有核红细胞在疾病诊断及预后评估中的作用研究进展*

doi:10.3969/j.issn.1671-2587.2025.06.019

临床输血与检验 ›› 2025, Vol. 27 ›› Issue (6): 859-866.DOI: 10.3969/j.issn.1671-2587.2025.06.019

有核红细胞在疾病诊断及预后评估中的作用研究进展^*

朱源源, 彭芳, 李宁

中南大学湘雅医院输血科,湖南长沙 410008

收稿日期:2025-05-26 出版日期:2025-12-20 发布日期:2025-12-24
通讯作者: 李宁,主要从事输血的临床及基础研究,E-mail：liningxy@csu.edu.cn。共同通信作者：彭芳,主要从事肿瘤发病机制研究,E-mail：pengfang@csu.edu.cn。
作者简介:朱源源,主要从事临床检验诊断学,E-mail：zhuyy0605@csu.edu.cn。
基金资助:
^*本课题受国家自然科学基金项目（No.82270633、No.82571796）资助

The Role of Nucleated Red Blood Cells in Diagnosis and Prognosis

ZHU Yuanyuan, PENG Fang, LI Ning

Department of Blood Transfusion, National Health Commission Key Laboratory of Cancer Proteomics, Xiangya Hospital, Central South University, Changsha 410008

Received:2025-05-26 Online:2025-12-20 Published:2025-12-24

摘要/Abstract

摘要： 有核红细胞（nucleated red blood cells, NRBCs）是红细胞生成过程中未成熟的红细胞前体,其显著特征是仍保留细胞核。在生理状态下,NRBCs主要见于孕妇及新生儿的外周血中,在健康成人外周血中几乎不可检出。然而,在血液系统疾病、感染性疾病及恶性肿瘤等病理状态下,NRBCs的外周血水平显著升高,并与患者的不良预后密切相关,已成为潜在的疾病诊断标志物和预后评估指标。本文旨在系统回顾近年来NRBCs作为生物标志物的研究进展,深入探讨其在疾病发生中的分子机制及其在临床诊断、治疗和预后评估中的应用潜力,为相关疾病的精准医疗提供新的视角和策略。

关键词: 有核红细胞, 生物标志物, 疾病诊断, 预后评估

Abstract: Nucleated red blood cells (NRBCs) are immature precursors of red blood cells that retain their nuclei during the process of erythropoiesis. Under physiological conditions, NRBCs are predominantly present in the peripheral blood of pregnant women and neonates, while they are rarely detected in healthy adults. However, their levels in peripheral blood increase significantly under various pathological conditions, including hematological disorders, infectious diseases, and malignancies. This elevation is closely associated with adverse clinical outcomes, making NRBCs promising candidates as diagnostic biomarkers and prognostic indicators. This article aims to provide a comprehensive review of recent advances in NRBC research, with a focus on their molecular mechanisms in disease progression, as well as their potential applications in clinical diagnosis, treatment monitoring, and prognosis evaluation, thereby offering a new insight and strategy for precision medicine.

Key words: Nucleated red blood cells, Biomarkers, Disease diagnosis, Prognosis assessment

中图分类号:

R446.11

朱源源, 彭芳, 李宁. 有核红细胞在疾病诊断及预后评估中的作用研究进展^*[J]. 临床输血与检验, 2025, 27(6): 859-866.

ZHU Yuanyuan, PENG Fang, LI Ning. The Role of Nucleated Red Blood Cells in Diagnosis and Prognosis[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2025, 27(6): 859-866.

参考文献

[1] DELYEA C,BOZORGMEHR N,KOLEVA P,et al.CD71⁺ erythroid suppressor cells promote fetomaternal tolerance through arginase-2 and PDL-1[J]. J Immunol, 2018,200(12):4044-4058.
[2] ELAHI S,ERTELT J M,KINDER J M,et al.Immunosuppressive CD71⁺ erythroid cells compromise neonatal host defence against infection[J]. Nature,2013,504(7478):158-162.
[3] LIU H Q,WANG G Q,ZHANG C S,et al.Nucleated red blood cell distribution in critically ill patients with acute pancreatitis: a retrospective cohort study[J]. BMC Gastroenterol,2024,24(1):353.
[4] ZHAO G J,JIANG D W,CAI W C,et al.CD71⁺ erythroid cell expansion in adult sepsis: potential causes and role in prognosis and nosocomial infection prediction[J]. Front Immunol,2022,13:830025.
[5] MENK M,GIEBELHÄUSER L,VORDERWÜLBECKE G,et al. Nucleated red blood cells as predictors of mortality in patients with acute respiratory distress syndrome (ARDS): an observational study[J]. Ann Intensive Care,2018,8(1):42.
[6] STEVENS-HERNANDEZ C J,FLATT J F,KUPZIG S,et al. Reticulocyte maturation and variant red blood cells[J]. Front Physiol,2022,13:834463.
[7] MINETTI G,ACHILLI C,PEROTTI C,et al.Continuous change in membrane and membrane-skeleton organization during development from proerythroblast to senescent red blood cell[J]. Front Physiol,2018,9:286.
[8] SCHEFFER M P,ELTSOV M,FRANGAKIS A S.Evidence for short-range helical order in the 30-nm chromatin fibers of erythrocyte nuclei[J]. Proc Natl Acad Sci USA,2011,108(41):16992-16997.
[9] PENG T,HOU Y P,MENG H W,et al.Mapping nucleolus-associated chromatin interactions using nucleolus Hi-C reveals pattern of heterochromatin interactions[J]. Nat Commun,2023,14(1):350.
[10] KONO M,KONDO T,TAKAGI Y,et al.Morphological definition of CD71 positive reticulocytes by various staining techniques and electron microscopy compared to reticulocytes detected by an automated hematology analyzer[J]. Clin Chim Acta,2009,404(2):105-110.
[11] LIU J,GUO X H,MOHANDAS N,et al.Membrane remodeling during reticulocyte maturation[J]. Blood, 2010,115(10):2021-2027.
[12] BAHR T M,OHLS R K,BASERGA M C,et al. Implications of an elevated nucleated red blood cell count in neonates with moderate to severe hypoxic-ischemic encephalopathy[J]. J Pediatr,2022,246:12-18.e2.
[13] CHEN Y Y,WU Z H,SUTLIVE J,et al.Noninvasive prenatal diagnosis targeting fetal nucleated red blood cells[J]. J Nanobiotechnology,2022,20(1):546.
[14] DUCAMP S,OSTUNI M A.Physiology of red cell lineage: from erythroblast progenitors to mature red blood cell[J]. Int J Mol Sci,2023,24(11):9715.
[15] LA GIOIA A,FIORINI F,FUMI M,et al.A prolonged microscopic observation improves detection of underpopulated cells in peripheral blood smears[J]. Ann Hematol,2017,96(10):1749-1754.
[16] DADELAHI A,JACKSON T,AGARWAL A M,et al.Applications of flow cytometry in diagnosis and evaluation of red blood cell disorders[J]. Clin Lab Med, 2024,44(3):495-509.
[17] LUCHINI C,PARCESEPE P,NOTTEGAR A,et al.CD71 in gestational pathology: a versatile immunohistochemical marker with new possible applications[J]. Appl Immunohistochem Mol Morphol, 2016,24(3):215-220.
[18] BELTRÁN A,SÁNCHEZ-VILLALOBOS M,SALIDO E,et al. Flow cytometry as a new accessible method to evaluate diagnostic osmotic changes in patients with red blood cell membrane defects[J]. Biomedicines,2024, 12(7):1607.
[19] ZHANG X Y,YANG Z Y,FU C M,et al.Emerging roles of liquid-liquid phase separation in liver innate immunity[J]. Cell Commun Signal,2024,22(1):430.
[20] GALANELLO R,ORIGA R.Beta-thalassemia[J]. Orphanet J Rare Dis,2010,5(1):11.
[21] PANSUWAN A,FUCHAROEN G,FUCHAROEN S, et al.Anemia,iron deficiency and thalassemia among adolescents in Northeast Thailand: results from two independent surveys[J]. Acta Haematol,2011,125(4): 186-192.
[22] SHAFEI N,HAKHAMANESHI M S,HOUSHMAND M,et al.Diagnostic value of non-invasive prenatal screening of β-thalassemia by cell free fetal DNA and fetal NRBC[J]. Curr Mol Med,2019,19(2):105-111.
[23] KARAKUKCU M,KARAKUKCU C,UNAL E,et al.The importance of nucleated red blood cells in patients with beta thalassemia major and comparison of two automated systems with manual microscopy and flow cytometry[J]. Clin Lab,2015,61(9):1289-1295.
[24] LIU J,DONG S X,RU Y X.Ultrastructural analysis of nucleated erythrocyte in patients with autoimmune hemolytic Anemia (AIHA)[J]. Ultrastruct Pathol, 2023, 47(4):271-277.
[25] YANG Z,WANG Z,WU L,et al.B lymphocytes transdifferentiate into immunosuppressive erythroblast-like cells[J]. Front Immunol,2023,14:1202943.
[26] MCGRAW K L,CHENG C H,CHEN Y A,et al.Non-del(5q) myelodysplastic syndromes-associated loci detected by SNP-array genome-wide association meta-analysis[J]. Blood Adv,2019,3(22):3579-3589.
[27] SHIH A H,LEVINE R L.Molecular biology of myelodysplastic syndromes[J]. Semin Oncol,2011,38(5): 613-620.
[28] MATARRAZ S,TEODOSIO C,FERNANDEZ C,et al.The proliferation index of specific bone marrow cell compartments from myelodysplastic syndromes is associated with the diagnostic and patient outcome[J]. PLoS One,2012,7(8):e44321.
[29] MILLAR L J,SHI L,HOERDER-SUABEDISSEN A,et al.Neonatal hypoxia ischaemia: mechanisms,models,and therapeutic challenges[J]. Front Cell Neurosci,2017,11: 78.
[30] LI J G,KOBATA K,KAMEI Y,et al.Nucleated red blood cell counts: an early predictor of brain injury and 2-year outcome in neonates with hypoxic-ischemic encephalopathy in the era of cooling-based treatment[J]. Brain Dev,2014,36(6):472-478.
[31] RAI R,TRIPATHI G,SINGH D K.Nucleated RBC count as predictor of neurological outcome in perinatal asphyxia[J]. Indian Pediatr,2014,51(3):231-232.
[32] BLACKWELL S C,REFUERZO J S,WOLFE H M, et al.The relationship between nucleated red blood cell counts and early-onset neonatal seizures[J]. Am J Obstet Gynecol,2000,182(6):1452-1457.
[33] BOSKABADI H,ZAKERIHAMIDI M,SADEGHIAN M H,et al.Nucleated red blood cells count as a prognostic biomarker in predicting the complications of asphyxia in neonates[J]. J Matern Fetal Neonatal Med,2017,30(21): 2551-2556.
[34] NITZAN I,ROBERTS C T,BHATIA R,et al.Nucleated red blood cells as markers of perinatal adaptation in preterm neonates receiving minimally invasive surfactant therapy[J]. Am J Perinatol,2022,39(16):1792-1795.
[35] CREMER M,ROLL S,GRÄF C,et al. Nucleated red blood cells as marker for an increased risk of unfavorable outcome and mortality in very low birth weight infants[J]. Early Hum Dev,2015,91(10):559-563.
[36] SCHAER C,SCHMUGGE M,FREY B.Prognostic value of nucleated red blood cells in critically ill children[J]. Swiss Med Wkly,2014,144:w13944.
[37] PIGGOTT K D,NORLIN C,LAVIOLETTE C,et al.Nucleated red blood cells as a biomarker for mortality in infants and neonates requiring veno-arterial extracorporeal membrane oxygenation for cardiac disease[J]. Perfusion, 2023,38(2):299-304.
[38] DE MOURA MONTEIRO JÚNIOR J G,DE OLIVEIRA CIPRIANO TORRES D,DA SILVA M C F C, et al. Nucleated red blood cells as predictors of all-cause mortality in cardiac intensive care unit patients: a prospective cohort study[J]. PLoS One,2015,10(12): e0144259.
[39] STACHON A,SEGBERS E,HOLLAND-LETZ T,et al.Nucleated red blood cells in the blood of medical intensive care patients indicate increased mortality risk: a prospective cohort study[J]. Crit Care,2007,11(3):R62.
[40] KUERT S,HOLLAND-LETZ T,FRIESE J,et al.Association of nucleated red blood cells in blood and arterial oxygen partial tension[J]. Clin Chem Lab Med, 2011,49(2):257-263.
[41] ZHANG J G,TANG K,ZHANG Y,et al.The presence of circulating nucleated red blood cells is associated with disease severity in patients of hemorrhagic fever with renal syndrome[J]. Front Med,2021,8:665410.
[42] NARCı H,OKTAY M M,AYRıK C,et al. Nucleated red blood cells as predictor of all-cause mortality in emergency department[J]. Am J Emerg Med,2021,46: 335-338.
[43] XU C X,WANG J,JIN X X,et al.Establishment of a predictive model for outcomes in patients with severe acute pancreatitis by nucleated red blood cells combined with Charlson complication index and APACHE Ⅱ score[J]. Turk J Gastroenterol,2020,31(12):936-941.
[44] LI H D,TU Q Q,FENG K,et al.Nucleated red blood cells as a novel biomarker in the diagnosis and prediction of sepsis severity in children[J]. Front Cell Infect Microbiol, 2023,13:1264607.
[45] DESAI S,JONES S L,TURNER K L,et al.Nucleated red blood cells are associated with a higher mortality rate in patients with surgical sepsis[J]. Surg Infect,2012, 13(6):360-365.
[46] CHEN J,QIAO Y D,LI X,et al.Intratumoral CD45+CD71⁺ erythroid cells induce immune tolerance and predict tumor recurrence in hepatocellular carcinoma[J]. Cancer Lett,2021,499:85-98.
[47] LI T J,LI H,ZHANG W H,et al.Human splenic TER cells: A relevant prognostic factor acting via the artemin-GFRα3-ERK pathway in pancreatic ductal adenocarcinoma[J]. Int J Cancer,2021,148(7): 1756-1767.
[48] NAMDAR A,DUNSMORE G,SHAHBAZ S,et al.CD71⁺ erythroid cells exacerbate HIV-1 susceptibility,mediate trans-infection,and harbor infective viral particles[J]. mBio,2019,10(6):e02767-19.
[49] SHAHBAZ S,XU L,OSMAN M,et al.Erythroid precursors and progenitors suppress adaptive immunity and get invaded by SARS-CoV-2[J]. Stem Cell Reports, 2021,16(5):1165-1181.
[50] RINCHAI D,ALTMAN M C,KONZA O,et al.Definition of erythroid cell-positive blood transcriptome phenotypes associated with severe respiratory syncytial virus infection[J]. Clin Transl Med,2020,10(8):e244.
[51] DUNSMORE G,KOLEVA P,GHOBAKHLOO N,et al.Lower abundance and impaired function of CD71⁺ erythroid cells in inflammatory bowel disease patients during pregnancy[J]. J Crohns Colitis,2019,13(2):230-244.
[52] ELAHI S.Neglected cells: immunomodulatory roles of CD71⁺ erythroid cells[J]. Trends Immunol,2019,40(3): 181-185.
[53] SELEDTSOV V I,SELEDTSOVA G V,SAMARIN D M, et al.Characterization of erythroid cell-derived natural suppressor activity[J]. Immunobiology,1998,198(4): 361-374.
[54] SHAHBAZ S,BOZORGMEHR N,KOLEVA P,et al.CD71⁺VISTA+ erythroid cells promote the development and function of regulatory T cells through TGF-β[J]. PLoS Biol,2018,16(12):e2006649.
[55] RINCON M R,OPPENHEIMER K,BONNEY E A.Selective accumulation of Th2-skewing immature erythroid cells in developing neonatal mouse spleen[J]. Int J Biol Sci,2012,8(5):719-730.
[56] CUI L L,TAKADA H,TAKIMOTO T,et al.Immunoregulatory function of neonatal nucleated red blood cells in humans[J]. Immunobiology,2016,221(8): 853-861.
[57] DALEY D,MANI V R,MOHAN N,et al.Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance[J]. Nat Med,2017,23(5):556-567.
[58] SANO Y,YOSHIDA T,CHOO M K,et al.Multiorgan signaling mobilizes tumor-associated erythroid cells expressing immune checkpoint molecules[J]. Mol Cancer Res,2021,19(3):507-515.
[59] GRZYWA T M,SOSNOWSKA A,MATRYBA P,et al.Myeloid cell-derived arginase in cancer immune response[J]. Front Immunol,2020,11:938.
[60] GHAFFARI S.Oxidative stress in the regulation of normal and neoplastic hematopoiesis[J]. Antioxid Redox Signal,2008,10(11):1923-1940.
[61] ZHAO B B,MEI Y,YANG J,et al.Erythropoietin-regulated oxidative stress negatively affects enucleation during terminal erythropoiesis[J]. Exp Hematol,2016, 44(10):975-981.
[62] CHATTERJEE S,SAXENA R K.Preferential elimination of older erythrocytes in circulation and depressed bone marrow erythropoietic activity contribute to cadmium induced Anemia in mice[J]. PLoS One,2015,10(7): e0132697.
[63] DOTY R T,PHELPS S R,SHADLE C,et al.Coordinate expression of heme and globin is essential for effective erythropoiesis[J]. J Clin Invest,2015,125(12): 4681-4691.
[64] ZHAO L T,HE R,LONG H X,et al.Late-stage tumors induce Anemia and immunosuppressive extramedullary erythroid progenitor cells[J]. Nat Med,2018,24(10): 1536-1544.
[65] 杨晓樨,赵营营,马吉芳,等. 硅芯片纳米微流体技术与磁激活细胞分选法对胎儿有核红细胞富集效果的比较[J]. 临床输血与检验,2024,26(1):86-91.

有核红细胞在疾病诊断及预后评估中的作用研究进展^*

The Role of Nucleated Red Blood Cells in Diagnosis and Prognosis

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 3

编辑推荐

Metrics

本文评价

关于本刊

作者中心

在线期刊

访问统计

联系我们

[1]	马筱洁, 陈伟. 静脉血栓栓塞症潜在生物标志物的研究进展^*[J]. 临床输血与检验, 2025, 27(1): 135-139.
[2]	杨晓樨, 赵营营, 马吉芳, 于政. 硅芯片纳米微流体技术与磁激活细胞分选法对胎儿有核红细胞富集效果的比较[J]. 临床输血与检验, 2024, 26(1): 86-91.
[3]	陈琪. 血清HE4联合CA125检测在卵巢癌早期诊断及预后评估中的临床价值[J]. 临床输血与检验, 2016, 18(5): 478-481.