Relationship between Plasma Soluble Urokinase Plasminogen Activator Receptor (suPAR) Levels and Disease Activity in Systemic Lupus Erythematosus
Engy Mostafa Yassine;
Abstract
SUMMARY
S
ystemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease with diverse clinical manifestations and serological markers. Multiple factors including genetic and environmental factors have been suggested as contributing to the development of the disease.
The pathogenesis is believed to relate to abnormal apoptosis and deficient elimination of apoptotic materials, such as nuclear proteins and nucleic acids, eventually leading to autoantibody production and formation of circulating or tissue-bound immune complexes.
The disease course is fluctuating, characterized by acute and often severe exacerbations. Several scoring systems have been validated to measure disease activity however, no objective laboratory marker has been identified that can reliably be used for the detection of ongoing inflammation in correlation with clinical symptoms in SLE.
The urokinase-type plasminogen activator receptor (uPAR), a membrane-linked receptor with extracellular protease activity that transduces intracellular signaling pathways, is expressed on the surface of several inflammatory cells, including neutrophils, lymphocytes, and monocytes, as well as on endothelial cells.
Soluble uPAR has been described as a valuable indicator of the activation state of the immune system. Elevated level of suPAR has been reported to be associated with increased risk of SIRS, cancer, cardiovascular disease, infectious diseases, HIV, and mortality.
The mechanism for the higher suPAR level in active lupus might be attributed to that the cell surface uPAR expression was upregulated on stimulation with growth factors and cytokines such as TNFα, IFNγ, IL-1 and IL-2, which were possibly involved in the pathogenesis of SLE.
Both membrane-bound and soluble uPARs have been shown to bind to integrins, and have been proposed to be involved in cell adhesion and suPAR has been reported to have direct chemotactic properties, which may facilitate recruitment of inflammatory cells such as neutrophils and monocytes causing increase in the inflammatory reaction which occur in patients with lupus.
The aim of this study was to determine plasma suPAR levels in SLE patients compared to healthy individuals and correlate it with disease activity, in order to reveal if suPAR could serve as an activity biomarker in this disease.
The present study was conducted on sixty patients diagnosed as systemic lupus erythematosus (55 females and 5 males). Their age ranged from 19 to 45. All patients were fulfilling the 1997 update of the 1982 ACR revised criteria. Patients with Cardiovascular disease, infectious diseases, Cancer, Multiple sclerosis were excluded.
SLE Patients were divided according to SLEDAI into three groups. In remission SLE group including 2 patients, SLE group with moderate activity including 27 patients and SLE group with high activity including 31 patients. The whole SLE patients' group was also divided into two subgroups according to nephritis; SLE patients with and without nephritis subgroups (n=17 and n=43, respectively). They were also divided according to vasculitis into SLE patients with and without vasculitis subgroups (n=17 and n=43, respectively).
A control group was also included in the study. It comprised twenty apparently healthy individuals of matched age and sex with no evidence of any rheumatologic disorder or chronic medical illness. The control group included 19 females and 1 male with their age ranging from 23 to 39 years.
Soluble uPAR level was assessed in comparison to ESR, CRP and C3.
Soluble uPAR and ESR levels have shown a highly significant increase in SLE patients compared to healthy controls. Moreover suPAR, ESR and C3 have shown significant differences between SLE subgroups as regard SLEDAI score where those with high disease activity (SLEDAI > 8) were showing higher suPAR and ESR levels and lower C3 level than those with moderate disease activity {SLEDAI (1-8)} or patients in remission (SLEDAI 0) but no significance was detected among activity subgroups as regards CRP.
Comparing the clinical impact of suPAR to C3 and ESR in discriminating SLE patients with high to those with moderate disease activity and in remission, suPAR has shown a better discriminatory ability than ESR and C3.
At the suggested cut-off value of 6.9 ng/ml for suPAR, a 100% sensitivity and a 93% specificity were obtained for discriminating SLE patients with high from those with moderate disease activity and in remission.
Soluble uPAR has also shown a higher level among nephritis patients than those free from nephritis. The same finding was noticed among vasculitis patients than those free from vasculitis.
S
ystemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease with diverse clinical manifestations and serological markers. Multiple factors including genetic and environmental factors have been suggested as contributing to the development of the disease.
The pathogenesis is believed to relate to abnormal apoptosis and deficient elimination of apoptotic materials, such as nuclear proteins and nucleic acids, eventually leading to autoantibody production and formation of circulating or tissue-bound immune complexes.
The disease course is fluctuating, characterized by acute and often severe exacerbations. Several scoring systems have been validated to measure disease activity however, no objective laboratory marker has been identified that can reliably be used for the detection of ongoing inflammation in correlation with clinical symptoms in SLE.
The urokinase-type plasminogen activator receptor (uPAR), a membrane-linked receptor with extracellular protease activity that transduces intracellular signaling pathways, is expressed on the surface of several inflammatory cells, including neutrophils, lymphocytes, and monocytes, as well as on endothelial cells.
Soluble uPAR has been described as a valuable indicator of the activation state of the immune system. Elevated level of suPAR has been reported to be associated with increased risk of SIRS, cancer, cardiovascular disease, infectious diseases, HIV, and mortality.
The mechanism for the higher suPAR level in active lupus might be attributed to that the cell surface uPAR expression was upregulated on stimulation with growth factors and cytokines such as TNFα, IFNγ, IL-1 and IL-2, which were possibly involved in the pathogenesis of SLE.
Both membrane-bound and soluble uPARs have been shown to bind to integrins, and have been proposed to be involved in cell adhesion and suPAR has been reported to have direct chemotactic properties, which may facilitate recruitment of inflammatory cells such as neutrophils and monocytes causing increase in the inflammatory reaction which occur in patients with lupus.
The aim of this study was to determine plasma suPAR levels in SLE patients compared to healthy individuals and correlate it with disease activity, in order to reveal if suPAR could serve as an activity biomarker in this disease.
The present study was conducted on sixty patients diagnosed as systemic lupus erythematosus (55 females and 5 males). Their age ranged from 19 to 45. All patients were fulfilling the 1997 update of the 1982 ACR revised criteria. Patients with Cardiovascular disease, infectious diseases, Cancer, Multiple sclerosis were excluded.
SLE Patients were divided according to SLEDAI into three groups. In remission SLE group including 2 patients, SLE group with moderate activity including 27 patients and SLE group with high activity including 31 patients. The whole SLE patients' group was also divided into two subgroups according to nephritis; SLE patients with and without nephritis subgroups (n=17 and n=43, respectively). They were also divided according to vasculitis into SLE patients with and without vasculitis subgroups (n=17 and n=43, respectively).
A control group was also included in the study. It comprised twenty apparently healthy individuals of matched age and sex with no evidence of any rheumatologic disorder or chronic medical illness. The control group included 19 females and 1 male with their age ranging from 23 to 39 years.
Soluble uPAR level was assessed in comparison to ESR, CRP and C3.
Soluble uPAR and ESR levels have shown a highly significant increase in SLE patients compared to healthy controls. Moreover suPAR, ESR and C3 have shown significant differences between SLE subgroups as regard SLEDAI score where those with high disease activity (SLEDAI > 8) were showing higher suPAR and ESR levels and lower C3 level than those with moderate disease activity {SLEDAI (1-8)} or patients in remission (SLEDAI 0) but no significance was detected among activity subgroups as regards CRP.
Comparing the clinical impact of suPAR to C3 and ESR in discriminating SLE patients with high to those with moderate disease activity and in remission, suPAR has shown a better discriminatory ability than ESR and C3.
At the suggested cut-off value of 6.9 ng/ml for suPAR, a 100% sensitivity and a 93% specificity were obtained for discriminating SLE patients with high from those with moderate disease activity and in remission.
Soluble uPAR has also shown a higher level among nephritis patients than those free from nephritis. The same finding was noticed among vasculitis patients than those free from vasculitis.
Other data
| Title | Relationship between Plasma Soluble Urokinase Plasminogen Activator Receptor (suPAR) Levels and Disease Activity in Systemic Lupus Erythematosus | Other Titles | العلاقة بين مستوى مستقبلات اليوروكيناز بلازمينوجين المنشط و نشاط مرض الذئبة الحمراء | Authors | Engy Mostafa Yassine | Issue Date | 2015 |
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