Differential immune response to xenobiotic‐modified self‐molecule in simple and connective tissue disease‐associated primary biliary cholangitis
Differential immune response to xenobiotic‐modified self‐molecule in simple and connective tissue disease‐associated primary biliary cholangitis
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单纯性和结缔组织病相关原发性胆汁性胆管炎中对异生素修饰自身分子的差异免疫反应
DOI：
10.1111/liv.15360
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发表时间：
2022-07
期刊：
影响因子：
--
通讯作者：
Zongwen Shuai
中科院分区：
文献类型：
--
作者：
Shangqing Ge;Qinyao Xu;Haiyan Li;Tihong Shao;Feng Zhong;Patrick S. C. Leung;Zongwen Shuai
我们先前的研究表明，2 - 辛炔酸（2OA）可能会改变丙酮酸脱氢酶复合物E2亚基（PDC - E2）中内硫辛酸（LA）结合域（ILD）的构象结构，导致单纯原发性胆汁性胆管炎（S - PBC）免疫耐受丧失。在此，我们进一步探究这种病因机制是否也适用于结缔组织病相关原发性胆汁性胆管炎（CTD - PBC）。
利用内含肽介导的蛋白质连接技术制备ILD、LA - ILD和2OA - ILD，并检测它们与124例S - PBC患者和132例CTD - PBC患者血清样本的反应性。通过酶联免疫吸附试验和免疫印迹法比较检测两组患者针对LA、2OA、LA - ILD和2OA - ILD的抗体以及针对LA、2OA和ILD抗体的同种型。
S - PBC中针对2OA的抗体百分比和反应性均显著高于CTD - PBC。两组之间针对2OA和LA的抗体分别具有相同的特征。值得注意的是，S - PBC中针对LA - ILD和2OA的抗体共存以及针对LA和2OA的抗体共存的频率均显著高于CTD - PBC，而S - PBC中无抗2OA抗体的抗LA抗体百分比明显低于CTD - PBC。此外，CTD - PBC中针对LA的抗体同种型主要是IgG，而S - PBC中该同种型主要是IgM。
外源性2OA在CTD - PBC中的致病作用可能不如在S - PBC中重要，这表明它们对PDC - E2的免疫不耐受涉及不同的潜在机制。
Our previous studies demonstrated that 2-octynoic acid (2OA) might alter the conformational structure of the inner lipoic acid (LA) binding domain (ILD) in the E2 subunit of pyruvate dehydrogenase complex (PDC-E2), leading to the loss of immune tolerance in simple primary biliary cholangitis (S-PBC). Here, we further explore if this etiological mechanism also accounts for connective tissue disease-associated PBC (CTD-PBC).Intein-mediated protein ligation was used to prepare ILD, LA-ILD and 2OA-ILD, and their reactivity with serum samples from 124 S-PBC and 132 CTD-PBC patients was examined. The antibodies to LA, 2OA, LA-ILD and 2OA-ILD, the isotypes of antibodies to LA, 2OA and ILD, were comparatively detected between the two patient groups by enzyme-linked immunosorbent assay and immunoblotting.Both the percentage and reactivity of antibody to 2OA in S-PBC were significantly higher than in CTD-PBC. Antibodies to 2OA and to LA between the two groups separately shared the same characteristics. Remarkably, coexistence of the antibodies to LA-ILD and to 2OA, and coexistence of the antibodies to LA and to 2OA in S-PBC were both significantly more frequent than in CTD-PBC, whereas the percentage of anti-LA antibody without anti-2OA antibody in S-PBC was markedly lower than in CTD-PBC. Moreover, the isotype of antibody to LA was predominantly IgG in CTD-PBC, whilst this isotype was mainly IgM in S-PBC.Xenobiotic 2OA might play less important pathogenic role in CTD-PBC than in S-PBC, suggesting that different underlying mechanisms are involved in their immune intolerance to PDC-E2.
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DOI：
10.1002/hep.29059
发表时间：
2017-05
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Shuai Z;Wang J;Badamagunta M;Choi J;Yang G;Zhang W;Kenny TP;Guggenheim K;Kurth MJ;Ansari AA;Voss J;Coppel RL;Invernizzi P;Leung PSC;Gershwin ME
通讯作者：
Gershwin ME
影响因子：
--
作者：
Petri, Michelle;Orbai, Ana-Maria;Alarcon, Graciela S.;Gordon, Caroline;Merrill, Joan T.;Fortin, Paul R.;Bruce, Ian N.;Isenberg, David;Wallace, Daniel J.;Nived, Ola;Sturfelt, Gunnar;Ramsey-Goldman, Rosalind;Bae, Sang-Cheol;Hanly, John G.;Sanchez-Guerrero, Jorge;Clarke, Ann;Aranow, Cynthia;Manzi, Susan;Urowitz, Murray;Gladman, Dafna;Kalunian, Kenneth;Costner, Melissa;Werth, Victoria P.;Zoma, Asad;Bernatsky, Sasha;Ruiz-Irastorza, Guillermo;Khamashta, Munther A.;Jacobsen, Soren;Buyon, Jill P.;Maddison, Peter;Dooley, Mary Anne;van vollenhoven, Ronald F.;Ginzler, Ellen;Stoll, Thomas;Peschken, Christine;Jorizzo, Joseph L.;Callen, Jeffrey P.;Lim, S. Sam;Fessler, Barri J.;Inanc, Murat;Kamen, Diane L.;Rahman, Anisur;Steinsson, Kristjan;Franks, Andrew G., Jr.;Sigler, Lisa;Hameed, Suhail;Fang, Hong;Ngoc Pham;Brey, Robin;Weisman, Michael H.;McGwin, Gerald, Jr.;Magder, Laurence S.
通讯作者：
Magder, Laurence S.
影响因子：
2.9
作者：
K. Wakabayashi;Zhe‐Xiong Lian;P. Leung;Y. Moritoki;K. Tsuneyama;Mark J. Kurth;Kit S. Lam;Katsunori Yoshida;Guo‐Xiang-X. Yang;T. Hibi;A. Ansari;W. Ridgway;R. Coppel;Ian R. Mackay;M. Gershwin
通讯作者：
K. Wakabayashi;Zhe‐Xiong Lian;P. Leung;Y. Moritoki;K. Tsuneyama;Mark J. Kurth;Kit S. Lam;Katsunori Yoshida;Guo‐Xiang-X. Yang;T. Hibi;A. Ansari;W. Ridgway;R. Coppel;Ian R. Mackay;M. Gershwin
影响因子：
27.4
作者：
van den Hoogen, Frank;Khanna, Dinesh;Pope, Janet E.
通讯作者：
Pope, Janet E.
影响因子：
29.4
作者：
Howard, MJ;Fuller, C;Yeaman, SJ
通讯作者：
Yeaman, SJ