Defining the role of Porphyromonas gingivalis peptidylarginine deiminase (PPAD) in rheumatoid arthritis through the study of PPAD biology.
Defining the role of Porphyromonas gingivalis peptidylarginine deiminase (PPAD) in rheumatoid arthritis through the study of PPAD biology.
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DOI：
10.1136/annrheumdis-2014-205385
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发表时间：
2015-11
影响因子：
27.4
通讯作者：
Andrade F
中科院分区：
文献类型：
--
作者：
Konig MF;Paracha AS;Moni M;Bingham CO 3rd;Andrade F
瓜氨酸化蛋白（ACPA）抗体是类风湿性关节炎（RA）的标志。牙龈卟啉单胞菌肽基精氨酸脱亚胺酶（PPAD）通过产生瓜氨酸化新抗原和自身瓜氨酸化能力参与RA的起始。确定瓜氨酸状态和牙龈卟啉单胞菌中PPAD的生物学，并描述RA和相关牙周病（PD）中抗PPAD抗体反应的特征。通过免疫印迹和质谱分析牙龈卟啉单胞菌细胞和培养上清液中的PPAD以检测瓜氨酸。重组PPAD（rPPAD）、失活突变体PPAD（rPPAD C351 S）和N端截短型PPAD（rPPAD Ntx）在大肠杆菌中克隆和表达。通过ELISA测定RA患者和健康对照的瓜氨酸化rPPAD和未修饰的rPPAD C351 S的IgG抗体。抗PPAD抗体与抗CCP 3抗体水平、RA疾病活动性和PD状态相关。来自牙龈卟啉单胞菌的PPAD在N-和C-末端结构域处被截短，并且不被瓜氨酸化。只有当在大肠杆菌中人工表达时，全长rPPAD，而不是截短的（完全活性的）rPPANDNtx，才是自瓜氨酸化的。抗PPAD抗体对瓜氨酸化rPPAD没有显示出增强的反应性，但仅针对未修饰的酶。抗PPAD抗体与抗CCP抗体水平和RA疾病活动性无关。相比之下，抗PPAD抗体水平显着降低RA患者PD。PPAD自身瓜氨酸酶不是连接PD和RA的潜在机制。N-末端加工保护PPAD免受自身瓜氨酸酶的影响，并增强酶活性。抗PPAD抗体可能对RA患者PD的发生具有保护作用。
Antibodies to citrullinated proteins (ACPAs) are a hallmark of rheumatoid arthritis (RA). Porphyromonas gingivalis peptidylarginine deiminase (PPAD) has been implicated in the initiation of RA by generating citrullinated neoantigens and due to its ability to autocitrullinate. To define the citrullination status and biology of PPAD in P gingivalis and to characterize the anti-PPAD antibody response in RA and associated periodontal disease (PD). PPAD in P gingivalis cells and culture supernatant was analyzed by immunoblotting and mass spectrometry to detect citrullination. Recombinant PPAD (rPPAD), inactive mutant PPAD (rPPADC351S), and N-terminal truncated PPAD (rPPADNtx) were cloned and expressed inE coli. Patients with RA and healthy controls were assayed for IgG antibodies to citrullinated rPPAD and unmodified rPPADC351S by ELISA. Anti-PPAD antibodies were correlated with anti-CCP3 antibody levels, RA disease activity, and PD status. PPAD from P gingivalis is truncated at the N- and C-terminal domains and not citrullinated. Only when artificially expressed in E coli, full-length rPPAD, but not truncated (fully active) rPPADNtx, is autocitrullinated. Anti-PPAD antibodies show no heightened reactivity to citrullinated rPPAD, but are exclusively directed against the unmodified enzyme. Antibodies against PPAD do not correlate with anti-CCP levels and disease activity in RA. By contrast, anti-PPAD antibody levels are significantly decreased in RA patients with PD. PPAD autocitrullination is not the underlying mechanism linking PD and RA. N-terminal processing protects PPAD from autocitrullination and enhances enzyme activity. Anti-PPAD antibodies may have a protective role for the development of PD in RA patients.
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影响因子：
4.9
作者：
Arvikar SL;Collier DS;Fisher MC;Unizony S;Cohen GL;McHugh G;Kawai T;Strle K;Steere AC
通讯作者：
Steere AC
影响因子：
3.1
作者：
Kuboniwa, M;Amano, A;Hamada, S
通讯作者：
Hamada, S
影响因子：
3
作者：
NIEDERMAN, R;BRUNKHORST, B;RYDER, MI
通讯作者：
RYDER, MI
影响因子：
9.4
作者：
Griffen, AL;Lyons, SR;Leys, EJ
通讯作者：
Leys, EJ
影响因子：
3.1
作者：
Gibson, FC;Genco, CA
通讯作者：
Genco, CA