expression of 3 or 4 MDR proteins was noted in 9 cases. The high expression of an MDR protein profile in RMS suggests various mechanisms acting simultaneously, which might explain chemotherapy resistance and a low percentage of long-time survival in this tumour

Applying plant lectins to assay the effect of environmental pollution on the glycosylation of human placenta

Our study was designed to establish whether air pollution in urbanized industrial centers of southern Poland affects the process of glycosylation in a full-term human placenta. This process of glycosylation was analyzed by the quantitative determination of the binding of WGA and LCA lectins to placental villi. The study was performed on human placentas collected in 1990-91 and 2000-01 in regions of southern Poland differing in their degree of environmental pollution: the highly polluted areas of Upper Silesia and Cracow agglomeration. The Bieszczady area with low pollution was considered the control. The concentrations of nitrogen and sulfur oxides and the concentration of aerosols were used as markers of the degree of air pollution. The direct immunofluorescence reaction of the placenta tissues with fluorescein-labeled (FITC) lec-tins was used. The staining of the placenta tissues was examined under a fluorescence microscope linked to an analysis system. A microdensytometric method was used to assay the amount of tissue-bound lectins. The results showed no significant effect of the three main air pollutants in the study areas in southern Poland, i.e. nitrogen and sulfur oxides and high level of aerosols, on the structure of WGA-and LCA-specific glycoconjugates in human placenta. However, the marked quantitative changes in th