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Clinical Chemistry 48: 1681-1688, 2002;
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(Clinical Chemistry. 2002;48:1681-1688.)
© 2002 American Association for Clinical Chemistry, Inc.

Neopterin and Quinolinic Acid Are Surrogate Measures of Disease Activity in the Juvenile Idiopathic Inflammatory Myopathies

Lisa G. Rider1,2,1a, Adam S. Schiffenbauer2,1, Mark Zito3, Ken L. Lim4,5, Alaa Ahmed6, Lawrence S. Zemel7, Robert M. Rennebohm8, Murray H. Passo9, Ronald M. Summers10, Jeanne E. Hicks11, Peter A. Lachenbruch12, Melvyn P. Heyes3,13 and Frederick W. Miller1,2 in cooperation with the Juvenile Dermatomyositis Disease Activity Collaborative Study Group

1 Laboratory of Molecular and Developmental Immunology, Division of Monoclonal Antibodies, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Bethesda, MD 20892, and Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, MD 20892.

2 Environmental Autoimmunity Group, National Institute of Environmental Health Sciences (NIEHS), NIH, Bethesda, MD 20892.

3 Laboratory of Neurotoxicology, National Institute of Mental Health (NIMH), NIH, Bethesda, MD 20892.

4 Department of Medicine and Rheumatology, University of Glasgow, Glasgow Royal Infirmary, Glasgow G31 2ER, Scotland.

5 Sherwood Forest Hospitals NHS Trust, Kings Mill Centre, Notts NG17 4JL, England.

6 Specialty Laboratories, Santa Monica, CA 90404.

7 Connecticut Children’s Medical Center, University of Connecticut, Hartford, CT 06106.

8 Columbus Children’s Hospital, Ohio State University, Columbus, OH 43205.

9 Children’s Hospital, University of Cincinnati, Cincinnati, OH 45229.
Departments of
10 Radiology and
11 Rehabilitation Medicine, Clinical Center (CC), NIH, Bethesda, MD 20892.

12 Division of Biostatistics, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Bethesda, MD 20852.

13 Curagen Inc., Branford, CT 06405.

aAddress correspondence to this author at: Environmental Autoimmunity Group, NIEHS, NIH, 9 Memorial Dr., Room 1W101, MSC 0958, Bethesda, MD 20892. Fax 301-480-4127; e-mail RIDER{at}niehs.nih.gov.

Objective: We evaluated the utility of neopterin and quinolinic acid (QUIN) as surrogate measures of disease activity in juvenile idiopathic inflammatory myopathies (IIMs).

Methods: Plasma and first morning void urine samples were measured for neopterin and QUIN using commercial ELISA, HPLC, or gas chromatography–mass spectrometry in 45 juvenile IIM patients and 79 healthy controls. Myositis disease activity assessments were obtained.

Results: Plasma and urine neopterin and QUIN concentrations were increased in juvenile IIM patients compared with healthy controls (P <0.017). Urine neopterin and QUIN highly correlated with each other (rs = 0.73; P <0.0001). Urine neopterin and QUIN correlated moderately with myositis disease activity assessments, including physician and parent global activity assessments, muscle strength testing, functional assessments (Childhood Myositis Assessment Scale, Childhood Health Assessment Questionnaire), skin global activity, and edema on magnetic resonance imaging (rs = 0.42–0.62; P <0.05), but generally not with muscle-associated enzymes in serum. Urine neopterin or QUIN, in combination with either serum lactate dehydrogenase (LD) or aspartate aminotransferase (AST), significantly predicted global disease activity (R2 =0.40–0.56; P <0.002), and both were more sensitive to change than these serum enzymes (standardized response means, -0.41 to -0.48).

Conclusions: Urinary neopterin and QUIN are candidate measures of disease activity in juvenile IIM patients and add significantly to the prediction of global disease activity in combination with serum LD or AST values. Measurement of these markers in first morning void urine specimens appears to be as good as, or possibly better than, measurements of their concentrations in plasma.







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