Anti-FHL1 autoantibodies in juvenile myositis are associated with anti-Ro52 autoantibodies but not with severe disease features
Authors: Sherman Matthew A , Graf Rose , Sabbagh Sara E , Galindo-Feria Angeles S , Pinal-Fernandez Iago , Pak Katherine , Kishi Takayuki , Flegel Willy A , Targoff Ira N , Miller Frederick W , Lundberg Ingrid E , Rider Lisa G , Mammen Andrew L ,   for the Childhood Myositis Heterogeneity Collaborative Study Group, Albert Daniel A , Arabshahi Bita , Balboni Imelda M , Ballinger Susan , Barillas-Arias Lilliana , Becker Mara L , Bingham C April , Bohnsack John F , Carrasco Ruy , Cartwright Victoria W , Cron Randy Q , Curiel Rodolfo , Dare Jason A , de la Pena Wendy , DeGuzman Marietta M , Eberhard B Anne , Edelheit Barbara S , Finkel Terri H , George Stephen W , Gewanter Harry L , Goldmuntz Ellen A , Groh Brandt P , Haftel Hillary H , Hannan William P , Henrickson Michael , Higgins Gloria C , Hobday Patricia M , Hopp Russell J , Huber Adam M , Imundo Lisa , Inman C J , Jansen Anna , Jarvis James , Jones Olcay Y , Kamdar Ankur , Kim Hanna , Kingsbury Daniel J , Lindsley Carol B , Mamyrova Gulnara , McCarthy Paul L , Mitchell Stephen R , Murphy Frederick T , Nanda Kabita , O’Hanlon Terrance , Oral Elif A , Pachman Lauren M , Perez Maria D , Person Donald A , Rabinovich C Egla , Ronis Tova , Schiffenbauer Adam , Shaham Bracha , Sinal Sara H , Soep Jennifer , Stoll Matthew L , Sule Sangeeta , Tarvin Stacey , Vogelgesang Scott A , Volochayev Rita , Wargula Jennifer C , White Patience H 
Published: August 2022

Objectives

Four-and-a-half LIM domains 1 (FHL1) is a muscle-specific protein. Autoantibodies against FHL1 were recently discovered in adults with idiopathic inflammatory myopathies (IIMs) and were found to be associated with clinical features and outcomes indicative of increased disease severity. Anti-FHL1 autoantibodies have not been described in children. Here, the prevalence and clinical features associated with anti-FHL1 autoantibodies were examined in a large North American cohort of juvenile patients with IIM.

Methods

Sera from 338 juvenile IIM patients and 91 juvenile healthy controls were screened for anti-FHL1 autoantibodies by ELISA. Clinical characteristics and HLA alleles of those with and without anti-FHL1 autoantibodies were compared among those with juvenile IIM.

Results

Anti-FHL1 autoantibodies were present in 10.9% of juvenile IIM patients and 1.1% of controls. The frequency of anti-FHL1 autoantibodies among clinical and serologic subgroups did not differ. A higher percentage of Asian patients had anti-FHL1 autoantibodies (11% vs 0.7%; P = 0.002). Myositis-associated autoantibodies (MAAs) [odds ratio (OR) 2.09 (CI 1.03, 4.32)], anti-Ro52 autoantibodies specifically [OR 4.17 (CI 1.83, 9.37)] and V-sign rash [OR 2.59 (CI 1.22, 5.40)] were associated with anti-FHL1 autoantibodies. There were no differences in other features or markers of disease severity. No HLA associations with anti-FHL1 autoantibodies in Caucasian myositis patients were identified.

Conclusion

Anti-FHL1 autoantibodies are present in ∼11% of juvenile IIM patients and commonly co-occur with MAAs, including anti-Ro52 autoantibodies. In contrast to adult IIM, anti-FHL1 autoantibodies in juvenile myositis are associated with V-sign rash but not with other distinctive clinical features or worse outcomes.