Rarity of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies in statin users, including those with self-limited musculoskeletal side effects

Abstract

Objective: Statins, among the most commonly prescribed medications, are associated with a wide range of musculoskeletal side effects. These include a progressive autoimmune myopathy with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibodies that requires immunosuppression. However, it remains unknown whether these antibodies are found in statin users with and without self-limited musculoskeletal side effects; this limits their diagnostic utility. The current work assessed the prevalence of anti-HMGCR antibodies in these groups of statin users.

Methods: We determined the prevalence of anti-HMGCR antibodies in 1,966 participants (including 763 current statin users) in a substudy of the community-based Atherosclerosis Risk in Communities (ARIC) Study and 98 French Canadian subjects with familial hypercholesterolemia, including 51 with documented statin intolerance.

Results: No participant in the ARIC substudy, including those with past or current statin exposure at the time of sample collection, had anti-HMGCR antibodies. Similarly, none of 51 patients with self-limited statin intolerance or 47 statin-tolerant patients receiving maximal statin therapy were anti-HMGCR positive.

Conclusion: The majority of patients with and without statin exposure, including those with self-limited statin intolerance, do not develop anti-HMGCR antibodies. Therefore, anti-HMGCR antibodies are highly specific for those with an autoimmune myopathy.

Figure 1. ELISA positive sera from ARIC subjects do not immunoprecipitate HMGCR

Immunoprecipitations were performed using full length ³⁵S-methionine labeled HMGCR. Lane 1 shows the input IVTT product. Immunoprecipitations using serum from anti-HMGCR negative (#485) and positive (#9190) controls are shown in lanes 2 and 3, respectively. Lanes 4–21 show immunoprecipitations using serum from those patients in the ARIC cohort with the highest anti-HMGCR titers by ELISA.