传染性单核细胞增多症并发肝损伤患儿外周血CD19+细胞百分比和血清C反应蛋白变化及其临床意义

摘要/Abstract

摘要： 目的探讨传染性单核细胞增多症(IM)并发肝损伤患儿外周血CD19⁺细胞百分比及血清降钙素原(PCT)和C反应蛋白(CRP)水平变化及其临床意义。方法 2021年3月—2024年3月南京大学医学院附属盐城第一医院儿科诊治的105例IM患儿,给予更昔洛韦治疗7～14 d,给予肝损伤患儿护肝治疗。使用BD FACSCanto II流式细胞仪检测外周血CD19⁺细胞百分比,采用电化学发光免疫分析法检测血清PCT水平,采用免疫透射比浊法检测血清CRP水平。应用多因素logistic回归分析影响IM患儿并发肝损伤的危险因素。结果在本组105例IM患儿中,发现肝损伤者64例(61.0%);肝损伤患儿体质指数为(21.7±1.2)kg/m²,显著小于非肝损伤组[(23.8±1.5)kg/m²,P<0.05],而肝肿大、人工喂养和临床疾病重度发生率分别为43.8%、43.8%和12.5%,均显著高于非肝损伤组的22.0%、12.2%和0.0%(均P<0.05),血清EBV DNA载量为(3.5±1.2)lg拷贝/mL,抗病毒治疗时长为(7.4±1.1)d,均显著高于或长于非肝损伤组[分别为(2.0±0.6)lg拷贝/mL和(3.6±0.5)d,P<0.05]; 肝损伤组外周血CD19⁺百分比和血清CRP水平分别为(8.4±1.9)%和(57.2±14.6)mg/L,均显著高于非肝损伤组[分别为(4.6±1.5)%和(12.4±2.9)mg/L,P<0.05];多因素logistic回归分析显示,肝肿大[OR=1.020, 95% CI: 1.003, 1.038, P=0.022]、人工喂养[OR=1.113, 95% CI: 1.011, 1.226, P=0.028]、用药时长[OR=10.502, 95% CI: 1.561, 70.663, P=0.016]、临床疾病严重程度[OR=1.121, 95% CI: 1.009, 1.245, P=0.033]、体质指数[OR=0.988, 95% CI: 0.978, 0.998, P=0.022]、EBV DNA水平[OR=1.777, 95% CI: 1.043, 3.028, P=0.035]、外周血CD19⁺细胞百分比[OR=1.471, 95% CI: 1.093, 1.980, P=0.011]和血清CRP水平[OR=2.807, 95% CI: 1.121,7.028,P=0.027]均是传染性单核细胞增多症患儿发生肝损伤的独立危险因素(P<0.05)。结论 IM患儿易并发肝损伤,临床应注意发现处于高危人群的患儿,避免过长时间的抗病毒治疗,外周血CD19+细胞百分比和血清CRP水平升高患者可能提示肝损伤的发生,而应给予积极的护肝治疗,预后良好。

关键词: 传染性单核细胞增多症, 肝损伤, CD19⁺细胞, C反应蛋白

Abstract: Objective To examine the changes in peripheral blood CD19⁺ cell percentage, along with serum procalcitonin (PCT) and C-reactive protein (CRP) levels, in children with infectious mononucleosis (IM) complicated by liver damage. Methods A total of 105 children diagnosed with IM were treated at Yancheng First Hospital, affiliated with Nanjing University Medical School, from March 2021 to March 2024. All patients received intravenous ganciclovir for one to two weeks. Those with liver injury were additionally managed with liver-protecting medicines until normalization of liver function tests. Peripheral blood CD19⁺ cell percentage were measured by flow cytometry (FCM), while serum procalcitonin (PCT) and C-reactive protein (CRP) levels were assayed throgh routine assays. Multivariate logistic regression analysis was used to identify risk factors associated with liver damage in children with IM. Results Among the 105 children with IM, liver injury was observed in 64 cases (61.0%). Children with liver injury had a significantly lower body mass index (BMI) [(21.7±1.2) kg/m²] compared to those without liver injury [(23.8±1.5) kg/m², P<0.05]. The incidence of hepatomegaly, artificial feeding, and severe clinical type was markedly higher in children with liver injury (43.8%, 43.8% and 12.5%, respectively) than in those without (22.0%, 12.2% and 0.0% all P<0.05). Serum EBV DNA load was significantly elevated [(3.5±1.2) lg copies/mL] and antiviral therapy duration was longer [(7.4±1.1) days] in children with liver injury compared to those without [(2.0±0.6) lg copies/mL and (3.6±0.5) days, respectively, P<0.05]. Peripheral blood CD19⁺ cells percentage [(8.4±1.9) %] and serum CRP levels [(57.2±14.6) mg/L] were also significantly higher in children with liver injury than in those without [(4.6±1.5) % and (12.4±2.9) mg/L, respectively, P<0.05]. Multivariate logistic regression identified hepatomegaly [OR=1.020, 95% CI: 1.003-1.038, P=0.022], artificial feeding [OR=1.113, 95% CI: 1.011-1.226,P=0.028], duration of antiviral therapy [OR=10.502, 95% CI: 1.561-70.663,P=0.016], severe clinical type [OR=1.121, 95% CI: 1.009-1.245, P=0.033], BMI [OR=0.988, 95% CI:0.978-0.998, P=0.022], serum EBV DNA load [OR=1.777, 95% CI: 1.043-3.028, P=0.035], peripheral blood CD19⁺ cell percentage [OR=1.471, 95% CI: 1.093-1.980, P=0.011], and serum CRP level [OR=2.807, 95% CI: 1.121-7.028, P=0.027] as independent risk factors for liver injury in children with IM (P<0.05). Conclusion Liver injury is a potential complication in children with IM, and clinicians should carefully consider associated risk factors. Extended antiviral therapy may not be advisable, and elevated peripheral blood CD19⁺ cell percentages and serum CRP levels could serve as indicators of liver injury, warranting appropriate management.

Key words: Infectious Mononucleosis, Liver injuries, CD19⁺ cells, C-reactive protein

陈蕾蕾, 刘志峰. 传染性单核细胞增多症并发肝损伤患儿外周血CD19⁺细胞百分比和血清C反应蛋白变化及其临床意义[J]. 肝脏, 2024, 29(11): 1418-1421.

CHEN Lei-lei, LIU Zhi-feng. Analysis of peripheral blood CD19⁺ cells and serum C-reactive protein in pediatric infectious mononucleosis with liver complications[J]. Chinese Hepatolgy, 2024, 29(11): 1418-1421.

/ 推荐

参考文献

[1] Naughton P, Healy M, Enright F, et al. Infectious mononucleosis: diagnosis and clinical interpretation[J]. Brit J Biomed Sci,2021,78(3):107-116.
[2] Kuri A, Jacobs B M, Vickaryous N, et al. Epidemiology of Epstein-Barr virus infection and infectious mononucleosis in the United Kingdom[J]. BMC Public Health,2020,20: 1-9.
[3] Fang Q, Deng Y, Liang R, et al. CD19+ CD24hiCD38hi regulatory B cells: a potential immune predictive marker of severity and therapeutic responsiveness of hepatitis C[J]. Am J Transl Res,2020,12(3):889.
[4] Kamat I S, Ramachandran V, Eswaran H, et al. Procalcitonin to distinguish viral from bacterial pneumonia: a systematic review and meta-analysis[J]. Clin Infect Dis,2020,70(3):538-542.
[5] Stanimirovic J, Radovanovic J, Banjac K, et al. Role of C-reactive protein in diabetic inflammation[J]. Mediators Inflamm,2022,2022:3706508.
[6] 中华医学会儿科学分会感染学组,全国儿童EB病毒感染协作组.儿童主要非肿瘤性EB病毒感染相关疾病的诊断和治疗原则建议[J]. 中华儿科杂志,2016,54(8):563-568.
[7] Zhang C, Cui S, Mao G, et al. Clinical characteristics and the risk factors of hepatic injury in 221 children with infectious mononucleosis[J]. Front Pediatr,2022,9:809005.
[8] Chen B, Han N, Gao L, et al. Comparison of immune responses in children with infectious mononucleosis caused by Epstein-Barr virus at different infection stages[J]. Int J Lab Hematol,2023,45(6): 890-898.
[9] Sayaf K, Gabbia D, Russo F P, et al. The role of sex in acute and chronic liver damage[J]. Int J Mol Sci,2022,23(18):10654.
[10] Liu M, Huang C, Zhou X, et al. Membrane-bound CD95 ligand modulates CD19-mediated B cell receptor signaling and EBV activation[J]. J Med Virol,2024,96(2):e29440.
[11] 丁芬芬,陈丹丹,蒋霞,等. 商陆皂苷甲基于CD19+IL-35+Breg细胞对MRL/lpr小鼠肾炎的影响[J]. 生物技术,2022,32(6):749-753,e703.
[12] 张颖,温晓敏,郑梅,等. 新生儿脓毒症外周血CD19+CD24hiCD38hiBreg表达水平及意义[J]. 中华医院感染学杂志,2022,32(14):2202-2206.
[13] Yang X, Wu Y, Zhang M, et al. Piceatannol protects against age-related hearing loss by inhibiting cellular pyroptosis and inflammation through regulated Caspase11-GSDMD pathway[J]. Biomed Pharmacother,2023,163:114704.
[14] Zhou Y Z, Teng X B, Han M F, et al. The value of PCT, IL-6, and CRP in the early diagnosis and evaluation of COVID-19[J]. Eur Rev Med Pharmacol Sci,2021,25(2):1097-1100.
[15] McFadyen J D, Zeller J, Potempa L A, et al. C-reactive protein and its structural isoforms: an evolutionary conserved marker and central player in inflammatory diseases and beyond. Vertebrate and invertebrate respiratory proteins[J], Subcell Biochem,2020,43:499-520.
[16] Hart P C, Rajab I M, Alebraheem M, et al. C-reactive protein and cancer—diagnostic and therapeutic insights[J]. Front Immunol,2020,11:595835.
[17] Guo R, Liang JH, Zhang Y, et al. Methionine metabolism controls the B cell EBV epigenome and viral latency[J]. Cell Metab,2022,34(9):1280-1297.
[18] Luttwak E, Hagin D, Perry C, et al. Anti-CD19 CAR-T therapy for EBV-negative posttransplantation lymphoproliferative disease—a single center case series[J]. Bone Marrow Transplant,2021,56(5):1031-1037.
[19] Guo Y, Feng K, Tong C, et al. Efficiency and side effects of anti-CD38 CAR T cells in an adult patient with relapsed B-ALL after failure of bi-specific CD19/CD22 CAR T cell treatment[J]. Cell Mol Immunol,2020,17(4):430-432.
[20] 高荣理,陈垂婉,蔡翠珠,等. EBV合并CMV感染的传染性单核细胞增多症患者T细胞免疫状态及炎症指标变化[J]. 中华医院感染学杂志,2020,30(19):2975-2978.