"Hyper" lymphocytes

1.
Preface

Infectiousmononucleosis (IM) is an acute, self-limited infectious disease caused by Epstein-Barr virus infection and is a common infectious disease in children [1].

Epstein-Barr virus infection can affect multiple systems throughout the body and is often misdiagnosed as a bacterial infectious disease
such as purulent tonsillitis due to the lack of specificity of its first symptoms.
In some children, the virus persists after infection and can progress to severe infection, and Epstein-Barr virus infection is closely related to malignant tumors such as nasopharyngeal carcinoma and lymphoma [2], so early diagnosis, correct intervention, and close monitoring are of great significance
for the efficacy and prognosis of IM.

2.
Case history

The patient, male, 4 years and 9 months, the child had fever and sore throat for 6 days without obvious causes, and the cold medicine at his own expense was ineffective, and he went to our hospital for outpatient treatment, and the outpatient doctor gave antibiotics for two days, and the child's symptoms did not improve significantly, and the outpatient doctor admitted the child to the hospital
for further diagnosis and treatment.

At the time of admission, the child's body temperature was 38.
1°C, R: 24 times/min
.
no chills, with sore throat, still fever; Pharyngeal hyperemia, bilateral tonsills II degree swelling, purulent discharge, palpable several lymph nodes in the neck, the largest pigeon egg size, soft, clear borders, good mobility, slightly tender, no redness and fluctuation on
the surface.

Laboratory tests are as follows:

(1) Blood routine:

White blood cell count (WBC): 11.
29×109/L↑, percentage of neutrophils (NEU%): 21.
5%↓, absolute neutrophils (NEU#): 2.
43×109/L, percentage of lymphocytes (LYM%): 72.
3%↑, absolute value of lymphocytes (LYM#): 8.
16×109/L↑, microscopic examination showed abnormal lymphocytes accounted for 16% (Figure 1).

Figure 1: Abnormal lymphocytes seen on the patient's leukocyte differential scatter plot and microscopy

(2) Biochemical examination

Lactate dehydrogenase: 482U/L ↑, globulin: 30.
7g/L↑, β2 microglobulin: 4.
03mg/L↑, the rest were not abnormal.

(3) Etiology-related examination:

Mycoplasma pneumoniae: negative, Epstein-Barr virus antibodies: positive, respiratory viral antigens: negative

(4) Immunological examination

Total T lymphocyte percentage: 84.
76%↑, absolute value of total T lymphocytes: 6038.
33/μL↑, % of helper T cells: 14.
73%↓, absolute value of helper T cells: 1049.
14/μL ↓, percentage of killer T cells: 68.
21%↑, absolute value of killer T cells: 4859.
59/μL ↑, helper/killer T cell ratio: 0.
22%↓, percentage of B lymphocytes: 8.
73%, Absolute value of B lymphocytes: 622.
11/μL↑, percentage of NK cells: 5.
97%↓, absolute value of NK cells: 425.
66/μL, CD3+HLA-DR+ activated subset: 73.
52%↑, CD3+CD8+CD38+ activated subset: 86.
2%↑, CD3+CD8+HLA-DR+ activated subset: 83.
09%↑ (Figure 2), neutrophil CD64 index: 23.
26
.

Fig.
2 CD8+ T cells were significantly increased and highly activated

(5) Other inflammation-related indicators:

CRP：7.
1mg/L，PCT：0.
10μg/L， IL-2：8.
45pg/mL↑， IL-5：4.
18pg/mL↑， IL-6：24.
19pg/mL↑， IL-10：23.
23pg/mL↑， IL-17：8.
61pg/mL↑， TNF-α：11.
1pg/mL↑， IFN-γ：7.
71pg/mL↑，IgE：385IU/mL

The clinician diagnosed the patient as infectious mononucleosis (glandular fever) according to the laboratory results, and judged the excessive activation of the patient's T cells according to the increase in the neutrophil CD64 index, and the patient's T cells were overactivated according to the results of the elevated neutrophil CD64 index, and the comprehensive intervention measures of antiviral drugs, immunomodulatory drugs, antibiotics, and rehydration symptomatic treatment were taken
.

3 Case studies

This is a very typical EV virus infection case, we recently followed up on the clinically found children with infectious mononucleosis, used immunology projects to systematically evaluate the children, the results showed that children with infectious mononucleosis of EBV infection showed similar immune system changes: that is, the innate immune system and adaptive immune system were fully activated, of which the activation of T lymphocytes was the most significant.
At the same time, it is accompanied by different degrees of activation of neutrophils and B lymphocytes and an increase
in inflammatory factors.

The elevation of T cell surface activation markers, especially CD38, is much higher than the percentage of atypic lymphocytes, which is a good auxiliary diagnostic index for
IM.
The high activation of T cells can explain the systemic inflammatory response and organ damage caused by Epstein-Barr virus infection, which is worthy of monitoring during the course of the disease, and has important reference significance
for guiding clinical intervention and preventing severe autoimmune damage.

Studies have shown that EBV infection is often complicated by bacterial infection [3], but conventional infection markers such as CRP and PCT are usually not significantly elevated, which makes clinicians confused
about the need for antibiotics.
We detected a significant increase in cytokine and neutrophil CD64 indices in the patient's peripheral blood, and the results were clinically consistent with the patient's co-infection
.

4 Summary

In summary, the above new immune markers can better reflect the immune status of patients with infectious mononucleosis, can better guide clinical diagnosis and treatment, and are worth promoting and applying, and the mechanism and intervention of this systemic immune status change are worthy of further study
.

References

[1] Hu Yamei, Jiang Zaifang.
Zhufutang practical pediatrics[M].
8th ed.
Beijing: People's Medical Publishing House.
2015， 916-922．

[2] Yao Yanqing, Cui Hong.
Clinical features of 80 children of different ages with EBV-associated infectious mononucleosis[J].
Chinese Medical Journal,2017,52(8):76-79.

WANG Tao, HUA Yimin, ZHOU Kaiyu, et al.
Clinical features and etiological analysis of nosocomial bacterial infection in children with secondary infectious mononucleosis[J].
Chinese Journal of Practical Pediatrics,2017,32(22):1717-1720.