146 | Untargeted Quantitative Serum Proteomics in Patients With Systemic Lupus Erythematosus Demonstrates Associations With Ethnicity and Disease Phenotypes

Aims: We aimed to generate unbiased serum mass spectrometry (MS) proteomic profiles in patients with systemic lupus erythematosus (SLE), and explore associations with socio-demographics and SLE phenotypes. Methods: Untargeted label-based proteomics was performed on serum from 60 SLE patients enrolled in the Australian Lupus Registry and Biobank, using liquid chromatography-tandem MS. The cohort was balanced for self-reported ethnicity (Asian or European) and disease activity (SLEDAI-2K). Proteins with missing values in > 50% of patients were excluded; imputation was performed in those with missing values in ≤ 50%. Associations between proteins and clinical features were assessed using differential abundance analysis (DA) with regression models and supervised learning with least absolute shrinkage and selection operator (LASSO). Age, sex, ethnicity and renal impairment (eGFR < 60 ml/min) were included as covariates in multivariable linear regression and LASSO models. Results: We quantified 1092 proteins in 59 SLE patients (1 dialysis patient excluded; median (IQR) age of 42 (35–52) years; 92% female; 49% Asian ethnicity, 51% European ethnicity; 49% active disease (SLEDAI-2K > 4)). Multiple overlapping protein associations between univariable and multivariable DA and LASSO were found. AMY1B, CFHR2, CFHR5, F12.1, FN1, FUCA1, MASP1.2, PVR, QPCT, QSOX1, ZMYND15 were associated with Asian ethnicity. APOC3, CSPG4, CTSS, FABP4 and LDHB were associated with organ damage. C3.4 and TNXB were associated with haematological disease across the study period. ACAN, AMBP, APOA4, ART3, CDH11, HYOU1, IGFBP6, LCAT, P4HB, PRKCSH, RBP4 showed associations with active lupus nephritis at the time of serum sample collection using univariable DA and LASSO, but not multivariable DA. Conclusions: Untargeted quantitative proteomics identified distinct protein patterns associated with Asian ethnicity, organ damage, haematological disease and active lupus nephritis in patients with SLE, highlighting the potential for this approach to generate biomarkers that could refine disease stratification and guide precision management.