Terminal complement complex formation is associated with intervertebral disc degeneration
Terminal complement complex formation is associated with intervertebral disc degeneration
复制标题
末端补体复合物的形成与椎间盘退变有关
DOI：
10.1007/s00586-020-06592-4
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发表时间：
2021
影响因子：
2.8
通讯作者：
Neidlinger-Wilke C
中科院分区：
文献类型：
--
作者：
Teixeira GQ;Yong Z;Goncalves RM;Kuhn A;Riegger-J;Brisby H;Henriksson HB;Barth T;Mauer UM;Ignatius A;Brenner R;Neidlinger-Wilke C
目的补体系统是先天免疫的重要组成部分。最近的研究表明，对组织的动态平衡和退化有意想不到的贡献。本研究首次探讨了补体激活产物补体末端补体复合体(TCC)及其抑制物CD59在人腰椎间盘组织中的沉积规律及其与退变程度的关系。方法收集腰椎间盘退变患者(n= 39，年龄63 ± 12)和青少年特发性脊柱侧弯(AIS，n= 10，年龄17 ± 4)患者的腰椎间盘组织标本，并与健康青年(n= 11，年龄7 ± 7)和老年(n= 10，年龄65 ± 15)供者的椎间盘组织进行比较。结果DD患者髓核(NP)、纤维环(AF)和终板(EP)中Tcc+细胞的百分率高于老年组(P<； )，青年组高于老年组(P<； 0.001)。在DD患者中，TCC沉积与Pfirmann分级呈正相关，但与MoDIC变化无关，而在年轻供者中，TCC沉积与年龄呈负相关，表明TCC不仅参与了DD，而且还参与了骨骼发育的早期阶段。CD 5 9阳性表达在AIS和DD组明显高于Young组(P<； 0.0 5)，且与患者年龄呈负相关。在DD中可能存在TCC的功能相关性，这代表了新疗法的潜在靶点。
PurposeThe complement system is a crucial part of innate immunity. Recent work demonstrated an unexpected contribution to tissue homeostasis and degeneration. This study investigated for the first time, in human disc tissues, the deposition profile of the complement activation product terminal complement complex (TCC), an inflammatory trigger and inducer of cell lysis, and its inhibitor CD59, and their correlation with the degree of disc degeneration (DD).MethodsDisc biopsies were collected from patients diagnosed with DD (n= 39, age 63 ± 12) and adolescent idiopathic scoliosis (AIS,n= 10, age 17 ± 4) and compared with discs from healthy Young (n= 11, age 7 ± 7) and Elder (n= 10, age 65 ± 15) donors. Immunohistochemical detection of TCC and CD59 in nucleus pulposus (NP), annulus fibrosus (AF) and endplate (EP) was correlated with age, Pfirrmann grade and Modic changes.ResultsHigher percentage of TCC+ cells was detected in the NP and EP of DD compared to Elder (P< 0.05), and in the EP of Young versus Elder (P< 0.001). In DD, TCC deposition was positively correlated with Pfirrmann grade, but not with Modic changes, whereas for Young donors, a negative correlation was found with age, indicating TCC’s involvement not only in DD, but also in early stages of skeletal development. Higher CD59 positivity was found in AIS and DD groups compared to Young (P< 0.05), and it was negatively correlated with the age of the patients.ConclusionTCC deposition positively correlated with the degree of disc degeneration. A functional relevance of TCC may exist in DD, representing a potential target for new therapeutics.
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影响因子：
6
作者：
Markiewski, Maciej M.;Lambris, John D.
通讯作者：
Lambris, John D.
在活动性类风湿性关节炎中，通过中性粒细胞 Fc gamma RIII、Fc gamma RII 和 CD59 发出的信号并未受损。
影响因子：
27.4
作者：
Jane Jones;I. Laffafian;Tom Lawson;Bryan D. Williams;Paul Morgan
通讯作者：
Paul Morgan
影响因子：
3.7
作者：
Andrades, JA;Nimni, ME;Sorgente, N
通讯作者：
Sorgente, N
影响因子：
7
作者：
Riegger, J.;Huber-Lang, M.;Brenner, R. E.
通讯作者：
Brenner, R. E.
影响因子：
16.8
作者：
Hajishengallis G;Lambris JD
通讯作者：
Lambris JD