The pathophysiologic significance of lymphocyte subset determination in children with infectious mononucleosis, mycoplasma pneumonia and Henoch–Schönlein purpura

Infectious mononucleosis (IM) is a proliferative disease of the monocyte–macrophage system that is caused by an Epstein–Barr virus (EBV) infection. Saliva transmission is the main route through which the infection occurs. Pediatric EBV infection is common, and primary EBV infection typically manifests as IM, particularly during adolescence [1, 2]. Globally, EBV is associated with nearly 200,000 cases of cancer and 18,000 multiple sclerosis deaths annually [3, 4], and EBV infection is associated with an increased risk of Hodgkin’s lymphoma and multiple sclerosis [5]. It is unclear why some people develop IM when they are infected with primary EBV but others do not [6]. There is currently a consensus that the vigorous increase in the number of EBV-specific CD8 + cells is a feature of IM, while the change in the proportion of other cell subsets is not well characterized [7].

Mycoplasma pneumonia, an important pathogen that causes human pneumonia, is common in children with respiratory tract infections and has a high incidence rate, and can seriously impact the growth and development of children and their overall health [8]. Most of the clinical manifestations of this disease are subacute. An irritating dry cough and headache are the main clinical manifestations in the initial stage. As the disease progresses, it may cause multiple organ dysfunction and even death [9].

In pediatrics, Henoch–Schönlein purpura (HSP) is a common systemic vasculitis disease involving small blood vessels. Its incidence rate is approximately 1/5,000, which decreases with age; more than 90% of HSP children are younger than 10 years old, and the age of peak incidence is 4–6 years old [10]. The main clinical feature is athrombopenic purpura, which often involves the joints, the gastrointestinal tract, the kidneys, and other organs. At present, the etiology and pathogenesis of HSP are not entirely clear. A study confirmed that the immune imbalance of Th1/Th2 and Th17/Treg cells plays an important role in the pathogenesis of HSP [11].

Infectious mononucleosis, mycoplasma pneumonia infection, and HSP are common diseases that frequently occur among children. Both humoral and cellular immune responses can occur in children with these diseases. The peripheral blood lymphocyte subsets of 45 children with IM, 20 children with pneumonia (mycoplasma infection, [P-MI]), and 31 children with HSP, who were treated in the pediatrics department of our hospital from April 2019 to February 2020, were determined by flow cytometry to explore the disease progression and pathogenesis, thus assisting in the understanding of the conditions noted above.

Infectious mononucleosis is characterized by fever, angina, lymphadenopathy, eyelid edema, and hepatosplenomegaly. Most Patients with IM have a good prognosis; rare patients develop chronic EBV infection, hemophagocytic lymphohistiocytosis, and malignant tumors. Our data of increased CD8 + and CD56 + cell counts in patients with IM are consistent with what is known about the pathophysiology of IM [13‐15], B cell numbers are often the same as those found in healthy controls [14], Why patients with IM had lower B cell numbers than patients with P-IM and HSP is unclear. EBV mainly infects B-cells, causing changes in the surface antigen of these cells, which, in turn, triggers a T-cell (CD3 + cell) defense response. CD3 + CD4 + T-lymphocytes is a type of helper T-lymphocyte, where the intracellular molecules are phosphorylated to activate the signal transduction process and assist in the activation of B-cells, cytotoxic T-cells, and natural killer cells by secreting cytokines, e.g., interleukin (IL)-2 and IL-4. CD3 + CD8 + T-lymphocyte is a cytotoxic type of T-lymphocyte with a killing effect that directly destroys target cells or induces the apoptosis of target cells by secreting perforin interferon-gamma, as well as granzyme [16]. The mean and median ages of our patients with IM, while older than those with P-MI and HSP (3 and 3.8 years; 3 and 3 years; 6.8 and 6 years, respectively) are lower than those seen in the West, where IM is seen mainly in older adolescents and young adults [17].

Mycoplasma pneumonia is a common cause of pneumonia in children. Why these patients had the highest number of CD3 + CD4 + cells of all 3 patients groups is unclear. HSP is a vascular inflammatory disease whose specific immunopathology remains unclear. At present, the excessive activation of autoreactive B-lymphocytes in children with HSP is considered to lead to the excessive production of immunoglobulin A antibody, which is the core mechanism of the disease’s pathogenesis [18]; this is consistent with our findings of the highest number of CD3–CD19 + cells in this condition, as compared with IM and P-IM.

One limitation of our study is the lack of age-matched control groups of healthy children.

In summary, children with IM, P-MI, and HSP experience immune dysfunction. The dynamic monitoring of peripheral blood lymphocyte subsets can be used to provide insight into the pathophysiology of these three illnesses.