NT5C1A, also known as cytosolic 5'-nucleotidase 1A or Mup44, is an enzyme involved in nucleotide metabolism. Mutations or alterations in its expression can lead to changed responses to treatment with nucleoside analogs, suggesting its role in drug-processing pathways [4].

In the context of myopathies, anti-NT5C1A autoantibodies have been widely studied. In sporadic inclusion body myositis (sIBM), these autoantibodies have a moderate sensitivity (0.49) and high specificity (0.92) for diagnosis using addressable laser bead immunoassay (ALBIA), and their presence may be associated with muscle weakness [1]. In Korean patients with inflammatory myopathies, anti-NT5C1A antibody was most frequently identified in IBM patients (40%), followed by dermatomyositis, immune-mediated necrotizing myopathy, and polymyositis, though seropositivity was also noted in non-IBM inflammatory myopathies [2]. In juvenile myositis, anti-NT5C1A autoantibodies are present in more than one-quarter of children, and patients with these autoantibodies have more severe disease, including greater pulmonary symptoms, more hospitalizations, and more medications required [3]. In idiopathic inflammatory myopathies, anti-NT5C1A antibody is associated with IBM, but seropositivity can also occur in non-IBM IIMs and does not correlate with prognostic factors or survival [5].

In conclusion, NT5C1A is an enzyme with a role in nucleotide metabolism and drug-processing. The study of anti-NT5C1A autoantibodies has revealed its association with various myopathies, especially sIBM. These findings from studies on patients contribute to understanding the diagnosis and disease severity in myopathy-related conditions, though the lack of information on KO/CKO mouse models limits a more in-depth exploration of its biological functions in vivo.

References:

1. Amlani, Adam, Choi, May Y, Tarnopolsky, Mark, Jung, Michelle, Fritzler, Marvin J. 2019. Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body Myositis. In Frontiers in immunology, 10, 745. doi:10.3389/fimmu.2019.00745. https://pubmed.ncbi.nlm.nih.gov/31024569/

2. Lee, Seung-Ah, Lee, Hyun Joon, Suh, Bum Chun, Choi, Young-Chul, Park, Hyung Jun. 2023. Clinical significance of anti-NT5c1A autoantibody in Korean patients with inflammatory myopathies. In PloS one, 18, e0284409. doi:10.1371/journal.pone.0284409. https://pubmed.ncbi.nlm.nih.gov/37058449/

3. Yeker, Richard M, Pinal-Fernandez, Iago, Kishi, Takayuki, Rider, Lisa G, Mammen, Andrew L. 2018. Anti-NT5C1A autoantibodies are associated with more severe disease in patients with juvenile myositis. In Annals of the rheumatic diseases, 77, 714-719. doi:10.1136/annrheumdis-2017-212436. https://pubmed.ncbi.nlm.nih.gov/29363513/

4. Saliba, Jason, Zabriskie, Ryan, Ghosh, Rajarshi, Tsai, Francis T F, Plon, Sharon E. . Pharmacogenetic characterization of naturally occurring germline NT5C1A variants to chemotherapeutic nucleoside analogs. In Pharmacogenetics and genomics, 26, 271-9. doi:10.1097/FPC.0000000000000208. https://pubmed.ncbi.nlm.nih.gov/26906009/

5. Ikenaga, Chiseko, Findlay, Andrew R, Goyal, Namita A, Pestronk, Alan, Weihl, Conrad C. 2021. Clinical utility of anti-cytosolic 5'-nucleotidase 1A antibody in idiopathic inflammatory myopathies. In Annals of clinical and translational neurology, 8, 571-578. doi:10.1002/acn3.51294. https://pubmed.ncbi.nlm.nih.gov/33556224/