Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Activation of c-Jun N-Terminal Kinase and Extracellular Signal-Regulated Kinase Predicts Damage in Systemic Lupus Erythematosus.
Amit-Vazina1, Mirit, Molad2, Yair, Yona3, Eliyahu, Amram3, Lily, Bloch4, Olga, Rapoport4, Micha J.
Rheumatology Service, Assaf Harofeh Medical Center and Sackler School of Medicine, Tel-Aviv University, Israel, Zerifin, Israel
Rheumatology Unit, Beilinson Hospital, Rabin Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Petah Tikva, Israel
Internal Medicine Division, Day Care Unit, Assaf Harofeh Medical Center and Sackler School of Medicine, Tel-Aviv University, Israel, Zerifin, Israel
Diabetes and Immunology Research Laboratory, Assaf Harofeh Medical Center and Sackler School of Medicine, Tel-Aviv University, Israel, Zerifin, Israel
Aberrant signaling along the p21ras/MAP kinase pathway has been demonstrated in systemic lupus erythematosus (SLE). We have previously reported that the activity of c-Jun N-terminal Kinase (JNK) and Extracellular Signal-Regulated Kinase (ERK) is associated with disease activity in SLE patients. The objective of the present study is to determine whether JNK and ERK activation predicts subsequent permanent end organ damage in a cohort of SLE patients.
Blood samples of 42 SLE patients were prospectively collected during four consecutive visits. Expression of total ERK and JNK kinases and their active forms (pERK and pJNK) was determined by western blot in whole protein lysates of peripheral blood mononuclear cells. Four years later the permanent damage attributed to SLE was assessed using the SLICC-ACR damage index (SLICC-DI). Correlations between SLICC-DI scores and mean and maximal expression of total ERK and JNK kinases and of pERK and pJNK were assessed by Spearman correlation test. Stepwise regression analysis was used to assess the most significant contributions to SLICC-DI.
Demographic and clinical data of 36 SLE patients who were available for long term follow-up and determination of SLICC-ACR are demonstrated in the table. During follow-up period one female patient died of congestive heart failure complicated by sepsis at the age of 51 after 19 years of disease.
|Mean ± SD||Median|
|Age (years)||48.25 ± 11.8||49.5|
|Females (%)||32 (89)|
|Disease Duration (years)||16.9 ± 4.3||16|
|Follow-up Duration Since Last Visit (years)||4.02 ± 0.68||4.25|
|SLICC-DI||1.9 ± 1.8||2|
Mean values of JNK, pJNK and pERK but not ERK obtained during the initial follow-up period correlated positively with SLICC-DI values obtained after long term follow-up (r =0.32, 0.35 and 0.38 respectively, p<0.05 for all). Maximal values of JNK, pJNK and pERK also correlated with SLICC-DI (r=0.45, 0.35 and 0.36 respectively, p<0.01 for JNK and p<0.05 for pJNK and pERK).
On stepwise regression analysis using square root transformation of SLICC-DI values and excluding SLE disease activity index (SLEDAI) maximal value of JNK and mean value of pERK were most significantly associated with SLICC-DI.
|Step 1||Mean pERK||0.51||0.28|
The results of this long-term follow-up study indicate that increased expression of JNK as well as activated forms of JNK and ERK is associated with permanent end-organ damage and can serve as predictors of damage in SLE patients.
To cite this abstract, please use the following information:
Amit-Vazina, Mirit, Molad, Yair, Yona, Eliyahu, Amram, Lily, Bloch, Olga, Rapoport, Micha J.; Activation of c-Jun N-Terminal Kinase and Extracellular Signal-Regulated Kinase Predicts Damage in Systemic Lupus Erythematosus. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2568