Autoantibodies against α-MSH, ACTH, and LHRH in anorexia and bulimia nervosa patients
Autoantibodies against α-MSH, ACTH, and LHRH in anorexia and bulimia nervosa patients
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DOI：
10.1073/pnas.222658699
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发表时间：
2002-12-24
影响因子：
11.1
通讯作者：
Hökfelt, T
中科院分区：
文献类型：
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作者：
Fetissov, SO;Hallman, J;Hökfelt, T
下丘脑弓状核参与能量摄入和支出的控制，可能参与神经性厌食症（AN）和神经性贪食症（BN）等饮食失调的发病机制。在这方面有两个系统特别令人感兴趣，分别是合成α-黑素细胞刺激激素（α-MSH）和合成神经肽Y。我们在此报告，在所研究的 57 名 AN 和/或 BN 患者中，有 42 名 (74%) 的血浆抗体与大鼠垂体中的促黑素细胞和/或促肾上腺皮质激素结合。在这些血清中，有 8 种被发现选择性地与 α-MSH 阳性神经元及其下丘脑和下丘脑外投射结合，如大鼠脑切片免疫染色所示。这些血清与 α-MSH 肽的吸附消除了这种免疫染色。在垂体中，免疫染色被 α-MSH 或促肾上腺皮质激素吸附阻断。此外，3份AN/BN血清与大鼠正中隆起的黄体生成素释放激素(LHRH)阳性末端结合，但其中只有2份被LHRH吸附。在对照受试者中，13 份血清中的 2 份 (16%) 显示出与 AN/BN 染色相似的结果。这些数据提供的证据表明，AN/BN 患者的一个重要亚群具有与 α-MSH 或促肾上腺皮质激素结合的自身抗体，这一发现也表明应激轴的参与。这些抗体是否干扰大脑黑皮质素回路/LHRH系统和/或与食物摄入调节相关的其他中枢和外周位点的正常信号转导，这些影响在多大程度上与AN/BN的病理生理学或临床表现有关和/或可能参与其中，以及压力增加在多大程度上是产生这些自身抗体的重要因素，仍有待确定。
The hypothalamic arcuate nucleus is involved in the control of energy intake and expenditure and may participate in the pathogenesis of eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). Two systems are of particular interest in this respect, synthesizing alpha-melanocyte-stimulating hormone (alpha-MSH) and synthesizing neuropeptide Y, respectively. We report here that 42 of 57 (74%) AN and/or BN patients studied had in their plasma Abs that bind to melanotropes and/or corticotropes in the rat pituitary. Among these sera, 8 were found to bind selectively to alpha-MSH-positive neurons and their hypothalamic and extrahypothalannic projections as revealed with immunostaining on rat brain sections. Adsorption of these sera with alpha-MSH peptide abolished this immunostaining. In the pituitary, the immunostaining was blocked by adsorption with alpha-MSH or adrenocorticotropic hormone. Additionally, 3 AN/BN sera bound to luteinizing hormone-releasing hormone (LHRH)-positive terminals in the rat median eminence, but only 2 of them were adsorbed with LHRH. In the control subjects, 2 of 13 sera (16%) displayed similar to AN/BN staining. These data provide evidence that a significant subpopulation of AN/BN patients have autoantibodies that bind to alpha-MSH or adrenocorticotropic hormone, a finding pointing also to involvement of the stress axis. It remains to be established whether these Abs interfere with normal signal transduction in the brain melanocortin circuitry/LHRH system and/or in other central and peripheral sites relevant to food intake regulation, to what extent such effects are related to and/or could be involved in the pathophysiology or clinical presentation of AN/BN, and to what extent increased stress is an important factor for production of these autoantibodies.