Elisa Camussi

Human mesenchymal stem cells modulate cellular immune response to islet antigen glutamic acid decarboxylase in type 1 diabetes.

CONTEXT Mesenchymal stem cells (MSCs) exert an immunosuppressive effect on the immune system. However, studies on the immunomodulatory potential of MSCs in type 1 diabetes are lacking. OBJECTIVE We aimed to evaluate whether human MSCs may inhibit in vitro pancreatic islet antigen-specific T cell activation in type 1 diabetes. DESIGN Human MSCs were isolated and characterized. Peripheral blood mononuclear cells (PBMCs) were obtained from nine type 1 diabetic patients at disease onset and 13 healthy control subjects. IFN-gamma, IL-10, and IL-4 enzyme-linked immunospot responses of lymphocytes incubated with glutamic acid decarboxylase 65 (GAD65) were investigated in PBMC cultures and PBMC/MSC cocultures. Levels of prostaglandin E2 (PGE2), IFN-gamma, IL-4, and IL-10 in supernatants were measured by ELISA. PGE2 inhibition experiments with NS-398 and indomethacin were also performed. RESULTS Five diabetic patients were identified with a positive PBMC IFN-gamma response to GAD65 and negative IL-10 and IL-4 response. PBMC/MSC cocultures resulted in a significant decrease in the number of spots and in detection of IL-4-secreting cells. PGE2 inhibitors abrogated the immune-suppressive effect, indicating an involvement of PGE2 production, and the constitutive production of PGE2 by MSCs was enhanced in PBMC/MSC coculture. Moreover, in GAD-responder patients, GAD-stimulated PBMC/MSC cocultures significantly decreased secretion of IFN-gamma and IL-10 and increased secretion of IL-4. CONCLUSIONS These results provide evidence that human MSCs abrogate in vitro a proinflammatory T helper type 1 response to an islet antigenic stimulus in type 1 diabetes. MSCs induce IL-4-producing cells, suggesting a possible switch to an antiinflammatory T helper type 2 signaling of T cells.

Cochlear, auditory brainstem responses in Type 1 diabetes: relationship with metabolic variables and diabetic complications

Few studies have analysed the presence of hearing abnormalities in diabetes. We assessed the presence of subclinical auditory alterations and their possible association with early vascular and neurological dysfunction in young adults with Type 1 diabetes of long duration.

Animal assisted intervention: A systematic review of benefits and risks

Abstract Introduction The therapeutic use of animals has been debated for decades, and its use explored in a variety of settings and populations. However, there is no uniformity on naming these interventions. Evidence based knowledge is essential to implement effective strategies in hospital. This review focused on the use of animal programs for hospitalized patients, and considered the potential risks. Methods The following databases were searched: PubMed, Scopus, PsychInfo, Ebsco Animals, PROQUEST, Web of Science, CINAHL, and MEDLINE, and PRISMA guidelines were adhered to. Results Out of 432 articles were identified 36 articles suitable for inclusion into the review. Data was heterogeneous in terms of age of patient, health issue, animals used and the length of interactions, which made comparison problematic. Studies on children, psychiatric and elderly patients were the most common. The animal-intervention programs suggested various benefits such as reducing stress, pain and anxiety. Other outcomes considered were changes in vital signs, and nutritional intake. Most studies used dogs, but other animals were effectively employed. The major risks outlined were allergies, infections and animal-related accidents. Zoonosis was a possible risk, as well as common infections as Methicillin-resistant Staphylococcus Aureus. The implementation of simple hygiene protocols was effective at minimizing risk. The literature suggested that the benefits outweighed by far the risks. Conclusion The human relationship with animals can be useful and relatively safe for inpatients with various problems. Moreover, the implementation of security precautions and the careful selection of patients should minimize the risks, particularly those infection-related. Many aspects remain unclear, further studies are required.

HIV screening in pregnant women: A systematic review of cost‐effectiveness studies

INTRODUCTION Vertical transmission represents the major route of HIV infection for children. However, the preventive interventions available are extremely effective. This review summarizes evidence regarding the cost-effectiveness of mother-to-child-transmission preventive screenings, to help policy makers in choosing the optimal antenatal screening strategy. METHODS A systematic review following PRISMA guidelines was conducted, using 3 databases: PubMed, Scopus, and Cost-Effectiveness Analysis Registry. All articles regarding HIV screening to avoid vertical transmission were included. RESULTS The review included 21 papers. Seven studies assessed the cost-effectiveness of universal antenatal screening during early gestation. Two papers considered the integration of HIV screening with other medical interventions. Eight works estimated the cost-effectiveness of HIV screening in late pregnancy. Finally, 4 papers considered the combination of multiple strategies. The selected papers focused on both developed and developing countries, with a different HIV prevalence. The characteristics and methodology of the studies were heterogeneous. However, all studies agreed about the main findings, outlining the cost-effectiveness of both universal antenatal screening and HIV rescreening in late pregnancy. Cost-effectiveness improved when HIV burden increased. The major findings were proved to be robust across various scenarios when tested in sensitivity analysis. CONCLUSIONS The review confirmed the cost-effectiveness not only of HIV universal antenatal screening but also of rescreening in late gestation in both developed and developing countries. Universal screening is cost-effective even in case of extremely low HIV prevalence. Therefore, to maximize screening, coverage appears as a worldwide priority. In certain settings, a targeted screening towards high-risk groups could be a valuable option.

Cost-effectiveness of HIV screening in high-income countries: A systematic review

INTRODUCTION Over 2 million people in high-income countries live with HIV. Early diagnosis and treatment present benefits for infected subjects and reduce secondary transmissions. Cost-effectiveness analyses are important to effectively inform policy makers and consequently implement the most cost-effective programmes. Therefore, we conducted a systematic review regarding the cost-effectiveness of HIV screening in high-income countries. METHODS We followed PRISMA statements and included all papers evaluating the cost-effectiveness of HIV screening in the general population or in specific subgroups. RESULTS Thirteen studies considered routine HIV testing in the general population. The most cost-effective option appeared to be associating one-time testing of the general population with annual screening of high-risk groups, such as injecting-drug users. Thirteen studies assessed the cost-effectiveness of HIV screening in specific settings, outlining the attractiveness of similar programmes in emergency departments, primary care, sexually transmitted disease clinics and substance abuse treatment programmes. DISCUSSION Evidence regarding the health benefits and cost-effectiveness of HIV screening is growing, even in low-prevalence countries. One-time screenings offered to the adult population appear to be a valuable choice, associated with repeated testing in high-risk populations. The evidence regarding the benefits of using a rapid test, even in terms of cost-effectiveness, is growing. Finally, HIV screening seems useful in specific settings, such as emergency departments and STD clinics.

Islet Endothelium: Role in Type 1 Diabetes and in Coxsackievirus Infections

The heterogeneity of microvascular endothelial cells derived from different organs, suggests that these cells have specialised functions at different anatomical sites. The microvasculature is, in fact, a key interface between blood and tissues and participates in numerous pathophysiological processes. Pancreatic islet microcirculation exhibits distinctive features, in an interdependent physical and functional relationship with ┚ cells, from organogenesis to adult life. The islet microendothelium behaves as an active “gatekeeper” in the control of leukocyte recruitment into the islets during autoimmune insulitis in type 1 diabetes. Furthermore, microvascular endothelial cells, forming the key lining between the vascular space and organ parenchyma, have been shown to influence organ and tissue specific susceptibility to viral infection, and to modulate the pathological expression of virusinduced diseases, which potentially includes type 1 diabetes. Endothelial cells expressing appropriate receptors would fail to act as effective barrier to infections, allowing viral particles to pass through, and replicate in, the vascular endothelium. Human Enteroviruses (EV), especially those of the Coxsackievirus B (CVB) group, are associated with a wide variety of clinical syndromes and have long been considered possible culprits of inflammatory conditions and immune-mediated pathological processes, such as chronic dilated cardiomyopathy, chronic myositis and type 1 diabetes mellitus (Rose et al., 1993; Luppi et al., 1998; Hyoty & Taylor, 2002). Several mechanisms, including molecular mimicry, bystander activation of autoreactive T cells, superantigenic activity of viral proteins, not mutually exclusive, have been proposed to explain the relationship between EV infections and induction of autoimmune diseases (Varela-Calvino & Peakman, 2003; Horwitz et al., 1998; Wucherpfennig, 2001). Evidences of a link between viral infections and initiation or acceleration of pancreatic islet autoimmunity have been under investigation for almost 30 years, and EVs, especially those of the Coxsackievirus B (CVB) group, are historically the prime suspects as important aetiological determinants in type 1 diabetes (Hyoty & Taylor, 2002; Varela-Calvino & Peakman, 2003). Endothelial cells derived from different organs show distinct susceptibility to CVB infections, and the behaviour against a viral challenge of endothelial cells in large vessels and microvessels may differ (Friedman et al. 1981; Huber et al., 1990; Conaldi et al. 1997; Zanone et al., 2003; Saijets et al., 2003).

Perspectives of Cell Therapy in Type 1 Diabetes

Type 1 diabetes is an autoimmune disease leading to the destruction of pancreatic cells. The reduction of cell mass results in insulin deficiency that leads to a failure of glucose homeostasis with increased levels of glucose in blood. Hyperglycemia which per se is detrimental for the organism and may be life-threatening, may in the long term associate with chronic complications involving blood vessels and nerves. The gold standard treatment for diabetes patients aimed to reach a tight control of glycemia, relies on intensive insulin therapy based on multiple daily injections or continuous subcutaneous infusion of insulin. A tight control of glycemia reached with such regimens was shown to significantly reduce the incidence of microvascular complications in respect to the conventional insulin therapy. Nevertheless, to reach an optimal control of blood levels may prove to be difficult when compared to the physiological condition where this is guaranteed by the pancreatic  cells (Suckale, 2008). Therefore, preservation of cell mass could be an important therapeutic target to reduce microvascular complications and to improve the glycemia control (Gonez & Knight, 2010). It is generally accepted that the endocrine pancreas has some regenerative capabilities, although it is still debated which cells are involved in cell turnover. In rodents the capability of adult pancreas to increase cell mass has been documented in physiological conditions and after injury. The understanding of mechanisms involved in  cell turnover may therefore be relevant to design new therapeutic strategies aimed to maintain a  cell mass or to favour regeneration of  cells. These strategies however, should take to account the problem of recurrent autoimmunity that in type 1 diabetes not only impairs the original cell mass, but may also limit the regenerative process. Indeed, autoimmune T lymphocytes may kill the cells newly formed in response to injury (Fan & Rudert, 2009).