Bikunin (Bkn) isoforms are serum chondroitin sulfate (CS) proteoglycans synthesized by the liver. They include two light forms, that is, the Bkn core protein and the Bkn linked to the CS chain (urinary trypsin inhibitor [UTI]), and two heavy forms, that is, pro‐α‐trypsin inhibitor and inter‐α‐trypsin inhibitor, corresponding to UTI esterified by one or two heavy chains glycoproteins, respectively. We previously showed that the Western‐blot analysis of the light forms could allow the fast and easy detection of patients with linkeropathy, deficient in enzymes involved in the synthesis of the initial common tetrasaccharide linker of glycosaminoglycans. Here, we analyzed all serum Bkn isoforms in a context of congenital disorders of glycosylation (CDG) and showed very specific abnormal patterns suggesting potential interests for their screening and diagnosis. In particular, genetic deficiencies in V‐ATPase (ATP6V0A2‐CDG, CCDC115‐CDG, ATP6AP1‐CDG), in Golgi manganese homeostasis (TMEM165‐CDG) and in the N‐acetyl‐glucosamine Golgi transport (SLC35A3‐CDG) all share specific abnormal Bkn patterns. Furthermore, for each studied linkeropathy, we show that the light abnormal Bkn could be further in‐depth characterized by two‐dimensional electrophoresis. Moreover, besides being interesting as a specific biomarker of both CDG and linkeropathies, Bkn isoforms' analyses can provide new insights into the pathophysiology of the aforementioned diseases.

中文翻译：

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先天性糖基化和连接病变中的血清 bikunin 异构体。

Bikunin (Bkn) 异构体是由肝脏合成的血清硫酸软骨素 (CS) 蛋白聚糖。它们包括两种轻质形式，即 Bkn 核心蛋白和与 CS 链相连的 Bkn（尿胰蛋白酶抑制剂 [UTI]），以及两种重质形式，即原α-胰蛋白酶抑制剂和间α-胰蛋白酶抑制剂，对应于分别被一个或两个重链糖蛋白酯化的UTI。我们之前表明，对光形式的蛋白质印迹分析可以快速、轻松地检测出患有链节病的患者，这些患者缺乏参与糖胺聚糖初始常见四糖接头合成的酶。这里，我们在先天性糖基化障碍 (CDG) 的背景下分析了所有血清 Bkn 同种型，并显示出非常具体的异常模式，表明其筛查和诊断的潜在兴趣。特别是 V-ATP 酶（ATP6V0A2-CDG、CCDC115-CDG、ATP6AP1-CDG）、高尔基锰稳态（TMEM165-CDG）和N-乙酰氨基葡萄糖高尔基体转运 (SLC35A3-CDG) 都具有特定的异常 Bkn 模式。此外，对于每个研究的链接病变，我们表明光异常 Bkn 可以通过二维电泳进一步深入表征。此外，除了作为 CDG 和连接病变的特异性生物标志物之外，Bkn 异构体的分析还可以为上述疾病的病理生理学提供新的见解。