Session Information
Session Type: Late-Breaking Abstract Session
Session Time: 7:30AM-9:00AM
Background/Purpose: Primary Sjögren’s syndrome (pSS) is a complex autoimmune disease with significant heterogeneity. Our study aimed to clarify the etiology and molecular variation of the target organ, salivary glands (SGs), in pSS by stratifying them into distinguishable subgroups, which could inform treatment choices in pSS.
Methods: Large-scale transcriptomic profiling of SGs was conducted on 396 pSS, 87 non-pSS, and 44 early-pSS individuals from a multicenter consecutive Chinese cohort. Unsupervised clustering methods were used for molecular classification and integrated analyses were performed to elucidate comprehensive clinical and biological features, immune-metabolic and genetic characteristics. Lymphoma risk and treatment response for pSS subgroups was also predicted for pSS subtypes.
Results: Three distinct subtypes were identified both in established and early-pSS, including “pauci-immune/C1”, “cold-immune/C2”, and “hot-immune/C3”. Pauci-immune/C1 exhibited a similar biologic pattern to non-pSS. The cold-immune/C2 displayed dramatic activation of classical adaptive immune and depressed metabolism, along with mitochondrial dysfunction and cGAS-STING-NFkB signaling overactivity. “Hot-immune/C3” had an innate immune inclination and predominantly active metabolism processes, especially for oxidative phosphorylation (OXPHOS). Among the three subtypes, C2 had a higher lymphoma risk with the highest immune cell and endothelial cell infiltration in SGs. Based on the distinct features of each group, we matched them with approved or exploratory treatment options the patient most likely would benefit from, including conventional medicine, JAK inhibitors, and biologics.
Conclusion: Overall, our findings provide a comprehensive and in-depth molecular landscape of SGs in pSS, shedding light on the disease heterogeneity and promoting the development of precise clinical intervention strategies for pSS patients.
To cite this abstract in AMA style:
Wang X, Luo J, Ying S, Hong J, Cheng H, Wang P, He Y, Ye W, Zhu X, Zhu C, Yang L, Li Z, Lin S, Chen D, Wu X, Xie Z, Wu J, Xu H. Immune-metabolic Heterogeneity and Clinical Implications in Primary Sjogren’s Syndrome Revealed by Molecular Classification of Salivary Glands [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/immune-metabolic-heterogeneity-and-clinical-implications-in-primary-sjogrens-syndrome-revealed-by-molecular-classification-of-salivary-glands/. Accessed .« Back to ACR Convergence 2023
ACR Meeting Abstracts - https://acrabstracts.org/abstract/immune-metabolic-heterogeneity-and-clinical-implications-in-primary-sjogrens-syndrome-revealed-by-molecular-classification-of-salivary-glands/