Dissociation of systemic and mucosal autoimmunity in cystic fibrosis.
Dissociation of systemic and mucosal autoimmunity in cystic fibrosis.
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DOI：
10.1016/j.jcf.2019.06.006
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发表时间：
2020-03
影响因子：
5.2
通讯作者：
Rigby, W. F. C.
中科院分区：
文献类型：
--
作者：
Theprungsirikul, J.;Skopelja-Gardner, S.;Meagher, R. E.;Clancy, J. P.;Zemanick, E. T.;Ashare, A.;Rigby, W. F. C.
关键词：
铜绿假单胞菌约占囊性纤维化 (CF) 气道感染的 80%。它显示出与杀菌/通透性增加蛋白（BPI）自身抗体的存在存在显着的相关性，但这一点尚不清楚。在这项研究中，我们试图更好地了解全身和粘膜自身免疫的特征及其与铜绿假单胞菌体液免疫的关系。通过 ELISA 和/或免疫印迹，对成人和儿童 CF 患者 (n=131) 的血清和支气管肺泡灌洗液 (BAL) 中 BPI 和铜绿假单胞菌的抗体滴度和同种型进行了表征。血清 BPI 自身抗体在成人中常见（~43%），而在儿童（≤18 岁）CF 患者中罕见（<5%）。血清BPI IgG自身抗体具有高亲和力并且与抗P强相关。铜绿假单胞菌 IgG 反应。在成人和儿童 CF 患者的 BAL 中观察到 IgA 反应与 IgG 反应存在平行关系。因此，BAL IgA 抗 BPI 抗体与年龄无关，并且与 BAL 中 BPI 裂解的存在相关。 CF 患者对 BPI 的 IgG 和 IgA 自身反应性分别在血清和 BAL 中得到证实，并与对铜绿假单胞菌的抗体反应同种型相关。抗 BPI 和抗 P 的同时出现。小儿 CF 患者 BAL 中的铜绿假单胞菌 IgA（而非血清）表明，铜绿假单胞菌感染的气道中 BPI 耐受性被破坏，随后可能通过单独的途径诱导血清学 IgG 自身抗体。铜绿假单胞菌、BPI 裂解和 BAL 中 IgA 自身抗体之间的关系表明，隐性表位的生成在破坏耐受性中发挥着重要作用。
Pseudomonas aeruginosa accounts for ~80% of cystic fibrosis (CF) airway infection. It shows a remarkable correlation with presence of autoantibody to bactericidal/permeability-increasing protein (BPI), which is not understood. In this study, we sought to better understand the characteristics of systemic and mucosal autoimmunity and their relation to humoral immunity to P. aeruginosa. Antibody titers and isotypes to BPI and P. aeruginosa were characterized in sera and bronchoalveolar lavage (BAL) of adult and pediatric CF patients (n=131), by ELISA and/or immunoblot. Serum BPI autoantibodies were common (~43%) in adult while rare (<5%) in pediatric (≤18yrs) CF patients. Serum BPI IgG autoantibodies were of high avidity and strongly correlated with anti-P. aeruginosa IgG responses. A parallel relationship was observed with IgA, but not IgG, responses in adult and pediatric CF patient in the BAL. Thus, BAL IgA anti-BPI antibodies were independent of age and correlated with the presence of BPI cleavage in BAL. IgG and IgA autoreactivity to BPI in CF patients was demonstrated in serum and BAL, respectively, and correlated with the isotype of the antibody response to P. aeruginosa. The co-occurrence of anti-BPI and anti-P. aeruginosa IgA in the BAL, but not serum, of pediatric CF patients suggests that BPI tolerance is broken in the P. aeruginosa-infected airway and that serologic IgG autoantibodies are later induced, potentially through a separate pathway. The relationship between P. aeruginosa, BPI cleavage, and IgA autoantibodies in the BAL suggests a role for cryptic epitope generation in the breaking of tolerance.
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影响因子：
4.1
作者：
Lindberg U;Carlsson M;Hellmark T;Segelmark M
通讯作者：
Segelmark M
神秘的表位如何触发自身免疫性？
影响因子：
15.3
作者：
Lanzavecchia, A
通讯作者：
Lanzavecchia, A
影响因子：
3.1
作者：
Aichele, Diana;Schnare, Markus;Gessner, Andre
通讯作者：
Gessner, Andre
影响因子：
8
作者：
Skopelja, Sladjana;Hamilton, B. JoNell;Rigby, William F. C.
通讯作者：
Rigby, William F. C.
影响因子：
8.3
作者：
Russell, Derek W.;Gaggar, Amit;Solomon, George M.
通讯作者：
Solomon, George M.