{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nCytosolic 5′-nucleotidase 1A (NT5C1A) has emerged as a key autoantigen in inflammatory myopathies, notably in sporadic inclusion body myositis (sIBM). Autoantibodies directed against NT5C1A are detected in a significant proportion of sIBM patients and appear to correlate with greater muscle weakness, which distinguishes sIBM from other myopathies such as polymyositis and dermatomyositis. These findings support the diagnostic utility of NT5C1A autoantibodies, as demonstrated by studies that assessed their prevalence and clinical associations in sIBM and related conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role as an autoantigen, NT5C1A functions intracellularly as part of the 5′-nucleotidase family that dephosphorylates non-cyclic nucleoside monophosphates into nucleosides and inorganic phosphate. Experimental suppression of NT5C1A expression in muscle cells and animal models has been shown to elevate the AMP/ATP ratio, thereby enhancing AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase phosphorylation. These alterations promote changes in glucose uptake, lipid oxidation, and overall metabolic flexibility—a finding that extends to its involvement in gemcitabine metabolism in pancreatic ductal adenocarcinoma and in modulating responses to nucleoside analogues in leukemia. Interestingly, while comparative studies in non-mammalian species indicated that NT5C1A transcript levels paralleled muscle fiber oxidative capacity, such correlations were not observed in humans, reflecting species-specific regulation of this enzyme."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast to the intracellular role of NT5C1A, related enzymes within the 5′-nucleotidase family—such as the ecto-5′-nucleotidase (E5′N)—operate on the cell surface and are pivotal in converting extracellular nucleotides into immunosuppressive adenosine. For instance, overexpression of human E5′N on endothelial cells has been shown to diminish natural killer cell cytotoxicity, thereby highlighting an alternative mechanism by which nucleotide metabolism can regulate immune responses. This juxtaposition underscores the diverse functional roles of nucleotidases, ranging from intracellular metabolic regulation to extracellular immune modulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Thomas E Lloyd, Lisa Christopher-Stine, Iago Pinal-Fernandez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytosolic 5'-Nucleotidase 1A As a Target of Circulating Autoantibodies in Autoimmune Diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arthritis Care Res (Hoboken) (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/acr.22600"}], "href": "https://doi.org/10.1002/acr.22600"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25892010"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25892010"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "N A Goyal, T M Cash, U Alam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Seropositivity for NT5c1A antibody in sporadic inclusion body myositis predicts more severe motor, bulbar and respiratory involvement."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurol Neurosurg Psychiatry (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jnnp-2014-310008"}], "href": "https://doi.org/10.1136/jnnp-2014-310008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25857661"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25857661"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Adam Amlani, May Y Choi, Mark Tarnopolsky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body Myositis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Immunol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fimmu.2019.00745"}], "href": "https://doi.org/10.3389/fimmu.2019.00745"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31024569"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31024569"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sameer S Kulkarni, Håkan K R Karlsson, Ferenc Szekeres, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Suppression of 5'-nucleotidase enzymes promotes AMP-activated protein kinase (AMPK) phosphorylation and metabolism in human and mouse skeletal muscle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.268292"}], "href": "https://doi.org/10.1074/jbc.M111.268292"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21873433"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21873433"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Melanie S Patzak, Vijayalakshmi Kari, Shilpa Patil, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytosolic 5'-nucleotidase 1A is overexpressed in pancreatic cancer and mediates gemcitabine resistance by reducing intracellular gemcitabine metabolites."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EBioMedicine (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ebiom.2019.01.037"}], "href": "https://doi.org/10.1016/j.ebiom.2019.01.037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30709769"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30709769"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "A Fyrberg, S Mirzaee, K Lotfi "}, {"type": "b", "children": [{"type": "t", "text": "Cell cycle dependent regulation of deoxycytidine kinase, deoxyguanosine kinase, and cytosolic 5'-nucleotidase I activity in MOLT-4 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleosides Nucleotides Nucleic Acids (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15257770600894386"}], "href": "https://doi.org/10.1080/15257770600894386"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17065091"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17065091"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Katarzyna Lechward, Kinga Tkacz-Stachowska "}, {"type": "b", "children": [{"type": "t", "text": "Expression of cytosolic 5' nucleotidase does not correlate with expression of oxidative metabolism marker: myoglobine in human skeletal muscles."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Biochim Biophys Sin (Shanghai) (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/abbs/gmp011"}], "href": "https://doi.org/10.1093/abbs/gmp011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19352542"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19352542"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jason Saliba, Ryan Zabriskie, Rajarshi Ghosh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pharmacogenetic characterization of naturally occurring germline NT5C1A variants to chemotherapeutic nucleoside analogs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pharmacogenet Genomics (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/FPC.0000000000000208"}], "href": "https://doi.org/10.1097/FPC.0000000000000208"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26906009"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26906009"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Foy N Osborne, Kameljit K Kalsi, Charlotte Lawson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of human ecto-5'-nucleotidase in pig endothelium increases adenosine production and protects from NK cell-mediated lysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Transplant (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1600-6143.2005.00868.x"}], "href": "https://doi.org/10.1111/j.1600-6143.2005.00868.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15888028"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15888028"}]}]}]}