From Diagnosis to Prognosis: Revisiting the Meaning of Muscle ISG15 Overexpression in Juvenile Inflammatory Myopathies
Objective Juvenile idiopathic inflammatory/immune myopathies (IIMs) constitute a highly heterogeneous group of disorders with diagnostic difficulties and prognostic uncertainties. Circulating myositis‐specific autoantibodies (MSAs) have been recognized as reliable tools for patient substratification...
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| Veröffentlicht in: | Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2021-06, Vol.73 (6), p.1044-1052 |
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| creator | Hou, Cyrielle Durrleman, Chloé Periou, Baptiste Barnerias, Christine Bodemer, Christine Desguerre, Isabelle Quartier, Pierre Melki, Isabelle Rice, Gillian I. Rodero, Mathieu P. Charuel, Jean‐Luc Relaix, Fréderic Bader‐Meunier, Brigitte Authier, FrançoisJérôme Gitiaux, Cyril |
| description | Objective
Juvenile idiopathic inflammatory/immune myopathies (IIMs) constitute a highly heterogeneous group of disorders with diagnostic difficulties and prognostic uncertainties. Circulating myositis‐specific autoantibodies (MSAs) have been recognized as reliable tools for patient substratification. Considering the key role of type I interferon (IFN) up‐regulation in juvenile IIM, we undertook the present study to investigate whether IFN‐induced 15‐kd protein (ISG‐15) could be a reliable biomarker for stratification and diagnosis and to better elucidate its role in juvenile IIM pathophysiology.
Methods
The study included 56 patients: 24 with juvenile dermatomyositis (DM), 12 with juvenile overlap myositis (OM), 10 with Duchenne muscular dystrophy, and 10 with congenital myopathies. Muscle biopsy samples were assessed by immunohistochemistry, immunoblotting, and real‐time quantitative polymerase chain reaction. Negative regulators of type I IFN (ISG15 and USP18) and positive regulators of type I IFN (DDX58 and IFIH1) were analyzed.
Results
ISG15 expression discriminated patients with juvenile IIM from those with nonimmune myopathies and, among patients with juvenile IIM, discriminated those with DM from those with OM. Among patients with juvenile DM, up‐regulation of the type I IFN positive regulators DDX58 and IFIH1 was similar regardless of MSA status. In contrast, the highest levels of the type I IFN negative regulator ISG15 were observed in patients who were positive for melanoma differentiation–associated gene 5 (MDA‐5). Finally, ISG15 levels were inversely correlated with the severity of muscle histologic abnormalities and positively correlated with motor performance as evaluated by the Childhood Myositis Assessment Scale and by manual muscle strength testing.
Conclusion
Muscle ISG15 expression is strongly associated with juvenile DM, with patients exhibiting a different ISG‐15 muscle signature according to their MSA class. Patients with juvenile DM who are positive for MDA‐5 have higher expression of ISG15 in both gene form and protein form compared to the other subgroups. Moreover, our data show that negative regulation of type I IFN correlates with milder muscle involvement. |
| doi_str_mv | 10.1002/art.41625 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_03367619v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2534006213</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4225-ebb5679077767950ceb0b95172b4f8e8b7a9fa8cfb1ed4c58a8e0814d2f6278d3</originalsourceid><addsrcrecordid>eNp1kU1v1DAQhi0EaqvSQ_8AssQFDtuO7ThOuK0K_UC7KurH2XKyk66rxN7aSWD_PV7SFgkJX2ZsPXpn_L6EHDM4YQD81IT-JGM5l2_IARc8n0kO8u1Lz0q2T45ifIR0SgU5yD2yL4RgmQJ5QMbz4Dv61ZoH56ONtPf0R_DT5Qu9wdFG21v3QPs10iUat-t9Q5dDrFukV7cXTNLrEQP-2gSM0XpHraPfhxGd3QGuaU3Xmd6HLV1u_cb0a4vxPXnXmDbi0XM9JPfn3-7OLmeL64urs_liVmecyxlWlcxVCUqpVCTUWEFVSqZ4lTUFFpUyZWOKuqkYrrJaFqZAKFi24k3OVbESh-TzpLs2rd4E25mw1d5YfTlf6N0bCJGrnJUjS-ynid0E_zRg7HVnY41taxz6IWqeHAOeFUok9OM_6KMfgks_0VyKDCDnTPwdXgcfY8DmdQMGepedTtnpP9kl9sOz4lB1uHolX5JKwOkE_Ey2bv-vpOc3d5Pkb5xRoco</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2534006213</pqid></control><display><type>article</type><title>From Diagnosis to Prognosis: Revisiting the Meaning of Muscle ISG15 Overexpression in Juvenile Inflammatory Myopathies</title><source>MEDLINE</source><source>Wiley Online Library All Journals</source><source>Alma/SFX Local Collection</source><creator>Hou, Cyrielle ; Durrleman, Chloé ; Periou, Baptiste ; Barnerias, Christine ; Bodemer, Christine ; Desguerre, Isabelle ; Quartier, Pierre ; Melki, Isabelle ; Rice, Gillian I. ; Rodero, Mathieu P. ; Charuel, Jean‐Luc ; Relaix, Fréderic ; Bader‐Meunier, Brigitte ; Authier, FrançoisJérôme ; Gitiaux, Cyril</creator><creatorcontrib>Hou, Cyrielle ; Durrleman, Chloé ; Periou, Baptiste ; Barnerias, Christine ; Bodemer, Christine ; Desguerre, Isabelle ; Quartier, Pierre ; Melki, Isabelle ; Rice, Gillian I. ; Rodero, Mathieu P. ; Charuel, Jean‐Luc ; Relaix, Fréderic ; Bader‐Meunier, Brigitte ; Authier, FrançoisJérôme ; Gitiaux, Cyril</creatorcontrib><description>Objective
Juvenile idiopathic inflammatory/immune myopathies (IIMs) constitute a highly heterogeneous group of disorders with diagnostic difficulties and prognostic uncertainties. Circulating myositis‐specific autoantibodies (MSAs) have been recognized as reliable tools for patient substratification. Considering the key role of type I interferon (IFN) up‐regulation in juvenile IIM, we undertook the present study to investigate whether IFN‐induced 15‐kd protein (ISG‐15) could be a reliable biomarker for stratification and diagnosis and to better elucidate its role in juvenile IIM pathophysiology.
Methods
The study included 56 patients: 24 with juvenile dermatomyositis (DM), 12 with juvenile overlap myositis (OM), 10 with Duchenne muscular dystrophy, and 10 with congenital myopathies. Muscle biopsy samples were assessed by immunohistochemistry, immunoblotting, and real‐time quantitative polymerase chain reaction. Negative regulators of type I IFN (ISG15 and USP18) and positive regulators of type I IFN (DDX58 and IFIH1) were analyzed.
Results
ISG15 expression discriminated patients with juvenile IIM from those with nonimmune myopathies and, among patients with juvenile IIM, discriminated those with DM from those with OM. Among patients with juvenile DM, up‐regulation of the type I IFN positive regulators DDX58 and IFIH1 was similar regardless of MSA status. In contrast, the highest levels of the type I IFN negative regulator ISG15 were observed in patients who were positive for melanoma differentiation–associated gene 5 (MDA‐5). Finally, ISG15 levels were inversely correlated with the severity of muscle histologic abnormalities and positively correlated with motor performance as evaluated by the Childhood Myositis Assessment Scale and by manual muscle strength testing.
Conclusion
Muscle ISG15 expression is strongly associated with juvenile DM, with patients exhibiting a different ISG‐15 muscle signature according to their MSA class. Patients with juvenile DM who are positive for MDA‐5 have higher expression of ISG15 in both gene form and protein form compared to the other subgroups. Moreover, our data show that negative regulation of type I IFN correlates with milder muscle involvement.</description><identifier>ISSN: 2326-5191</identifier><identifier>ISSN: 2326-5205</identifier><identifier>EISSN: 2326-5205</identifier><identifier>EISSN: 2326-5191</identifier><identifier>DOI: 10.1002/art.41625</identifier><identifier>PMID: 33314705</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Abnormalities ; Adolescent ; Autoantibodies ; Autoantibodies - immunology ; Biomarkers ; Biopsy ; Case-Control Studies ; Child ; Child, Preschool ; Children ; Correlation ; Cytokines - metabolism ; DEAD Box Protein 58 - metabolism ; Dermatomyositis ; Dermatomyositis - diagnosis ; Dermatomyositis - metabolism ; Dermatomyositis - physiopathology ; Diagnosis ; Duchenne's muscular dystrophy ; Dystrophy ; Female ; Humans ; Immunoblotting ; Immunohistochemistry ; Inflammation ; Interferon ; Interferon-Induced Helicase, IFIH1 - metabolism ; Life Sciences ; Male ; Melanoma ; Motor task performance ; Muscle strength ; Muscle, Skeletal - metabolism ; Muscular dystrophy ; Muscular Dystrophy, Duchenne - metabolism ; Myopathies, Structural, Congenital - metabolism ; Myositis ; Myositis - diagnosis ; Myositis - metabolism ; Myositis - physiopathology ; Polymerase chain reaction ; Prognosis ; Proteins ; Real-Time Polymerase Chain Reaction ; Receptors, Immunologic - metabolism ; Regulation ; Strength testing ; Subgroups ; Ubiquitin Thiolesterase - metabolism ; Ubiquitins - metabolism ; USP18 protein</subject><ispartof>Arthritis & rheumatology (Hoboken, N.J.), 2021-06, Vol.73 (6), p.1044-1052</ispartof><rights>2020, American College of Rheumatology</rights><rights>2020, American College of Rheumatology.</rights><rights>2021 American College of Rheumatology</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4225-ebb5679077767950ceb0b95172b4f8e8b7a9fa8cfb1ed4c58a8e0814d2f6278d3</citedby><cites>FETCH-LOGICAL-c4225-ebb5679077767950ceb0b95172b4f8e8b7a9fa8cfb1ed4c58a8e0814d2f6278d3</cites><orcidid>0000-0002-2190-6843 ; 0000-0002-8057-333X ; 0000-0002-0258-4738 ; 0000-0002-1300-0187 ; 0000-0002-4223-0571 ; 0000-0002-1769-549X ; 0000-0001-8772-0905</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fart.41625$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fart.41625$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33314705$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-03367619$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Hou, Cyrielle</creatorcontrib><creatorcontrib>Durrleman, Chloé</creatorcontrib><creatorcontrib>Periou, Baptiste</creatorcontrib><creatorcontrib>Barnerias, Christine</creatorcontrib><creatorcontrib>Bodemer, Christine</creatorcontrib><creatorcontrib>Desguerre, Isabelle</creatorcontrib><creatorcontrib>Quartier, Pierre</creatorcontrib><creatorcontrib>Melki, Isabelle</creatorcontrib><creatorcontrib>Rice, Gillian I.</creatorcontrib><creatorcontrib>Rodero, Mathieu P.</creatorcontrib><creatorcontrib>Charuel, Jean‐Luc</creatorcontrib><creatorcontrib>Relaix, Fréderic</creatorcontrib><creatorcontrib>Bader‐Meunier, Brigitte</creatorcontrib><creatorcontrib>Authier, FrançoisJérôme</creatorcontrib><creatorcontrib>Gitiaux, Cyril</creatorcontrib><title>From Diagnosis to Prognosis: Revisiting the Meaning of Muscle ISG15 Overexpression in Juvenile Inflammatory Myopathies</title><title>Arthritis & rheumatology (Hoboken, N.J.)</title><addtitle>Arthritis Rheumatol</addtitle><description>Objective
Juvenile idiopathic inflammatory/immune myopathies (IIMs) constitute a highly heterogeneous group of disorders with diagnostic difficulties and prognostic uncertainties. Circulating myositis‐specific autoantibodies (MSAs) have been recognized as reliable tools for patient substratification. Considering the key role of type I interferon (IFN) up‐regulation in juvenile IIM, we undertook the present study to investigate whether IFN‐induced 15‐kd protein (ISG‐15) could be a reliable biomarker for stratification and diagnosis and to better elucidate its role in juvenile IIM pathophysiology.
Methods
The study included 56 patients: 24 with juvenile dermatomyositis (DM), 12 with juvenile overlap myositis (OM), 10 with Duchenne muscular dystrophy, and 10 with congenital myopathies. Muscle biopsy samples were assessed by immunohistochemistry, immunoblotting, and real‐time quantitative polymerase chain reaction. Negative regulators of type I IFN (ISG15 and USP18) and positive regulators of type I IFN (DDX58 and IFIH1) were analyzed.
Results
ISG15 expression discriminated patients with juvenile IIM from those with nonimmune myopathies and, among patients with juvenile IIM, discriminated those with DM from those with OM. Among patients with juvenile DM, up‐regulation of the type I IFN positive regulators DDX58 and IFIH1 was similar regardless of MSA status. In contrast, the highest levels of the type I IFN negative regulator ISG15 were observed in patients who were positive for melanoma differentiation–associated gene 5 (MDA‐5). Finally, ISG15 levels were inversely correlated with the severity of muscle histologic abnormalities and positively correlated with motor performance as evaluated by the Childhood Myositis Assessment Scale and by manual muscle strength testing.
Conclusion
Muscle ISG15 expression is strongly associated with juvenile DM, with patients exhibiting a different ISG‐15 muscle signature according to their MSA class. Patients with juvenile DM who are positive for MDA‐5 have higher expression of ISG15 in both gene form and protein form compared to the other subgroups. Moreover, our data show that negative regulation of type I IFN correlates with milder muscle involvement.</description><subject>Abnormalities</subject><subject>Adolescent</subject><subject>Autoantibodies</subject><subject>Autoantibodies - immunology</subject><subject>Biomarkers</subject><subject>Biopsy</subject><subject>Case-Control Studies</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Children</subject><subject>Correlation</subject><subject>Cytokines - metabolism</subject><subject>DEAD Box Protein 58 - metabolism</subject><subject>Dermatomyositis</subject><subject>Dermatomyositis - diagnosis</subject><subject>Dermatomyositis - metabolism</subject><subject>Dermatomyositis - physiopathology</subject><subject>Diagnosis</subject><subject>Duchenne's muscular dystrophy</subject><subject>Dystrophy</subject><subject>Female</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Immunohistochemistry</subject><subject>Inflammation</subject><subject>Interferon</subject><subject>Interferon-Induced Helicase, IFIH1 - metabolism</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Melanoma</subject><subject>Motor task performance</subject><subject>Muscle strength</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscular dystrophy</subject><subject>Muscular Dystrophy, Duchenne - metabolism</subject><subject>Myopathies, Structural, Congenital - metabolism</subject><subject>Myositis</subject><subject>Myositis - diagnosis</subject><subject>Myositis - metabolism</subject><subject>Myositis - physiopathology</subject><subject>Polymerase chain reaction</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Receptors, Immunologic - metabolism</subject><subject>Regulation</subject><subject>Strength testing</subject><subject>Subgroups</subject><subject>Ubiquitin Thiolesterase - metabolism</subject><subject>Ubiquitins - metabolism</subject><subject>USP18 protein</subject><issn>2326-5191</issn><issn>2326-5205</issn><issn>2326-5205</issn><issn>2326-5191</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1v1DAQhi0EaqvSQ_8AssQFDtuO7ThOuK0K_UC7KurH2XKyk66rxN7aSWD_PV7SFgkJX2ZsPXpn_L6EHDM4YQD81IT-JGM5l2_IARc8n0kO8u1Lz0q2T45ifIR0SgU5yD2yL4RgmQJ5QMbz4Dv61ZoH56ONtPf0R_DT5Qu9wdFG21v3QPs10iUat-t9Q5dDrFukV7cXTNLrEQP-2gSM0XpHraPfhxGd3QGuaU3Xmd6HLV1u_cb0a4vxPXnXmDbi0XM9JPfn3-7OLmeL64urs_liVmecyxlWlcxVCUqpVCTUWEFVSqZ4lTUFFpUyZWOKuqkYrrJaFqZAKFi24k3OVbESh-TzpLs2rd4E25mw1d5YfTlf6N0bCJGrnJUjS-ynid0E_zRg7HVnY41taxz6IWqeHAOeFUok9OM_6KMfgks_0VyKDCDnTPwdXgcfY8DmdQMGepedTtnpP9kl9sOz4lB1uHolX5JKwOkE_Ey2bv-vpOc3d5Pkb5xRoco</recordid><startdate>202106</startdate><enddate>202106</enddate><creator>Hou, Cyrielle</creator><creator>Durrleman, Chloé</creator><creator>Periou, Baptiste</creator><creator>Barnerias, Christine</creator><creator>Bodemer, Christine</creator><creator>Desguerre, Isabelle</creator><creator>Quartier, Pierre</creator><creator>Melki, Isabelle</creator><creator>Rice, Gillian I.</creator><creator>Rodero, Mathieu P.</creator><creator>Charuel, Jean‐Luc</creator><creator>Relaix, Fréderic</creator><creator>Bader‐Meunier, Brigitte</creator><creator>Authier, FrançoisJérôme</creator><creator>Gitiaux, Cyril</creator><general>Wiley Subscription Services, Inc</general><general>Wiley</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TM</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><orcidid>https://orcid.org/0000-0002-2190-6843</orcidid><orcidid>https://orcid.org/0000-0002-8057-333X</orcidid><orcidid>https://orcid.org/0000-0002-0258-4738</orcidid><orcidid>https://orcid.org/0000-0002-1300-0187</orcidid><orcidid>https://orcid.org/0000-0002-4223-0571</orcidid><orcidid>https://orcid.org/0000-0002-1769-549X</orcidid><orcidid>https://orcid.org/0000-0001-8772-0905</orcidid></search><sort><creationdate>202106</creationdate><title>From Diagnosis to Prognosis: Revisiting the Meaning of Muscle ISG15 Overexpression in Juvenile Inflammatory Myopathies</title><author>Hou, Cyrielle ; Durrleman, Chloé ; Periou, Baptiste ; Barnerias, Christine ; Bodemer, Christine ; Desguerre, Isabelle ; Quartier, Pierre ; Melki, Isabelle ; Rice, Gillian I. ; Rodero, Mathieu P. ; Charuel, Jean‐Luc ; Relaix, Fréderic ; Bader‐Meunier, Brigitte ; Authier, FrançoisJérôme ; Gitiaux, Cyril</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4225-ebb5679077767950ceb0b95172b4f8e8b7a9fa8cfb1ed4c58a8e0814d2f6278d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Abnormalities</topic><topic>Adolescent</topic><topic>Autoantibodies</topic><topic>Autoantibodies - immunology</topic><topic>Biomarkers</topic><topic>Biopsy</topic><topic>Case-Control Studies</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Children</topic><topic>Correlation</topic><topic>Cytokines - metabolism</topic><topic>DEAD Box Protein 58 - metabolism</topic><topic>Dermatomyositis</topic><topic>Dermatomyositis - diagnosis</topic><topic>Dermatomyositis - metabolism</topic><topic>Dermatomyositis - physiopathology</topic><topic>Diagnosis</topic><topic>Duchenne's muscular dystrophy</topic><topic>Dystrophy</topic><topic>Female</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Immunohistochemistry</topic><topic>Inflammation</topic><topic>Interferon</topic><topic>Interferon-Induced Helicase, IFIH1 - metabolism</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Melanoma</topic><topic>Motor task performance</topic><topic>Muscle strength</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscular dystrophy</topic><topic>Muscular Dystrophy, Duchenne - metabolism</topic><topic>Myopathies, Structural, Congenital - metabolism</topic><topic>Myositis</topic><topic>Myositis - diagnosis</topic><topic>Myositis - metabolism</topic><topic>Myositis - physiopathology</topic><topic>Polymerase chain reaction</topic><topic>Prognosis</topic><topic>Proteins</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Receptors, Immunologic - metabolism</topic><topic>Regulation</topic><topic>Strength testing</topic><topic>Subgroups</topic><topic>Ubiquitin Thiolesterase - metabolism</topic><topic>Ubiquitins - metabolism</topic><topic>USP18 protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hou, Cyrielle</creatorcontrib><creatorcontrib>Durrleman, Chloé</creatorcontrib><creatorcontrib>Periou, Baptiste</creatorcontrib><creatorcontrib>Barnerias, Christine</creatorcontrib><creatorcontrib>Bodemer, Christine</creatorcontrib><creatorcontrib>Desguerre, Isabelle</creatorcontrib><creatorcontrib>Quartier, Pierre</creatorcontrib><creatorcontrib>Melki, Isabelle</creatorcontrib><creatorcontrib>Rice, Gillian I.</creatorcontrib><creatorcontrib>Rodero, Mathieu P.</creatorcontrib><creatorcontrib>Charuel, Jean‐Luc</creatorcontrib><creatorcontrib>Relaix, Fréderic</creatorcontrib><creatorcontrib>Bader‐Meunier, Brigitte</creatorcontrib><creatorcontrib>Authier, FrançoisJérôme</creatorcontrib><creatorcontrib>Gitiaux, Cyril</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>Arthritis & rheumatology (Hoboken, N.J.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hou, Cyrielle</au><au>Durrleman, Chloé</au><au>Periou, Baptiste</au><au>Barnerias, Christine</au><au>Bodemer, Christine</au><au>Desguerre, Isabelle</au><au>Quartier, Pierre</au><au>Melki, Isabelle</au><au>Rice, Gillian I.</au><au>Rodero, Mathieu P.</au><au>Charuel, Jean‐Luc</au><au>Relaix, Fréderic</au><au>Bader‐Meunier, Brigitte</au><au>Authier, FrançoisJérôme</au><au>Gitiaux, Cyril</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>From Diagnosis to Prognosis: Revisiting the Meaning of Muscle ISG15 Overexpression in Juvenile Inflammatory Myopathies</atitle><jtitle>Arthritis & rheumatology (Hoboken, N.J.)</jtitle><addtitle>Arthritis Rheumatol</addtitle><date>2021-06</date><risdate>2021</risdate><volume>73</volume><issue>6</issue><spage>1044</spage><epage>1052</epage><pages>1044-1052</pages><issn>2326-5191</issn><issn>2326-5205</issn><eissn>2326-5205</eissn><eissn>2326-5191</eissn><abstract>Objective
Juvenile idiopathic inflammatory/immune myopathies (IIMs) constitute a highly heterogeneous group of disorders with diagnostic difficulties and prognostic uncertainties. Circulating myositis‐specific autoantibodies (MSAs) have been recognized as reliable tools for patient substratification. Considering the key role of type I interferon (IFN) up‐regulation in juvenile IIM, we undertook the present study to investigate whether IFN‐induced 15‐kd protein (ISG‐15) could be a reliable biomarker for stratification and diagnosis and to better elucidate its role in juvenile IIM pathophysiology.
Methods
The study included 56 patients: 24 with juvenile dermatomyositis (DM), 12 with juvenile overlap myositis (OM), 10 with Duchenne muscular dystrophy, and 10 with congenital myopathies. Muscle biopsy samples were assessed by immunohistochemistry, immunoblotting, and real‐time quantitative polymerase chain reaction. Negative regulators of type I IFN (ISG15 and USP18) and positive regulators of type I IFN (DDX58 and IFIH1) were analyzed.
Results
ISG15 expression discriminated patients with juvenile IIM from those with nonimmune myopathies and, among patients with juvenile IIM, discriminated those with DM from those with OM. Among patients with juvenile DM, up‐regulation of the type I IFN positive regulators DDX58 and IFIH1 was similar regardless of MSA status. In contrast, the highest levels of the type I IFN negative regulator ISG15 were observed in patients who were positive for melanoma differentiation–associated gene 5 (MDA‐5). Finally, ISG15 levels were inversely correlated with the severity of muscle histologic abnormalities and positively correlated with motor performance as evaluated by the Childhood Myositis Assessment Scale and by manual muscle strength testing.
Conclusion
Muscle ISG15 expression is strongly associated with juvenile DM, with patients exhibiting a different ISG‐15 muscle signature according to their MSA class. Patients with juvenile DM who are positive for MDA‐5 have higher expression of ISG15 in both gene form and protein form compared to the other subgroups. Moreover, our data show that negative regulation of type I IFN correlates with milder muscle involvement.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33314705</pmid><doi>10.1002/art.41625</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-2190-6843</orcidid><orcidid>https://orcid.org/0000-0002-8057-333X</orcidid><orcidid>https://orcid.org/0000-0002-0258-4738</orcidid><orcidid>https://orcid.org/0000-0002-1300-0187</orcidid><orcidid>https://orcid.org/0000-0002-4223-0571</orcidid><orcidid>https://orcid.org/0000-0002-1769-549X</orcidid><orcidid>https://orcid.org/0000-0001-8772-0905</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Arthritis & rheumatology (Hoboken, N.J.), 2021-06, Vol.73 (6), p.1044-1052 |
| issn | 2326-5191 2326-5205 2326-5205 2326-5191 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_hal_03367619v1 |
| source | MEDLINE; Wiley Online Library All Journals; Alma/SFX Local Collection |
| subjects | Abnormalities Adolescent Autoantibodies Autoantibodies - immunology Biomarkers Biopsy Case-Control Studies Child Child, Preschool Children Correlation Cytokines - metabolism DEAD Box Protein 58 - metabolism Dermatomyositis Dermatomyositis - diagnosis Dermatomyositis - metabolism Dermatomyositis - physiopathology Diagnosis Duchenne's muscular dystrophy Dystrophy Female Humans Immunoblotting Immunohistochemistry Inflammation Interferon Interferon-Induced Helicase, IFIH1 - metabolism Life Sciences Male Melanoma Motor task performance Muscle strength Muscle, Skeletal - metabolism Muscular dystrophy Muscular Dystrophy, Duchenne - metabolism Myopathies, Structural, Congenital - metabolism Myositis Myositis - diagnosis Myositis - metabolism Myositis - physiopathology Polymerase chain reaction Prognosis Proteins Real-Time Polymerase Chain Reaction Receptors, Immunologic - metabolism Regulation Strength testing Subgroups Ubiquitin Thiolesterase - metabolism Ubiquitins - metabolism USP18 protein |
| title | From Diagnosis to Prognosis: Revisiting the Meaning of Muscle ISG15 Overexpression in Juvenile Inflammatory Myopathies |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T21%3A43%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_hal_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=From%20Diagnosis%20to%20Prognosis:%20Revisiting%20the%20Meaning%20of%20Muscle%20ISG15%20Overexpression%20in%20Juvenile%20Inflammatory%20Myopathies&rft.jtitle=Arthritis%20&%20rheumatology%20(Hoboken,%20N.J.)&rft.au=Hou,%20Cyrielle&rft.date=2021-06&rft.volume=73&rft.issue=6&rft.spage=1044&rft.epage=1052&rft.pages=1044-1052&rft.issn=2326-5191&rft.eissn=2326-5205&rft_id=info:doi/10.1002/art.41625&rft_dat=%3Cproquest_hal_p%3E2534006213%3C/proquest_hal_p%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2534006213&rft_id=info:pmid/33314705&rfr_iscdi=true |