Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.

Biomarkers of Juvenile Dermatomyositis (JDM) Aid in Assessing Disease Activity Over Enzymes Alone

Rider¹, L., Li¹, L., Chipman¹, J., Costello², R., O'Hanlon¹, T., Fleisher², T., Csako², G.

NIEHS, NIH, Bethesda, MD,
Laboratory Medicine, Clinical Center, Bethesda, MD

Purpose:

To evaluate the utility of acute phase reactants, serum muscle enzymes, lymphocyte flow cytometry and von Willebrand Factor VIII related antigen (vWF) as correlates of disease activity in juvenile dermatomyositis (JDM).

Method:

Serum or plasma was measured for acute phase reactants, and muscle enzymes using commercial assays (BN-II immunoturbidimetry [Siemens], Hitachi 736 [Roche] and Synchron LX-20 [Beckman Coulter]) in 33 JDM patients (median age 11.5 yrs) and 37 age, gender and race-matched controls, after holding morning medications. Flow cytometry assessed for T, B and NK cell subsets. vWF antigen was quantified by agglutination (STA-R, Roche/Stago). Disease activity measures were assessed by physicians blinded to laboratory results.

Results:

Serum levels of muscle enzymes (CK, LDH, AST, ALT, and CK-MB/CK ratio [P < 0.004 for all]), acute phase reactants (albumin, alpha-1-acid glycoprotein [AAG], serum amyloid A [SAA], ferritin, haptoglobin, erythrocyte sedimentation rate [ESR]), and vWF lets were increased in JDM patients compared to controls. Lymphocyte subsets (CD3% and CD8% were also increased but NK% was decreased in JDM patients (P = 0.0001– 0.045). Many measures correlated moderately with each other (r_s= 0.25–0.68, P = 0.0001–0.046) and only two were redundant (AST with ALT, r_s= 0.74). vWF, CK-MB/CK ratio, albumin, LDH, AAG, AST, ALT, ESR, hematocrit (Hct), and NK% all correlated with MD global activity (r_s= 0.39–0.60, P = 0.001–0.046). Many of these also correlated with muscle strength by manual muscle testing (MMT) as well as C reactive protein (hsCRP), CD8%, and complement components C3c and C4 (r_s= 0.39 – 0.62, P = 0.001 – 0.048). Extramuscular activity (ExMA) by the Myositis Disease Activity Assessment Tool correlated with several of these markers, but also with SAA, ferritin, C3c, hsCRP, cystatin C and IgA (r_s= 0.41– 0.67, P = 0.001– 0.049). Multivariable linear regression modeling using backwards elimination yielded a model that best predicted MD global activity and included vWF, CK-MB/CK, ALT, AST, ESR, Hct and AAG (R²= 0.69, P = 0.004). This was improved from a model that included only muscle enzymes (CK-MB/CK alone, R²= 0.30, P = 0.01). Predictors of strength included CK-MB/CK, CD8%, and albumin (R²= 0.75, P < 0.001), which was also improved over a model consisting of only enzymes (CK-MB/CK alone, R²= 0.19, P = 0.042). ExMA was highly predicted by the combination of vWF, CK-MB/CK, hsCRP, and AAG (R²= 0.85, P < 0.001) and not predicted by muscle enzymes in isolation (R²= 0.0).

Conclusion:

An endothelial activation marker vWF, as well acute phase reactants, peripheral blood lymphocyte subsets, and muscle enzymes are good biomarkers of disease activity for JDM. In various combinations, these predict global activity, strength, and are most helpful in assessing ExMA. The addition of these biomarkers appears to improve upon the assessment of disease activity over muscle enzymes measured in isolation.

To cite this abstract, please use the following information:
Rider, L., Li, L., Chipman, J., Costello, R., O'Hanlon, T., Fleisher, T., et al; Biomarkers of Juvenile Dermatomyositis (JDM) Aid in Assessing Disease Activity Over Enzymes Alone [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1514
DOI: 10.1002/art.26588

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