Objective: Aberrant signaling along the p21RAS/MAP kinase pathway has been demonstrated in SLE. We examined whether expression and activity of the MAP kinases ERK and JNK reflect disease activity in SLE patients.
Methods: Blood samples of 42 outpatient SLE patients were prospectively collected during 4 consecutive visits. The control group included 20 healthy subjects. Disease activity was assessed using the SLE Disease Activity Index (SLEDAI). Expression of total ERK and JNK kinases and their active forms (pERK and pJNK) were determined in whole protein lysates of peripheral blood mononuclear cells.
Results: The mean levels of the active kinases pERK and pJNK were significantly increased in patients with active disease (SLEDAI 4-20) as compared to patients with inactive disease (SLEDAI 0-3) p=0.04 as well as to healthy controls p=0.03 and p=0.003, respectively. The percentage of activated forms of ERK and JNK of the total expression of these MAP kinases was also gradually increased reaching 50% for pERK and over 40% for pJNK in SLE patients with moderate to severe disease (SLEDAI 7-20) p=0.005, p=0.005 and p=0.02, p=0.05 as compared to controls and inactive patients, respectively. A decrease of more than 3 SLEDAI points was associated with a significant reduction in the expression of both total and activated forms of ERK and JNK p= 0.03, p=0.01, respectively.
Conclusions: Our results demonstrate that ERK and JNK activity reflect disease activity in SLE patients. These MAP kinases may serve as additional tools for the evaluation of disease activity and management of these patients.
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