Background/Purpose: Disease activity assessment in systemic lupus erythematosus (SLE) remains a challenge due to lack of reliable biomarkers and disease heterogeneity. Ongoing tissue inflammation can be difficult to distinguish from irreversible damage caused by previous flares or side-effects of medication. Soluble urokinase plasminogen activator receptor (suPAR) is a part of the plasminogen activation system and is involved in inflammation, tissue remodelling and cancer metastasis. Cell-surface expression of uPAR on endothelial cells, megakaryocytes, monocytes, neutrophils and activated T cells is up-regulated upon stimulation with growth factors and cytokines, such as IL-1β and TNF. suPAR is released by protease-mediated shedding of cell-bound uPAR, and has emerged as a useful biomarker in disparate conditions (e.g. sepsis, malignancies, and focal segmental glomerulosclerosis). Herein, we evaluated suPAR as a marker of disease activity and organ damage in lupus.

Methods: Cross-sectional sera from 100 healthy blood donors and 198 SLE patients fulfilling the 1982 American College of Rheumatology (ACR) classification criteria (81%) and/or the ‘Fries criteria’ (a clinical SLE diagnosis based upon a history of abnormal ANA titre and ≥2 typical organ manifestations) were analyzed for suPAR by enzyme immunoassay. Patients were recruited consecutively; most were prevalent cases (91%), but a few (9%) had recent-onset disease at the time of sampling. Disease activity was assessed by SLE disease activity index-2K (SLEDAI) and the physician’s global assessment (PGA). Organ damage was evaluated by SLE international collaborating clinics (SLICC)/ACR damage index (DI). Routine analyses included blood cell counts, erythrocyte sedimentation rate, C-reactive protein (CRP), C3, C4, creatinine, creatine kinase, urinalysis and anti-dsDNA (Crithidia luciliae IF test, CLIFT). Informed consent was obtained from all subjects and the research protocol was approved by the Regional Ethics Committee in Linköping (M75-08).

Results: No significant difference was found comparing suPAR in healthy controls and patients. In SLE, suPAR levels were highly associated with leukocyte count; and thus, this was adjusted for, as well as for age, sex and glucocorticoid dose in further analyses. Yet, no associations were recorded between suPAR levels and disease activity reflected by SLEDAI or PGA. However, a highly significant association was observed between suPAR and global SLICC/ACR DI (p<0.0005), and a borderline significant association was found between CRP and SLICC/ACR DI (p=0.05). Dissecting SLICC/ACR DI into organ systems in a multiple regression analysis, we found renal, ocular, neuropsychiatric, skin and peripheral vascular damage to have a significant positive impact on suPAR levels, whereas no separate organ system had significant impact on CRP.

Conclusion: This study demonstrates a strong association between suPAR and organ damage, but not with disease activity, in lupus. The high association between suPAR and leukocyte count could possibly explain why no difference in suPAR was found between patients and healthy blood donors. Analysis of suPAR may be a valuable clinical tool to assess disease outcome in SLE.

---

« Back to 2012 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/soluble-urokinase-plasminogen-activator-receptor-supar-levels-reflect-organ-damage-in-systemic-lupus-erythematosus/