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Abstract Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by loss of tolerance to nuclear antigen, resulting in production of pathogenic antibodies that cause inflammation and multiple organs injury. Lupus nephritis (LN) is a severe renal manifestation developed with 60% of SLE patients. In USA, not only the prevalence of SLE is greater in the African ethnicity than the Caucasian and Hispanic, but also higher proportion of patients developed LUPUS with higher prognosis, on the other hand, no available recent data demonstrating the incidence or prevalence of LUPUS or even SLE in Egypt. Environmental factors in susceptible individuals showing predisposing genetic variants can develop SLE. Diminished apoptotic clearance mechanisms will cause formation of ICs which deposit in the kidney tissue. This by its role will trigger the cytokines and chemokines release, resulting in cascade of innate and adaptive immune responses. The programmed death-1(PD-1) and its ligand; the programmed death ligand-1 (PD-L1) which works as a negative co-stimulatory and may play a role in controlling the autoimmunity, and the B-cell lymphoma-2 (Bcl-2) which is an anti-apoptotic protein may play a role in the prolonged proliferation and prevention of the cell death in the mesangial and glomerular cells. The current study aimed to determine the PD-1/PD-L1 expression on lymphocytes, monocytes and granulocytes and Bcl-2 serum level in LUPUS patients. In addition, correlation between these parameters and the disease activity was performed. The study was conducted on 30 patients suffering from LUPUS, recruited to the Internal Medicine Department - Nephrology Unit, Medical Research Institute Hospital, University of Alexandria and 15 healthy subjects age and sex matched as a control group. Summary 100 All patients subjected to history taking, full clinical examination, CBC, renal function tests, liver function tests, complete urine analysis, urinary protein excretion, autoimmunity and inflammatory markers. The percentage and the mean fluorescence intensity of the PD-1/PD-L1 expression on lymphocytes, monocytes and granulocytes have been studied. The Bcl-2 serum level was measured. Correlation study has been investigated the relation between these parameters with the disease activity through the calculation of the systemic lupus erythematosus disease activity index (SLEDAI) and the renal activity score. The results showed a higher expression of PD-1 in the healthy control individuals and increased PD-L1 expression in the lupus patients. PD-L1 and PD-1 expression on lymphocytes showed a positive correlation with significant differences with the disease activity indices used in the current study. The expression of PD-L1 on monocytes was directly proportional to disease activity while, the expression of PD-1 on monocytes was inversely proportional with the disease activity. The renal parameters were inversely proportional to the expression of the PD-L1 on lymphocytes, monocytes and granulocytes. The autoimmunity markers were directly proportional with the expression of PD-1 on lymphocytes with statistically significant difference. The obtained results showed a statistically significant increase in the serum level of Bcl-2 in LUPUS patients compared to healthy control group. Moreover, a highly significant difference between the active and inactive lupus patients according to the Bcl-2 serum concentration was seen. The serum Bcl-2 concentration was positively correlating with the disease activity with a highly significant difference. No significant correlation between PD-L1 an PD-1 with the Bcl-2 serum concentration. In conclusion, PD-1/PD-L1 pathway and Bcl-2 protein may be involved in the immunopathogenesis of LN. This can be used as a target of biological therapy to help in the treatment of LUPUS patients. |