Department of Biomedical Sciences, School of Dental Medicine, University of Nevada Las Vegas, Las Vegas, Nevada, USA.
Center for Oral Health Research, College of Dentistry, University of Kentucky, Lexington, Kentucky, USA.
J Periodontal Res. 2022 Aug;57(4):780-798. doi: 10.1111/jre.13000. Epub 2022 May 18.
This study used a nonhuman primate model of ligature-induced periodontitis to document the characteristics of immunoglobulin (Ig) gene usage in gingival tissues with disease and affected by age.
Adaptive immune responses to an array of oral bacteria are routinely detected in local gingival tissues and the systemic circulation across the human population. The level and diversity of antibody increases with periodontitis, reflecting the increased quantity of B cells and plasmacytes in the tissues at sites of periodontal lesions.
Macaca mulatta (n = 36) in four groups (young - ≤3 years; adolescent >3-7 years; adult - 12-15 years; aged - 17-23 years) were used in this study. Gingival tissues were sampled at baseline (health), 2 weeks (initiation), 1 and 3 months (progression), and 5 months (resolution) of the lesion development and transcriptomic analysis included 78 Ig-related genes.
The results demonstrated extensive variation in Ig gene usage patterns and changes with the disease process that was substantially affected by the age of the animal. Of note was that the aged animals generally demonstrated elevated expression on multiple Ig genes even in the baseline/healthy gingival tissues. The expression levels revealed 5 aggregates of Ig gene change profiles across the age groups. The number of gene changes were greatly increased in adult animals with the initiation of disease, while the young and adolescent animals showed extensive changes with disease progression. Elevated Ig gene transcripts remained with disease resolution except in the aged animals. The response profiles demonstrated selective heavy/light change gene transcripts that differed with age and clustering of the transcript expression was dominated by the age of the animals.
The results suggested potential critical variations in the molecular aspects of Ig gene expression in gingival tissues that can contribute to understanding the kinetics of periodontal lesions, as well as the variation in episodes, rapidity of progression, and role in resolution that are impacted by age.
本研究采用结扎诱导的牙周炎非人类灵长类动物模型，记录疾病相关和受年龄影响的牙龈组织中免疫球蛋白（Ig）基因使用的特征。
适应性免疫反应对一系列口腔细菌的检测在人类中是常规的，可在局部牙龈组织和全身循环中检测到。随着牙周炎的发展，抗体的水平和多样性增加，反映了组织中牙周病变部位的 B 细胞和浆细胞数量增加。
本研究使用了 4 组（年轻组 - ≤3 岁；青少年组 >3-7 岁；成年组 - 12-15 岁；老年组 - 17-23 岁）的猕猴（n=36）。在病变发展的 2 周（起始）、1 个月和 3 个月（进展）和 5 个月（缓解）时，对牙龈组织进行采样，并进行了转录组分析，包括 78 个 Ig 相关基因。
结果表明，Ig 基因使用模式存在广泛的变化，且随着疾病过程的变化受到动物年龄的显著影响。值得注意的是，即使在基线/健康的牙龈组织中，老年动物通常表现出多种 Ig 基因的高表达。表达水平揭示了 Ig 基因变化谱在年龄组中的 5 个聚集。随着疾病的开始，成年动物的基因变化数量大大增加，而年轻和青少年动物则在疾病进展中表现出广泛的变化。除了老年动物，在疾病缓解时，Ig 基因转录本仍然升高。反应谱显示出选择性的重链/轻链变化基因转录本，这些变化因年龄而异，且转录表达的聚类主要由动物的年龄决定。
结果表明，在牙龈组织中 Ig 基因表达的分子方面可能存在潜在的重要差异，这有助于理解牙周病损的动力学，以及受年龄影响的发病情况、进展速度和缓解作用的差异。
