Anti-Pituitary and Anti-Hypothalamus Autoantibody Associations with Inflammation and Persistent Hypogonadotropic Hypogonadism in Men with Traumatic Brain Injury.
Anti-Pituitary and Anti-Hypothalamus Autoantibody Associations with Inflammation and Persistent Hypogonadotropic Hypogonadism in Men with Traumatic Brain Injury.
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抗垂体和抗下丘脑自身抗体与创伤性脑损伤男性炎症和持续性低促性腺激素性腺功能减退症的关联。
DOI：
10.1089/neu.2019.6780
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发表时间：
2020
影响因子：
4.2
通讯作者：
Wagner,AmyK
中科院分区：
文献类型：
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作者：
Vijapur,SushuptaM;Yang,Zhihui;Barton,DavidJ;Vaughan,Leah;Awan,Nabil;Kumar,RajG;Oh,Byung-Mo;Berga,SarahL;Wang,KevinK;Wagner,AmyK
创伤性脑损伤（TBI）可导致持续性低促性腺激素性性腺功能减退症（PHH）和不良预后。我们假设自身免疫和炎症机制导致 PHH 发病机制。将患有中度至重度 TBI 的男性 (n= 143) 与健康男性 (n= 39) 进行比较。 TBI 组在受伤后 1-12 个月提供血液样本 (n= 1225)。对 TBI 和健康对照 (n=≥39) 样本进行睾酮 (T) 和黄体生成素 (LH) 测定，以判断 PHH 状态。对受伤后 1-6 个月的 TBI 样本和对照样本进行免疫球蛋白 M (IgM)/免疫球蛋白 G (IgG) 抗垂体自身抗体 (APA) 和抗下丘脑自身抗体 (AHA) 的检测。通过免疫组织化学 (IHC) 证实了 APA 和 AHA 的组织抗原特异性。评估神经胶质原纤维酸性蛋白 (GFAP) (AGA) 的 IgM 和 IgG 自身抗体，以测量 APA 和 AHA 的产生作为对 TBI 的广义自身免疫反应，并评估 APA 和 AHA 对 PHH 状态的特异性。使用炎症标记物组来评估与自身抗体谱和 PHH 状态的关系。 51 名患有 TBI 的男性 (36%) 患有 PHH。观察到 TBI 和 PHH 状态与年龄相关的 T 水平下降。受伤男性的 APA IgM、APA IgG、AHA IgM、AHA IgG、AGA IgM 和 AGA IgG 高于对照组（所有比较 p< 0.0001）。然而，在多变量分析中，PHH 组中只有 APA IgM (p= 0.03) 和 AHA IgM (p= 0.03) 水平低于非 PHH 组。 PHH 状态的 IgG 水平没有差异。多种炎症标志物与 IgM 自身抗体的产生呈正相关。 PHH 与较高的可溶性肿瘤坏死因子受体 I/II（sTNFRI、sTNFRII）相关，受激活、正常 T 细胞表达和分泌 (RANTES) 以及可溶性白细胞介素 2-受体-α (sIL-2Rα) 水平的调节。在没有 PHH 的情况下，较高的 IgM APA 和 AHA（但不是 AGA）可能表明神经内分泌组织特异性 IgM 自身抗体的产生对 TBI 后 PHH 的发展具有有益或修复作用。
Traumatic brain injury (TBI) and can lead to persistent hypogonadotropic hypogonadism (PHH) and poor outcomes. We hypothesized that autoimmune and inflammatory mechanisms contribute to PHH pathogenesis. Men with moderate-to-severe TBI (n= 143) were compared with healthy men (n= 39). The TBI group provided blood samples 1–12 months post-injury (n= 1225). TBI and healthy control (n= 39) samples were assayed for testosterone (T) and luteinizing hormone (LH) to adjudicate PHH status. TBI samples 1–6 months post-injury and control samples were assayed for immunoglobulin M (IgM)/immunoglobulin G (IgG) anti-pituitary autoantibodies (APA) and anti-hypothalamus autoantibodies (AHA). Tissue antigen specificity for APA and AHA was confirmed via immunohistochemistry (IHC). IgM and IgG autoantibodies for glial fibrillary acid protein (GFAP) (AGA) were evaluated to gauge APA and AHA production as a generalized autoimmune response to TBI and to evaluate the specificity of APA and AHA to PHH status. An inflammatory marker panel was used to assess relationships to autoantibody profiles and PHH status. Fifty-one men with TBI (36%) had PHH. An age-related decline in T levels by both TBI and PHH status were observed. Injured men had higher APA IgM, APA IgG, AHA IgM, AHA IgG, AGA IgM, and AGA IgG than controls (p< 0.0001 all comparisons). However, only APA IgM (p= 0.03) and AHA IgM (p= 0.03) levels were lower in the PHH than in the non-PHH group in multivariate analysis. There were no differences in IgG levels by PHH status. Multiple inflammatory markers were positively correlated with IgM autoantibody production. PHH was associated with higher soluble tumor-necrosis-factor receptors I/II, (sTNFRI, sTNFRII), regulated on activation, normal T-cell expressed and secreted (RANTES) and soluble interleukin-2-receptor-alpha (sIL-2Rα) levels. Higher IgM APA, and AHA, but not AGA, in the absence of PHH may suggest a beneficial or reparative role for neuroendocrine tissue-specific IgM autoantibody production against PHH development post-TBI.