Abstract
Objectives: Anti-transcriptional intermediary factor 1γ (TIF1γ) autoantibodies are associated with malignancy in adult-onset idiopathic inflammatory myopathy (IIM) and this risk is attenuated if patients are also positive for anti-specificity protein 4 (Sp4) or anti-cell division cycle apoptosis regulator protein 1 (CCAR1). In anti-TIF1γ positive dermatomyositis (DM) patients from the USA, anti-Sp4 and anti-CCAR1 autoantibody frequencies are reported as 32% and 43% in adults and 9% and 19% in juveniles, respectively. This study aims to identify the frequency of anti-Sp4 and anti-CCAR1 in adult and juvenile UK anti-TIF1γ-positive myositis populations and report clinical associations. Methods: Serum samples from 51 UK participants with adult-onset IIM and 55 UK participants with JDM, all anti-TIF1γ autoantibody positive, and 24 healthy control samples were screened for anti-Sp4 and anti-CCAR1 autoantibodies by ELISA. Results: In UK adult anti-TIF1γ positive IIM patients, anti-Sp4 and anti-CCAR1 frequencies were 4% (2/51) and 16% (8/51). Both adult patients with anti-Sp4 were also positive for anti-CCAR1. In UK juveniles, anti-Sp4 was not detected and 13% (7/55) had anti-CCAR1 autoantibodies. Nineteen (37%) anti-TIF1γ positive UK adult myositis patients had cancer; neither of the two patients with anti-Sp4 autoantibodies and 25% (2/8) of anti-CCAR1 autoantibody-positive patients had cancer. No anti-Sp4 or anti-CCAR1 clinical associations were identified. Conclusion: Anti-Sp4 and anti-CCAR1 autoantibodies are less common in the adult UK anti-TIF1γ-positive myositis population compared with published data from the USA, limiting their use as biomarkers for cancer risk. In patients with juvenile onset disease, anti-Sp4 is less frequent in UK patients compared with the USA, but the prevalence of anti-CCAR1 autoantibodies is similar.
| Original language | English |
|---|---|
| Pages (from-to) | 3900-3905 |
| Number of pages | 6 |
| Journal | Rheumatology |
| Volume | 64 |
| Issue number | 6 |
| Early online date | 7 Nov 2024 |
| DOIs | |
| Publication status | Published - 1 Jun 2025 |
Bibliographical note
Publisher Copyright:© The Author(s) 2024.
Data Availability Statement
The data underlying this article will be shared on reasonable request to the corresponding author.Funding
L.R. is supported by the intramural research program of the National Institutes of Environmental Health Sciences, National Institutes of Health (ZIA ES101081). Funding for the UK JDM Cohort and Biomarker study (JDCBS) has been by grants from the Wellcome Trust UK [085860]; Action Medical Research UK [SP4252]; the Myositis UK Charity, Arthritis Research UK now Versus Arthritis [14518, 20164, 21593]; the Henry Smith Charity and Great Ormond Street Children's Charity [V1268]; Tiny Hearts Society, The Myositis Association, Remission Charity, Cure JM (GOSH042019), the Medical Research Council [MR/N003322/1], and the National Institute for Health Research (NIHR) via the NIHR-Biomedical Research Centre at GOSH. H.C. is supported by the National Institution for Health Research (NIHR) Manchester Biomedical Research Centre [NIHR203308]. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. F.K.M.\u2019s post is supported by grants from CureJM [Bath0121] and the Bath Institute of Rheumatic Diseases [RAG-ST-18\u2013210222]. L.R. is supported by the intramural research program of the National Institutes of Environmental Health Sciences, National Institutes of Health (ZIA ES101081). Funding for the UK JDM Cohort and Biomarker study (JDCBS) has been by grants from the Wellcome Trust UK [085860]; Action Medical Research UK [SP4252]; the Myositis UK Charity, Arthritis Research UK now Versus Arthritis [14518, 20164, 21593]; the Henry Smith Charity and Great Ormond Street Children's Charity [V1268]; Tiny Hearts Society, The Myositis Association, Remission Charity, Cure JM (GOSH042019), the Medical Research Council [MR/ N003322/1], and the National Institute for Health Research (NIHR) via the NIHR-Biomedical Research Centre at GOSH. H.C. is supported by the National Institution for Health Research (NIHR) Manchester Biomedical Research Centre [NIHR203308]. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. F.K.M.\u2019s post is supported by grants from CureJM [Bath0121] and the Bath Institute of Rheumatic Diseases [RAG-ST-18\u2013210222]. The Juvenile Dermatomyositis Cohort Biomarker Study & Repository (JDCBS) would like to thank all of the patients and their families who contributed to the JDCBS research study. We thank all local research coordinators and principal investigators who have made this research possible. Clinical, research and administrative contributors to JDCBS members were as follows: Dr Kate Armon, Ms Louise Coke, Ms Julie Cook and Ms Amy Nichols (Norfolk and Norwich University Hospitals); Dr Liza McCann, Mr Ian Roberts, Dr Eileen Baildam, Ms Louise Hanna, Ms Olivia Lloyd, Susan Wadeson, Ms Michelle Andrews, Ms Olivia Lloyd and Mrs Jane Roach (The Royal Liverpool Children\u2019s Hospital, Alder Hey, Liverpool); Dr Phil Riley, Ms Ann McGovern and Ms Verna Cuthbert (Royal Manchester Children\u2019s Hospital, Manchester); Dr Clive Ryder, Ms Janis Scott, Ms Beverley Thomas, Professor Taunton Southwood, Dr Eslam Al-Abadi and Ms Ruth Howman (Birmingham Children\u2019s Hospital, Birmingham); Dr Sue Wyatt, Mrs Gillian Jackson, Dr Mark Wood, Dr Tania Amin, Dr Vanessa VanRooyen, Ms Deborah Burton, Ms Louise Turner, Ms Heather Rostron and Ms Sarah Hanson (Leeds General Infirmary, Leeds); Dr Joyce Davidson, Dr Janet Gardner-Medwin, Dr Neil Martin, Ms Sue Ferguson, Ms Liz Waxman, Mr Michael Browne, Ms Roisin Boyle, Ms Emily Blyth and Ms Susanne Cathcart (The Royal Hospital for Sick Children, Yorkhill, Glasgow); Dr Mark Friswell, Professor Helen Foster, Ms Alison Swift, Dr Sharmila Jandial, Ms Vicky Stevenson, Ms Debbie Wade, Dr Ethan Sen, Dr Eve Smith, Ms Lisa Qiao, Mr Stuart Watson, Ms Claire Duong, Dr Stephen Crulley, Mr Andrew Davies, Miss Caroline Miller, Ms Lynne Bell, Dr Flora McErlane, Dr Sunil Sampath, Dr Josh Bennet and Mrs Sharon King (Great North Children\u2019s Hospital, Newcastle); Dr Helen Venning, Dr Rangaraj Satyapal, Mrs Elizabeth Stretton, Ms Mary Jordan, Dr Ellen Mosley, Ms Anna Frost, Ms Lindsay Crate, Dr Kishore Warrier, Ms Stefanie Stafford, Mrs Brogan Wrest, Ms Chia-Ping Chou and Mr Paul Pryce (Queens Medical Centre, Nottingham); Professor Lucy Wedderburn, Dr Clarissa Pilkington, Dr Nathan Hasson, Dr Muthana Al-Obadi, Dr Giulia Varnier, Dr Sandrine Lacassagne, Ms Sue Maillard, Mrs Lauren Stone, Ms Elizabeth Halkon, Ms Virginia Brown, Ms Audrey Juggins, Dr Sally Smith, Ms Sian Lunt, Ms Elli Enayat, Ms Hemlata Varsani, Ms Laura Kassoumeri, Miss Laura Beard, Ms Katie Arnold, Mrs Yvonne Glackin, Ms Stephanie Simou, Dr Beverley Almeida, Dr Kiran Nistala, Dr Raquel Marques, Dr Claire Deakin, Dr Parichat Khaosut, Ms Stefanie Dowle, Dr Charalampia Papadopoulou, Dr Shireena Yasin, Dr Christina Boros, Dr Meredyth Wilkinson, Dr Chris Piper, Ms Cerise Johnson-Moore, Ms Lucy Marshall, Ms Kathryn O\u2019Brien, Ms Emily Robinson, Mr Dominic Igbelina, Dr Polly Livermore, Dr Socrates Varakliotis, Ms Rosie Hamilton, Ms Lucy Nguyen and Mr Dario Cancemi (Great Ormond Street Hospital, London); Dr Kevin Murray (Princess Margaret Hospital, Perth, Western Australia); Dr Coziana Ciurtin, Dr John Ioannou, Mrs Caitlin Clifford, Ms Linda Suffield and Ms Laura Hennelly (University College London Hospital, London); Ms Helen Lee, Ms Sam Leach, Ms Helen Smith, Dr Anne-Marie McMahon, Ms Heather Chisem, Ms Jeanette Hall and Ms Amy Huffenberger (Sheffield\u2019s Children\u2019s Hospital, Sheffield); Dr Nick Wilkinson, Ms Emma Inness, Ms Eunice Kendall, Mr David Mayers, Ms Ruth Etherton, Ms Danielle Miller and Dr Kathryn Bailey (Oxford University Hospitals, Oxford); Dr Jacqui Clinch, Ms Natalie Fineman, Ms Helen Pluess-Hall, Ms Suzanne Sketchley, Ms Melanie Marsh, Ms Anna Fry, Ms Maisy Dawkins-Lloyd and Ms Mashal Asif (Bristol Royal Hospital for Children, Bristol); Dr Joyce Davidson, Margaret Connon and Ms Lindsay Vallance (Royal Aberdeen Children\u2019s Hospital); Dr Kirsty Haslam, Ms Charlene Bass-Woodcock, Ms Trudy Booth and Ms Louise Akeroyd (Bradford Teaching Hospitals); Dr Alice Leahy, Amy Collier, Rebecca Cutts, Emma Macleod, Dr Hans De Graaf, Dr Brian Davidson, Sarah Hartfree, Ms Elizabeth Fofana and Ms Lorena Caruana (University Hospital Southampton); and all the Children, young people and their families who have contributed to this research. Childhood Myositis Heterogeneity Study Group: Gulnara Mamyrova, Payam Noroozi-Farhadi, Matthew Sherman, Ira Targoff.
| Funders | Funder number |
|---|---|
| Tiny Hearts Society | |
| Myositis Association | |
| Bristol Royal Hospital for Children | |
| National Institute on Handicapped Research | |
| Myositis UK Charity | |
| Ms Amy Huffenberger | |
| Remission Charity | |
| National Institute for Health and Care Research | |
| Queens Medical Centre | |
| Henry Smith Charity | |
| Mrs Caitlin Clifford | |
| National Institute of Environmental Health Sciences | |
| Dr Sue Wyatt, Mrs Gillian Jackson | |
| Hospital for Sick Children | |
| Arthritis Research UK | |
| Versus Arthritis | 14518, 20164, 21593 |
| Great Ormond Street Children's Charity | V1268 |
| CureJM | Bath0121 |
| Medical Research Council | MR/N003322/1 |
| Bath Institute of rheumatic Diseases | RAG-ST-18–210222 |
| Cure JM Foundation | GOSH042019 |
| Manchester Biomedical Research Centre | NIHR203308 |
| National Institutes of Health | ZIA ES101081 |
| The Wellcome Trust | 085860 |
| Action Medical Research | SP4252 |
Keywords
- Juvenile dermatomyositis
- autoantibodies
- cancer
- dermatomyositis
- myositis
ASJC Scopus subject areas
- Rheumatology
- Pharmacology (medical)
