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AB0005 Cytokine mrna gene expression associated with systemic lupus erythematosus
  1. L Miteva1,
  2. M Ivanova Goycheva2,
  3. I Manolova1,
  4. G Vasilev2,
  5. R Stoilov2,
  6. S Stanilova1
  1. 1Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty, Trakia University, Stara Zagora
  2. 2Clinic of Rheumatology, University Hospital “St. Iv. Rilski”, Medical Faculty, Medical University, Sofia, Bulgaria


Background Systemic lupus erythematosus (SLE) is a complex polygenic autoimmune disease, characterized by autoantibody production, inflammatory manifestation and imbalanced cytokine production. In accordance with the pivotal role of Th17 cell in autoimmunity and the altered Th17/Tregs balance in response to changes in the cytokine milieu we analyzed mRNA expression of several cytokines in peripheral blood of SLE patients. Quantification of mRNA expression in peripheral blood could be useful to assess the disease activity of SLE patients.

Objectives The aim of the present study was to investigate the gene expressions at mRNA level of proinflammatory (TNFA, IL18, IL12B); Th17-related (IL23A); immunosuppressive (TGFB1 and IL10) cytokines and Treg-specific transcription factor Foxp3 in peripheral blood of women with SLE.

Methods Total RNA from peripheral blood was isolated from 28 female patients with SLE and 17 healthy women. Quantitative real-time polymerase chain reaction was performed for 7 genes of interests, using the TaqMan detection system. Relative quantitative evaluation of mRNAs was performed by the comparative ΔΔCt method and results are presented as n-fold mean difference (RQ-relative quantity) of target genes relative to calibrator (healthy controls) after normalization to the reference gene-GAPDH. Disease activity in SLE was determined by SLEDAI and divided into three categories: mild (0–5), moderate (6–10) and high (>10).

Results The results reveal considerable overexpression of IL23A in SLE patients compared to healthy controls (RQ=5.347; p<0.001). According to the level of disease activity we found the highest elevation of IL23A in patients with SLEDAI>10 (RQ=8.54; p<0.001) compared to the controls. In inactive to mild (SLEDAI 0–5) and moderate SLE (SLEDAI 6–10), IL23A was also upregulated in approximately equal rate (RQ=4.976; p<0.001 and RQ=4.64; p<0.001). In addition, immunosuppressive cytokines IL10 and TGFB1 mRNA were elevated significantly in SLE patients than in controls (RQ=1.79; p=0.0077 and RQ=1.78; p=0.02, respectively). We also found that the expression of proinflammatory TNFA and IL12B were significantly downregulated approximately 2-fold. The mRNA level of Foxp3 was downregulated only for patients with SLEDAI>10. A significant good correlation between IL18 and the SLEDAI score was found (r=0.5548; p=0.002). Higher IL18 expression was observed among patients with worsened SLE compared to those with mild (RQ=1.656; p=0.008) and moderate (RQ=1.474; p=0.034) disease activity. We further demonstrated positively correlation between the expression levels of IL23A and TGFB1 (r=0.7276; p<0.001) among SLE patients.

Conclusions These results suggest that upregulation of IL23 and TGFB1 in addition to downregulated Foxp3 expression may contribute to skewing towards Th17 profile in SLE pathogenesis and this was the most markedly manifested at the highest level of disease activity. Our results support indirectly the idea for restoring Th17/Treg balance as a therapeutic target in SLE.

Disclosure of Interest None declared

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