Background:Primary Sjogren’s syndrome (pSS) is a chronic systemic autoimmune disease characterized by disorders of effector T cell subpopulations such as Th1, Th2, Th17, regulatory T cells, and follicular helper T cells 1 2. Autophagy is an evolutionarily conserved self-digestion process that plays an important role in T cell-mediated immune response3. The relationship between autophagy and T cell subsets was unclear in pSS up till now.Objectives:To landscape the autophagy-related multiple gene expression signature in pSS classification and discover the influence of autophagy in T cell subsets.Methods:Gene expression profiles of pSS samples (GSE66795, GSE51092, GSE154926) were acquired from GEO database. A set of significant G-ATGs were intersected from the global gene of patients and 232 autophagy genes (ATGs) which were obtained from the Human Autophagy Database (HADb, http://www.autophagy.lu/). In training dataset (GSE66795, including 155 patients and 29 healthy controls), non-negative matrix factorization was used to divided patients by G-ATGs expression microarray data. An autophagy score model divided patients into the high-autophagy score and low groups by ssGSEA scores of gene according to normalized G-ATGs training data. Further, new classifications were validated by both peripheral blood samples (GSE51092, 90 patients) and salivary gland tissue (GSE154926, 43 participants).Results:Two distinct subtypes were identified and validated by 206 selected significant G-ATGs in training datasets (figure 1A,B) and validation datasets according to the autophagy score (figure 1D,E,F) Combined with clinical information of salivary gland dataset, it was found that most patients with early pSS were grouped in the high autophagy, while advanced patients were grouped in the low (figure 1G). Patients in high-autophagy group had higher levels of Treg cells and Th2 cells but lower concentrations of Th17 and Th1 in peripheral blood (figure 1C, P <0.05). Similar results were also observed in salivary gland tissue (figure 1H, P <0.05).Conclusion:Patients with different autophagy status differs from each other. Autophagy is closely corelated with lymphocyte subpopulations in patients with pSS. This work may help inform therapeutic decision-making for the treatment of pSS.References:[1]Colafrancesco S, Vomero M, Iannizzotto V, et al. Autophagy occurs in lymphocytes infiltrating Sjögren’s syndrome minor salivary glands and correlates with histological severity of salivary gland lesions. Arthritis research & therapy 2020;22(1):238. doi: 10.1186/s13075-020-02317-6 [published Online First: 2020/10/15].[2]Alessandri C, Ciccia F, Priori R, et al. CD4 T lymphocyte autophagy is upregulated in the salivary glands of primary Sjögren’s syndrome patients and correlates with focus score and disease activity. Arthritis research & therapy 2017;19(1):178. doi: 10.1186/s13075-017-1385-y [published Online First: 2017/07/27].[3]Wei J, Long L, Yang K, et al. Autophagy enforces functional integrity of regulatory T cells by coupling environmental cues and metabolic homeostasis. Nature immunology 2016;17(3):277-85. doi: 10.1038/ni.3365 [published Online First: 2016/01/26].Acknowledgements:This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078).Disclosure of Interests:None declared
OP0275 THE PI3KΔ INHIBITOR INCB050465 AMELIORATES SALIVARY GLAND PATHOLOGY AND REDUCES AUTOANTIBODY FORMATION IN A MURINE MODEL OF SJÖGREN’S SYNDROME