新型体外检测方法可将胰岛素受体自身抗体与 B 型胰岛素抵抗患者的空腹胰岛素相关联。
A Novel In Vitro Assay Correlates Insulin Receptor Autoantibodies With Fasting Insulin in Type B Insulin Resistance.
机构信息
Institute for Experimental Endocrinology, Max Rubner Center (MRC) for Cardiovascular Metabolic Renal Research, Charité-Universitätsmedizin Berlin, D-10115, Berlin, Germany.
National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA.
出版信息
J Clin Endocrinol Metab. 2023 Aug 18;108(9):2324-2329. doi: 10.1210/clinem/dgad125.
CONTEXT
Severe insulin resistance (IR) in the presence of insulin receptor autoantibodies (InsR-aAb) is known as type B insulin resistance (TBIR). Considerable progress in therapy has been achieved, but diagnosis and monitoring of InsR-aAb remains a challenge.
OBJECTIVE
This work aimed to establish a robust in vitro method for InsR-Ab quantification.
METHODS
Longitudinal serum samples from patients with TBIR at the National Institutes of Health were collected. A bridge-assay for InsR-aAb detection was established using recombinant human insulin receptor as bait and detector. Monoclonal antibodies served as positive controls for validation.
RESULTS
The novel assay proved sensitive, robust, and passed quality control. The measured InsR-aAb from TBIR patients was associated with disease severity, decreased on treatment, and inhibited insulin signaling in vitro. Titers of InsR-aAb correlated positively to fasting insulin in patients.
CONCLUSION
Quantification of InsR-aAb from serum samples via the novel in vitro assay enables identification of TBIR and monitoring of successful therapy.
背景
存在胰岛素受体自身抗体（InsR-aAb）时的严重胰岛素抵抗（IR）被称为 B 型胰岛素抵抗（TBIR）。在治疗方面已经取得了相当大的进展，但 InsR-aAb 的诊断和监测仍然是一个挑战。
目的
本研究旨在建立一种用于 InsR-Ab 定量的可靠的体外方法。
方法
从美国国立卫生研究院的 TBIR 患者中收集纵向血清样本。使用重组人胰岛素受体作为诱饵和探测器建立了用于检测 InsR-aAb 的桥接测定法。单克隆抗体作为验证的阳性对照。
结果
新型检测法灵敏、稳健且通过了质量控制。从 TBIR 患者中测量的 InsR-aAb 与疾病严重程度相关，治疗后降低，并在体外抑制胰岛素信号传导。患者的 InsR-aAb 滴度与空腹胰岛素呈正相关。
结论
通过新型体外检测法从血清样本中定量 InsR-aAb 可识别 TBIR 并监测治疗的成功。
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