Discussion
The immune state in the chronic stage of schistosomiasis infection is mainly mediated by granulomatous inflammatory responses to schistosome eggs deposited in different organs and tissues. Schistosoma japonicum mainly attacks the liver, and granuloma formation caused by egg deposition in the liver leads to periportal fibrosis, which will finally lead to the advanced stage of schistosomiasis japonica characterized by portal hypertension and hepatosplenomegaly33. Ascites and variceal hemorrhage are two serious and common complications at this stage, which can lead to the death of the patient. Although characteristics of immune cells peripheral in schistosomiasis mansoni was well defined, the features of peripheral immune state in patients with schistosomiasis japonica remain not well defined. In this study, we characterized the percentages and the absolute number of lymphocytes in the peripheral. We found that the percentage of CD4+T cells was lower in the advanced group, but the percentage of CD19+B cells was higher in the advanced group. In addition, the number of CD3+T cells, CD3+CD4+T cells, CD3+CD8+T cells, and NK cells was less in the advanced group when compared with those in the chronic group. Our results indicated that the immune state in the peripheral may facilitate differential diagnosis of different stages of schistosomiasis japonica and they can be a potential prognostic factor.
Our study showed the differences in the liver function of the patients. Liver fibrosis and portal hypertension can be mediated by schistosomiasis3. Consistent with previous studies, we found advanced schistosomiasis is a wasting disease and can lead to a reduction in albumin in patients34. This is corroborated by the lower lipids in patients with advanced schistosomiasis. Also, differences in blood counts between patients at different stages of the disease have been confirmed. The reduction in various immune cells may be associated with hypersplenism, which is common in advanced schistosomiasis.
The peripheral immune state showed the potential to assist in the differential diagnosis of different stages of schistosomiasis35. It is well known that schistosomiasis infection is a process in which the immune status changes and the immunological diagnosis is widely used in the diagnosis of schistosomiasis1, 36. The conventional ELISA test has been widely used, but it can often only determine whether a patient is infected with schistosomiasis but cannot differentiate the disease progression of schistosomiasis.
Schistosome infection leads to significant changes in immune function in patients, with the Th1 response dominating in the acute phase, but gradually shifting to a Th2 response as the schistosomes mature over time16, 18, 22, 37. And it in turn gradually diminishes with the formation of chronic granulomas16, 22. Cytokines have received more attention in many studies, but direct immune cells have been less frequently mentioned16. Combining the cytokine profile and the immune cell profile will provide further help in understanding the immune state of patients with schistosomiasis.
Flow cytometry is a relatively convenient test, which can gives rapid results and provides more direct insight into the immune status of the patient. The use of peripheral lymphocytes alone as a biomarker to differentiate schistosomiasis progression may not be accurate, but we believe it has some value as an adjunctive diagnostic tool.
Immune status is different between the different stages of schistosomiasis. Patients with advanced schistosomiasis exhibit a higher percentage of haemocytopenia, which is related to hypersplenism in patients with advanced schistosomiasis. Splenectomy is one of the more commonly used and effective treatments for severe cases of this condition13, 38-40. The deterioration in liver function indicators is a direct indication of the more severe liver damage in patients with advanced schistosomiasis. If the markers mentioned in this article can be used to determine early that a patient with chronic schistosomiasis is progressing towards advanced schistosomiasis rather than remaining stable, and to guide early prevention and treatment, this can make a considerable difference to survival and quality of the life.
Abdominal ultrasound is also a common tool for screening for schistosomes, and the clinical impact of more severe and long-term infections often reveals fish-scale and cobweb changes in the liver, which are also referred to as ”schistosomal liver”. 29, 41We reclassified the patients according to imaging and analyzed their peripheral lymphocyte status, which also suggested a correlation between CD4+ T-cell percentage and liver fibrosis. As the patient’s liver fibrosis worsened, the patient’s CD4+T-cell percentage subsequently decreased. This is also in line with the unique decline in CD4+ T-cell percentage seen in advanced schistosomiasis that we mentioned before. Of course, not all patients presenting with the schistosomal liver are advanced schistosomiasis some of the most severely ill patients are chronic, and there is a proportion of patients who have not regressed to advanced schistosomiasis after years of persistent infection, but we do not think this affects our studies on peripheral lymphocytes in patients, which can still suggest the progression of disease in our patients.
In summary, Schistosoma japonicum patients at different stages of the disease differ in several indicators. CD4+ T cells may be a potential biomarker that can assist in the differential diagnosis between chronic schistosomiasis and advanced schistosomiasis and may be a potential prognostic factor.