Background: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease, with unpredictable course and flares. Many autoantibodies are associated with disease expression, but age-specific validation of such potential diagnostic biomarkers is lacking [1-5].

Objectives: This study aimed to identify common and distinctive novel biomarkers that may be used in disease activity in juvenile (jSLE) and adult patients with SLE (aSLE).

Methods: Proximity extension immunoassay (PEA, Olink) was used to assess the serum levels of 92 inflammation proteins in patients with jSLE (n = 19) and age-matched healthy controls (HCs; n = 9), and patients with aSLE (n = 19) and age-matched HCs (n = 22). SLE Disease Activity Index (SLEDAI) and SLE Disease Activity Score (SLE-DAS) were assessed in SLE patients to characterize the disease status of all patients. To evaluate the contribution of molecular profiles to the course of disease, we also assessed the association of serum vitamin D levels with differentially expressed proteins.

Results: Several circulating proteins related to inflammation were altered in the serum of SLE patients in relation to HCs. This analysis differentiated two clusters presenting low-inflammatory and high-inflammatory proteomic profiles. Twelve upregulated proteins were identified in jSLE, respectively nineteen in aSLE. TNF was expressed at significantly higher levels in both SLE groups compared to HCs, whereas CXCL10, CXCL9, CCL19, IL10, PD-L1, CX3-CL1 only in the aSLE group compared to HCs. Abnormalities included alterations in the expression of IFN inducible chemokines, alterations in B cell receptor signaling and alterations in the expression of cytokines related to leucocyte, neutrophil and macrophage trafficking. Patients with jLES presented significantly higher status of disease activity (SLEDAI and SLEDAS scores), renal and hematologic manifestations at diagnosis and during flares in comparison to aLES patients, but no significant correlation could be established with a specific protein profile. Pearson’s correlation between inflammatory proteins in both adult and juvenile cohorts and vitamin D levels revealed that CX3CL1 is significantly positively correlated with Vitamin D serum levels.

Conclusion: This highly sensitive proteomic analysis including several novel candidate proteins identified molecular patterns distinguishing juvenile and adult SLE patients with high disease activity. The observed proteomic signature further supports the need for a personalized age-specific approach to treatment in SLE.

REFERENCES: [1] Jingquan, H.; Donger, T.; Dongzhou, L.; Xiaoping, H.; Chiyu, M.; Fengping, Z.; Zhipeng, Z.; Yumei, C.; Jie, D.; Lin, K.; Lianghong, Y.; Qianjin, L.; Yong, D. Serum proteome and metabolome uncover novel biomarkers for the assessment of disease activity and diagnosing of systemic lupus erythematosus. Clinical Immunology . 2023 (251 ):109330.

[2] Su, K.Y.C.; Reynolds, J.A.; Reed, R. et al. Proteomic analysis identifies subgroups of patients with active systemic lupus erythematosus. Clin Proteom. 2023( 20): 29.

[3] Zhou, G.; Wei, P.; Lan, J.; He, Q.; Guo, F.; Guo, Y.; Gu, W.; Xu, T.; Liu, S. TMT-based quantitative proteomics analysis and potential serum protein biomarkers for systemic lupus erythematosus. Clin Chim Acta . 2022 (534 ):43-49.

[4] Xie, T.; Dong, J.; Zhou, X. et al. Proteomics analysis of lysine crotonylation and 2-hydroxyisobutyrylation reveals significant features of systemic lupus erythematosus. Clin Rheumatol. 2022( 41): 3851–3858.

[5] Dörner T, Tanaka Y, Dow ER , et al. Mechanism of action of baricitinib and identification of biomarkers and key immune pathways in patients with active systemic lupus erythematosus. Annals of the Rheumatic Diseases. 2022( 81): 1267-1272.

Acknowledgements: The authors have nothing to acknowledge.

Disclosure of Interests: None declared.