Division of Rheumatology, Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Republic of Korea.
Division of Rheumatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.
Sci Rep. 2022 Nov 16;12(1):19636. doi: 10.1038/s41598-022-21788-y.
Association between exposure to periodontal bacteria and development of autoantibodies related to rheumatoid arthritis (RA) has been widely accepted; however, direct causal relationship between periodontal bacteria and rheumatoid factor (RF) is currently not fully understood. We investigated whether periodontal bacteria could affect RF status. Patients with preclinical, new-onset, or chronic RA underwent periodontal examination, and investigation of subgingival microbiome via 16S rRNA sequencing. Degree of arthritis and RF induction was examined in collagen-induced arthritis (CIA) mice that were orally inoculated with different periodontal bacteria species. Subsequently, single-cell RNA sequencing analysis of the mouse spleen cells was performed. Patients with preclinical RA showed an increased abundance of the Porphyromonadacae family in the subgingival microbiome compared to those with new-onset or chronic RA, despite comparable periodontitis severity among them. Notably, a distinct subgingival microbial community was found between patients with high-positive RF and those with negative or low-positive RF (p=0.022). Oral infections with the periodontal pathogens P. gingivalis and Treponema denticola in CIA mice similarly enhanced arthritis score, but resulted in different levels of RF induction. Genes related to B cell receptor signaling, B cell proliferation, activation, and differentiation, and CD4 T cell costimulation and cytokine production were involved in the differential induction of RF in mice exposed to different bacteria. In summary, periodontal microbiome might shape RF status by affecting the humoral immune response during RA pathogenesis.
牙周细菌与类风湿关节炎 (RA) 相关自身抗体的发展之间的关联已被广泛接受；然而，牙周细菌与类风湿因子 (RF) 之间的直接因果关系目前尚未完全理解。我们研究了牙周细菌是否会影响 RF 状态。接受过临床前、新发或慢性 RA 检查的患者接受了牙周检查，并通过 16S rRNA 测序调查了龈下微生物组。通过口腔接种不同牙周细菌物种的胶原诱导关节炎 (CIA) 小鼠，检查关节炎程度和 RF 诱导。随后，对小鼠脾细胞进行单细胞 RNA 测序分析。与新发或慢性 RA 患者相比，临床前 RA 患者的龈下微生物组中卟啉单胞菌科的丰度增加，尽管他们的牙周炎严重程度相当。值得注意的是，高阳性 RF 患者和阴性或低阳性 RF 患者之间存在明显不同的龈下微生物群落（p=0.022）。CIA 小鼠中牙周病原体 P. gingivalis 和 Treponema denticola 的口腔感染同样增强了关节炎评分，但导致不同水平的 RF 诱导。在接触不同细菌的小鼠中，与 B 细胞受体信号、B 细胞增殖、激活和分化以及 CD4 T 细胞共刺激和细胞因子产生相关的基因参与了 RF 的差异诱导。总之，牙周微生物组可能通过影响 RA 发病过程中的体液免疫反应来塑造 RF 状态。
