Abstract
ObjectiveThe soluble urokinase plasminogen activator receptor (suPAR) has potential as a prognosis and severity biomarker in several inflammatory and infectious diseases. In a previous cross-sectional study, suPAR levels were shown to reflect damage accrual in cases of systemic lupus erythematosus (SLE). Herein, we evaluated suPAR as a predictor of future organ damage in recent-onset SLE. MethodsIncluded were 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who met the 1997 American College of Rheumatology classification criteria with 5-years of follow-up data available. Baseline sera from patients and age- and sex-matched controls were assayed for suPAR. Organ damage was assessed annually using the SLICC/ACR damage index (SDI). ResultsThe levels of suPAR were higher in patients who accrued damage, particularly those with SDI≥2 at 5 years (N = 32, 46.8% increase, p = 0.004), as compared to patients without damage. Logistic regression analysis revealed a significant impact of suPAR on SDI outcome (SDI≥2; OR = 1.14; 95% CI 1.03–1.26), also after adjustment for confounding factors. In an optimized logistic regression to predict damage, suPAR persisted as a predictor, together with baseline disease activity (SLEDAI-2K), age, and non-Caucasian ethnicity (model AUC = 0.77). Dissecting SDI into organ systems revealed higher suPAR levels in patients who developed musculoskeletal damage (SDI≥1; p = 0.007). ConclusionPrognostic biomarkers identify patients who are at risk of acquiring early damage and therefore need careful observation and targeted treatment strategies. Overall, suPAR constitutes an interesting biomarker for patient stratification and for identifying SLE patients who are at risk of acquiring organ damage during the first 5 years of disease.
Highlights
Systemic lupus erythematosus (SLE) is an autoimmune disease with unpredictable disease course, diverse manifestations, and fluctuating disease activity
A deficiency in the system for disposing of dying cells, the production of antinuclear autoantibodies (ANA), neutrophil extracellular trap (NET) formation, activation of type I interferon (IFN) signalling, and subsequent tissue damage appear to be important in the pathogenesis of SLE, which is often manifested as rash, arthritis, and nephritis
Caucasian Asian African ancestry Other (Mixed, Native American, Hispanic) SLEDAI-2K at baseline estimated glomerular filtration rate (eGFR) at baseline Abnormal eGFR (< 90) Antimalarials Immunosuppressants Corticosteroids Corticosteroid dose at baseline Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) damage index (SDI≥1) at 1 year SLICC/ACR damage index (SDI≥1) at 2 years SLICC/ACR damage index (SDI≥1) at 3 years SLICC/ACR damage index (SDI≥1) at 4 years SLICC/ACR damage index (SDI≥1) at 5 years Domains of damage (SDI≥1) at 5 years Ocular Musculoskeletal Neuropsychiatric Skin Pulmonary Renal Peripheral vascular Cardiovascular Gastrointestinal Malignancy Premature gonadal failure Diabetes
Summary
Systemic lupus erythematosus (SLE) is an autoimmune disease with unpredictable disease course, diverse manifestations, and fluctuating disease activity. The persistent inflammation and drug-related side-effects eventually cause permanent organ damage, which is strongly linked to mortality [1,2,3]. Apart from a few useful laboratory measures to assess SLE disease activity, i.e., specific autoantibodies and complement proteins, biomarkers that indicate the prognosis and the risk of acquiring damage over time are sparse, possibly due to the heterogeneity of the disease. It is challenging to distinguish symptoms caused by active disease from those that arise following permanent organ damage [4]. Creactive protein (CRP), which is the standard biomarker of inflammation, gives limited information about SLE disease activity, possibly due to negative regulation by IFN-α, in combination with a CRP polymorphism that is more frequently found in patients with SLE [5,6]. ANAs have yielded ambiguous results [1,9] and osteopontin was of limited value [10]
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