Autoantibodies against 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase in patients with statin‐associated autoimmune myopathy

摘要: Statins lower cholesterol levels by specifically inhibiting HMGCR, a key enzyme in the biosynthetic pathway. These drugs significantly reduce cardiovascular endpoints and are among most commonly prescribed medications, with almost 30 million people U.S. statin 2005 (1). Musculoskeletal symptoms well-known complication of use range from myalgias cramps, which occur 9–20% users (2–4) to life-threatening rhabdomyolysis, rare event occurring at rate ~0.4 per 10,000 patient years (5). In cases, statin-induced myopathic events self-limited, complete recovery weeks or months after is discontinued (6). However, two recent studies have described 33 patients who developed an autoimmune myopathy following exposure, did not abate discontinuing statins (7, 8). Taking different approach, we recently identified sixteen necrotizing had novel autoantibody recognizing ~200 ~100 kDa proteins (9). Given that these proximal muscle weakness, elevated CK levels, MHC I expression on non-necrotic fibers, autoantibodies, responded immunosuppression, concluded IMNM. Of 12 anti-200/100 positive over age 50, 10 prior exposure (83%). This was higher than frequency age-matched controls polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM). We reasoned statin-associated autoantibodies provides model system for defining mechanistic relationship between drug developing specific response. Identification autoantigen(s) targeted immune response critical first step. In this study, demonstrated upregulates autoantigens. also increases ~97 HMGCR (10, 11), investigated whether might be autoantigen. Serum recognized intracellular catalytic domain HMGCR. Based finding, ELISA assay rapidly screen sera anti-HMGCR autoantibodies. We found 45 750 disease were (6%). Anti-HMGCR IMNM phenotype greater 90% those 50 exposure. Interestingly, upregulated regenerating fibers patients. suggest trigger against upregulating Even statins, presence high may perpetuate