Nephrology Research Group, Hospital Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
Nephrology Department, Hospital Vall d'Hebrón, Barcelona, Spain.
Sci Rep. 2020 Jan 24;10(1):1159. doi: 10.1038/s41598-020-58197-y.
Apolipoprotein A-Ib (ApoA-Ib) is a high molecular weight form of Apolipoprotein A-I (ApoA-I) found specifically in the urine of kidney-transplanted patients with recurrent idiopathic focal segmental glomerulosclerosis (FSGS). To determine the nature of the modification present in ApoA-Ib, we sequenced the whole APOA1 gene in ApoA-Ib positive and negative patients, and we also studied the protein primary structure using mass spectrometry. No genetic variations in the APOA1 gene were found in the ApoA-Ib positive patients that could explain the increase in its molecular mass. The mass spectrometry analysis revealed three extra amino acids at the N-Terminal end of ApoA-Ib that were not present in the standard plasmatic form of ApoA-I. These amino acids corresponded to half of the propeptide sequence of the immature form of ApoA-I (proApoA-I) indicating that ApoA-Ib is a misprocessed form of proApoA-I. The description of ApoA-Ib could be relevant not only because it can allow the automated analysis of this biomarker in the clinical practice but also because it has the potential to shed light into the molecular mechanisms that cause idiopathic FSGS, which is currently unknown.
载脂蛋白 A-Ib（ApoA-Ib）是载脂蛋白 A-I（ApoA-I）的高分子量形式，仅存在于复发性特发性局灶节段性肾小球硬化症（FSGS）的肾移植患者的尿液中。为了确定 ApoA-Ib 中存在的修饰的性质，我们对 ApoA-Ib 阳性和阴性患者的整个 APOA1 基因进行了测序，并且我们还使用质谱法研究了蛋白质的一级结构。在 ApoA-Ib 阳性患者中，未发现 APOA1 基因中的遗传变异可以解释其分子量的增加。质谱分析显示，ApoA-Ib 的 N 端末端有三个额外的氨基酸，而在标准的 ApoA-I 血浆形式中不存在。这些氨基酸对应于 ApoA-I 不成熟形式的前肽序列的一半（proApoA-I），表明 ApoA-Ib 是 proApoA-I 的错误加工形式。ApoA-Ib 的描述不仅可能因为它可以允许在临床实践中自动分析这种生物标志物，而且还因为它有可能揭示导致特发性 FSGS 的分子机制，目前尚不清楚。
