ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 0697

Detection of Autoantibodies Against Muscle-Specific Four-and-a-Half-LIM Domain 1 (FHL1) in Inflammatory Myopathies: Results from a Single-Center Cohort

Angeles Shunashy Galindo-Feria1, Begum Horuluoglu1, Jessica Day2, Catia Cerqueira3, Edvard Wigren4, Susanne Gräslund4, Susanna Proudman5, Ingrid E Lundberg4 and Vidya Limaye6, 1Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, 2Rheumatology Unit, Royal Adelaide Hospital, Adelaide, Australia and Discipline of Medicine, University of Adelaide, Adelaide, Australia, 34Dcell, Montreuil, France, 4Karolinska Institutet, Karolinska University Hospital, Division of Rheumatology, Department of Medicine Solna, Stockholm, Sweden, Stockholm, Sweden, 5University of Adelaide, Medindie, Australia, 6Royal Adelaide Hospital, Adelaide, Australia

Meeting: ACR Convergence 2021

Keywords: , , , ,

Session Information

Date: Sunday, November 7, 2021

Session Title: Muscle Biology, Myositis & Myopathies Poster (0683–0722)

Session Type: Poster Session B

Session Time: 8:30AM-10:30AM

Background/Purpose: Autoantibodies targeting a muscle-specific autoantigen, four-and-a-half-LIM-domain 1 (FHL1), have been previously identified in patients with idiopathic inflammatory myopathies (IIM) (1).

The aim of this study was to determine the prevalence and associations of anti-FHL1 antibody in South Australian patients with histologically-confirmed IIM and autoimmune disease control group (systemic sclerosis (SSc)).

Methods: Sera from patients with IIM (n=267) from the South Australian Myositis Database (SAMD), and SSc (n=174) from the Australian Scleroderma Cohort Study (ASCS) followed at the Royal Adelaide Hospital, and healthy controls (HC, n=100) were analyzed for anti-FHL1 autoantibodies by Enzyme-Linked ImmunoSorbent Assay (ELISA) and transformed to Arbitrary Units (AU). Clinical, serological, and histological details were retrieved from the SAMD and the ASCS.

Results: Autoantibodies to FHL1 were more frequent in patients with IIM (37/267, 13.8%) compared with SSc (12/174, 7%) (p< 0.02) and HC (2/100, 2%) (p< 0.001) (Figure 1). There were no other myositis-specific autoantibodies (MSA) present in 28/37 (75%) anti-FHL1+ patients (Figure 2). When analyzing the IIM subgroups, the presence of anti-FHL1 autoantibodies was more frequently found in the subgroups polymyositis (PM, 11/37) and Inclusion Body Myositis (IBM, 9/37) (Figure 3). In anti- FHL1+ patients that were seronegative for other MSA (n=28), we found a higher frequency of vessel inflammation and marked fiber atrophy in muscle biopsies, less myalgia, lower CK median levels, and lower cellularity in the biopsy compared to anti-FHL1– patients. Objective weakness and marked fiber atrophy y in muscle biopsies was more frequent in anti-FHL1+ compared to anti-FHL1- IBM patients. In the SSc patients, the presence of anti-FHL1 autoantibodies was more frequent in limited compared to diffuse SSc, but did not have more frequent clinical diagnosis of myositis or atrophy in the muscle biopsy compared to anti-FHL1– patients.

Conclusion: The presence of anti-FHL1 autoantibodies was confirmed in a cohort of histologically-defined adult IIM of mixed ethnicity, and most anti-FHL1 positive cases were negative for known MSAs. We confirmed a clinical phenotype dominated by skeletal muscle involvement in patients with anti-FHL1 autoantibodies. We also found the presence of anti-FHL1 in SSc, and this finding warrants investigation in further SSc cohorts.

Figure 1. Sera from patients with IIM (DM, PM, IBM, IMNM and MNOS; n=267), SSc (n=174) and HC (n=100) were analyzed by ELISA using recombinant His-tagged FHL1. A cut-off value of 1.06 AU was calculated using a receiver operating characteristic (ROC) curve based on the HC, with an area under the curve (AUC) of 0.62 (CI 95% 0.56-0.68), sensitivity 15.52%, specificity 98%, and a likelihood ratio (LR) of 7.52. IIM, idiopathic inflammatory myopathy; HC, healthy controls; SSc, systemic sclerosis.

Figure 2. Frequency of IIM patients presenting MSA and MAA in anti-FHL1+ group. MSA, myositis-specific autoantibodies; MAA, myositis-associated autoantibodies

Figure 3. Frequency of IIM patients by disease subsets according to the presence of anti-FHL1+ or anti-FHL1- autoantibodies. IIM, idiopathic inflammatory myopathy; DM, dermatomyositis; PM, polymyositis; IBM, inclusion body myositis; IMNM, immune-mediated necrotizing myopathy; MNOS, myositis not-otherwise-specified

Disclosures: A. Galindo-Feria, None; B. Horuluoglu, None; J. Day, None; C. Cerqueira, None; E. Wigren, None; S. Gräslund, None; S. Proudman, Boehringer-Ingelheim, 1, Janssen, 1, Gossamer, 1, Janssen, 5; I. Lundberg, Corbus Pharmaceutical,, 2, EMD Serono Research & Development Institute, 2, Argenx, 2, Bristol Myers Squibb, 2, Janssen, 2, Kezaar, 2, Octapharma, 1, Orphazyme, 1, Roche, 11, Novartis, 11; V. Limaye, None.

To cite this abstract in AMA style:

Galindo-Feria A, Horuluoglu B, Day J, Cerqueira C, Wigren E, Gräslund S, Proudman S, Lundberg I, Limaye V. Detection of Autoantibodies Against Muscle-Specific Four-and-a-Half-LIM Domain 1 (FHL1) in Inflammatory Myopathies: Results from a Single-Center Cohort [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/detection-of-autoantibodies-against-muscle-specific-four-and-a-half-lim-domain-1-fhl1-in-inflammatory-myopathies-results-from-a-single-center-cohort/. Accessed October 3, 2022.

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