Zanone M M, Banga J P, Peakman M, Edmonds M, Watkins P J
Diabetic Department, King's College Hospital, London, UK.
Diabet Med. 1994 May;11(4):378-83. doi: 10.1111/j.1464-5491.1994.tb00289.x.
Nerve growth factor (NGF) is required for development and maintenance of autonomic nervous function and is highly expressed in the iris. An association between sensory and autonomic diabetic neuropathy and NGF function has been postulated. In light of the evidence for an autoimmune component to the pathogenesis of autonomic neuropathy in Type 1 diabetes mellitus, an enzyme linked immunosorbent assay (ELISA) was established to investigate the presence of autoantibodies to mNGF in: 20 patients with long-standing Type 1 diabetes with abnormal autonomic function tests, of whom 14 had symptomatic autonomic neuropathy, 3 had an episode of iritis, and 6 had no autonomic symptoms; 9 age-matched patients with Type 1 diabetes and no complications; 10 healthy control subjects. Insulin antibodies by ELISA and autoantibodies to other endocrine targets were also measured. The specificity of anti-mNGF autoantibody ELISA was further confirmed by immunodepletion on mNGF-Sepharose 4B. No differences in antibody binding to mNGF were detected, between any of the patient groups and control subjects. There was no relationship between age, sex, and diabetes duration and mNGF binding. High levels of anti-mNGF autoantibodies were found in only one diabetic patient who had no evidence of neuropathy, raising the possibility that an autoimmune component to NGF might precede the development of autonomic dysfunction. It remains to be established whether autoantibodies to NGF play a role in diabetic autonomic neuropathy and prospective studies will be required to investigate whether the autoantibodies are a feature of evolving but not established neuropathy.
神经生长因子（NGF）对于自主神经功能的发育和维持是必需的，且在虹膜中高度表达。已有研究推测感觉性和自主性糖尿病神经病变与NGF功能之间存在关联。鉴于1型糖尿病自主神经病变发病机制中存在自身免疫成分的证据，建立了一种酶联免疫吸附测定（ELISA）法，以研究以下人群中抗小鼠神经生长因子（mNGF）自身抗体的存在情况：20例长期患有1型糖尿病且自主神经功能测试异常的患者，其中14例有症状性自主神经病变，3例有虹膜炎发作，6例无自主神经症状；9例年龄匹配的无并发症的1型糖尿病患者；10名健康对照者。还通过ELISA法检测了胰岛素抗体以及针对其他内分泌靶点的自身抗体。通过在mNGF-琼脂糖4B上进行免疫去除进一步证实了抗mNGF自身抗体ELISA的特异性。在任何患者组和对照者之间，均未检测到抗体与mNGF结合的差异。年龄、性别、糖尿病病程与mNGF结合之间均无关联。仅在一名无神经病变证据的糖尿病患者中发现了高水平的抗mNGF自身抗体，这增加了NGF自身免疫成分可能先于自主神经功能障碍发生的可能性。NGF自身抗体是否在糖尿病自主神经病变中起作用仍有待确定，并需要进行前瞻性研究以调查这些自身抗体是否是正在发展但尚未确诊的神经病变的一个特征。
