Autoantibodies From Single Circulating Plasmablasts React With Citrullinated Antigens and Porphyromonas gingivalis in Rheumatoid Arthritis.
Autoantibodies From Single Circulating Plasmablasts React With Citrullinated Antigens and Porphyromonas gingivalis in Rheumatoid Arthritis.
复制标题
DOI：
10.1002/art.39455
复制
发表时间：
2016-03
期刊：
影响因子：
--
通讯作者：
Su K
中科院分区：
文献类型：
--
作者：
Li S;Yu Y;Yue Y;Liao H;Xie W;Thai J;Mikuls TR;Thiele GM;Duryee MJ;Sayles H;Payne JB;Klassen LW;O'Dell JR;Zhang Z;Su K
Anti–citrullinated protein antibodies (ACPAs) are highly specific for rheumatoid arthritis (RA). However, the molecular basis for ACPA production is still unclear. The purpose of this study was to determine if circulating plasmablasts from RA patients produce ACPAs and whether Porphyromonas gingivalis facilitates the generation of ACPAs. Using a single-cell antibody cloning approach, we generated 217 and 110 monoclonal recombinant antibodies from circulating plasmablasts from 7 RA patients and 4 healthy controls, respectively. Antibody reactivity with citrullinated antigens was tested by a second-generation anti–cyclic citrullinated peptide (anti-CCP) kit and by enzyme-linked immunosorbent assays (ELISAs) against citrullinated human antigens. Antibody reactivity with P gingivalis was tested by ELISAs against outer membrane antigens (OMAs) and citrullinated enolase from P gingivalis. Approximately 19.5% of plasmablast-derived antibodies from anti-CCP–positive RA patients, but none from 1 anti-CCP–negative RA patient or the healthy controls, specifically recognized citrullinated antigens. The immunoglobulin genes encoding these ACPAs were highly mutated, with increased ratios of replacement mutations to silent mutations, suggesting the involvement of active antigen selection in ACPA generation. Interestingly, 63% of the ACPAs cross-reacted with OMAs and/or citrullinated enolase from P gingivalis. The reactivity of ACPAs against citrullinated proteins from P gingivalis was confirmed by immunoblotting and mass spectrometry. Furthermore, some germline-reverted ACPAs retained their reactivity with P gingivalis antigens but completely lost their reactivity with citrullinated human antigens. These results suggest that circulating plasmablasts in RA patients produce ACPAs and that this process may be facilitated by anti–P gingivalis immune responses.
登录
查看更多内容
影响因子：
27.4
作者：
Quirke AM;Lugli EB;Wegner N;Hamilton BC;Charles P;Chowdhury M;Ytterberg AJ;Zubarev RA;Potempa J;Culshaw S;Guo Y;Fisher BA;Thiele G;Mikuls TR;Venables PJ
通讯作者：
Venables PJ
影响因子：
15.3
作者：
Samuels, J;Ng, YS;Meffre, E
通讯作者：
Meffre, E
影响因子：
--
作者：
Giudicelli, Veronique;Brochet, Xavier;Lefranc, Marie-Paule
通讯作者：
Lefranc, Marie-Paule
影响因子：
4.9
作者：
Kinloch, Andrew;Tatzer, Verena;Wait, Robin;Peston, David;Lundberg, Karin;Donatien, Phillipe;Moyes, David;Taylor, Peter C;Venables, Patrick J
通讯作者：
Venables, Patrick J
影响因子：
15.9
作者：
Kuhn, KA;Kulik, L;Holers, VM
通讯作者：
Holers, VM