Statin-associated autoimmune myopathy: A distinct new IFL pattern can increase the rate of HMGCR antibody detection by clinical laboratories

Autoimmun Rev. 2016 Dec;15(12):1161-1166. doi: 10.1016/j.autrev.2016.09.005. Epub 2016 Sep 15.

Abstract

Background and objective: Statin-associated autoimmune myopathy (SAAM) with anti-HMGCR antibodies has recently been described. Several specific immunoassays are in use to detect HMGCR antibodies. In the course of systematic autoantibody screening we recognized a new distinct IFL staining pattern on rat liver sections that regularly coincided with anti-HMGCR antibodies. In this study we investigated whether this new IFL pattern is specifically associated to statin-associated autoimmune myopathy and corresponds to anti-HMGCR antibodies.

Patients and methods: Twenty-three patients positive for anti-HMGCR antibodies (14 diagnosed with SAAM) were investigated for anti-HMGCR antibodies by two ELISA assays and confirmed by immmunoblot. HMGCR associated liver IFL pattern (HALIP) was detected by indirect IFL and the reactivity against HMGCR was confirmed by immunoabsorption using purified human HMGCR antigen. 90 patients with other autoimmune diseases and 45 non-autoimmune statin treated patients were studied as controls.

Results: 21 out of 23 (91%) anti-HMGCR positive patients were HALIP positive. The staining was completely and specifically removed by immunoabsorption with human purified HMGCR. None of the control sera from autoimmune patients or non-autoimmune statin treated subjects was positive for HALIP. Statistical concordance between HALIP and anti-HMGCR antibody specific tests was 98.7%, kappa 0.95.

Conclusions: A new and distinct IFL staining pattern (HALIP) is associated to HMGCR associated myopathy. Absorption and concordance studies indicate that the antigen recognized in the liver by HALIP is HMGCR or a closely related protein. Awareness of this new pattern can help to detect HMGCR autoantibodies in statin treated patients tested for autoimmune serology.

Keywords: Anti-HMGCR; Blot; ELISA; HALIP pattern; Immunofluorescence pattern; Myositis; Statin-associated autoimmune myopathy.

Publication types

  • Review

MeSH terms

  • Autoantibodies / immunology*
  • Autoimmune Diseases / etiology*
  • Autoimmune Diseases / immunology
  • Enzyme-Linked Immunosorbent Assay / methods*
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / immunology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Middle Aged
  • Muscular Diseases / etiology*

Substances

  • Autoantibodies
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • HMGCR protein, human
  • Hydroxymethylglutaryl CoA Reductases