Eosinophil activation status, cytokines and liver fibrosis in Schistosoma mansoni infected patients.

We have been investigating whether human eosinophils play an important role in schistosomiasis mansoni morbidity. Our main focus has been on the activation-related cell surface markers (CD23/CD69/CD25/HLA-DR/CD28/CD80) and the detection of TNF-alpha, IL-4 and IL-5 in peripheral blood eosinophils from chronic Schistosoma mansoni-infected patients. Our studies compare both, intestinal (INT) and individuals with periportal fibrosis (FIB). Our major findings, point to distinct profile of activation-related surface markers on eosinophils as the hallmark of disease morbidity during chronic S. mansoni infection. Up-regulation of several activation-related markers was observed on eosinophils from FIB group, but not INT, which include early activation markers, such as CD69 and CD23. INT displayed a distinct profile, with up-regulation of molecules related to the late activation (CD25, HLA-DR, CD28 and CD80). These results suggest that some immunoregulatory events may take place controlling the early eosinophil activation in the INT group. Higher levels of eosinophil-derived cytokines were observed in FIB, regardless the antigen stimulation in vitro. A mixed cytokine pattern, characterized by positive correlation between TNF-alpha, IL-4 and IL-5 was observed in both INT and FIB. However, lack of correlation between the cytokine expression and the eosinophil activation status points out that even those FIB patients presenting minor increment on eosinophil activation displayed higher levels of cytokine-positive eosinophils. Indeed, the positive association between lymphocyte-derived IL-10 and the eosinophils cytokine profile was observed exclusively in INT further emphasize our hypothesis that immunoregulatory events take place controlling disease morbidity in human schistosomiasis. The impaired IL-10-driven immunoregulatory function may play an important role on the establishment of pathology in patients bearing periportal fibrosis.

Characterization of nickel-induced allergic contact stomatitis associated with fixed orthodontic appliances.

INTRODUCTION: In some orthodontic patients, an oral inflammatory response is induced by corrosion of orthodontic appliances and subsequent nickel release. This inflammatory response is manifested as stomatitis (nickel-induced allergic contact stomatitis [NiACS]). The etiology and diagnosis of NiACS are difficult to determine. The purpose of this retrospective analysis was to investigate the roles of age, sex, previous allergic history, and time of exposure to fixed orthodontic appliances in the etiopathogeny of NiACS. METHODS: Forty-four orthodontic patients (range, 10-44 years) were divided into 2 groups, depending on their NiACS clinical manifestations. RESULTS: Young patients, especially females with a history of allergic reactions, had a greater predisposition to NiACS clinical manifestations; time of exposure to orthodontic appliances was not a significant factor. CONCLUSIONS: A previous allergic reaction should be considered a predictive factor of NiACS clinical manifestations and should be noted in the patient's medical history.

Evaluation of immunologic profile in patients with nickel sensitivity due to use of fixed orthodontic appliances.

The aim of this study was to develop a new approach to testing the impact of nickel antigen on in vitro cell-proliferation assay, to identify adverse reactions to casting alloys among orthodontic patients. Cell-proliferation assay in vitro was used as the basic methodology to assess the influence of such variables as source of nickel antigen, type of serum used to supplement the culture medium, and number of cells in the culture. We selected 35 orthodontic patients who were classified as nickel sensitive and non-nickel sensitive, based on their clinical records. Our results showed that hexahydrated nickel sulfate at 10 microg/mL, 10% of autologous sera, and 2 x 10(5) cells was the best condition for inducing the most marked nickel proliferation response in vitro. This optimized method was able to distinguish nickel-sensitive from non-nickel-sensitive dental patients and also to discriminate those with positive skin tests. Our data suggest that continuous exposure to nickel casting alloys might lead to oral tolerance mechanisms that modulate nickel sensitivity, as evidenced by the lower cell proliferation index in patients undergoing orthodontic treatment over 24 months. Finally, our findings demonstrated a known nickel-induced type 2 immune response and a marked lack of type 1 immunity (interferon gamma) as the hallmarks of nickel-sensitive patients. Further studies are needed to clarify the major cell phenotype associated with this type 2 immune response and the lack of type 1 immunity observed in nickel-sensitive people.