Autologous human cytomegalovirus-specific cytotoxic T cells as rescue therapy for ulcerative enteritis in primary immunodeficiency

Patients affected by primary immunodeficiency usually undergo a wide range of infections, including reactivation of latent ones. Here we report two cases suffering from late-onset combined immunodeficiency in which ulcerative enteritis due to human Cytomegalovirus caused a life-threatening malabsorption syndrome

Long-Term Follow-Up of Crohn Disease Fistulas After Local Injections of Bone Marrow-Derived Mesenchymal Stem Cells

To assess the long-term outcome of patients treated with serial intrafistular injections of autologous bone marrow-derived mesenchymal stem cells (MSCs) for refractory Crohn fistulas in terms of safety and efficacy

A Refractory Celiac Patient Successfully Treated With Mesenchymal Stem Cell Infusions

Type II refractory celiac disease (RCD), as defined according to the amount of aberrant intraepithelial lymphocytes, is a condition characterized by severe malabsorption syndrome and poor prognosis, with no effective treatment. Based on the regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs), we investigated the feasibility, safety, and efficacy of serial infusions of autologous bone marrow-derived MSCs in a 51-year-old woman with type II RCD. Mesenchymal stem cells were isolated, expanded, and characterized following standard protocols. Monitoring of the patient's malabsorption indexes, mucosal architecture, and percentage of aberrant intraepithelial lymphocytes was scheduled for the time of enrollment, at each infusion, and after 6 months. Determination of mucosal expression of interleukin (IL)-15 and its receptor was also performed. Expansion of MSCs was feasible, and the patient underwent 4 systemic infusions of 2 × 10(6) MSCs/kg body weight 4 months apart, without adverse effects. During the treatment period, she experienced gradual and durable amelioration of her general condition, with normalization of stool frequency, body mass index, laboratory test results, and mucosal architecture. Remarkably, the expression of IL-15 and its receptor almost completely disappeared. Thus, treatment of RCD with serial MSC infusions seems promising, leading to recovery from the life-threatening condition while blocking the IL-15 pathogenic pathway

The Circulating Level of Soluble Receptor for Advanced Glycation End Products Displays Different Patterns in Ulcerative Colitis and Crohn's Disease: A Cross-Sectional Study

RAGE is a transmembrane receptor expressed on immune and endothelial cells, whose binding with its ligands, the S100 calgranulins, leads to chronic inflammation. Conversely, its soluble form (sRAGE) plays a protective role by acting as a decoy. We carried out a cross-sectional analysis of the sRAGE and S100A12 serum levels in patients with Crohn's disease (CD) and ulcerative colitis (UC) and searched for a correlation with clinical and biological markers of activity

Sensitivity and specificity of a commercial ELISA test for anti-MAG antibodies in patients with neuropathy

For the diagnosis of anti-MAG polyneuropathy the commercial ELISA manufacturer currently recommends a cut-off of 1000 Biihlmann Titer Units (BTU). We analyzed sera from 80 anti-MAG neuropathy patients and 383 controls (with other neuropathies or healthy controls) to assess the ELISA sensitivity and specificity at different thresholds. A better combination of sensitivity/specificity was found at a threshold > 1500 BTU than at > 1000 BTU. The best value of specificity was obtained at threshold > 7000 BTU. There was a diagnostic grey area between 1500 and 7000 BTU in which the clinical phenotypes as well as electrophysiological studies need to be carefully assessed particularly to differentiate CIDP and anti-MAG neuropathy

Strong Notch activation hinders bevacizumab efficacy in advanced colorectal cancer

Aim: To assess the role of Notch activation in predicting bevacizumab efficacy in colorectal cancer (CRC). Materials & methods: Notch activation was evaluated by immunohistochemistry (IHC) on 65 CRC enrolled within randomized clinical trials assessing first-line bevacizumab-based chemotherapy and on 21 CRC treated with chemotherapy alone. Results: Strong Notch (IHC 3+) activation was negatively associated with response (18 vs 62% in low Notch cases [IHC 0, 1, 2+]; p = 0.016), progression-free survival (4.9 vs 12.1 months; p = 0.002) and overall survival (19.3 vs 30.4 months; p = 0.039). No correlation was found between Notch activation and clinical outcome in CRC treated with chemotherapy alone. Conclusion: A potential role of Notch activation in the antitumor activity of bevacizumab could be hypothesized

Additional file 1: of Ex vivo immunosuppressive effects of mesenchymal stem cells on Crohn’s disease mucosal T cells are largely dependent on indoleamine 2,3-dioxygenase activity and cell-cell contact

Mesenchymal stem cells with T cells from inflamed Crohn’s mucosa. Representative time-lapse imaging of a co-culture with bone marrow-derived mesenchymal stem cells of a healthy donor and T cells isolated from inflamed mucosa of a patient with Crohn’s disease. A dynamic and intense interaction is clearly evident mostly during the first 6 h, when the binding between these two cell populations is non-fixed but instead appears as a continuous attachment and detachment, after which a growing number of cells with morphological features of apoptosis (those with nuclear fragmentation and cellular swelling) and apoptotic bodies become evident. The images were serially recorded every 30 min for 12 h. Magnification: 100×. (ZIP 6780 kb

Human cardiac and bone marrow stromal cells exhibit distinctive properties related to their origin

Aims Bone marrow mesenchymal stromal cell (BMStC) transplantation into the infarcted heart improves left ventricular function and cardiac remodelling. However, it has been suggested that tissue-specific cells may be better for cardiac repair than cells from other sources. The objective of the present work has been the comparison of in vitro and in vivo properties of adult human cardiac stromal cells (CStC) to those of syngeneic BMStC.Methods and resultsAlthough CStC and BMStC exhibited a similar immunophenotype, their gene, microRNA, and protein expression profiles were remarkably different. Biologically, CStC, compared with BMStC, were less competent in acquiring the adipogenic and osteogenic phenotype but more efficiently expressed cardiovascular markers. When injected into the heart, in rat a model of chronic myocardial infarction, CStC persisted longer within the tissue, migrated into the scar, and differentiated into adult cardiomyocytes better than BMStC.ConclusionOur findings demonstrate that although CStC and BMStC share a common stromal phenotype, CStC present cardiovascular-associated features and may represent an important cell source for more efficient cardiac repair