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Abstract Number: 2667

Anti-Mi2 Autoantibodies in Dermatomyositis Patients Also Recognize Autoimmune Regulator (AIRE) Protein

Jon Musai1, Sahana Jayaraman2, katherine Pak3, Iago Pinal-Fernandez4, Sandra Muñoz-braceras5, Maria Casal-Dominguez6, Eric Cho5, Fa'alataitaua Fitisemanu5, jose milisenda7, Lisa Rider8, Adam Schiffenbauer3, Albert Selva-O’Callaghan9, Thomas E Lloyd10, Lisa Christopher-Stine11, Peter Burbelo12, Benjamin Larman11 and Andrew Mammen13, 1National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, 2Johns Hopkins University School of Medicine, Baltimore, MD, 3National Institutes of Health, Bethesda, MD, 4NIAMS/National Institutes of Health, Bethesda, MD, 5National Institute of Arthritis and Musculoskeletal and Skin Disease, Bethesda, MD, 6NIAMS, NIH, Bethesda, MD, 7Hospital Clinic de Barcelona, Barcelona, Spain, 8NIEHS, NIH, Garrett Park, MD, 9Systemic Autoimmune Disease Unit, Vall d’Hebron Institute of Research, Barcelona, Spain, 10Johns Hopkins University School of Medicine, Lutherville, MD, 11Johns Hopkins University, Baltimore, MD, 12National Institute of Dental and Craniofacial Research, Bethesda, MD, 13NIH, Bethesda, MD

Meeting: ACR Convergence 2024

Keywords: Autoantibody(ies), autoantigens, immunology, Myositis

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Session Information

Date: Tuesday, November 19, 2024

Title: Abstracts: Muscle Biology, Myositis & Myopathies – Basic & Clinical Science II

Session Type: Abstract Session

Session Time: 11:00AM-12:30PM

Background/Purpose: Many myositis patients have myositis-specific autoantibodies (MSA) that define unique clinical phenotypes. For instance, dermatomyositis (DM) patients with anti-Mi2 autoantibodies have weaker muscles, higher levels of serum muscle enzymes, and more severe inflammatory infiltrates on muscle biopsies compared to DM patients with other MSAs. The aim of this study was to identify novel myositis-specific autoantibodies.

Methods: Phage Immunoprecipitation Sequencing (PhIP-Seq) was conducted using sera from 804 healthy controls and 411 patients with adult or juvenile myositis. PhIP-Seq suggested that autoimmune regulator (AIRE) is a novel autoantigen in myositis patients with anti-Mi2 autoantibodies. To confirm these findings, we performed an enzyme-linked immunosorbent assay (ELISA) to screen for anti-AIRE autoantibodies. We tested serum samples from a separate group of 72 myositis patients (27 with anti-Mi2, 7 with anti-NXP2, 6 with anti-TIF1, 9 with anti-MDA5, 8 with anti-Jo1, 5 with anti-HMGCR, 4 with anti-SRP autoantibodies, and 6 with IBM) and 63 healthy comparators. To determine if the same autoantibodies that bind Mi2 also target AIRE, we affinity purified anti-Mi2 autoantibodies from the sera of three different anti-Mi2 myositis patients who tested positive for anti-AIRE autoantibodies by ELISA. We also collected the immunoglobulin fraction depleted of these anti-Mi2 autoantibodies. Then, we assessed anti-AIRE reactivity by ELISA in both the anti-Mi2 enriched and depleted fractions.

Results: PhIP-Seq suggested that anti-AIRE autoantibodies are present in sera only from anti-Mi2 dermatomyositis patients, and not in the other myositis patients that were screened. The AIRE peptides recognized by PhIP-Seq were highly homologous to Mi2 protein sequences. Assessing anti-AIRE reactivity by ELISA showed that 88.9% of anti-Mi2-positive DM patients, 0% of other myositis patients, and 1.6% of healthy comparators had anti-AIRE autoantibodies (Figure 1). Affinity-purified anti-Mi2 autoantibodies were positive for both anti-Mi2 and anti-AIRE reactivity by ELISA. In contrast, anti-Mi2-depleted immunoglobulin fractions were negative for both anti-Mi2 and anti-AIRE reactivity by ELISA.

Conclusion: In this study, we have discovered that anti-AIRE autoantibodies exist specifically in patients with anti-Mi2 dermatomyositis. Given AIRE’s critical role in maintaining immune tolerance and preventing autoimmune reactions, future studies are needed to explore the pathological implications of anti-AIRE reactivity within muscle tissue.

Supporting image 1

Figure 1: Anti-AIRE antibody titers (AU: arbitrary units) determined by ELISA in sera from 63 healthy comparators and 72 patients with a myositis-specific autoantibody or inclusion body myositis. The dotted line indicates the cutoff used to define anti-AIRE-positive sera.


Disclosures: J. Musai: None; S. Jayaraman: None; k. Pak: None; I. Pinal-Fernandez: None; S. Muñoz-braceras: None; M. Casal-Dominguez: None; E. Cho: None; F. Fitisemanu: None; j. milisenda: None; L. Rider: AstraZeneca, 5, Bristol-Myers Squibb(BMS), 5, Cabaletta Bio, 1, 12, no financial support, Cure JM Foundation, 1, 5, Hope Pharmaceuticals, 5, Horizon Therapeuetics, 1, 12, no financial support, Pfizer, 1, 12, no financial support; A. Schiffenbauer: AstraZeneca, 11, Hope Pharmaceuticals, 5; A. Selva-O’Callaghan: None; T. Lloyd: None; L. Christopher-Stine: Allogene, 2, ArgenX, 2, Boehringer-Ingelheim, 2, Corbus Pharmaceuticals, 5, Dysimmune Disease Foundation, 2, EMD Serono, 2, Horizon, 5, Janssen, 5, Kezar Life Sciences, 5, Mallinckrodt, 2, Octapharma, 2, Pfizer Inc, 5, Priovant Therapeutics, 2, Roivant Sciences, 2; P. Burbelo: None; B. Larman: Infinity Bio, Inc, 4, 8; A. Mammen: None.

To cite this abstract in AMA style:

Musai J, Jayaraman S, Pak k, Pinal-Fernandez I, Muñoz-braceras S, Casal-Dominguez M, Cho E, Fitisemanu F, milisenda j, Rider L, Schiffenbauer A, Selva-O’Callaghan A, Lloyd T, Christopher-Stine L, Burbelo P, Larman B, Mammen A. Anti-Mi2 Autoantibodies in Dermatomyositis Patients Also Recognize Autoimmune Regulator (AIRE) Protein [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/anti-mi2-autoantibodies-in-dermatomyositis-patients-also-recognize-autoimmune-regulator-aire-protein/. Accessed .
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