[1]张 琪,刘华蔚.复发性口腔溃疡患儿血清IRF4，RANKL水平与其他免疫学指标相关性及对再复发的预测价值[J].现代检验医学杂志,2025,40(01):110-115.[doi:10.3969/j.issn.1671-7414.2025.01.021]
　ZHANG Qi,LIU Huawei.Predictive Value of Serum IRF4 and RANKL Levels for Recurrence and Correlation with other Immunological Indicators in Children with Recurrent Oral Ulcers after Treatment[J].Journal of Modern Laboratory Medicine,2025,40(01):110-115.[doi:10.3969/j.issn.1671-7414.2025.01.021]
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复发性口腔溃疡患儿血清IRF4，RANKL水平与其他免疫学指标相关性及对再复发的预测价值()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第40卷
期数:
2025年01期
页码:
110-115
栏目:
论著
出版日期:
2025-01-15

文章信息/Info

Title:
Predictive Value of Serum IRF4 and RANKL Levels for Recurrence and Correlation with other Immunological Indicators in Children with Recurrent Oral Ulcers after Treatment
文章编号:
1671-7414（2025）01-110-06
作者:
张 琪1; 刘华蔚2
（1. 首都医科大学附属北京朝阳医院口腔科，北京 100020；2. 解放军总医院第一医学中心口腔颌面外科，北京 100853）
Author(s):
ZHANG Qi1; LIU Huawei2
（1. Department of Stomatology，Beijing Chaoyang Hospital，Capital Medical University，Beijing 100020，China；2. Department of Oral and Maxillofacial Surgery，the First Medical Center of PLA General Hospital，Beijing 100853，China）
关键词:
复发性口腔溃疡; 干扰素调节因子4; 核因子κB 受体活化因子配体
分类号:
R781.5；R392.11
DOI:
10.3969/j.issn.1671-7414.2025.01.021
文献标志码:
A
摘要:
目的 探究血清干扰素调节因子4（IRF4）、核因子κB 受体活化因子配体（RANKL）水平与其他免疫学指标相关性及对复发性口腔溃疡患儿再复发的预测价值。方法 选取首都医科大学附属北京朝阳医院2019年1 月～ 2022 年6 月收治的复发性口腔溃疡患儿80 例为病例组，根据随访结果分为未复发组（n=61）和复发组（n=19），另选取同期进行体检的口腔健康志愿者49 例为对照组。采用ELISA 检测血清IRF4，RANKL 水平，收集并分析患者一般临床资料。Logistic 回归分析复发性口腔溃疡患儿复发的影响因素，Pearson 法分析IRF4，RANK 与免疫学指标的相关性，绘制受试者工作特征（ROC）曲线分析血清IRF4，RANKL 水平对复发性口腔溃疡患儿治疗后复发的预测价值。结果 与对照组相比，复发组、未复发组的IRF4（9.67±1.03 ng/ml，7.86±0.92 ng/ml vs 6.19±0.71 ng/ml），RANK（192.95±19.86 pg/ml，152.56±15.98 pg/ml vs 83.96±9.85 pg/ml） 水平显著升高，且与未复发组相比，复发组的IRF4，RANKL 水平显著升高，差异具有统计学意义（F=121.514，487.250，均P ＜ 0.05）。两组患儿的炎症因子白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6） 以及CD4 ＋，CD4 ＋ /CD8 ＋ 之间差异具有统计学差异（t=6.926 ～ 15.648， 均P ＜ 0.05）。Logistic 回归分析IRF4[OR（95%CI）：1.529（1.079 ～ 2.167）]，RANKL[OR（95%CI）：1.421（1.049 ～ 1.925）]，IL-1β[OR（95%CI）：1.322（1.007 ～ 1.736）] 均为影响复发性口腔溃疡患儿治疗后复发的危险因素（均P ＜ 0.05），CD4＋[OR（95%CI）：0.788（0.641 ～ 0.968）] 为影响复发性口腔溃疡患儿治疗后复发的保护因素（P ＜ 0.05）。Pearson 相关性分析，IRF4，RANKL 与炎症因子呈正相关（r=0.453 ～ 0.533，均P ＜ 0.05），与CD4＋（r=-0.407，-0.409）和CD4＋ /CD8 ＋（r=-0.425，-0.412）呈负相关（均P ＜ 0.05）。ROC 曲线结果显示血清IRF4，RANK 以及联合预测复发性口腔溃疡患儿复发的AUC（95%CI）分别为0.840（0.741 ～ 0.913），0.832（0.732 ～ 0.906），0.928（0.847 ～ 0.974），联合预测显著优于IRF4，RANKL 单独预测（Z=1.984，2.071，P=0.047，0.038）。结论 复发性口腔溃疡患儿血清IRF4，RANKL 水平显著升高，均为影响患儿治疗后复发的危险因素，对患儿治疗后复发具有一定辅助预测价值。
Abstract:
Objective To investigate the predictive value of serum interferon regulatory factor 4 (IRF4) and receptor activator of nuclear factor-κB ligand (RANKL) levels for recurrence and correlation with other immunological indicators in children with recurrent oral ulcers after treatment. Methods Eighty children with recurrent oral ulcers admitted to Beijing Chaoyang Hospital，Capital Medical University from January 2019 to June 2022 were collected as the diseased group. They were separated into a nonrecurrent group (n=61) and a recurrent group (n=19) based on follow-up results. Additionally, 49 oral health volunteers who underwent physical examinations were regarded as the control group. ELISA was applied to detect serum levels of IRF4 and RANKL. General clinical data of patients were collected and analyzed. Multivariate logistic regression was applied to analyze the factors affecting the recurrence of children with recurrent oral ulcers. The Pearson method was applied to analyze the correlation between IRF4, RANKL, and immunological indicators. The receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of serum IRF4 and RANKL levels for recurrence in children with recurrent oral ulcers after treatment. Results Compared with the control group, the levels of IRF4(9.67±1.03ng/ml，7.86±0.92ng/ml vs 6.19±0.71ng/ml) and RANK(192.95±19.86pg/ml，152.56±15.98pg/ml vs 83.96±9.85pg/ml) in the non recurrent group and the recurrent group，compared with the non recurrent group, the levels of IRF4 and RANKL in the recurrent group were increased，and the differences were statistically significant (F=121.514, 487.250, all P<0.05). There were statistical difference between the two groups in terms of inflammatory factors such as IL-1β, TNF-α, IL-6 and CD4+，CD4+/ CD8+(t=6.926 ～ 15.648，all P<0.05). Logistic regression analysis, IRF4[OR(95%CI)：1.529(1.079 ～ 2.167)]， RANKL[OR(95%CI)：1.421(1.049 ～ 1.925)] and IL-1β[OR(95%CI)：1.322(1.007 ～ 1.736)] were all risk factors for recurrence in children with recurrent oral ulcers ( all P<0.05)，while CD4+[OR(95%CI)：0.788(0.641 ～ 0.968)] was protective factor for recurrence in children with recurrentoral ulcers (P<0.05). Pearson correlation analysis,IRF4,RANKL were positively correlated with inflamnatory factors (r=0.453 ～ 0.533, all P<0.05). CD4+ (r=-0.407，-0.409) and CD4+/CD8+ (r=-0.425，-0.412) were positively correlated with inflammatory factors (P<0.05), ROC curve results revealed that the AUC(95%CI)of serum IRF4, RANK, and their combination in predicting recurrence in children with recurrent oral ulcers was 0.840(0.741 ～ 0.913)， 0.832(0.732 ～ 0.906) and 0.928(0.847 ～ 0.974) respectively. The combined prediction was better than that of IRF4 and RANKL alone prediction（Z=1.984，2.071，P=0.047，0.038）. Conclusion The serum levels of IRF4 and RANKL in children with recurrent oral ulcers obviously increase, both of which are risk factors affecting recurrence in children after treatment, and have certain auxiliary predictive values for recurrence in children after treatment.

参考文献/References:

[1] VERMA S, SRIKRISHNA K, SRISHTI K, et al. Recurrent oral ulcers and its association with stress among dental students in the northeast indian population: a cross-sectional questionnaire-based survey [J]. Cureus, 2023, 15(2): e34947.
[2] NOUJEIM Z, NASR L, HAJJ R, et al. Prevalence of recurrent oral ulcers and association with ABO/Rh group systems in a Lebanese sample[J]. Anais Brasileiros de Dermatologia, 2022, 97(3): 390-394.
[3] S?NCHEZ-BERNAL J, CONEJERO C, CONEJERO R. Recurrent aphthous stomatitis [J].Actas Dermo-Sifiliográficas (English Edition), 2020, 111(6): 471-480.
[4] GASMI BENAHMED A, NOOR S, MENZEL A, et al. Oral aphthous: pathophysiology, clinical aspects and medical treatment[J]. Archives of Razi Institute, 2021, 76(5): 1155-1163.
[5] WONG R W J, ONG J Z L, THEARDY M S, et al. IRF4 as an oncogenic master transcription factor[J]. Cancers, 2022, 14(17): 4314.
[6] SASAKI K, TERKER A S, PAN Yu, et al. Deletion of myeloid interferon regulatory factor 4 (Irf4) in mouse model protects against kidney fibrosis after ischemic injury by decreased macrophage recruitment and activation[J]. Journal of the American Society of Nephrology, 2021, 32(5): 1037-1052.
[7] TOBEIHA M, MOGHADASIAN M H, AMIN N, et al. RANKL/RANK/OPG pathway: a mechanism involved in exercise-induced bone remodeling[J]. BioMed Research International, 2020, 2020: 6910312.
[8] GLASNOVI? A, O’MARA N, KOVA?I? N, et al. RANK/RANKL/OPG signaling in the brain: a systematic review of the literature [J]. Frontiers in Neurology, 2020, 11: 590480.
[9] 李振华，李保双，刘启泉，等．消化系统常见病复发性口腔溃疡中医诊疗指南( 基层医生版)[J]. 中华中医药杂志，2019, 34(11):5284-5290． LI Zhenhua, LI Baoshuang, LIU Qiquan, et al．Clinical practice guideline of TCM for common digestive system diseases: recurrent oral ulcer(edition for primary physician)[J]．China Journal of Traditional Chinese Medicine and Pharmacy, 2019, 34(11): 5284-5290.
[10] 王薇，周煜奇.T 细胞亚群联合微量元素检测在诊断复发性口腔溃疡中的应用研究[J]．中国卫生检验杂志, 2020,30(10):1204-1206. WANG Wei, ZHOU Yuqi. Application of T cell subsets combined with trace element detection in the diagnosis of recurrent oral ulcer [J]. Chinese Journal of Health Laboratory Technology, 2020, 30(10): 1204-1206.
[11] YAN Hang, JIN Zhao, JIN Wenqin, et al. A systematic review and meta-analysis of acupuncture treatment for oral ulcer[J]. Medicine, 2020, 99(29): e21314.
[12] LIU Chuanxia, CHEN Qianming. Clinical diagnosis of oral erosive and ulcerative diseases in children[J]. Journal of Zhejiang University (Medical Sciences), 2021, 50(2): 155-161.
[13] AL MAMUN A, CHAUHAN A, QI Shaohua, et al. Microglial IRF5-IRF4 regulatory axis regulates neuroinflammation after cerebral ischemia and impacts stroke outcomes[J]. Proceedings of the National Academy of Sciences of the U S A, 2020, 117(3): 1742-1752.
[14] UMPREECHA C, BHALANG K, CHARNVANICH D, et al. Efficacy and safety of topical 0.1% cannabidiol for managing recurrent aphthous ulcers: a randomized controlled trial [J]. BMC Complementary Medicine and Therapies, 2023, 23(1): 57.
[15] ZIAEI S, RAEISI SHAHRAKI H, DADVAND DEHKORDI S. The association of recurrent aphthous stomatitis with general health and oral health related quality of life among dental students[J]. International Journal of Physiology Pathophysiology and Pharmacology, 2022, 14(4): 254-261.
[16] SRIVASTAVA A, GC S, PATHAK S, et al. Evidencebased effectiveness of herbal treatment modality for recurrent aphthous ulcers - a systematic review and meta-analysis [J].National Journal of Maxillofacial Surgery, 2021, 12(3): 303-310.
[17] LAU C B, SMITH G P. Recurrent aphthous stomatitis: A comprehensive review and recommendations on therapeutic options[J]. Dermatologic Therapy, 2022, 35(6): e15500.
[18] LU Jing, LIANG Taobao, LI Ping, et al. Regulatory effects of IRF4 on immune cells in the tumor microenvironment [J]. Frontiers in Immunology, 2023, 14(1): 1086803.
[19] YAN Hui, DAI Yulin, ZHANG Xiaolong, et al. The transcription factor IRF4 determines the anti-tumor immunity of CD8+ T cells [J]. iScience, 2023, 26(11): 108087.
[20] SUNDARARAJ S, CASAROTTO M G. Molecular interactions of IRF4 in B cell development and malignancies[J]. Biophysical Reviews, 2021, 13(6): 1219-1227.
[21] SCHLEUSSNER N, CAUCHY P, FRANKE V, et al. Transcriptional reprogramming by mutated IRF4 in lymphoma[J]. Nature Communications, 2023, 14(1): 6947.
[22] ONO T, HAYASHI M, SASAKI F, et al. RANKL biology: bone metabolism, the immune system, and beyond [J]. Inflammation and Regeneration, 2020, 40: 2.
[23] XING Baodi, YU Jie, ZHANG Huabing, et al. RANKL inhibition: a new target of treating diabetes mellitus?[J]. Therapeutic Advances in Endocrinology and Metabolism, 2023, 14:20420188231170754.
[24] WALSH M C, CHOI Y. Regulation of T cell-associated tissues and T cell activation by RANKL-RANKOPG[J]. Journal of Bone and Mineral Metabolism, 2021, 39(1): 54-63.
[25] ETHIRAJ P, SAMBANDAM Y, HATHAWAYSCHRADER J D, et al. RANKL triggers resistance to TRAIL-induced cell death in oral squamous cell carcinoma[J]. Journal of Cellular Physiology, 2020, 235(2): 1663-1673.

备注/Memo

备注/Memo:
作者简介：张琪（1995-)，女，本科，主要从事儿童口腔溃疡、老年牙周炎疾病的口腔研究，E- mail：o45wjc@163.com。
通讯作者：刘华蔚（1984-)，男，博士，副主任医师，主要从事颌骨缺损修复，面神经缺损修复方向，E- mail：m59rjs@163.com。
更新日期/Last Update: 2025-01-15