| Objective: Infectious mononucleosis is an acute or subacute lymphocytic benign hyperplasia disease caused by EB virus.Most of the primary EBV infections were occult infection,and nearly 50% of the patients with clinical manifestations were IM.The pathogenesis of IM has not been fully clarified,and it is agreed that immunopathological injury is closely related to the disease.3 ~ 5 years old is the peak age of EBV infection in Chinese children and the infection rate is as high as 90%.The clinical manifestations of the disease are diverse,including various degrees of fever,cervical lymph node enlargement,pharyngitis,eyelid edema,hepatosplenomegaly,rash,liver function damage,proliferation of peripheral blood lymphocytes and allogeneic lymphocytes,etc.Due to lack of specificity in clinical manifestations and diversity of initial symptoms,it is easy to be misdiagnosed.Due to the self-development characteristics of the children,especially the immature cellular immunity and humoral immune system of infants have not developed completely.so some conventional experimental methods have some limitations on the diagnosis of the IM in children,in addition,because some of that experiment require special equipment,the cost is more expensive and is not easy to be carried out,in particular to the vast number of grass-roots hospitals.At present,there are no new testing methods.?2-microglobulin(?2-MG)is the ? chain(light chain)of human lymphocyte antigen(HLA)on the cell surface,which is similar to the structure of immunoglobulin stable region.Serum ?2-MG exists in nucleated cells except red blood cells and placental trophoblast cells and is mainly produced by lymphocytes.At present,domestic and foreign studies have reported that ?2-MG is significantly increased in some lymphoproliferative diseases.Adenosine deaminase(ADA)is a metabolic enzyme closely related to the immune system.It is involved in cellular immunity and is a marker of T lymphocyte activity.Most of the children with IM showed the proliferation of B lymphocytes and the activation of T lymphocytes.Therefore,the purpose of this study is to explore new detection index.By detecting the expression levels of serum lymphocyte-related ?2-MG and ADA in children with IM,the clinical value of the combined detection of ?2-MG and ADA in the diagnosis of IM in children was discussed,and the causes of the changes were preliminarily discussed.?2-MG and ADA can be detected in common biochemical analyzers with stable results,good repeatability,high sensitivity,simple,rapid and low cost.It has the advantage of being developed in general laboratory.Methods: 1 Subjects The cases came from the Department of Pediatrics,First Affiliated Hospital of Hebei North University from January 2018 to January 2019.The patients were divided into three groups:(1)IM group: 80 children were diagnosed with IM,including 44 males and 36 females,the age ranged from 6 months to 13 years with an average age of 4.61 ± 3.40 years.(2)Non-IM group: the symptoms of the first diagnosis symptom were similar to those of IM,there were 61 males and 59 females,aged from 3 months to 14 years old,who were diagnosed as non-IM,with an average age of 4.26 ± 3.51 years(including 30 children with final diagnosis of mycoplasma pneumoniae infection and 68 children with viral infection).(3)Healthy control group: 40 healthy children,including 20 males and 20 females,aged from 6 months to 12 years with an average age of 4.55 ± 4.20 years.There was no significant difference in sex and age among all groups.All candidates signed hospital scientific research ethics and informed consent.2 Test contents Two blood samples were collected from each of the children tested,and the following items were tested respectively.2.1 Separation of serum The content of ?2-MG was determined by latex enhanced immunoturbidimetry,the content of cystatin C(Cys C)was determined by colloidal gold enhanced immunoassay,and the activity of ADA was measured by enzymatic method,the activities of glutamic-oxaloacetic transaminase(AST)and glutamic-pyruvic transaminase(ALT)were measured by rate method.The specific antibodies of EBV were detected by indirect immunofluorescence assay,including EBV capsid antibody Ig M,EBV early antibody Ig G,EBV core antibody,EBV capsid antibody Ig G and antibody affinity.2.2 Whole blood White blood cell(WBC)count and lymphocyte(LYM)count were detected by the method of semiconductor laser flow cytometry,the percentage of abnormal lymphocytes was counted by the smear method.2.3 The detection index was compared among the groups,and the clinical diagnosis value of ?2-MG and ADA was established by ROC analysis.The data were analyzed by SPSS 24.0 software.The data were expressed as mean ± standard deviation,independent sample t test was used for comparison between groups,and analysis of variance was used for pairwise comparisons of multiple averages(variance is tested by SNK-q test,and the variance uneven using Dunnett-t test).The diagnostic efficacy of the ?2-MG and ADA was assessed by using the ROC curve and the area under the curve(AUC),and the correlation of the indexes of the laboratory was studied by Pearson correlation analysis.Results: 1.The content of ?2-MG and Cys C,the activity of ADA,AST and ALT,WBC and LYM,the percentage of atypical lymphocytes in IM group were significantly higher than those in non-IM group and healthy control group In IM group,?2-MG content was 4.30 ± 1.05 mg/L,Cys C content was 0.96 ± 0.22 mg/L,the activity of ADA was 55.19 ± 18.97 U/L,the activity of AST was 64.68 ± 26.37 U/L,the activity of ALT was 69.09 ± 23.82 U/L,WBC was 14.38 ± 7.01(×10 9),LYM was 10.31 ± 6.14(×10 9),the percentage of atypical lymphocytes was 10.37 ± 8.55(%)(32 of them were more than 10%,the lowest was 2%,the highest was 40%).In non-IM group,?2-MG content was 2.40 ± 0.99 mg/L,Cys C content was 0.85 ± 0.21 mg/L,the activity of ADA was 29.68 ± 15.43 U/L,the activity of AST was 33.61 ± 18.43 U/L,the activity of ALT was 22.90 ± 13.16 U/L,WBC was 9.47 ± 4.14(×10 9),LYM was 4.30 ± 2.26(×10 9),and the percentage of atypical lymphocytes was 5.15 ± 4.39(%).In the healthy control group,?2-MG content was 1.60 ± 0.51 mg/L,Cys C content was 0.85 ± 0.11 mg/L,the activity of ADA was 16.81 ± 3.27 U/L,the activity of AST was 21.95 ± 4.94 U/L,the activity of ALT was 11.0 ± 4.24 U/L,WBC was 6.21 ± 1.27(×10 9),LYM was 2.73 ± 0.85(×10 9),the percentage of atypical lymphocytes was 0.78 ± 0.73(%).The contents of ?2-MG and Cys C,the activity of ADA,AST and ALT,WBC,LYM,and the percentage of atypical lymphocytes in IM group were significantly higher than those in non-IM group and healthy control group(P<0.05).The content of ?2-MG,the activity of ADA,AST and ALT,WBC,LYM,and the percentage of atypical lymphocyte in non-IM group were higher than those in healthy control group(P<0.05).There was no significant difference in Cys C content between the two groups(P>0.05).2.There was no significant difference in ?2-MG and ADA level between anti-VCA-Ig M positive children and anti-VCA-Ig M negative children in IM group In 80 cases of IM,23 cases were positive for anti-VCA-Ig M,44 cases were positive for anti-EA-Ig G,and 80 cases were positive for anti-VCA-Ig G,and all of them were low affinity antibodies.Anti-VCA-Ig M is a specific antibody in the early stage of EBV infection in children with IM.According to the results of anti-VCA-Ig M,80 cases of IM were divided into anti-VCA-Ig M positive group(23 cases)and anti-VCA-Ig M negative group(57 cases).The content of ?2-MG in anti-VCA-Ig M positive children was 4.34 ± 1.14 mg/L,and the activity of ADA was 56.78 ± 19.24 U/L.The level of ?2-MG and the activity of ADA in anti-VCA-Ig M negative children were 3.96 ± 1.00 mg/L and 54.55 ± 18.99 U/L,respectively.There was no significant difference in ?2-MG,ADA between the two groups(P>0.05).3.There is no correlation between ?2-MG,ADA level and lymphocyte count and percentage of allogeneic lymphocytes in IM children The correlation between ?2-MG and LYM was r=0.157,P>0.05.The correlation between ADA and LYM was r=0.092,P>0.05.The correlation between ?2-MG and the percentage of atypical lymphocytes was r=0.034,P>0.05.The correlation between ADA and the percentage of atypical lymphocytes was r=0.111,P>0.05.?2-MG and ADA had no correlation with lymphocyte count and percentage of atypical lymphocytes.4.The activity of ADA in IM children with liver damage was higher than that in IM children with normal liver function;the activity of ADA in normal liver function IM group was significantly higher than that in non-IM group and healthy control group Among the 80 cases of IM,52 cases(65%)had liver damage,which accounted for 65% of all children with IM.The activity of ADA in IM children with liver damage(59.0 ± 18.86 U/L)was higher than that in children with normal liver function(49.04 ± 14.28 U/L),and the difference was statistically significant(p<0.05).The activity of ADA in normal IM group was significantly higher than that in non-IM group(29.68 ± 15.43 U/L)and healthy control group(16.81 ± 3.27 U/L)(p<0.05).5.The levels of ?2-MG and ADA in IM group were higher than those in mycoplasma pneumoniae group and viral group The content of ?2-MG in IM group was 4.30 ± 1.05 mg/L,the activity of ADA was 55.19 ± 18.97 U/L,the ?2-MG content in mycoplasma pneumonia group was 2.33 ± 1.02 mg/L,the activity of ADA was 27.69 ± 11.68 U/L.The content of ?2-MG in virus group was 2.40 ± 0.93 mg/L,the activity of ADA was 29.54 ± 17.76 U/L.IM was significantly higher than that in mycoplasma pneumoniae group and virus group(influenza B virus,coxsackie A1,B7,parainfluenza virus,echo virus,respiratory syncytial virus,cytomegalovirus,rubella virus)were significantly different(P<0.05).6.The combined detection of ?2-MG and ADA by ROC curve analysis has higher accuracy,sensitivity and specificity in the diagnosis of IM in children The area under ROC curve(AUC)of ?2-MG for diagnosis of IM was 0.884,the sensitivity was 88.8%,the specificity was 83.3%,and the Youden index was 0.721.The AUC of ADA for diagnosis of IM was 0.884,the sensitivity was 82.5%,the specificity was 83.3%,and the Youden index was 0.658.The AUC of ?2-MG and ADA for diagnosis of IM was 0.91,the sensitivity was 90.0%,the specificity was 84.2%,the Youden index was 0.742.The accuracy,specificity and sensitivity of ?2-MG,ADA and ?2-MG combined with ADA were higher than those of AST,ALT,WBC,LYM,Cys C and percentage of atypical lymphocytes.The sensitivity and specificity of ?2-MG combined with ADA were higher than those of ?2-MG and ADA individual.The best cutoff value of ?2-MG was 3.05 mg/L,ADA was 39.50 U/L.Conclusion: 1.The accuracy,sensitivity and specificity of serum ?2-MG,ADA in the diagnosis of infectious mononucleosis in children are higher than those of AST,ALT,WBC,LYM,Cys C and the percentage of abnormal lymphocytes.It has certain clinical value for auxiliary diagnosis of IM in children.And the joint detection of the two is superior to the single one.2.Liver damage may not be the main reason for the increase of serum ADA activity in children with IM,but liver damage can enhance the degree of increase in ADA activity.There is no correlation between ?2-MG,ADA level and lymphocyte count and percentage of allogeneic lymphocytes in IM children.3.?2-MG and ADA have certain reference value in differential diagnosis of IM infection,Mycoplasma pneumoniae infection and some other virus infections. |
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