| China is one of the countries severely threatened by Schistosomiasis Japonica (S. japonica), especially in the Yangtze River valley and southern provinces. Although the number of patients with S. japonica levels off in recent years, this disease still relapses. Vaccines for Schistosomiasis may offer long lasting prevention against Schistosomiasis for the susceptible population. However, studies on vaccines for Schistosomiasis have not made a significant breakthrough. The reasons may lie in the fact that the mechanisms and pathways of immune response induced by Schistosomiasis have not been thoroughly clarified. The present study with an observational design recruited patients with different types of S. japonica, including patients with acute S. japonica, patients with chronic S. japonica and patients with advanced S. japonica. Healthy controls were also recruited. The participants were interviewed with questionnaires, experienced with medical examination and had serum immunological tests. This study aims to:1) compare serum profiles of T helper cells (Th) related cytokines and schistosoma-specific antibodies in patients with different types of S. japonica;2) explore the Th-related cytokines mediated cellular immunity and schistosoma-specific antibodies mediated humoral immunity;3) evaluate the correlation of pathological changes and function of the liver, history of splenectomy to the immunity response levels in patients with advanced S. japonica. This study is devided into three parts as follows.I Basic Characteristics of Patients with Different Types of S. japonica and ControlsObjective To describe the basic characteristics of patients with different types of S. japonica and controls. Methods The study was conducted from September,2010to December,2011in Xingzi county of Jiangxi province and Yueyang city of Hunan province. Participants were recruited from inpatient department or by Schistosomiasis census, while controls were recruited outside the schistosomiasis endemic areas in Jiujiang City. Questionnaires were filled by mode of interview, and blood was collected. Patients were asked to experience with medical examinations. Results There were222participants recruited in the study with165patients (5patients with acute S. japonica,22patients with a confirmed diagnosis of chronic S. japonica (Conf),57patients with a clinical diagnosis of chronic S. japonica (Clin.), and81 patients with advanced S. japonica) and57controls. No statistical differences were presented in gender distribution among the groups. The ages of patients with advanced S. japonica were older than those in other groups. Farmers and fisherman were the main occupations for patients. Ways of exposure to infested water were grazing, fishing and mowing lake grass for chronic and advanced patients, while swimming and bathing for acute patients. There were no statistical differences in BMI among the groups, but a higher proportion of low weight was shown in patients with advanced S. japonica. Conclusions The participants in the study were representative of the patients in schistosomiasis endemic lake areas.II Serum Profiles of Th-related Cytokines and Schistosoma-specific Antibodies and their Correlations in Patients with Different Types of S. japonicaObjective To analyze the serum profiles of Th-related cytokines and schistosoma-specific antibodies and their correlations in patients with different types of S. japonica, and depict the dynamics of serum Th-related cytokines and schistosoma-specific antibodies in a patient with acute S. japonica. Methods Blood was collected and serum was separated for immuno logical test. Luminex Multiplex technology was used to exam the serum levels of Thl cytokines (IL-2, IL-12p70, IFN-y, TNF-a), Th2cytokines (IL-4, IL-5, IL-6, IL-13) and Th17cytokine (IL-17A). Enzyme-linked immunosorbent assays were applied to exam IL-33, soluble ST2(sST2), schistosoma-specific IgG and IgM. Results The serum concentrations of IL-2and IFN-y were the highest in patients with acute S. japonica and lower in patients with advanced S. japonica. The serum concentrations/detection rates of Th2cytokines were highest in patients with acute S. japonica, and higher in patients with advanced S. japonica compared with those in patients with chronic S. japonica and controls. Detection rate of serum Th2cytokines in patients with chronic S. japonica was lower or approaching those in controls. Concentration of IL-17A was the highest in patients with acute S. japonica, and higher in patients with advanced S. japonica versus those in patients with chronic S. japonica (Clin.). Serum IL-33and sST2were both detected in patients with acute S. japonica, patients with chronic S. japonica (Conf), patients with chronic S. japonica (Clin.), patients with advanced S. japonica and controls from higher level to lower level in order. Both IgG and IgM were positive in all patients with acute S. japonica. IgG(+) results were presented in patients with acute S. japonica, patients with chronic S. japonica (Conf), patients with chronic S. japonica (Clin.) and patients with advanced S. japonica from higher proportion to lower proportion in order. The positive rate of IgM in patients with acute S. japonica and patients with chronic S. japonica (Conf.) were both significantly higher than those with chronic S. japonica (Clin.). Serum concentrations of most Thl cytokines and all Th2cytokines rose from6th to7week followed by a decline till11th week after infection. IL-17A, IL-33and sST2decreased gradually from6th to11th week after infection. Both IgG and IgM were constantly positive in the phase of acute infection. Serum levels of TNF-a were significantly higher in individuals with IgM (-) versus those with IgM (+) among patients with chronic S. japonica (Clin.). Individuals with IgM (+) had lower serum levels of IL-6than those with IgM (-) among patients with chronic S. japonica. Conclusion Both Th-related cytokines mediated cellular immune response and schistosoma-specific antibodies mediated humoral immune response initiated and peaked in the phase of acute infection (patients with acute S. japonica)-Th17cytokines began to amplify and peaked before6th week after infection, while Thl and Th2cytokines simultaneously peak around7th week after infection. IL-33may be involved in the initiation of Th2immune response and act as a proinflammatory factor. sST2may be involved in a mechanism to down-regulate inflammation and also act as a negative regulator of Th2immune response. Chronic infection may lead to a suppression of Thl, Th2and Th17cytokine response in patients, and a down-regulation in humoral immune response. The development of advanced stage of S. japonica may be accounted for by the amplification of Th2cytokines (much lower than in the phase of acute infection).Ⅲ Correlations of Pathological Changes and Function of the Liver, History of Splenectomy to Serum Profiles of Th-related Cytokines and Schistosoma-specific Antibodies in Patients with Advanced S. JaponicaObjective To analyse the correlation of pathological changes and function of the liver, history of splenectomy to serum profiles of Th-related cytokines and schistosoma-specific antibodies in patients with advanced S. Japonica, and evaluate the interrelation between hepatic pathological progress and outcome and immune response, as well as access the impact of splenectomy on patient’s immune function.Methods Patient’s information, such as history of splenectomy, was collected via questionnaire survey. Medical examinations for patients included HBsAg test, liver function test, B ultrasound evaluation for liver and spleen and serum indices of liver fibrosis. Results Individuals with and without HBsAg(+) showed no statistical difference in the serum cytokines and schistosoma-specific IgG and IgM profiles among patients with advanced S. japonica. In participants with advanced S. japonica, those who had an abnormal level of serum A/G or y-GT presented higher serum concentrations of sST2than those with normal results. Patients with hepatic fibrosis grade II and those with grade III showed no statistical differences (except IL-2) in serum cytokine profiles and schistosoma-specific IgM positive status. Patient with a history of splenectomy had higher (not significantly) levels of serum cytokine (except TNF-a) than those lived with spleen. Conclusion A Hepatitis B infection was unlikely to affect the immune responses in patients with advanced S. japonica. The hepatic pathological progress and outcome may be related to the levels of sST2, which may reflect the severity of liver injury. There was unlikely a close relationship between the degree of liver fibrosis and serum levels of Th-related cytokines. Splenectomy may not suppress the immune function of patients with advanced S. japonica. |
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