Miteva Lyuba D, Manolova Irena M, Ivanova Mariana G, Stoilov Rumen M, Stanilova Spaska A
Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty, Trakia University, Armeiska 11 St, 6000, Stara Zagora, Bulgaria.
Clinic of Rheumatology, Medical Faculty, University Hospital "St. Ivan Rilski", Medical University, Sofia, Bulgaria.
Rheumatol Int. 2020 May;40(5):727-735. doi: 10.1007/s00296-020-04542-3. Epub 2020 Mar 9.
Gene expression analysis of peripheral blood cells may provide valuable information about the triggered molecular processes in systemic lupus erythematosus (SLE). The study aimed to quantify the mRNA in peripheral blood of seven target genes, including inflammatory cytokine genes (IL23A, IL12B, TNFA, IL18), and T regulatory-related genes (FOXP3, TGFB1, IL10) in patients with SLE and to correlate expression levels with disease activity and/or clinical manifestations. The relative quantification of target genes was performed using real-time polymerase chain reaction in peripheral blood obtained from 28 adult SLE females and 17 healthy women. The highest up-regulation in the blood of SLE patients was observed for IL23A with a median 9.54 (p < 0.0001), followed by TGFB1 (median: 2.07; p = 0.047) and IL10 (median: 1.84; p = 0.013). IL12B and TNFA were significantly down-regulated in patients compared to controls (median: 0.521; p = 0.0023, and median: 0.519; p = 0.0003, respectively). FOXP3 mRNA was lower among patients with higher degree of disease activity (median: 0.338; p = 0.029) and showed inverse correlation with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). IL18 mRNA correlated positively with the SLEDAI and was highly expressed during severe flares (median: 1.216; p = 0.021). IL18 up-regulation was associated with anti-dsDNA antibody positivity, while FOXP3 down-regulation with lupus nephritis. Our study pointed out the relationship of SLE disease activity and particular clinical manifestations with IL18 and FOXP3 expression, and the significant contribution of IL23A in the SLE immunopathogenesis. Hence, the peripheral blood cytokine mRNAs should be exploited as novel prognostic and diagnostic biomarkers.
外周血细胞的基因表达分析可能为系统性红斑狼疮（SLE）中触发的分子过程提供有价值的信息。该研究旨在对SLE患者外周血中七个靶基因的mRNA进行定量，这些基因包括炎性细胞因子基因（IL23A、IL12B、TNFA、IL18）和T调节相关基因（FOXP3、TGFB1、IL10），并将表达水平与疾病活动度和/或临床表现相关联。使用实时聚合酶链反应对从28名成年女性SLE患者和17名健康女性获取的外周血进行靶基因的相对定量。在SLE患者血液中观察到IL23A上调最为明显，中位数为9.54（p < 0.0001），其次是TGFB1（中位数：2.07；p = 0.047）和IL10（中位数：1.84；p = 0.013）。与对照组相比，患者中IL12B和TNFA显著下调（中位数分别为：0.521；p = 0.0023和中位数：0.519；p = 0.0003）。在疾病活动度较高的患者中，FOXP3 mRNA较低（中位数：0.338；p = 0.029），并且与系统性红斑狼疮疾病活动指数（SLEDAI）呈负相关。IL18 mRNA与SLEDAI呈正相关，并且在严重发作期间高表达（中位数：1.216；p = 0.021）。IL18上调与抗双链DNA抗体阳性相关，而FOXP3下调与狼疮性肾炎相关。我们的研究指出了SLE疾病活动度和特定临床表现与IL18和FOXP3表达之间的关系，以及IL23A在SLE免疫发病机制中的重要作用。因此，外周血细胞因子mRNA应被用作新的预后和诊断生物标志物。
