{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T23:10:43Z","timestamp":1770333043108,"version":"3.49.0"},"posted":{"date-parts":[[2025,3,5]]},"group-title":"Rheumatology","reference-count":24,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Plant homeodomain (PHD) fingers are present in many chromatin-binding proteins. We recently discovered that anti-Mi2 autoantibodies recognize PHD fingers in Mi2 and AIRE. The purpose of this study was to characterize anti-Mi2 autoantibody recognition of PHD fingers in SP140L and TIF1\u03b3 as well as to explore recognition of TIF1\u03b3 by both anti-TIF1\u03b3 and anti-Mi2 autoantibodies.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Luciferase immunoprecipitation system (LIPS) assays were performed to detect autoantibodies against full-length and protein fragments of SP140L and TIF1\u03b3 in serum samples from myositis patients, disease controls, and healthy controls.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Anti-Mi2 autoantibodies recognized SP140L. When a 49 amino acid fragment of the PHD finger of SP140L was used as the target, the specificity for selectively detecting anti-Mi2 autoantibodies increased. Additionally, anti-Mi2 autoantibodies weakly bound TIF1\u03b3 compared to anti-TIF1\u03b3 autoantibodies. Excluding the TIF1\u03b3 PHD finger from the TIF1\u03b3 target autoantigen eliminated cross-reactivity with anti-Mi2 autoantibodies, confirming that anti-Mi2 autoantibodies specifically target the PHD finger of TIF1\u03b3. Switching two amino acids in the TIF1\u03b3 PHD finger to resemble those in AIRE markedly enhanced anti-Mi2 autoantibody immunoreactivity. Anti-TIF1\u03b3 autoantibodies primarily recognized the N-terminal fragment outside of the PHD finger, indicating this region contains the immunodominant epitopes.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Anti-Mi2 autoantibodies recognize the PHD fingers of SP140L and TIF1\u03b3. TIF1\u03b3 is recognized by two different myositis-specific autoantibodies: anti-Mi2 autoantibodies bind the C-terminal PHD domain and anti-TIF1\u03b3 autoantibodies predominantly bind the N-terminal region. Removing the PHD finger from the anti-TIF1\u03b3 target autoantigen can improve the specificity of anti-TIF1\u03b3 autoantibody assays by reducing cross-reactivity with anti-Mi2 autoantibodies.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.03.04.25323364","type":"posted-content","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T01:45:23Z","timestamp":1741225523000},"source":"Crossref","is-referenced-by-count":1,"title":["Anti-Mi2 autoantibodies target the PHD fingers of SP140L and TIF1\u03b3, while anti-TIF1\u03b3 autoantibodies primarily recognize epitopes outside the PHD region of TIF1\u03b3"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6338-9218","authenticated-orcid":false,"given":"Iago","family":"Pinal-Fernandez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jon","family":"Musai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Casal-Dominguez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Pak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"Kaplan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blake M.","family":"Warner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa G.","family":"Rider","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rohit","family":"Aggarwal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chester V.","family":"Oddis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siamak","family":"Moghadam-Kia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria","family":"Garrabou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert","family":"Selva-O\u2019Callaghan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose C.","family":"Milisenda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A.","family":"Chiorini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew L.","family":"Mammen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter D.","family":"Burbelo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025031023301363000_2025.03.04.25323364v1.1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41964"},{"key":"2025031023301363000_2025.03.04.25323364v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30254-0"},{"issue":"19","key":"2025031023301363000_2025.03.04.25323364v1.3","first-page":"e1768","article-title":"More prominent muscle involvement in patients with dermatomyositis with anti-Mi2 autoantibodies","volume":"93","year":"2019","journal-title":"Neurology"},{"issue":"11","key":"2025031023301363000_2025.03.04.25323364v1.4","first-page":"1771","article-title":"Antinuclear Matrix Protein 2 Autoantibodies and Edema","volume":"69","year":"2017","journal-title":"Muscle Disease, and Malignancy Risk in Dermatomyositis Patients. 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