Table_1_SIGIRR and TNFAIP3 Are Differentially Expressed in Both PBMC and TNF-α Secreting Cells of Patients With Major Depressive Disorder.pdf

Background: Major depressive disorder (MDD) is associated with the activation of the immune/inflammatory system. TNF-α is associated with MDD and poor treatment response. Toll-like receptors (TLR) are responsible in innate immune response, and is associated with MDD and antidepressant response. Some negative regulators of TLR pathway such as SOCS1, TOLLIP, SIGIRR, TNFAIP3, and MyD88s, are reported to be differentially expressed in the peripheral blood samples of patients of MDD.
Methods: We recruited patients with MDD and healthy controls, collect their demographic data, and measured their mRNA levels of negative TLR regulators, using peripheral blood mononuclear cells (PBMC) and isolated TNF-α secreting cells. Clinical symptoms were evaluated using Halmiton Depression Rating Scale (Ham-D). Some patients were evaluated again after 4 weeks of antidepressant treatment.
Results: Forty-seven patients with MDD and 52 healthy controls were recruited. Between the PBMC samples of 37 MDD patients and 42 controls, mRNA levels of SOCS1, SIGIRR, TNFAIP3, and MyD88s were significantly different. Between TNF-α secreting cells of 10 MDD patients and 10 controls, mRNA levels of SIGIRR and TNFAIP3 were significantly different. Change of Ham-D score only correlated significantly with TOLLIP mRNA level after treatment.
Conclusion: SIGIRR and TNFAIP3, two negative regulators of TLR immune response pathways, were differentially expressed in both PBMC and TNF-α secreting cells of patients with MDD as compared to healthy controls. The negative regulations of innate immune response could contribute to the underlying mechanism of MDD.

背景：重度抑郁症（Major Depressive Disorder, MDD）与免疫/炎症系统激活相关。肿瘤坏死因子-α（TNF-α）与MDD及不良治疗应答存在关联。Toll样受体（TLR）参与固有免疫应答，且与MDD及抗抑郁治疗应答相关。已有研究表明，SOCS1、TOLLIP、SIGIRR、TNFAIP3及MyD88s等Toll样受体通路负调控因子在MDD患者的外周血样本中存在差异表达。
方法：本研究招募MDD患者与健康对照人群，收集其人口学特征资料，通过外周血单个核细胞（PBMC）及分离的肿瘤坏死因子-α分泌细胞，检测上述Toll样受体通路负调控因子的mRNA表达水平。采用汉密尔顿抑郁量表（Hamilton Depression Rating Scale, Ham-D）评估临床症状；部分患者在接受4周抗抑郁治疗后再次接受评估。
结果：本研究共纳入47例MDD患者及52名健康对照者。在37例MDD患者与42例对照者的外周血单个核细胞样本中，SOCS1、SIGIRR、TNFAIP3及MyD88s的mRNA表达水平存在显著差异。在10例MDD患者与10例对照者的肿瘤坏死因子-α分泌细胞中，SIGIRR与TNFAIP3的mRNA表达水平存在显著差异。接受4周抗抑郁治疗后，汉密尔顿抑郁量表评分变化仅与TOLLIP的mRNA表达水平呈显著相关。
结论：作为Toll样受体免疫应答通路的两个负调控因子，SIGIRR与TNFAIP3在MDD患者的外周血单个核细胞及肿瘤坏死因子-α分泌细胞中均存在差异表达（相较于健康对照者）。固有免疫应答的负调控过程可能参与了MDD的潜在发病机制。