Swedish Medical Center, Englewood, CO, United States of America; Rocky Vista University, Parker, CO, United States of America; St. Anthony Hospital, Lakewood, CO, United States of America; Medical City Plano, Plano, TX, United States of America; Penrose Hospital, Colorado Springs, CO, United States of America; Research Medical Center, Kansas City, MO, United States of America.
Swedish Medical Center, Englewood, CO, United States of America; Rocky Vista University, Parker, CO, United States of America.
Clin Chim Acta. 2019 Dec;499:70-74. doi: 10.1016/j.cca.2019.08.034. Epub 2019 Aug 31.
Commercial solutions of human serum albumin (HSA) are administered to critically ill patients for the treatment of shock, restoration of blood volume, and the acute management of burns. Previously, conflicting results on the effects of HSA administration have been reported varying from a favorable increase in total plasma antioxidant capacity to a higher mortality rate in traumatic brain injury (TBI) patients. These results could be partially explained due to the known heterogeneity of HSA solutions. We report the discovery of S-sulfonated human transthyretin (hTTR) in HSA solutions.
Proteomics was performed on commercially available solutions of 5% HSA by LC-MS analysis. The MS charge envelope for hTTR was deconvolved to the uncharged native hTTR parent mass (13,762 Da). The parent mass was then integrated, and relative proportions of the 2 major species of hTTR, native and S-sulfonated hTTR (13,842 Da), were calculated.
The majority of hTTR found in 5% commercial HSA solutions is in the S-sulfonated form regardless of the age of the HSA solution. S-sulfonation of hTTR at the free cysteine residue in position 10 appears to be the result of a mixed disulfide exchange possibly with S-cysteinylated hTTR or S-cysteinylated HSA. hTTR is a tetramer composed of four identical monomers each containing a reduced cysteine residue in position 10. S-sulfonation of hTTR at this cysteine residue can destabilize the hTTR tetramer, an important step in the formation of TTR-related amyloid fibrils.
Administration of a commercial HSA solution that already contains S-sulfonated hTTR could potentially contribute to the development of amyloid-related/polyneuropathy in the critically ill.
人血清白蛋白（HSA）的商业制剂被用于治疗休克、恢复血容量和急性烧伤的危重症患者。先前，关于 HSA 给药的效果的报告结果相互矛盾，从总血浆抗氧化能力的有利增加到创伤性脑损伤（TBI）患者的死亡率更高不等。这些结果部分可以通过 HSA 制剂的已知异质性来解释。我们报告了在 HSA 溶液中发现 S-磺化人转甲状腺素蛋白（hTTR）。
通过 LC-MS 分析对 5%HSA 的市售制剂进行蛋白质组学分析。hTTR 的 MS 电荷包络被解卷积为未带电的天然 hTTR 母体质量（13762 Da）。然后对母体质量进行积分，并计算 hTTR 的 2 种主要形式，天然和 S-磺化 hTTR（13842 Da）的相对比例。
无论 HSA 溶液的年龄如何，在 5%的商业 HSA 溶液中发现的 hTTR 大多数都处于 S-磺化形式。位置 10 的游离半胱氨酸残基上的 hTTR 的 S-磺化似乎是混合二硫键交换的结果，可能与 S-半胱氨酸化的 hTTR 或 S-半胱氨酸化的 HSA 有关。hTTR 是由四个相同单体组成的四聚体，每个单体在位置 10 都含有一个还原的半胱氨酸残基。hTTR 上此半胱氨酸残基的 S-磺化可以使 hTTR 四聚体不稳定，这是形成 TTR 相关淀粉样纤维的重要步骤。
给予已经含有 S-磺化 hTTR 的商业 HSA 溶液可能会导致危重症患者发生与淀粉样变性相关的多发性神经病。
