Elina Tan^1-3, Chris Bundell^2,8, Aaron Bahadori⁴, Merrilee Needham^4-7, Anna Brusch^{1-2, 5,9}

¹Department of Clinical Immunology, Sir Charles Gairdner Hospital, Western Australia, Australia
²Department of Immunology, PathWest Laboratory Medicine, Nedlands, Australia
³Department of Clinical Immunology, Royal Perth Hospital, Perth, Australia
⁴Department of Neurology, Fiona Stanley Hospital, Murdoch, Australia,
⁵Neuromuscular Clinic, Perron Institute for Neurological and Translational Science, QEII Medical Centre, Nedlands, Australia,
⁶Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Australia
⁷School of Medicine, University of Notre Dame, Western Australia, Australia

⁸School of Biomedical Sciences, University of Western Australia, Nedlands, Western Australia
⁹Centre for Neuromuscular Disorders, University of Western Australia

 

Background: Anti–3-hydroxy-3-methylglutaryl-CoA-reductase (HMGCR) antibodies are associated with immune-mediated necrotising myopathy (IMNM), a rare disease typically requiring multi-modal immunosuppression.^{1, 2} PathWest Laboratory Medicine (PathWest) has been the sole provider in Western Australia (WA) of an anti-HMGCR ELISA assay since 2015. Positive predictive value (PPV) of this assay for a WA cohort (2015 - 2019) was calculated as 88%.³ This was the benchmark for performance set for audit of a WA cohort encompassing 2020 to 2023.

Methods:  Identified anti-HMGCR requests to PathWest between January 2020 – December 2023, and identified positive results (reference: < 11 relative units). Exclusion criteria: aged under 18 years; non-WA resident; requested outside a tertiary public hospital. Electronic records reviewed to confirm HMGCR-IMNM diagnosis by Immunologist, Rheumatologist or Neurologist. Calculated PPV.

Results: The number of anti-HMGCR requests from WA between 2020 – 2023 was 1,120. Twenty-five (2%) were positive. Of these, three were considered false positives resulting in a PPV of 88%. The PPV was previously calculated as 88% from a WA cohort of patients between 2015 – 2019 with application of the same exclusion criteria.  This audit demonstrates the assay remains robust in its performance and meets the benchmark PPV of 88% provided by analysis of our index cohort.

 

1          Allenbach Y, Benveniste O, Stenzel W, Boyer O. Immune-mediated necrotizing myopathy: clinical features and pathogenesis. Nature Reviews Rheumatology. 2020; 16: 689-701.

2          Mammen AL, Chung T, Christopher-Stine L, Rosen P, Rosen A, Doering KR, et al. Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy. Arthritis and rheumatism. 2011; 63: 713-21.

3          Tan E, Knight J, Khonasti S, Nolan D, McGettigan B, Bundell C, et al. Clinical associations of patients with anti-3-hydroxy-3-methylglutaryl CoA reductase antibody-associated immune-mediated necrotising myopathy. Intern Med J. 2023; 53: 1846-53.

 

Statement of originality: ET designed audit, collated data, reviewed medical records and wrote abstract. CB assisted with acquisition and review of data. ABa, MN, ABr assisted with data collection and review of medical records.