Department of Hematology, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
Mol Med Rep. 2019 Feb;19(2):1194-1202. doi: 10.3892/mmr.2018.9754. Epub 2018 Dec 12.
A type of aplastic anemia (AA), non-severe aplastic anemia (NSAA) is defined as AA that does not meet the diagnostic criteria of severe aplastic anemia (SAA). Complement component 1q (C1q) has an important role in the pathogenesis of various autoimmune diseases; however, the role of C1q in the immune pathogenesis of NSAA is not clear. The current study aimed to determine whether C1q has an important role in the pathogenesis of NSAA. Isobaric tags for relative and absolute quantitation (iTRAQ) was used to compare the protein expression in bone marrow mononuclear cells from patients with NSAA and healthy volunteers. Pathway enrichment analysis was performed to determine the biological functions involved in NSAA. The differential expression of C1q was marked compared with other proteins. Subsequently, the concentration of C1q in serum samples was determined using ELISA and the correlation of C1q levels and NSAA severity was evaluated. The serum concentrations of C1q were significantly lower in untreated patients with newly diagnosed NSAA compared with NSAA cases in remission and normal controls. Furthermore, there was no significant difference in C1q concentration between newly diagnosed patients with NSAA and patients with autoimmune hemolytic anemia or immune thrombocytopenia. The serum concentration of C1q in newly diagnosed NSAA was significantly lower in patients with SAA (P<0.0001); whereas, there was no significant difference between the patients with SAA, patients with NSAA remission and normal controls (P>0.05). Additionally, the serum C1q concentration was significantly correlated with granulocyte counts, the level of hemoglobin, platelet counts, reticulocyte percentage and remission in patients with NSAA. The serum C1q concentration was also positively correlated with the myeloid/plasmacytoid dendritic cell ratio, and negatively correlated with the CD4(+)/CD8(+) ratio. These findings suggested that C1q may be a reliable serological marker for monitoring and evaluating disease severity in patients with NSAA. C1q may have an important role in the immune pathogenesis of NSAA.
一种再生障碍性贫血(AA),非重型再生障碍性贫血(NSAA)定义为不符合重型再生障碍性贫血(SAA)诊断标准的 AA。补体成分 1q(C1q)在各种自身免疫性疾病的发病机制中具有重要作用;然而,C1q 在 NSAA 的免疫发病机制中的作用尚不清楚。本研究旨在确定 C1q 在 NSAA 的发病机制中是否具有重要作用。采用同位素相对和绝对定量标记(iTRAQ)比较 NSAA 患者和健康志愿者骨髓单个核细胞的蛋白表达。进行通路富集分析以确定涉及 NSAA 的生物学功能。与其他蛋白相比,C1q 的差异表达更为明显。随后,采用 ELISA 法测定血清样本中 C1q 的浓度,并评估 C1q 水平与 NSAA 严重程度的相关性。与缓解期 NSAA 患者和正常对照组相比,未经治疗的新发 NSAA 患者的血清 C1q 浓度明显降低。此外,新发 NSAA 患者与自身免疫性溶血性贫血或免疫性血小板减少症患者的 C1q 浓度无显著差异。新发 SAA 的 NSAA 患者的血清 C1q 浓度明显低于 SAA(P<0.0001);然而,SAA 患者、NSAA 缓解患者和正常对照组之间无显著差异(P>0.05)。此外,NSAA 患者的血清 C1q 浓度与粒细胞计数、血红蛋白水平、血小板计数、网织红细胞百分比和缓解呈显著相关。血清 C1q 浓度与髓系/浆细胞样树突状细胞比值呈正相关,与 CD4+/CD8+比值呈负相关。这些发现表明,C1q 可能是监测和评估 NSAA 患者疾病严重程度的可靠血清标志物。C1q 可能在 NSAA 的免疫发病机制中具有重要作用。