Hellin Joan Lopez, Bech-Serra Joan J, Moctezuma Enrique Lara, Chocron Sara, Santin Sheila, Madrid Alvaro, Vilalta Ramon, Canals Francesc, Torra Roser, Meseguer Anna, Nieto Jose L
Fisopatologia Renal, CIBBIM, Institut de Recerca, Hospital Vall d'Hebron, Barcelona, Spain.
Am J Kidney Dis. 2009 Nov;54(5):871-80. doi: 10.1053/j.ajkd.2009.07.011. Epub 2009 Sep 25.
Primary focal segmental glomerulosclerosis (FSGS) is a glomerular disease that frequently does not respond to treatment and progresses to kidney failure. FSGS can be of either genetic origin, caused by mutations in slit diaphragm proteins, such as podocin, or idiopathic origin of unknown cause.
Case series.
SETTING & PARTICIPANTS: Children with FSGS (aged 3-18 years); 15 with idiopathic and 11 with genetic forms of FSGS.
Genetic versus idiopathic forms.
OUTCOMES & MEASUREMENTS: Differentially expressed proteins in the plasma proteome, detected using 2-dimensional electrophoresis and identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, Western blot, and liquid chromatography electron spray ionization tandem mass spectrometry for fragmentation and identification of the peptides.
We found 3 very low-molecular-mass (9.2, 6.9, and 4.7 kDa; isoelectric point, 5.7) spots that were present in pooled samples from patients with genetic FSGS, but missing in patients with idiopathic FSGS and healthy individuals. Spots were identified using mass spectrometry as fragments of albumin, 2 of them apparently containing peptides from both C- and N-terminal parts of the whole protein. Proteomic analyses were carried out on all genetic patients individually; of these, 10 of 11 patients had > or =1 albumin fragment detected in the pool. We did not find an evident relationship between type of mutation or clinical status of patients and albumin fragments observed.
Very low-molecular-weight albumin fragments also can be produced by other diseases.
We describe for the first time the presence of very low-molecular-mass albumin fragments in plasma of patients with FSGS with podocyte protein mutations that are absent in patients with idiopathic FSGS or healthy individuals. Additional studies are necessary to determine whether these fragments could be potential biomarkers to distinguish between genetic and idiopathic forms of FSGS.
原发性局灶节段性肾小球硬化（FSGS）是一种肾小球疾病，常常对治疗无反应并进展为肾衰竭。FSGS 可能源于遗传，由裂孔隔膜蛋白（如足突蛋白）的突变引起，或者病因不明，属于特发性。
病例系列研究。
FSGS 患儿（年龄 3 - 18 岁）；15 例特发性 FSGS 患儿和 11 例遗传性 FSGS 患儿。
遗传性与特发性类型。
血浆蛋白质组中差异表达的蛋白质，通过二维电泳检测，并用基质辅助激光解吸/电离飞行时间质谱、蛋白质印迹法以及液相色谱电喷雾电离串联质谱对肽段进行碎裂和鉴定。
我们发现 3 个极低分子量（9.2、6.9 和 4.7 kDa；等电点 5.7）的斑点存在于遗传性 FSGS 患者的混合样本中，但在特发性 FSGS 患者和健康个体中缺失。通过质谱鉴定这些斑点为白蛋白片段，其中 2 个明显包含来自整个蛋白质 C 端和 N 端的肽段。对所有遗传性患者个体进行了蛋白质组分析；其中，11 例患者中有 10 例在混合样本中检测到≥1 个白蛋白片段。我们未发现患者的突变类型或临床状态与观察到的白蛋白片段之间存在明显关系。
其他疾病也可产生极低分子量的白蛋白片段。
我们首次描述了足细胞蛋白突变的 FSGS 患者血浆中存在极低分子量的白蛋白片段，而特发性 FSGS 患者或健康个体中不存在。需要进一步研究以确定这些片段是否可能是区分遗传性和特发性 FSGS 的潜在生物标志物。
