School of Dentistry, Cellular and Molecular Immunology Group/INMUBO, Universidad El Bosque, Bogotá, Colombia.
School of Medicine, Clinical Immunology Group, Universidad Militar Nueva Granada, Bogotá, Colombia.
Int J Rheum Dis. 2020 Dec;23(12):1698-1706. doi: 10.1111/1756-185X.13977. Epub 2020 Nov 4.
Antibodies against carbamylated proteins/peptide (CarP) have been associated with severity in rheumatoid arthritis (RA) patients. However, their role in risk groups, specific targets and relation with periodontal disease (PD) is uncertain yet. The aim of this study was evaluated the association between the levels of anti-CarP with clinical manifestation, human leukocyte antigen (HLA) alleles, periodontal activity markers, PD diagnosis, PD severity, and presence of Porphyromonas gingivalis (P gingivalis) in relatives of patients with RA.
One hundred and twenty-four individuals with a family history of RA in first-degree relatives (FDR) and 124 healthy individuals gender- and age-matched, RA activity was assessed. Antibodies against carbamylated protein anti-FCS-Carp and 2 carbamylated peptides of fibrinogen were selected (anti-Ca-Fib2, anti-Ca-Fib3).
Anti-FCS-Carp-positive, anti-Ca-Fib2 and anti-Ca-Fib3 were more frequent in FDR than controls (25.0% vs 14.5%, 34.7% vs 15.3% and 33.1% vs 11.3%, respectively). Anti-FCS-CarP were associated with the HLA-DRB1-SE* 1402 allele (P = .035) and highly sensitive C-reactive protein levels (P = .016), the anti-Ca-Fib2 antibodies were associated with the HLA-DRB1-SE* 1501 allele (P = .03), with non-SE* 0901 allele (P = .01), the anti-Ca-Fib3 was associated with positive rheumatoid factor (P = .0012). The FDR condition was associated with the presence of anti-Ca-Fib3 (odds ratio [OR] =4.7; 95% CI = 1.8-11.7; P = .001) and painful joints (OR = 2.2; 95% CI = 1.01-4.68; P = .045); we also detected an important trend toward the presence of P gingivalis (OR = 1.9; 95% CI = 0.9-3.7; P = .062).
The presence of anti-FCS-Carp, anti-Ca-Fib3 and anti-Ca-Fib2 antibodies may have a role for these antibodies as early biomarkers in the development of RA, probably including additional mechanisms related with other non-SE alleles; the anti-peptide antibodies proposed in the present study may represent a simpler way to identify antibodies directed to a specific target.
针对氨甲酰化蛋白/肽（CarP）的抗体与类风湿关节炎（RA）患者的严重程度有关。然而，它们在风险群体、特定靶点以及与牙周病（PD）的关系尚不确定。本研究旨在评估抗 CarP 水平与临床表现、人类白细胞抗原（HLA）等位基因、牙周活动标志物、PD 诊断、PD 严重程度以及 RA 患者一级亲属（FDR）中牙龈卟啉单胞菌（P.gingivalis）之间的关系。
选择 124 名有 RA 家族史的个体（FDR）和 124 名性别和年龄匹配的健康个体，评估 RA 活动。选择针对氨甲酰化蛋白抗 FCS-Carp 和 2 种纤维蛋白原氨甲酰肽的抗体（抗 Ca-Fib2、抗 Ca-Fib3）。
FDR 中抗-FCS-Carp 阳性、抗-Ca-Fib2 和抗-Ca-Fib3 的频率高于对照组（分别为 25.0%、34.7% 和 33.1% vs. 14.5%、15.3%和 11.3%）。抗-FCS-CarP 与 HLA-DRB1-SE1402 等位基因相关（P=0.035）和高敏 C 反应蛋白水平相关（P=0.016），抗-Ca-Fib2 抗体与 HLA-DRB1-SE1501 等位基因相关（P=0.03），与非 SE*0901 等位基因相关（P=0.01），抗-Ca-Fib3 与类风湿因子阳性相关（P=0.0012）。FDR 状态与抗-Ca-Fib3 的存在相关（比值比 [OR] =4.7；95%置信区间 [CI] =1.8-11.7；P=0.001）和疼痛关节（OR=2.2；95%CI=1.01-4.68；P=0.045）；我们还检测到 P 牙龈卟啉单胞菌存在的重要趋势（OR=1.9；95%CI=0.9-3.7；P=0.062）。
抗-FCS-Carp、抗-Ca-Fib3 和抗-Ca-Fib2 抗体的存在可能使这些抗体作为 RA 发展的早期生物标志物发挥作用，可能包括与其他非 SE 等位基因相关的额外机制；本研究中提出的抗肽抗体可能代表一种更简单的方法来识别针对特定靶标的抗体。
