Discussion
Asthma is generally diagnosed based on the clinical manifestations of
recurrent wheezing combined with reversible airflow obstruction. Unlike
for adults, there are no objective criteria for the diagnosis of asthma
in children under 6 years of age, and especially for those under 3 years
of age. At present, the diagnosis and treatment of asthma in this age
group is mainly based on the frequency of wheezing attacks and the
prediction of high asthma risk based on the mAPI(4,
5). However, the positive rate of asthma prediction based on mAPI is
limited (6, 7). Therefore, although atopy is a
high-risk factor for asthma, many these children will not develop
asthma. There is an urgent need for stable and specific biological
indicators to assist in the diagnosis of asthma, and a major focus of
research in the field is to find specific biological indicators through
the immunological mechanism of asthma(8, 9).
In this study, a small-sample cohort of 43 wheezing children was
established. The relationship
between the level of circulating
CD4+CCR6+CRTh2+memory Th2 cells and a diagnosis of asthma was determined. We found that
the level of
CD4+CCR6+CRTh2+memory Th2 cells in the asthma group was significantly higher than that
in the non-asthma group. Logistic regression analysis further indicated
that
CD4+CCR6+CRTh2+memory Th2 cells were an independent risk factor for the diagnosis of
asthma. In this study, 74.4% of the subjects showed inhaled and/or food
allergen sensitization, indicating that most of the included patients
had allergic physique. Therefore, we analyzed whether there were
differences in
CD4+CCR6+CRTh2+memory Th2 cells among other allergic diseases. The increase in
CD4+CCR6+CRTh2+memory Th2 cells is specifically related to asthma and is not affected
by AR or AD.
CD4+CCR6+CRTh2+memory Th2 cells have certain tissue specificity and reflect allergic
airway inflammation. This result can be further demonstrated by the fact
that higher level of
CD4+CCR6+CRTh2+memory Th2 cells in asthmatic children than non-asthmatic children in
atopic population.
CD4+CCR6+CRTh2+memory Th2 cell is a type of pathogenic memory-type Th2 cell. Pathogenic
memory-type Th2 cells are mainly distributed in local tissues for long
periods of time and play key roles in the maintenance of chronic
allergic inflammation(10-12).
CD4+CRTH2+CCR6+cells are memory Th2 cells that produce IL-17, which is mainly found in
the airway.
CD4+CRTH2+CCR6+cells secrete IL-17, IL-4, and IL-13, leading to the infiltration
neutrophils and eosinophils, which is responsible for chronic
inflammation associated with asthma. This course of events reflects the
immune memory of allergic airway inflammation in the lung tissue. A
small number of pathogenic memory-type Th2 cells can enter the
circulation(10, 11). Therefore, the detection of
circulating
CD4+CRTH2+CCR6+memory Th2 cells producing IL-17 is an indicator of previous and chronic
airway allergic inflammation, an important immunological feature of
asthma.
In conclusion, despite of small sample, our exploratory study found that
because
CD4+CCR6+CRTh2+memory Th2 cells have certain lung tissue specificity and an increase in
circulating memory Th2 cells reflects previous and present allergic
chronic inflammation, these cells can be used as a potential biological
indicator for diagnosis of asthma in preschool children, especially in
atopic children. We will further expand the sample size and prolong the
follow-up time to validate the current results.