We thank Stenzel et al. for their comment on our article1 and agree that muscle biopsy analysis should ideally use more “modern” pathologic analysis to help distinguish polymyositis (PM) from inclusion body myositis (IBM). We have recently shown that transcriptomics2,3 or reverse transcription PCR detection of mis-splicing events from muscle biopsies because of TAR DNA-binding protein 43 loss of function is sensitive and specific for a diagnosis of IBM.4 This finding confirms a recent report that detection of mis-splicing predicts clinical development of IBM among patients diagnosed pathologically with “PM-Mito.”5
In clinical practice, however, many clinical pathology laboratories in the United States do not routinely perform extensive immunohistochemical studies to help distinguish PM from IBM. Furthermore, the specificity of some pathologic features reported in IBM, for example, the presence of p62-positive aggregates,5 have been questioned and require further validation. For these reasons, the 2011 European Neuromuscular Centre (ENMC) consensus diagnostic criteria use a combination of clinical and pathologic features to help establish the diagnosis.6 Recent and ongoing international IBM clinical trials use the 2011 ENMC criteria, although an ENMC meeting is planned this year to update the diagnostic criteria.7
Hopefully, development of more precise pathologic criteria can be widely agreed upon and used to diagnose IBM more accurately in the future.
Footnotes
Contributor Information
Thomas E. Lloyd, (Baltimore)
E. Harlan Michelle, (Baltimore).
Iago Pinal-Fernandez, (Bethesda, MD).
Andrew L. Mammen, (Bethesda, MD)
References
- 1.Michelle EH, Pinal-Fernandez I, Casal-Dominguez M, et al. Clinical subgroups and factors associated with progression in patients with inclusion body myositis. Neurology. 2023;100(13):e1406-e1417. doi: 10.1212/WNL.0000000000206777 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Ikenaga C, Date H, Kanagawa M, et al. Muscle transcriptomics shows overexpression of cadherin 1 in inclusion body myositis. Ann Neurol. 2022;91(3):317-328. doi: 10.1002/ana.26304 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Pinal-Fernandez I, Casal-Dominguez M, Derfoul A, et al. Machine learning algorithms reveal unique gene expression profiles in muscle biopsies from patients with different types of myositis. Ann Rheum Dis. 2020;79(9):1234-1242. doi: 10.1136/annrheumdis-2019-216599 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Britson KA, Ling JP, Braunstein KE, et al. Loss of TDP-43 function and rimmed vacuoles persist after T cell depletion in a xenograft model of sporadic inclusion body myositis. Sci Transl Med. 2022;14(628):eabi9196. doi: 10.1126/scitranslmed.abi9196 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Kleefeld F, Uruha A, Schänzer A, et al. Morphologic and molecular patterns of polymyositis with mitochondrial pathology and inclusion body myositis. Neurology. 2022;99(20):e2212-e2222. doi: 10.1212/WNL.0000000000201103 [DOI] [PubMed] [Google Scholar]
- 6.Milisenda JC, Pinal-Fernandez I, Lloyd TE, et al. Accumulation of autophagosome cargo protein p62 is common in idiopathic inflammatory myopathies. Clin Exp Rheumatol. 2021;39(2):351-356. doi: 10.55563/clinexprheumatol/6mp37n [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Rose MR; ENMC IBM Working Group. 188th ENMC International Workshop: inclusion body myositis, 2-4 December 2011, Naarden, The Netherlands. Neuromuscul Disord. 2013;23(12):1044-1055. doi: 10.1016/j.nmd.2013.08.007 [DOI] [PubMed] [Google Scholar]