Dr. Christopher-Stine has received consulting fees, speaking fees, and/or honoraria from Novartis, MedImmune, and Questcor (less than $10,000 each). Drs. Christopher-Stine and Mammen have patented and licensed a test for anti–3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies.
Antibody levels correlate with creatine kinase levels and strength in anti–3-hydroxy-3-methylglutaryl-coenzyme A reductase–associated autoimmune myopathy
Article first published online: 28 NOV 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 12, pages 4087–4093, December 2012
How to Cite
Werner, J. L., Christopher-Stine, L., Ghazarian, S. R., Pak, K. S., Kus, J. E., Daya, N. R., Lloyd, T. E. and Mammen, A. L. (2012), Antibody levels correlate with creatine kinase levels and strength in anti–3-hydroxy-3-methylglutaryl-coenzyme A reductase–associated autoimmune myopathy. Arthritis & Rheumatism, 64: 4087–4093. doi: 10.1002/art.34673
- Issue published online: 28 NOV 2012
- Article first published online: 28 NOV 2012
- Accepted manuscript online: 29 AUG 2012 03:08PM EST
- Manuscript Accepted: 9 AUG 2012
- Manuscript Received: 12 APR 2012
- NIH. Grant Numbers: K23-AR-053197, K08-NS062890, K08-AR-054783
- Huayi and Siuling Zhang Discovery Fund
- Ira T. Fine Discovery Fund
- Donald B. and Dorothy L. Stabler Foundation
Autoantibodies recognizing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) are found in patients with statin-associated immune-mediated necrotizing myopathy and, less commonly, in statin-unexposed patients with autoimmune myopathy. The main objective of this study was to define the association of anti-HMGCR antibody levels with disease activity.
Anti-HMGCR levels, creatine kinase (CK) levels, and strength were assessed in anti-HMGCR–positive patients. Associations of antibody level with CK level and strength at visit 1 were analyzed in 55 patients, 40 of whom were exposed to statins. In 12 statin-exposed and 5 statin-unexposed patients with serum from 5 serial visits, the evolution of antibody levels, CK levels, and strength was investigated.
Antibody levels were associated with CK levels (P < 0.001), arm strength (P < 0.05), and leg strength (P < 0.05) at visit 1, but these associations were only significant among statin-exposed patients in stratified analyses. With immunosuppressive treatment over 26.2 ± 12.6 months (mean ± SD), antibody levels declined (P < 0.05) and arm abduction strength improved (P < 0.05) in the 17 patients followed up longitudinally. The separate analysis showed that statin-exposed patients developed decreased antibody levels (P < 0.01), decreased CK levels (P < 0.001), improved arm strength (P < 0.05), and improved hip flexion strength (P < 0.05) with treatment. Anti-HMGCR antibody levels did not normalize in any patient.
In the entire cohort, initial anti-HMGCR levels correlated with indicators of disease activity; with immunosuppressive treatment, antibody levels declined and arm strength improved. Statin-exposed patients had significant improvements in CK levels and strength whereas statin-unexposed patients did not, suggesting a phenotypic difference between statin-exposed and statin-unexposed anti-HMGCR–positive patients.