eQTL Highlights the Potential Role of Negative Control of Innate Immunity in Kawasaki Disease

Sirui Song,1 Liqin Chen,1 Qianqian Ning,2 Danying Zhu,1 Feng Qiu,2 Guang Li,2 Hong Zhang,3 Tingting Xiao,1 Guohui Ding,4 Min Huang1 1Department of Cardiology, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Shanghai Center for Bioinformation Technology, Shanghai, People’s Republic of China; 3Department of Laboratory, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4International Human Phenome Institutes, Shanghai, 200235, People’s Republic of ChinaCorrespondence: Min HuangDepartment of Cardiology, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China, Email huangmin@sjtu.edu.cnGuohui DingInternational Human Phenome Institutes, Shanghai, 200235, People’s Republic of China, Email dingguohui@ihup.org.cnPurpose: Kawasaki disease (KD) is an acute systemic vasculitis mainly found in the medium-sized arteries, especially the coronary arteries. Immune system is involved in the pathogenesis of acute KD in children, but the functional differences in the immune system between healthy children and KD patients remain unclear.Patients and Methods: A total of 190 KD patients and 119 healthy controls were recruited for the next-generation sequencing of 512 targeted genes from 4 immune-related pathways. Subsequently, the peripheral blood mononuclear cells (PBMCs) were isolated. RNA sequencing of the LPS treated PBMCs from additional 20 KD patients and 20 healthy controls was used to examine the differentially expressed genes (DEGs). Then, an expression quantitative trait locus (eQTL) analysis combined with previously analyzed RNA data were used to examine the DEGs. Finally, the serum levels of 13 cytokines were detected before and after LPS treatment in 40 samples to confirm the findings from eQTL analysis.Results: A total of 319 significant eQTL were found, and both eQTL analysis and RNA sequencing showed some DEGs were involved in the connective tissue disorders and inflammatory diseases. DEGs that function to negatively regulate immunity were closely related to the pathogenesis of KD. In addition, the serum levels of IL-10 (an inflammatory and immunosuppressive factor) and SCD25 (an important immunosuppressant) reduced significantly in the KD patients.Conclusion: Our study shows the expression of factors responsible for the negative control of innate immunity is altered, which plays an important role in the etiology of KD.Keywords: Kawasaki disease, innate immunity, inflammation, next generation sequencing, cytokines