Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Nov;53(11):e2250326.
doi: 10.1002/eji.202250326. Epub 2023 Oct 10.

Toll-like receptors and IL-7 as potential biomarkers for immune-mediated necrotizing myopathies

Cristina Cappelletti  1 , Raffaella Brugnoni  1 , Silvia Bonanno  1 , Francesca Andreetta  1 , Franco Salerno  1 , Eleonora Canioni  1 , Gaetano Nicola Alfio Vattemi  2 , Paola Tonin  2 , Renato Mantegazza  1 , Lorenzo Maggi  1
Affiliations
Free article

Toll-like receptors and IL-7 as potential biomarkers for immune-mediated necrotizing myopathies

Cristina Cappelletti et al. Eur J Immunol. 2023 Nov.
Free article

Abstract

We aimed to verify whether the immune system may represent a source of potential biomarkers for the stratification of immune-mediated necrotizing myopathies (IMNMs) subtypes. A group of 22 patients diagnosed with IMNM [7 with autoantibodies against signal recognition particle (SRP) and 15 against 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR)] and 12 controls were included. A significant preponderance of M1 macrophages was observed in both SRP+ and HMGCR+ muscle samples (p < 0.0001 in SRP+ and p = 0.0316 for HMGCR+ ), with higher values for SRP+ (p = 0.01). Despite the significant increase observed in the expression of TLR4 and all endosomal Toll-like receptors (TLRs) at protein level in IMNM muscle tissue, only TLR7 has been shown considerably upregulated compared to controls at transcript level (p = 0.0026), whereas TLR9 was even decreased (p = 0.0223). Within IMNM subgroups, TLR4 (p = 0.0116) mRNA was significantly increased in SRP+ compared to HMGCR+ patients. Within IMNM group, only IL-7 was differentially expressed between SRP+ and HMGCR+ patients, with higher values in SRP+ patients (p = 0.0468). Overall, innate immunity represents a key player in pathological mechanisms of IMNM. TLR4 and the inflammatory cytokine IL-7 represent potential immune biomarkers able to differentiate between SRP+ and HMGCR+ patients.

Keywords: Cytokines; Immune-mediated necrotizing myopathies (IMNMs); Innate immunity; Macrophages; Toll-like receptors.

PubMed Disclaimer

References

    1. Allenbach, Y., Mammen, A. L., Benveniste, O. and Stenzel, W., the Immune-Mediated Necrotizing Myopathies Working Group, 224th ENMC international workshop: clinico-sero-pathological classification of immune-mediated necrotizing myopathies Zandvoort, The Netherlands, 14-16 October 2016. Neuromuscul. Disord. 2018. 28: 87-99.
    1. Day, J. A. and Limaye, V., Immune-mediated necrotising myopathy: a critical review of current concepts. Semin. Arthritis Rheum. 2019. 49: 420-429.
    1. Pinal-Fernandez, I., Casal-Dominguez, M., Carrino, J. A., Lahouti, A. H., Basharat, P., Albayda, J., Paik, J. J. et al., Thigh muscle MRI in immune-mediated necrotising myopathy: extensive oedema, early muscle damage and role of anti-SRP autoantibodies as a marker of severity. Ann. Rheum. Dis. 2016. 76: 681-687.
    1. Watanabe, Y., Uruha, A., Suzuki, S., Nakahara, J., Hamanaka, K., Takayama, K., Suzuki, N. et al., Clinical features and prognosis in anti-SRP and anti-HMGCR necrotising myopathy. J. Neurol. Neurosurg. Psychiatry 2016. 87: 1038-1044.
    1. Allenbach, Y. and Benveniste, O., Peculiar clinicopathological features of immune-mediated necrotizing myopathies. Curr. Opin. Rheumatol. 2018. 30: 655-663.

Publication types

LinkOut - more resources