Prophylactic and/or therapeutic vaccines have an important potential to control Trypanosoma cruzi (T. cruzi)infection. The involvement of regulatory/suppressor immune cells after an immunization treatment and T. cruzi infection has never been addressed. Here we show that a new trans-sialidase-based immunogen (TSf) was able to confer protection, correlating not only with beneficial changes in effector immune parameters, but also influencing populations of cells related to immune control.Regarding the effector response, mice immunized with TSf showed a TS-specific antibody response, significant delayed-type hypersensitivity (DTH) reactivity and increased production of IFN-γ by CD8+ splenocytes. After a challenge with T. cruzi, TSf-immunized mice showed 90% survival and low parasitemia as compared with 40% survival and high parasitemia in PBS-immunized mice.In relation to the regulatory/suppressor arm of the immune system, after T. cruzi infection TSf-immunized mice showed an increase in spleen CD4+ Foxp3+ regulatory T cells (Treg) as compared to PBS-inoculated and infected mice. Moreover, although T. cruzi infection elicited a notable increase in myeloid derived suppressor cells (MDSC) in the spleen of PBS-inoculated mice, TSf-immunized mice showed a significantly lower increase of MDSC.Results presented herein highlight the need of studying the immune response as a whole when a vaccine candidate is rationally tested.

The use of chimeric molecules fusing several antigenic determinants is a promising strategy for the development of low-cost, standardized and reliable kits to determine specific antibodies. In this study, we designed and assessed a novel recombinant chimera that complements the performance of our previously developed chimera, CP1 [FRA and SAPA antigens (Ags)], to diagnose chronic Chagas disease. The new chimeric protein, named CP3, is composed of MAP, TcD and TSSAII/V/VI antigenic determinants. We compared the performance of both chimeric Ags using a panel of 67 Trypanosoma cruzi-reactive sera and 67 non-reactive ones. The sensitivity of CP3 vs CP1 was 100 and 90.2%, and specificity was 92.5 and 100%, respectively. The mixture of CP1 + CP3 achieved 100% of sensitivity and specificity. More importantly, an additional subset of 17 sera from patients with discordant results of conventional serological methods was analysed; the CP1 + CP3 mixture allowed us to accurately classify 14 of them with respect to IIF, the usual technique used in most of the reference centres. These results show an improved performance of the CP1 + CP3 mixture in comparison with enzyme-linked immunosorbent assay and indirect haemagglutination commercial assays.

Taken together, our results showed that the TS overcomes the performance of other antigens when the same model is employed, confirming that TS is a promising antigen that could be used as a vaccine against T. cruzi.

This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. Conclusions: Anti-B13 antibodies were significantly higher in chronic Chagas disease stage III patients, suggesting that these antibodies may be involved in disease progression and that they might be a useful marker of poor prognosis in terms of heart compromise. Our results also reveal an important correlation between the level of anti-B13 autoantibodies and symptomatic heart failure and/or dilated cardiomyopathy. ß 2013 Sociedad Españ ola de Cardiología. Published by Elsevier Españ a, S.L. All rights reserved.Valoració n de anticuerpos con reactividad cruzada pató geno-hué sped en pacientes con diferentes estadios de cardiopatía chagá sica cró nicaPalabras clave: Enfermedad de Chagas Trypanosoma cruzi Insuficiencia cardiaca Autoanticuerpos anti-B13 R E S U M E N Introduccio´n y objetivos: La infecció n por Trypanosoma cruzi induce una respuesta autoinmunitaria humoral contra diferentes antígenos del hué sped. En especial, los anticuerpos que presentan reactividad cruzada con antígenos del miocardio tienen un papel importante en el desarrollo de las formas graves de la cardiopatía chagá sica cró nica. En este trabajo se analiza la asociació n del estadio clínico de la enfermedad con la presencia de autoanticuerpos en pacientes con cardiopatía chagá sica cró nica. Me´todos: Estudio transversal con pacientes con serología positiva para enfermedad de Chagas, categorizados en tres grupos segú n la clasificació n de cardiopatía chagá sica de Storino et al. Se realizó a todas las personas incluidas un examen clínico completo y se usaron las muestras de suero para cuantificar los autoanticuerpos. Resultados: Todos los pacientes presentaron cantidades detectables de anti-p2b y anti B13; el antiNa-K-ATPasa fue negativo en todos los casos. No se halló asociació n significativa entre las alteraciones electrocardiográ ficas y los valores de autoanticuerpos. Los pacientes con cardiopatía chagá sica en estadio III presentaron mayor concentració n de anti-B13 y riesgo de mortalidad alto, lo que muestra una clara asociació n entre el estadio de la enfermedad y la puntuació n de mortalidad. Conclusiones: La concentració n del autoanticuerpo anti-B13 fue significativamente mayor en los pacientes con cardiopatía chagá sica en estadio III, lo que indica que este anticuerpo puede estar involucrado en la progresió n de la enfermedad y podría usarse como marcador de mal pronó stico

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Studies indicate that Trypanosoma cruzi is capable of inducing immunological disturbances such as decreased expression of molecules involved in T-cell survival and costimulation for antigen-driven T-cell responses. On the other hand, several reports have described that BCG vaccination induces a T-helper 1-type immune response with protective effects in different pathologies. In this regard, we evaluated whether BCG vaccination coexists with a better clinical and immunological profile of chronic Chagas heart disease (CCHD). We performed a cross-sectional study in T. cruzi seropositive patients categorized according the BCG vaccine background and to the well-established CCHD classification provided by Storino et al. All individuals were subjected to a complete clinical examination. All patients presented detectable levels of autoantibodies anti-p2β, anti-B13, anti-FRA and antiparasite homogenate immunoglobulins, which were unrelated to age and sex distribution or blood pressure values. Comparisons according to BCG vaccination revealed that individuals who had not been vaccinated presented higher values of antibodies, and patients without BCG vaccine had an OR of 6.1 (95 % CI 1.23-29.25, p = 0.02) for globally dilated cardiomyopathy with reduced ejection fraction (Hosmer and Lemeshow test of 5.2 p = 0.73). Our results suggest that BCG vaccination coexists with a better clinical and immunological profile of CCHD, associated with lower cardiac involvement.

Conflict of interest: noneIntroduction: ascites is one of the most common complications of cirrhosis associated with a high rate of mortality. Although several scores have been developed in order to assess the prognosis of the disease, they were designed for predicting liver transplantation requirements and mortality in the short term, but not while in hospital. The aim of this study was to weigh risk factors for in-hospital mortality in adult patients with ascites due to alcoholic cirrhosis. Material and methods: we performed a cross-sectional study in 180 adult patients with diagnosis of cirrhosis with portal hypertension associated with high alcohol intake. The diagnosis of cirrhosis was made by liver echography and portal hypertension was defined by clinical features plus serum-ascites albumin gradient. Sampled individuals were subjected to complete clinical examination. Child Pugh and the MELD scores were applied in all the patients. Results: nineteen patients died while in-hospital. Mortality was associated with increased levels of serum white blood cell, urea, creatinine, prolonged prothrombin time, aspartate aminotransferase and alanine aminotransferase. We conducted a multiple binary logistic to predict in-hospital mortality which yielded that serum urea, creatinine and prothrombin time made a significant contribution to prediction with an OR 14 (95% CI 12.8 -16.7 p = 0.03), 2 (95% CI 0.5 -3.47, p = 0.04), and 2 (95% CI 1.03 -2.31, p = 0.01) linearly-related. Conclusions: our results suggest that acute renal failure and prolonged prothrombin time are predictors of in-hospital mortality in patients with portal hypertension due to alcoholic cirrhosis.

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