title: Increased ERK and JNK activation and decreased  ERK/JNK ratio are associated with long-term  organ damage in patients with systemic  lupus erythematosus.
abstract: OBJECTIVE
  The activities of two mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), correlate with disease severity in SLE patients. Whether they are also associated with long-term organ damage is unknown. The aim of the present work was to determine whether impaired expression and activity of ERK and JNK correlate with long-term damage in SLE.
  
  
  METHODS
  The expression of ERK and JNK and their phosphorylated active forms was determined by western blot analysis four times during the first year of follow-up in peripheral blood mononuclear cells from 36 SLE patients. A correlation analysis was performed between ERK and JNK expression and longterm organ damage estimated by the SLICC/ARC Damage Index (SDI) 4 years later.
  
  
  RESULTS
  Mean levels of ERK and JNK activities during the first year correlated with long-term organ damage severity (r = 0.38 and r = 0.35, respectively; P = 0.05). Overall JNK expression increased with the severity of chronic damage (P = 0.01; P = 0.05 for SDI score 2 and 3, respectively). In contrast, overall ERK expression significantly decreased in patients with maximal organ damage (SDI score 3) compared with patients with an SDI score of 2 (P = 0.03). The ERK/JNK ratio decreased by approximately 40% and 30% in patients with an SDI score of 3 as compared with patients without organ damage and healthy controls, respectively.
  
  
  CONCLUSIONS
  These results demonstrate that early activation of ERK and JNK along with decreased overall ERK expression and reduced ERK/JNK ratio may predict the severity of long-term organ damage in SLE patients.
authors: Olga
authors: O
authors: Bloch
authors: Mirit
authors: M
authors: Amit-Vazina
authors: Eli
authors: E
authors: Yona
authors: Yair
authors: Y
authors: Molad
authors: Micha J
authors: MJ
authors: Rapoport
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000097:blood*; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000188:drug therapy / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D011241:Prednisone