| 1. IntroductionSystemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease characterized by various immunological abnormalities, including dysregulated activation of both T and B lymphocytes with the production of a large quantity of autoreactive antibodies. The aetiology and pathogenic mechanism of this immunological disorder have not been clearly elucidated. Aberrant production and imbalance of T-helper(Th) cell cytokines have been implicated in the pathogenesis of antoimmunity. It is caused by multiple factors, including inheritance, sex hormone, environment, infection, drug, immunologic reaction. SLE is a systemic autoimmune disease characterized clinically by protean manifestations, most commonly including arthralgia, arthritis, rash, alopecia, oral ulcer, serositis, leukopenia, central nervous system and renal involvement. Renal failure, infection and the damage to the central nervous system are the main lethal causes.Osteopontin (OPN, early T-lymphocyte activation protein 1, Eta-1) is a newly found extracellular matrix cell adhesion phosphoprotein. OPN is a multifunctional protein, and although highly expressed in bone, it is also expressed by various cell types including macrophages, endothelial cells, smooth muscle cells and epithelial cells. During inflammation, OPN is expressed by cells of both innate and adaptive immunity, such as natural killer cells, activated T cells, macrophages and resident flbroblasts. OPN is also called early T-lymphocyte activation protein 1 (Eta-1) because of its early production upon cell activation. It has been shown to enhance Thl but inhibit Th2 response. OPN plays a variety of biological roles for host defence, bone formation, osteoclast activation and wound healing. Its cytokine activities include the stimulation of macrophage and T-cell migration, the stimulation of B-cell proliferation and antibody synthesis, protection against herpes viruses and bacterial infections through the activation of the Thl response, and induction of Thl-cell-mediated autoimmunity.Several clinical studies have indicated that there is an unbalanced cytokine profile with significant Thl predominance in patients with SLE. Kidney is often involved in SLE. The expression of OPN correlates with macrophage infiltration in various animal and human of acute or chronic renal injury. In addition, upregulation of OPN expression precedes the macrophage infiltration in injured kidneys. Meanwhile OPN enhances Thl but inhibit Th2 response. Elevation in Thl cytokines, including IL-12, TNF-a and IFN-y, can mediate the inflammatory process that leads to irreversible organ damage, such as renal failure in SLE.Therefore we suspect that OPN is possibly involved in the pathogenesis of SLE. Toinvestigate the role of OPN in SLE, and the relationship between the plasma concentration of OPN and disease activity in patients with SLE, plasma concentration of OPN of 38 SLE patients and 28 controls were measured by ELISA.2. Materials and methodsThirty eight plasma samples of SLE inpatients (33 females and 5 males, mean age 29+10 years, range 15-46 years) were collected from Dermatology Department, the Second Affiliated Hospital, College of Medicine, Zhejiang University from January to August in year 2005 .The mean interval from the diagnosis of SLE to the time when the patients were evaluated for this study was 1 month to 15 years. Diagnosis of SLE was established according to the 1997 revised ACR criteria and disease activity was evaluated with the SLEDAI. 28 sex- and age-matched healthy volunteers (23 females and 5 males, mean age 30+8 years, range 15-45 years) were recruited as controls. 12 plasma samples of SLE inpatients were collected again after the treatment of 40-80mg prednisone per day. Plasma concentration of OPN was measured by ELISA. The data were analyzed by SPSS11.5.3. ResultsA significant increase of OPN plasma concentration was found in SLE patients as compared to that in healthy controls [(420+203) ng/ml vs (73 +14) ng/ml, PO.001]. Additionally a clear elevation of OPN plasma concentration was also found between the patients with proteinurineand without [(623 + 88) ng/ml vs (288+135) ng/ml, PO.001]. Plasma concentration of OPN was higher in active stage than those in inactive stage, namely (529±143) ng/ml vs (185+66) ng/ml (PO.001). Plasma concentration of OPN was higher before treatment (556±130) ng/ml than after treatment (142 + 22) ng/ml (PO.001). Nevertheless there was no significant difference of OPN plasma concentration between the patients with arthritis and without [(489+ 153) ng/ml vs (375+222) ng/ml, P>0.05]. Our data of OPN plasma concentration showed a remarkable positive correlation with SLEDAI score (r=0.93, PO.001), and a remarkable negative correlation with serum C3 concentration (r=-0.49, P<0.05). However plasma concentration of OPN was not correlated with either antinuclear antibodies titre, erythrocyte sedimentation rate, or serum C4 concentration (.P>0.05).4. ConclusionsThe present data show that plasma OPN concentration has some kind of relation with SLE activity, renal damage and disease progression or amelioration. OPN may also be involved in the pathogenesis of SLE. |
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