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SIGLEC1 enables straightforward assessment of type I interferon activity in idiopathic inflammatory myopathies
OBJECTIVE: To evaluate sialic acid binding Ig-like lectin 1 (SIGLEC1) expression on monocytes by flow cytometry as a type I interferon biomarker in idiopathic inflammatory myopathies (IIM). METHODS: We performed a retrospective analysis of adult and paediatric patients with the diagnosis of IIM. SIG...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8860073/ https://www.ncbi.nlm.nih.gov/pubmed/35177553 http://dx.doi.org/10.1136/rmdopen-2021-001934 |
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author | Graf, Manuel von Stuckrad, Sae Lim Uruha, Akinori Klotsche, Jens Zorn-Pauly, Lydia Unterwalder, Nadine Buttgereit, Thomas Krusche, Martin Meisel, Christian Burmester, Gerd R Hiepe, Falk Biesen, Robert Kallinich, Tilmann Stenzel, Werner Schneider, Udo Rose, Thomas |
author_facet | Graf, Manuel von Stuckrad, Sae Lim Uruha, Akinori Klotsche, Jens Zorn-Pauly, Lydia Unterwalder, Nadine Buttgereit, Thomas Krusche, Martin Meisel, Christian Burmester, Gerd R Hiepe, Falk Biesen, Robert Kallinich, Tilmann Stenzel, Werner Schneider, Udo Rose, Thomas |
author_sort | Graf, Manuel |
collection | PubMed |
description | OBJECTIVE: To evaluate sialic acid binding Ig-like lectin 1 (SIGLEC1) expression on monocytes by flow cytometry as a type I interferon biomarker in idiopathic inflammatory myopathies (IIM). METHODS: We performed a retrospective analysis of adult and paediatric patients with the diagnosis of IIM. SIGLEC1 expression was assessed by flow cytometry and was compared with Physician Global Assessment or Childhood Myositis Assessment Scale disease activity scores. Mann Whitney U test and receiver operating characteristic curves were used for cross-sectional data analysis (n=96), two-level mixed-effects linear regression model for longitudinal analyses (n=26, 110 visits). Response to treatment was analysed in 14 patients within 12 months, using Wilcoxon test. SIGLEC1 was compared with interferon-stimulated gene 15/MxA status by immunohistochemical staining of muscle biopsies (n=17). RESULTS: 96 patients with adult (a) and juvenile (j) dermatomyositis (DM, n=38), antisynthetase syndrome (AS, n=19), immune-mediated necrotising myopathy (IMNM, n=8), inclusion body myositis (IBM, n=9) and overlap myositis (n=22) were included. SIGLEC1 distinguished significantly between active and inactive disease with an area under the curve of 0.92 (95% CI 0.83 to 1) in DM and correlated with disease activity longitudinally (aDM: standardised beta=0.54, p<0.001; jDM: standardised beta=−0.70, p<0.001). Response to treatment in DM was associated with a decreasing SIGLEC1 (p<0.01, Wilcoxon test). SIGLEC1 was found upregulated in 8 of 19 patients with AS, 2 of 9 patients with IBM but not in IMNM. CONCLUSION: SIGLEC1 is a candidate biomarker to assess type I interferon activity in IIM and proved useful for monitoring disease activity and response to treatment in juvenile and adult DM. |
format | Online Article Text |
id | pubmed-8860073 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-88600732022-03-08 SIGLEC1 enables straightforward assessment of type I interferon activity in idiopathic inflammatory myopathies Graf, Manuel von Stuckrad, Sae Lim Uruha, Akinori Klotsche, Jens Zorn-Pauly, Lydia Unterwalder, Nadine Buttgereit, Thomas Krusche, Martin Meisel, Christian Burmester, Gerd R Hiepe, Falk Biesen, Robert Kallinich, Tilmann Stenzel, Werner Schneider, Udo Rose, Thomas RMD Open Connective Tissue Diseases OBJECTIVE: To evaluate sialic acid binding Ig-like lectin 1 (SIGLEC1) expression on monocytes by flow cytometry as a type I interferon biomarker in idiopathic inflammatory myopathies (IIM). METHODS: We performed a retrospective analysis of adult and paediatric patients with the diagnosis of IIM. SIGLEC1 expression was assessed by flow cytometry and was compared with Physician Global Assessment or Childhood Myositis Assessment Scale disease activity scores. Mann Whitney U test and receiver operating characteristic curves were used for cross-sectional data analysis (n=96), two-level mixed-effects linear regression model for longitudinal analyses (n=26, 110 visits). Response to treatment was analysed in 14 patients within 12 months, using Wilcoxon test. SIGLEC1 was compared with interferon-stimulated gene 15/MxA status by immunohistochemical staining of muscle biopsies (n=17). RESULTS: 96 patients with adult (a) and juvenile (j) dermatomyositis (DM, n=38), antisynthetase syndrome (AS, n=19), immune-mediated necrotising myopathy (IMNM, n=8), inclusion body myositis (IBM, n=9) and overlap myositis (n=22) were included. SIGLEC1 distinguished significantly between active and inactive disease with an area under the curve of 0.92 (95% CI 0.83 to 1) in DM and correlated with disease activity longitudinally (aDM: standardised beta=0.54, p<0.001; jDM: standardised beta=−0.70, p<0.001). Response to treatment in DM was associated with a decreasing SIGLEC1 (p<0.01, Wilcoxon test). SIGLEC1 was found upregulated in 8 of 19 patients with AS, 2 of 9 patients with IBM but not in IMNM. CONCLUSION: SIGLEC1 is a candidate biomarker to assess type I interferon activity in IIM and proved useful for monitoring disease activity and response to treatment in juvenile and adult DM. BMJ Publishing Group 2022-02-17 /pmc/articles/PMC8860073/ /pubmed/35177553 http://dx.doi.org/10.1136/rmdopen-2021-001934 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Connective Tissue Diseases Graf, Manuel von Stuckrad, Sae Lim Uruha, Akinori Klotsche, Jens Zorn-Pauly, Lydia Unterwalder, Nadine Buttgereit, Thomas Krusche, Martin Meisel, Christian Burmester, Gerd R Hiepe, Falk Biesen, Robert Kallinich, Tilmann Stenzel, Werner Schneider, Udo Rose, Thomas SIGLEC1 enables straightforward assessment of type I interferon activity in idiopathic inflammatory myopathies |
title | SIGLEC1 enables straightforward assessment of type I interferon activity in idiopathic inflammatory myopathies |
title_full | SIGLEC1 enables straightforward assessment of type I interferon activity in idiopathic inflammatory myopathies |
title_fullStr | SIGLEC1 enables straightforward assessment of type I interferon activity in idiopathic inflammatory myopathies |
title_full_unstemmed | SIGLEC1 enables straightforward assessment of type I interferon activity in idiopathic inflammatory myopathies |
title_short | SIGLEC1 enables straightforward assessment of type I interferon activity in idiopathic inflammatory myopathies |
title_sort | siglec1 enables straightforward assessment of type i interferon activity in idiopathic inflammatory myopathies |
topic | Connective Tissue Diseases |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8860073/ https://www.ncbi.nlm.nih.gov/pubmed/35177553 http://dx.doi.org/10.1136/rmdopen-2021-001934 |
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