Primary Sjogren’s Syndrome New Prediction Model, Action Pathway And Differential Gene Research

Objective To explore the predictive factors for determining the therapeutic response and prognosis of severe thrombocytopenia(TP)in patients with primary Sjogren syndrome(pSS).Method Patients with pSS and severe TP(platelet count≤50×109/l)from the Peking Union Medical College Hospital admitted between 2006 and 2016 were classified according to their therapeutic response and analyzed retrospectively.The evalutation between therapeutic reaction and clinical features and laboratory findings were performed.Result Thirty patients were collected,20 among them with appreciable bone marrow aspiration results.14 and 7 patients achieved a complete response(CR)and a partial response(PR)respectively,with 9 patients had no response(NR).The megakaryocyte counts in bone marrow(BM-MK)counts in each group were 13.0(9.2,23.5)/slide(CR),7.0(7.0,20.0)/slide(PR),and 5.0(1.0,6.0)/slide(NR),the counts of BM-MK between patients who achieved a clinical response(CR+PR)were significantly higher than those who did not(NR)with a p value of 0.006.A receiver-operation characteristic analysis was performed,revealed a cutoff value of BM-MK counts at 6.5 stratify patients by different responses to therapeutic intervention definitely,with a sensitivity of 92.3%,a specificity of 85.7%,and area under the curve(AUC)of 0.879.A significant negative correlation was found between the BM-MK and CD8+T cells in peripheral blood(r=-0.707,p=0.005).A decision curve analysis were performed,and the combining model of CD8+T cells and BM-MK showed a higher net profit with a risk threshold of 0.1 to 0.5 than CD8+T cell-model and BM-MK-model respectively.Conclusion BM-MK count and the proportion of CD8+T cells in lymphocytes showed a predictive value in revealing immunotherapeutic response among patients with pSS and severe TP,those with BM-MK counts≤6.5 per slide and the proportion of CD8+T cells>34.2%exhibiting worse clinical response.Net profit was greater in the combining model of CD8+T cells proportion and BM-BK count.Purpose Primary Sjogren Syndrom(pSS)is characterized by activitition of B cells,increased production of RNA-associated antibodies and elevated proportion of transitonal B cell.Toll-like receptors 7(TLR7)have been reported promoting the effects above in some murine models of SS.We took up this study to identify if TLR7 expression is associated with disease activity and the role of TLR7 in pSS.Methods 21 pSS patients and 12 healthy controls(HCs)were selected.The mRNA expression of TLR7 was determined by real-time PCR on peripheral B cells of both pSS patients and HCs.We measured BAFF serum concentrations by ELISA,and the BAFF-R,TACI and BCMA expression was analyzed on transitional B cells(CD27-CD24hiCD38hi/transitional B cell)by flow cytometry.The results were compared among patients with diversed degree of disease activity and damage to HCs.Results The expression level of TLR7 mRNA were elevated in pSS patients compared with HCs(p=0.004),and correlated with the SSDAI(SS disease activity index)(r=0.7545;p=0.0001)and the SSDI(SS damage index)(r=0.7298;p=0.0003).Serum BAFF concentrations increased in pSS patients compared with HCs(p=0.041),but not corrleted with TLR7 expression.TACI expression in pSS patients in total B cells and traditional B cells compared to HCs were elevated,TACI expression in B cells is associated with TLR7 expression(r=0.763,p=0.004).A lower BAFFR expression was seen in transitional B cell compared with HCs(p=0.018).BCMA expression was of no significance.Conclusions Increased TLR7 expression on peripheral B cells were associated with disease activity and damage,suggesting that TLR7 may play a role in the development in pSS.Increased serum BAFF concentrition and TACI expression were associated with TLR7 expression,indicating that BAFF may regulate TLR7 expression through TACI according to previous studies.TLR7 may be a potential treatment target of pSS and worth of further study.Introduction Primary Sjogren’s syndrome(pSS)is one of the most prevalent autoimmune disease.We performed this study to identify differentially expressed genes(DEGs)in pSS patients and to explore their biological mechanisms.Methods We downloaded the gene expression profiles of GSE40611 from the GEO database.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes pathway(KEGG)enrichment analyses were performed;Cytoscape software was used for the protein-protein interaction(PPI)network and module analysis of the DEGs.Results 155 upregulated DEGs(uDEGs)and 24 downregulated DEGs(dDEGs)of TSCC were identified.The GO analysis results indicated that the uDEGs were markedly associated with the processes of immune response,signal transduction,innate immune response,the dDEGs were significantly enriched in response to drug,keratan sulfate biosynthetic process.In KEGG pathway analysis,The uDEGs were enriched in cell adhesion molecules(CAMs)pathway,pathways in influenza A,herpes simplex infection,phagosome patyway,and intestinal immune network for IgA production pathway,the dDEGs were enriched in glycosaminoglycan biosynthesis-keratan sulfate pathway.Then we identified the top centrality hub genes CXCL9,HLA-DRB1,FYN,LCP2,HLA-DRB5,ITK,STAT1 and MX1 from the PPI network.Funtional analysis of significant module revealed that pSS was associated with chemokine signaling pathway,cytokine-cytokine receptor interaction and Toll-like receptor signaling pathway.Conclusions Our work revealed the top centrality hub genes and significant pathways in pSS with bioinformatics analysis,these genes and patyways may be promising as therapeutic targets for the intervention of pSS.However,more studies and experiment validation should be performed to further verify our observation and speculation.