The Research Of Adult Onset Still’s Disease Pathogenesis And Its Related Clinical Studies

Background: Adult-onset still’s disease(AOSD) is a rare autoimmune disorder of uncertain aetiology. Our previous work has certified the significantly elevated level of macrophage migration inhibitory factor(MIF) in AOSD patients and proved the correlationship between them through genetics research. In addition, as the studies about inflammasome which mainly prompt the secretion of IL-1βand IL-18 indepth, we can’t help deeming the association between inflammasome and AOSD in which the specific IL-1βtarget treatment functions well, inflammasome may be one of the pathogenesis for AOSD. Although low incidence and mainly affected adult people of 16~35yr, there are a lot of reports about elder AOSD patients. As a special group of patients, there must have its own characteristics for elder AOSD patients. Objective: 1.To investigate the possible pathogenic pathways of MIF in AOSD from a cytological perspective. 2. To explore the genetic mechanism of inflammasome in AOSD, so that it can provide specific pathogenesis basis and establish a rapid diagnostic method for clinic. 3. To investigate the clinical characteristics of late-onset AOSD patients and try to provide a theoretical basis for clinical practice. Methods: 1. To separate PBMC of AOSD patients and volunteers by density gradient centrifugation, and determine the best time point and concentration of stimulating agents(MIF, Con A) by detecting supernatant with ELISA and discover the expression of PBMC by RT-PCR. Silencing MIF gene by transfecting siRNA through RNAimax or adding in MIF inhibitor 4-IPP. 2.Genomic DNA were collected from 49 AOSD patients and 94 healthy donors, the polymerase chain reaction was used to amplify objective fragments, then sent to official company to detect sepuence and compared with published decoded fragments to ascertain gene mutations in genomic DNA of AOSD patients. 3. To collect related clinical data by medical records and telephone follow-up of AOSD patients who hospitalized from 2004 to 2013, then statistic its related characteristics. Results: 1.We failed to certify the pathogenic pathways of MIF which take part in the elevated expression of IL-17.2. We did not figure out NLRP3 Q705 K gene mutation in inflammasome related researches.3. In the related study of the clinical characteristics of LOAOSD patients we found that incidence of arthritis, hepatomegaly and slpenomegaly was significantly lower among LOAOSD as compared with YOAOSD patients(68.8%VS80.9%, 2.6%VS12%, 13%VS35.3%; P<0.05), however, incidence of pleurisy and interstitial pneumonia was obviously higher in LOAOSD patients than YOAOSD patients(36.3%VS15.5%, 24.7%VS12.7%; P<0.05). In treatment, when compared with YOAOSD patients, MTX was used less in LOAOSD patients and DMARDs were less combined with prednisone in therapy when they discharged. However, there were no differences between both groups according to disease course, prognosis and treatment through long-term following up. The level of MIF in two groups was notably higher than volunteers(P<0.05), and was positively correlated with the level of CRP and ESR. Conclusions: We failed to certify the pathogenic pathways of MIF in excess production of IL-17 in AOSD patients. We did not find NLRP3 Q705 K mutations in AOSD patients, there may be no correlationgship between Q705 K and AOSD. Although LOAOSD patients showed diversity in their clinical features, their little differences in long-term prognosis, treatment and serologic features made LOAOSD as a non-separate subgroup of AOSD.