title: Statin-associated autoimmune myopathy: A distinct new IFL pattern can increase the rate of HMGCR antibody detection by clinical laboratories.
abstract: 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.
  
  
  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.
authors.affiliation: Internal Medicine Department, Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Alvarado-Cardenas
authors.affiliation: Immunology Division, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Marin-Sánchez
authors.affiliation: Immunology Department, Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Martínez
authors.affiliation: Immunology Department, Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Martínez-Martínez
authors.affiliation: Internal Medicine Department, Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Pinal-Fernandez
authors.affiliation: Internal Medicine Department, Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Labrador-Horrillo
authors.affiliation: Internal Medicine Department, Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Balada
authors.affiliation: Unitat de Suport a la Recerca Barcelona ciutat, IDIAP Jordi Gol, Universitat Autónoma de Barcelona, Barcelona, Spain.
authors.forename: X
authors.initials: X
authors.lastname: Mundet-Tuduri
authors.affiliation: Neurology, Hospital de Viladecans, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Gonzalez-Mera
authors.affiliation: Internal Medicine, Sant Pau Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Casademont
authors.affiliation: Neurology, Hospital Infanta Leonor, Madrid, Spain.
authors.forename: E Martínez
authors.initials: EM
authors.lastname: Acebes
authors.affiliation: Muscle Research Group, Internal Medicine, Hospital Clinic, Universitat de Barcelona, Barcelona, and CIBERER, Spain.
authors.forename: P J
authors.initials: PJ
authors.lastname: Moreno
authors.affiliation: Immunology Department, Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Juarez
authors.affiliation: Muscle Research Group, Internal Medicine, Hospital Clinic, Universitat de Barcelona, Barcelona, and CIBERER, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Grau-Junyent
authors.affiliation: Immunology Division, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain; Department of Cell Biology, Physiology and Immunology, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Pujol-Borrell
authors.affiliation: Internal Medicine Department, Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain. Electronic address: aselva@vhebron.net.
authors.forename: A
authors.initials: A
authors.lastname: Selva-O'Callaghan
mesh_terms: D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000276:immunology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D008875:Middle Aged; D009135:Muscular Diseases / Q000209:etiology*
chemical_list: D001323:Autoantibodies; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C553220:HMGCR protein, human; D006903:Hydroxymethylglutaryl CoA Reductases
keywords: Anti-HMGCR; Blot; ELISA; HALIP pattern; Immunofluorescence pattern; Myositis; Statin-associated autoimmune myopathy