Apoptosis in lupus nephritis patients: a study of Bcl-2 to assess glomerular and tubular damage

Abstract

Abstract Background Systemic lupus erythematosus (SLE) is an immune-mediated disease, due to exposure of self-antigens, through impairment of apoptosis and failure of lymphocytic tolerance. Impaired regulation of the pro- and anti-apoptotic gene products which coordinate programmed cell death may result in autoreactive B and T cells and autoimmunity. Genetically engineered mice that over-express the anti-apoptotic molecule Bcl-2, B cell lymphoma 2 (Bcl2) in B-lymphocytes advance a lupus-like illness. Lupus nephritis (LN) is one of the most serious manifestations of this autoimmune disorder. Glomerulonephritis (GN) is caused by either impaired regulation of apoptosis and/or clearance of apoptotic cells leading to a T cell-mediated autoimmune reaction with initiation of pathological immune complex deposits. Objective To evaluate the correlation between Bcl2 glomerular and tubular expression and pathological findings and laboratory data in different types of SLE GN. Results Compared to the control group, patients with lupus nephritis have significantly higher glomerular, interstitial and tubular expression level (P value < 0.001). BCL2 expression was positively correlated with serum anti-ds-DNA, urine 24-h protein and with the chronicity index. All LN patients had significant glomerular, interstitial and tubular deposits of BCL2, P value < 0.001, P value 0.004, and P value 0.03, respectively. Conclusion The intrinsic pathway of apoptosis interferes not only with the pathogenesis of lupus glomerulonephritis but also interferes with the pathogenesis of tubulointerstitial lupus nephritis. tubulointerstitial lesions may not only be a result of glomerular injury but also a significant factor in lupus nephritis.