Celiac disease associated with ulcerative colitis.

The article provides clinical observation of a patient who was diagnosed with celiac disease when he was 52 years (Marsh stage IIIB). Following gluten-free diet (GFD) clinical remission and restoration of small intestinal mucosa (SIM) structure occurred, however in 6 years ulcerative colitis developed and an impairment of SIM morphological structure was identified (Marsh stage IIIA). Ulcerative colitis and celiac disease remission is supported by GFD, anti-cytokine therapy (adalimumab) in combination with mesalazine.

[Immune response to biological therapy of inflammatory bowel diseases].

AIM: To study biological (cell and anticytokine) therapy-induced changes in the levels of proinflammatory cytokines in patients with inflammatory bowel diseases (IBD). SUBJECTS AND METHODS: Forty-four patients with chronic continuous or chronic recurrent IBD were examined. According to the performed therapy, the patients were divided into 3 groups: 1) 16 patients who took infliximab; 2) 14 patients who received combination anti-inflammatory therapy with the cultured mesenchymal stromal cells (MSC) being administered; 3) 14 patients who had standard anti-inflammatory therapy with 5-aminosalycilic acid preparations and glucocorticosteroids. The concentrations of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (INF-gamma), and interleukins (IL)-2, -5, -8, -12, and -15 were determined in the patients' sera before and 2 months after therapy initiation. RESULTS: The elevation in the serum levels of the proinflammatory cytokines TNF-alpha, INF-gamma, and IL-2, -5, -8, -12, and -15 indicates their implication in the pathogenesis of ulcerative colitis and Crohn's disease. Their levels may evaluate both the activity of an inflammatory process and the efficiency of the therapy. The higher level of these cytokines is accompanied by the enhanced activity of diseases, which may be used to diagnose their activity, to predict the course of IBD, and to perform adequate therapy. The decreased level of the proinflammatory cytokines is indicative of the efficiency of the therapy in patients with IBD. CONCLUSION: By reducing TNF-alpha levels, infliximab therapy results in a decrease in the concentrations of other proinflammatory cytokines (IL-1, -2, -5, -8), thus lowering the inflammatory activity of IBD. MSC transplantation also reduces the level of most proinflammatory cytokines, thus diminishing the intensity of immunopathological processes, which is shown by positive changes in the clinical picture of the disease.

[New possibilities for overcoming the secondary inefficiency of anti-cytokine therapy in patients with inflammatory bowel diseases].

A search for ways to overcome the secondary inefficiency of anti-cytokine therapy (ACT) with infliximab (IFX) in patients with inflammatory bowel diseases (IBD) remains relevant and determines the need for new approaches to solving this problem. The secondary inefficiency of ACT has been found to depend on the level of antibodies to IFX (anti-IFX Ab). The Department of Intestinal Pathology, Central Research Institute of Gastroenterology, is investigating the mechanisms for the occurrence of primary and secondary inefficiency of ACT, as well as ways to overcome them by cultured allogenic bone marrow mesenchymal stromal cells (MSC). In the framework of the searching investigation evaluating the efficiency and safety of MSC in patients with IBD, the investigators revealed that was a phenomenon of a decrease in anti-IFX Ab and came to the conclusion that the secondary inefficiency of ACT should be overcome in a patient with ulcerative colitis (UC). The elevated anti-IFX Ab levels were directly associated with the worsening clinical and endoscopic picture of UC and with the enhanced activity of an inflammatory process. The administration of cultures MSC contributed to lower anti-IFX Ab levels, overcome secondary inefficiency (an escape phenomenon) during ACT, and enhanced IFX sensitivity. The clinical observation indicated that MSC administration reduced anti-IFX concentrations and promoted UC remission during IFX therapy. Thus, MSC transplantation can be considered as a promising method for overcoming the secondary inefficiency of ACT, which aids in increasing the previously lost response to anti-inflammatory therapy.

[Fecal calprotectin as a biomarker effectiveness of various interventions in patients with inflammatory bowel disease].

Among the chronic diseases of the gastrointestinal tract of the special place occupied by inflammatory bowel disease (IBD), in which the lining of the intestine produces a significant number of neutrophils, which has prompted researchers and clinicians use a protein derived from neutrophils as a biomarker for the assessment of the intestinal wall and the effectiveness of treatment in patients IBD. One of these proteins is calprotectin (CP), which can be considered as a biomarker of activation, destruction and loss of neutrophil cells, to a lesser extent-- the activated monocytes and macrophages. Various studies have shown that the concentration of fecal calprotectin (FCP) correlates well with endoscopic and histological parameters of intestinal inflammation. Test the FCP can be used in healthy first-degree relatives of patients with IBD to assess the possible presence of subclinical variant of intestinal inflammation in this population. Thus, a simple test of the FCP can reduce the needs of various expensive and invasive method, including costs associated with them, especially in younger patients, where in terms of differential diagnosis of IBD is often not included neoplasia of the intestine. FCP is a non-invasive, inexpensive and at the same time, highly sensitive and specific biomarker that can be used successfully in the diagnosis, evaluation of the efficacy of treatment and predicting recurrence.

[Cell adhesion molecules in evaluation of Crohn's disease therapy].

The treatment of inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn's disease (CD) is one of actual problems of modern gastroenterology and coloproctology. In recent years a great attention is paid to the molecules of adhesion. Adhesion proteins play a significant role in the development of inflammation in patients with IBD. They cause the migration of cells from the capillaries into the center of inflammation, i.e. do much to increase the inflammatory infiltration of the mucosa and homing of lymphocytes. Changes in the levels of adhesion factors under the influence of biological therapy have been insufficiently studied. So the aim of our study was to determine the diagnostic value of adhesion molecules--integrin-sVCAM-1 and selectins P-, E-, L- for the assessment of the effectiveness of therapy in patients with UC and CD and prognosis of the disease. 15 patients with IBD were examined (15 patients with Crohn's disease (CD)). 9 patients were treated using infliximab 5 mg/kg according to the standard scheme (0-2-6 and then every 8 weeks). 3 patients with IBD received anti-inflammatory therapy with the introduction of the culture of MSC in the number of 150 x 108 cells suspended in 200 ml of physiological solution with the addition of heparin (10 IU/ml). 3 patients received azathioprine (2 mg/kg) and glucocorticosteroids (GCS) 1 mg/kg. The clinical symptoms, the level of leukocytes, erythrocyte sedimentation rate, C-reactive protein and also were analyzed before and after the treatment with infliximab and transplantation of MSC. The status of the colonic mucosa was evaluated using colonoscopy with biopsy. The concentration of adhesion molecules L-selectin, E-selectin, P-selectin, integrin-sVCAM-1 in blood serum was analyzed using immunoenzyme method twice before the beginning of treatment and after 2 months. It is established that after the standard therapy with the use of corticosteroids and azathioprine clinical and laboratory signs of IBD activity and increased levels of adhesion molecules remained in all patients. It is reliably determined that under the influence of infliximab the levels of P-selectin, E-selectin and integrin-sVCAM-1 decrease to 8.9 +/- 1.0 ng/ml, 5.5 +/- 1.7 ng/ml, 9.5 +/- 4.4 ng/ml, respectively (p < 0.001) in all patients with IBD. This point to the suppression of the synthesis of the main inflammatory cytokine alpha-TNF. Transplantation of MSC causes significant decrease of P-selectin, E-selectin to 6.9 +/- 1.1 ng/ml and 5.7 +/- 1.3 ng/ml, respectively (p < 0.001). Integrin-sVCAM-1 has decreased slightly to 12.2 +/- 2.2 ng/ml, p > 0.1. This is associated with the onset of the maximum therapeutic effect only in 1-2 months after transplantation. The levels of P-selectin, E-selectin, integrin-sVCAM-1, reflecting the acute phase of inflammation, decreased after MSC transplantation and infliximab induction therapy. The level of L-selectin, reflecting a chronic autoimmune inflammation, practically does not decrease after the MSC transplantation (8.9 +/- 0.5 ng/ml, p < 0.05) and infliximab induction therapy (9.6 +/- 0.8 ng/ml, p > 0.1). These include the appointment of long-term infliximab therapy and repeated MSC transplantations. P-selectin, E-selectin, L-selectin, integrin-sVCAM-1 are modern markers of inflammation and may be used to assess the effectiveness of standard and biological therapy in patients with IBD, and to predict the course of the disease.

[Complete elimination of cytomegalovirus without antiviral therapy after systemic mesenchymal stromal cell transplantation in a patient with ulcerative colitis (a clinical case)].

Cytomegalovirus (CMV) is one of the common pathogens of opportunistic infections in patients with inflammatory bowel diseases. When the patients are treated with immunosuppressants that make them more susceptible to CMV, the course of ulcerative colitis (UC) becomes considerably worse. Antiviral therapy sometimes can reduce the risk of complications and the rate of colectomies. At the same time, antiviral therapy is not mandatory for all UC patients with CMV infection, as shown by the results of numerous investigations. One of the properties of mesenchymal stromal cells (MSC) is to suppress the body's immune reactions to allostimulation, rather than to infection invasion. In vivo and in vitro studies have demonstrated that MSCs have antiviral and antimicrobial activities. The described clinical case shows that clinical improvement occurred and a drastic activation of proliferative processes in the colonic mucosa was detected in the patient with UC after MSC transplantation. Administration of cultured MSCs also promoted the elimination of CMV without antiviral therapy and the overcoming of hormone dependence/ resistance in the patient with UC.

[Dynamics of proinflammatory cytokine in biological therapy of inflammatory bowel disease].

Chronic inflammation in IBD is accompanied by an imbalance in the production of TX1 and Th2 cytokines. Imbalance of cytokine profile is important pathogenetic value at chronic inflammatory process, since the formation of a defective immune response to pathogenic agent promotes recurrence of the disease. Analysis of the dynamics of proinflammatory cytokines allows to estimate the activity of the inflammatory process, and effectiveness of the therapy. Increased levels of proinflammatory cytokines: TNF-alpha, IFN-gamma, IL-2, IL-5, IL-8, IL-12, IL-15 in serum of patients with IBD, indicating their possible involvement in the mechanisms of development of CD and UC. The increase in the content of these cytokines was accompanied by increased activity of disease that can be used to diagnose IBD activity.

[Isolation of antibodies to Chlamydia and Mycoplasma pneumoniae during the immunosuppressive therapy of patients with inflammatory bowel disease].

UNLABELLED: Detection of IgM and IgG Chlamydia and Mycoplasma pneumoniae indicates an aggravation of intracellular infections, including, possibly, due to immunosuppressive therapy. It is possible that the intracellular infection may mediate the occurrence of certain extraintestinal manifestations of inflammatory bowel disease (IBD), such as bronchitis, pneumonia, etc. Chronic persistent chlamydial and mycoplasmal infections lead to disruption of both cellular and humoral immunity, resulting in the formation of autoimmune processes in patients with IBD, and in the future--reduce the immune status against the immunosuppressive therapy. Detection of antibodies to Chlamydia and Mycoplasma pneumoniae accompanies with increased total immunoglobulin IgM, IgG in blood serum. Determining the level of proinflammatory and antiinflammatory cytokines in the acute stage of the disease allows to evaluate the activity of the inflammatory process and the nature of the immune response to intracellular infection. THE CONCLUSION: to prevent extraintestinal septic complications in patients with IgM antibodies to Chlamydia and Mycoplasma pneumoniae, is recommended to combine the long-term immunosuppressive therapy of IBD with antibiotic therapy, usually with macrolides.

[Dynamics of proinflammatory cytokines during biologic therapy of inflammatory bowel disease].

Chronic inflammation in IBD is accompanied by an imbalance in the production of Tx1 and Tx2 cytokines. Imbalance of cytokine profile is important pathogenetic importance in chronic inflammatory process, since the formation of defective immune response to pathogenic agent promotes recurrence of the disease. Analysis of the dynamics of proinflammatory cytokines allows both the activity of inflammatory process and effectiveness. Increased levels of proinflammatory cytokines: TNF-alpha, IFN-gamma, IL-2, IL-5, IL-8, IL-12, IL-15 in serum of patients with IBD, indicate their possible involvement in the mechanisms of development of CD and UC. Increasing content of these cytokines is accompanied by increased activity of disease, which can be used in diagnose IBD activity.

[Complete elimination of cytomegalovirus without antiviral therapy after systemic transplantation of mesenchymal bone marrow stromal cells in a patient with ulcerative colitis].

Cytomegalovirus infection (CMV) has become in the last 15-20 years one of the most important problems of scientific research and clinical high attention. This is due to new information discovered about its leading role in the origin, development, and the outcome of a large group of serious diseases. Cytomegalovirus (CMV) is one of the most common causative agents of opportunistic infections (OI) in patients with IBD, which are mandatory feature of the state of immunodeficiency. Numerous studies in vivo and in vitro studies have demonstrated that mesenchymal stromal cells (MSCs) suppress immune reactions to allogeneic stimulation, but not the invasion of infection, as well as themselves possess antiviral and antimicrobial activity, as demonstrated in this clinical case.