The Potential Therapeutic Target Of Primary Sjogren's Syndrome With Interstial Lung Disease:miR146a/TRAF6,IRAK1

Objective:In primary Sjogren's syndrome, in addition to involvement of exocrine glands and still involvement of Multi-system damage symptom which caused by other organs glands damage. In all organ lesions, Interstitial lung disease is the leading cause of death,so PSS-ILD has become a hot in clinical and immunological studies. In previous studys, we have found it is closely related to PSS-ILD incidence that alveolar inflammation caused by TNF-a, TGF-?1 and MMP9 excessive release.But MyD88-IRAKI-TRAF6 signal complex form by the TNF-a, TGF-?1 and MMP9 secretion and NF-?B signaling pathway activation which in turn caused IRAK1 phosphorylation by TLR binding MyD88 and later activate TRAF6. So, we hypothesized:pSS-ILD is related with miR-146a and its target genes'expression of IRAK1, TRAF6. To confirm this hypothesis, we will evaluate the expression of miR-146a and its target genes IRAK1, TRAF6 in the peripheral blood mononuclear cells from the patients with pSS-ILD. Meanwhile, test the healthy controls, pSS patients for comparing with pSS-ILD patients to seek new therapeutic targets. Methods:1. Filter and collect primary Sjogren's syndrome with interstitial lung disease cases and signed informed consent, it immunosuppressant sequential therapy and collected peripheral blood to test.2. Separated peripheral blood mononuclear cells (PBMC) for total RNA. Test by FQ-PCR, RT-PCR to detect miR-146a and its target gene TRAF6, IRAK1. And statistical analysis whether the results of each groups are statistically significant.3. Test TNF-a, IL-2, IL-1? with ELISA and statistics whether there is a correlation with miR-146a. Analyze the role of each group of cytokines in the pathogenesis relevant.4. Test and collect clinical parameters of patients in each group including ESR, CRP, IgA, IgM, IgG. Statistical analysis to test whether there is a linear relationship among the miR146a, IRAK-1 and TRAF-6.5. Through statistical analysis, educt miR-146a and its target genes TRAF6, IRAK1 is primary Sjogren's syndrome with interstitial lung disease's potential therapeutic targets. Results: ? miR-146a relative expression in the patients(pSS and pSS-ILD) was significantly lower than healthy controls (n=10, P< 0.05),and the pSS significantly below pSS ILD (n=10, P< 0.05).? IRAKI relative expression in pSS is lower than the healthy control group (n=10, P< 0.05); In pSS-ILD relative expression is significantly higher than healthy control (n=10, P< 0.05); In pSS the relative expression significantly below pSS-ILD(n=10, P< 0.05). ? Relative expression of TRAF6 in healthy control was obviously higher than that of pSS and pSS-ILD (n=10, P< 0.05); In patients with pSS and pSS-ILD has no obvious differences. ? The expression of TNF-a in the healthy controls was lower than that in groups pSS and pSS-ILD (n=10, P< 0.05); The pSS and pSS-ILD group have no obvious differences.?The expression of IL-1? in healthy controls was lower than that in group pSS and pSS-ILD (n=10, P< 0.05); The pSS group was lower than pSS-ILD (n=10, P< 0.05). ? The expression of IL-2 in the healthy control group was lower than that in group pSS and pSS-ILD (n=10, P< 0.05); The pSS group was lower than that in group pSS-ILD (n=10, P< 0.05). ?MiR-146a negative correlation with all the inflammatory factors. Conclusions:The results suggest that miR-146a for pSS-ILD development has played a key role, and may be associated with the severity of the disease, its expression level can be used as pSS-ILD as an important biological marker of the severity of disease and therapeutic targets for diseases to intervene.