Anti-Sp4 and anti-CCAR1 autoantibodies in UK vs US patients with adult and juvenile-onset anti-TIF1γ-positive myositis
Authors: McMorrow Fionnuala K , Wedderburn Lucy R , Chinoy Hector , Oldroyd Alexander , Lamb Janine A , Rider Lisa G , Mammen Andrew L , Casciola-Rosen Livia , McHugh Neil J , Tansley Sarah L ,   UK JDCBS and Childhood Myositis Heterogeneity Study Group, Armon Kate , Coke Louise , Cook Julie , Nichols Amy , McCann Liza , Roberts Ian , Baildam Eileen , Hanna Louise , Lloyd Olivia , Wadeson Susan , Andrews Michelle , Lloyd Olivia , Roach Jane , Riley Phil , McGovern Ann , Cuthbert Verna , Ryder Clive , Scott Janis , Thomas Beverley , Southwood Taunton , Al-Abadi Eslam , Howman Ruth , Wyatt Sue , Jackson Gillian , Wood Mark , Amin Tania , VanRooyen Vanessa , Burton Deborah , Turner Louise , Rostron Heather , Hanson Sarah , Davidson Joyce , Gardner-Medwin Janet , Martin Neil , Ferguson Sue , Waxman Liz , Browne Michael , Boyle Roisin , Blyth Emily , Cathcart Susanne , Friswell Mark , Foster Helen , Swift Alison , Jandial Sharmila , Stevenson Vicky , Wade Debbie , Sen Ethan , Smith Eve , Qiao Lisa , Watson Stuart , Duong Claire , Crulley Stephen , Davies Andrew , Miller Miss Caroline , Bell Lynne , McErlane Flora , Sampath Sunil , Bennet Josh , King Sharon , Venning Helen , Satyapal Rangaraj , Stretton Elizabeth , Jordan Mary , Mosley Ellen , Frost Anna , Crate Lindsay , Warrier Kishore , Stafford Stefanie , Wrest Brogan , Chou Chia-Ping , Pryce Paul , Wedderburn Lucy , Pilkington Clarissa , Hasson Nathan , Al-Obadi Muthana , Varnier Giulia , Lacassagne Sandrine , Maillard Sue , Stone Lauren , Halkon Elizabeth , Brown Virginia , Juggins Audrey , Smith Sally , Lunt Sian , Enayat Elli , Varsani Hemlata , Kassoumeri Laura , Beard Miss Laura , Arnold Katie , Glackin Yvonne , Simou Stephanie , Almeida Beverley , Nistala Kiran , Marques Raquel , Deakin Claire , Khaosut Parichat , Dowle Stefanie , Papadopoulou Charalampia , Yasin Shireena , Boros Christina , Wilkinson Meredyth , Piper Chris , Johnson-Moore Cerise , Marshall Lucy , O’Brien Kathryn , Robinson Emily , Igbelina Dominic , Livermore Polly , Varakliotis Socrates , Hamilton Rosie , Nguyen Lucy , Cancemi Dario , Murray Kevin , Ciurtin Coziana , Ioannou John , Clifford Caitlin , Suffield Linda , Hennelly Laura , Lee Helen , Leach Sam , Smith Helen , McMahon Anne-Marie , Chisem Heather , Hall Jeanette , Huffenberger Amy , Wilkinson Nick , Inness Emma , Kendall Eunice , Mayers David , Etherton Ruth , Miller Danielle , Bailey Kathryn , Clinch Jacqui , Fineman Natalie , Pluess-Hall Helen , Sketchley Suzanne , Marsh Melanie , Fry Anna , Dawkins-Lloyd Maisy , Asif Mashal , Davidson Joyce , Connon Margaret , Vallance Lindsay , Haslam Kirsty , Bass-Woodcock Charlene , Booth Trudy , Akeroyd Louise , Leahy Alice , Collier Amy , Cutts Rebecca , Macleod Emma , De Graaf Hans , Davidson Brian , Hartfree Sarah , Fofana Elizabeth , Caruana Lorena 
Published: November 2024

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.