Histological heterogeneity in a large clinical cohort of juvenile idiopathic inflammatory myopathy: analysis by myositis autoantibody and pathological features

S A Yasin; P W Schutz; C T Deakin; E Sag; H Varsani; S Simou; L R Marshall; S L Tansley; N J McHugh; J L Holton; L R Wedderburn; T S Jacques; UK Juvenile Dermatomyositis Research Group (UK and Ireland)

doi:10.1111/nan.12528

Histological heterogeneity in a large clinical cohort of juvenile idiopathic inflammatory myopathy: analysis by myositis autoantibody and pathological features

Neuropathol Appl Neurobiol. 2019 Aug;45(5):495-512. doi: 10.1111/nan.12528. Epub 2019 Mar 11.

Authors

S A Yasin¹, P W Schutz^{1

2}, C T Deakin¹, E Sag¹, H Varsani¹, S Simou¹, L R Marshall¹, S L Tansley³, N J McHugh³, J L Holton^{4

2}, L R Wedderburn^{1

5

6}, T S Jacques^{7

8}; UK Juvenile Dermatomyositis Research Group (UK and Ireland)

Collaborators

UK Juvenile Dermatomyositis Research Group (UK and Ireland):
Kate Armon, Joe Ellis-Gage, Holly Roper, Vanja Briggs, Joanna Watts, Liza McCann, Ian Roberts, Eileen Baildam, Lou Hanna, Olivia Lloyd, Susan Wadeson, Phil Riley, Ann McGovern, Clive Ryder, Janis Scott, Beverley Thomas, Taunton Southwood, Eslam Al-Abadi, Sue Wyatt, Gillian Jackson, Tania Amin, Mark Wood, Vanessa VanRooyen, Deborah Burton, Joyce Davidson, Janet Gardner-Medwin, Neil Martin, Sue Ferguson, Liz Waxman, Michael Browne, Mark Friswell, Helen Foster, Alison Swift, Sharmila Jandial, Vicky Stevenson, Debbie Wade, Ethan Sen, Eve Smith, Lisa Qiao, Stuart Watson, Claire Duong, Helen Venning, Rangaraj Satyapal, Elizabeth Stretton, Mary Jordan, Ellen Mosley, Anna Frost, Lindsay Crate, Kishore Warrier, Stefanie Ord, Clarissa Pilkington, Nathan Hasson, Sue Maillard, Elizabeth Halkon, Virginia Brown, Audrey Juggins, Sally Smith, Sian Lunt, Elli Enayat, Laura Kassoumeri, Laura Beard, Katie Arnold, Yvonne Glackin, Stephanie Simou, Beverley Almeida, Kiran Nistala, Raquel Marques, Stefanie Dowle, Charis Papadopoulou, Cer Johnson-Moore, Emily Robinson, Kevin Murray, John Ioannou, Linda Suffield, Muthana Al-Obaidi, Helen Lee, Sam Leach, Helen Smith, Anne-Marie McMahon, Heather Chisem, Ruth Kingshott, Nick Wilkinson, Emma Inness, Eunice Kendall, David Mayers, Ruth Etherton, Danielle Miller, Kathryn Bailey, Jacqui Clinch, Natalie Fineman, Helen Pluess-Hall, Lindsay Vallance, Lou Akeroyd, Alice Leahy, Amy Collier, Rebecca Cutts, Emma Macleod, Hans De Graaf, Brian Davidson, Sarah Hartfree, Danny Pratt

Affiliations

¹ Infection, Immunity, Inflammation Programme, UCL GOS Institute of Child Health, London, UK.
² Division of Neuropathology, UCL Institute of Neurology, London, UK.
³ Department of Pharmacy and Pharmacology, University of Bath, Bath, UK.
⁴ Department of Molecular Neuroscience, MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, London, UK.
⁵ Arthritis Research UK Centre for Adolescent Rheumatology at UCL, UCLH and GOSH, London, UK.
⁶ NIHR Biomedical Research Centre at Great Ormond Street Hospital, London, UK.
⁷ Developmental Biology and Cancer Programme, Developmental Biology of Birth Defects, UCL GOS Institute of Child Health, London, UK.
⁸ Department of Histopathology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.

Abstract

Aim: Juvenile idiopathic inflammatory myopathies have been recently reclassified into clinico-serological subgroups. Myopathological correlates of the subgroups are incompletely understood.

Methods: We studied muscle biopsies from 101 children with clinically and serologically defined juvenile idiopathic inflammatory myopathies from the UK JDM Cohort and Biomarker Study by applying the international JDM score tool, myopathological review and C5b-9 complement analysis.

Results: Autoantibody data were available for 90/101 cases with 18/90 cases positive for anti-TIF1γ, 15/90 anti-NXP2, 11/90 anti-MDA5, 5/90 anti-Mi2 and 6/90 anti-PmScl. JDM biopsy severity scores were consistently low in the anti-MDA5 group, high in the anti-Mi2 group, and widely distributed in the other groups. Biopsies were classified histologically as perifascicular atrophy (22/101), macrophage-rich necrosis (6/101), scattered necrosis (2/101), clustered necrosis (2/101), inflammatory fibre invasion (2/101), chronic myopathic change (1/101), diffuse endomysial macrophage infiltrates (40/101) and minimal change (24/101). MDA5 cases segregated with the minimal change group and showed no capillary C5b-9-deposition. The Mi2 group displayed high severity scores and a tendency towards sarcolemmal complement deposition. NXP2 and TIF1γ groups showed a variety of pathologies with a high proportion of diffuse endomysial macrophage infiltrates and a high proportion of capillary C5b-9 deposition.

Conclusion: We have shown that juvenile idiopathic inflammatory myopathies have a spectrum of histopathological phenotypes and show distinct complement attack complex deposition patterns. Both correlate in some cases with the serological subtypes. Most cases do not show typical histological features associated with dermatomyositis (e.g. perifascicular atrophy). In contrast, more than half show relatively mild histopathological changes.

Keywords: JDM score tool; anti-SRP; dermatomyositis; immune mediated necrotizing myopathy; polymyositis; principal component analysis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autoantibodies / immunology*
Autoantigens / immunology
Child
Child, Preschool
Cohort Studies
Female
Humans
Male
Myositis / immunology*
Myositis / pathology*
Phenotype

Substances

Autoantibodies
Autoantigens

Abstract

Publication types

MeSH terms

Substances

Grants and funding