Scand J Immunol. 2026 Oct;104(4):e70158. doi: 10.1111/sji.70158.
ABSTRACT
Lupus nephritis (LN) confers a disproportionate thrombotic risk in systemic lupus erythematosus (SLE) that is not fully explained by conventional cardiovascular risk factors. The underlying molecular mechanisms remain largely unknown. We aimed to characterize the thrombo-inflammatory profiles in LN compared with SLE without nephritis (SLE-NonLN), and contextualized these findings to primary antiphospholipid syndrome (APS), primary Sjögren's disease (SjD), and healthy controls. In a cross-sectional design, we included 325 patients with SLE from two Danish cohorts, 10 with primary APS, 45 with primary SjD, and 100 healthy controls. A predefined thrombo-inflammatory panel encompassing endothelial and platelet activation, coagulation, fibrinolysis, and complement pathways was assessed using immunoassays. Group differences were adjusted for clinical covariates and multiple testing. Multivariate patterns were examined using principal component analysis, correlation networks, and logistic regression. Thrombomodulin levels were higher in SLE-LN than in SLE-NonLN and remained associated with LN after multiple testing correction and adjustment for age, treatment exposure, and disease activity. Thrombomodulin showed a modest association with albuminuria but not with disease activity, anti-double-stranded DNA antibody levels, or secondary APS. Correlation networks demonstrated a dense, integrated thrombo-inflammatory structure in SLE-LN. In multivariable logistic regression, thrombomodulin and prednisolone use emerged as independent factors associated with LN. LN is characterized by a distinct thrombo-inflammatory profile dominated by endothelial activation, with thrombomodulin emerging as the most consistent biological marker of renal involvement in SLE. The coordinated alterations observed across multiple pathways highlight the potential value of systems-oriented approaches for advancing mechanistic understanding in LN.
PMID:42839558 | DOI:10.1111/sji.70158