Laboratory for the Analysis of Medicines, Center for Interdisciplinary Research on Medicines (CIRM), ULiege, Quartier Hopital, Avenue Hippocrate 15, 4000 Liege, Belgium.
Laboratory for the Analysis of Medicines, Center for Interdisciplinary Research on Medicines (CIRM), ULiege, Quartier Hopital, Avenue Hippocrate 15, 4000 Liege, Belgium; Laboratory of Rheumatology, GIGA-Inflammation, Infection & Immunity, ULiege and CHU de Liege, Quartier Hopital, Avenue Hippocrate 15, 4000 Liege, Belgium.
Talanta. 2019 Nov 1;204:507-517. doi: 10.1016/j.talanta.2019.06.044. Epub 2019 Jun 11.
Serum amyloid A (SAA) and S100 (S100A8, S100A9 and S100A12) proteins were previously identified as biomarkers of interest for rheumatoid arthritis (RA). Among SAA family, two closely related isoforms (SAA-1 and SAA-2) are linked to the acute-phase of inflammation. They respectively exist under the form of three (α, β, and γ) and two (α and β) allelic variants. We developed a single run quantitative method for these protein variants and investigated their clinical relevance in the context of RA. The method was developed and validated according to regulations before being applied on plasma coming from RA patients (n = 46), other related inflammatory pathologies (n = 116) and controls (n = 62). Depending on the activity score of RA, SAA1 isoforms (mainly of SAA1α and SAA1β subtypes) were found to be differentially present in plasma revealing their dual role during the development of RA. In addition, the weight of SAA1α in the total SAA response varied from 32 to 80% depending on the pathology studied. A negative correlation between SAA1α and SAA1β was also highlighted for RA early-onset (r = -0.41). SAA2 and S100A8/S100A9 proteins were significantly overexpressed compared to control samples regardless of RA stage. The pathophysiological relevance of these quantitative and qualitative characteristics of the SAA response remains unknown. However, the significant negative correlation observed between SAA1α and SAA1β levels in RA early-onset suggests the existence of still unknown regulatory mechanisms in these diseases.
血清淀粉样蛋白 A（SAA）和 S100（S100A8、S100A9 和 S100A12）蛋白以前被认为是类风湿关节炎（RA）的有意义的生物标志物。在 SAA 家族中，两种密切相关的亚型（SAA-1 和 SAA-2）与炎症的急性期有关。它们分别以三种（α、β 和γ）和两种（α 和β）等位基因变体的形式存在。我们开发了一种单运行定量方法来检测这些蛋白质变体，并在 RA 背景下研究它们的临床相关性。该方法根据规定进行了开发和验证，然后应用于来自 RA 患者（n=46）、其他相关炎症性疾病（n=116）和对照（n=62）的血浆。根据 RA 的活动评分，发现 SAA1 异构体（主要是 SAA1α 和 SAA1β 亚型）在血浆中存在差异，这表明它们在 RA 发展过程中具有双重作用。此外，SAA1α 在总 SAA 反应中的权重根据所研究的病理学从 32%到 80%不等。还强调了 RA 早期发病时 SAA1α 和 SAA1β 之间的负相关（r=-0.41）。与对照样本相比，SAA2 和 S100A8/S100A9 蛋白的表达显著上调，无论 RA 阶段如何。SAA 反应的这些定量和定性特征的病理生理学相关性尚不清楚。然而，在 RA 早期发病时观察到 SAA1α 和 SAA1β 水平之间的显著负相关，这表明这些疾病中存在仍未知的调节机制。
