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.