PMID- 38368769 OWN - NLM STAT- MEDLINE DCOM- 20240417 LR - 20240506 IS - 1095-9157 (Electronic) IS - 0896-8411 (Linking) VI - 144 DP - 2024 Apr TI - The enigma of sclera-specific autoimmunity in scleritis. PG - 103178 LID - S0896-8411(24)00012-X [pii] LID - 10.1016/j.jaut.2024.103178 [doi] AB - Scleritis is a severe and painful ophthalmic disorder, in which a pathogenic role for collagen-directed autoimmunity was repeatedly suggested. We evaluated the presence of sclera-specific antibodies in a large cohort of patients with non-infectious scleritis. Therefore, we prospectively collected serum samples from 121 patients with non-infectious scleritis in a multicenter cohort study in the Netherlands. In addition, healthy (n = 39) and uveitis controls (n = 48) were included. Serum samples were tested for anti-native human type II collagen antibodies using a validated enzyme-linked immunosorbent assay (ELISA). Further, sclera-specific antibodies were determined using indirect immunofluorescence (IIF) on primate retinal/scleral cryosections. Lastly, human leukocyte antigen (HLA) typing was performed in 111 patients with scleritis. Anti-type II collagen antibodies were found in 13% of scleritis patients, in 10% of healthy controls and in 11% of uveitis controls (p = 0.91). A specific reaction to scleral nerve tissue on IIF was observed in 33% of patients with scleritis, which was higher than in healthy controls (11%; p = 0.01), but similar to uveitis controls (25%; p = 0.36). Reactivity to the scleral nerve tissue was significantly associated with earlier onset of scleritis (48 versus 56 years; p < 0.001), bilateral involvement (65% versus 42%; p = 0.01), and less frequent development of scleral necrosis (5% versus 22%; p = 0.02). HLA-B27 was found to be twice as prevalent in patients with scleritis (15.3%) compared to a healthy population (7.2%). In conclusion, scleral nerve autoantibody reactivity was more common in scleritis and uveitis patients in contrast to healthy controls. Further research is needed to characterize these scleral-nerve directed antibodies and assess their clinical value. CI - Copyright (c) 2024 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Vergouwen, Daphne P C AU - Vergouwen DPC AD - Department of Ophthalmology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Immunology, Laboratory Medical Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. Electronic address: d.vergouwen@erasmusmc.nl. FAU - van Beek, Adriaan A AU - van Beek AA AD - Department of Immunology, HLA laboratory, Leiden University Medical Center, Leiden, the Netherlands. FAU - de Hoog, Joeri AU - de Hoog J AD - Department of Ophthalmology, Amsterdam UMC, Amsterdam, the Netherlands. FAU - de Boer, Joke H AU - de Boer JH AD - Department of Ophthalmology, UMC Utrecht, Utrecht, the Netherlands. FAU - Los, Leonoor I AU - Los LI AD - Department of Ophthalmology, UMC Groningen, Groningen, the Netherlands. FAU - Gijs, Marlies AU - Gijs M AD - University Eye Clinic, Maastricht UMC+, Maastricht, the Netherlands. FAU - Erckens, Roel J AU - Erckens RJ AD - University Eye Clinic, Maastricht UMC+, Maastricht, the Netherlands. FAU - Verdijk, Rob M AU - Verdijk RM AD - Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. FAU - Haasnoot, Geert W AU - Haasnoot GW AD - Eurotransplant Reference Laboratory, Leiden University Medical Center, Leiden, the Netherlands. FAU - Roelen, Dave L AU - Roelen DL AD - Department of Immunology, HLA laboratory, Leiden University Medical Center, Leiden, the Netherlands. FAU - Rothova, Aniki AU - Rothova A AD - Department of Ophthalmology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. FAU - Ronnelid, Johan AU - Ronnelid J AD - Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. FAU - Ten Berge, Josianne C AU - Ten Berge JC AD - Department of Ophthalmology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. FAU - Schreurs, Marco W J AU - Schreurs MWJ AD - Department of Immunology, Laboratory Medical Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20240217 PL - England TA - J Autoimmun JT - Journal of autoimmunity JID - 8812164 SB - IM MH - Animals MH - Humans MH - Autoimmunity MH - Cohort Studies MH - Sclera/pathology MH - *Scleritis/pathology MH - *Uveitis/pathology OTO - NOTNLM OT - Autoantibodies OT - Autoimmunity OT - HLA-Association OT - Scleritis OT - Type II collagen antibodies EDAT- 2024/02/19 00:42 MHDA- 2024/04/17 06:43 CRDT- 2024/02/18 18:08 PHST- 2023/07/05 00:00 [received] PHST- 2023/12/29 00:00 [revised] PHST- 2024/02/08 00:00 [accepted] PHST- 2024/04/17 06:43 [medline] PHST- 2024/02/19 00:42 [pubmed] PHST- 2024/02/18 18:08 [entrez] AID - S0896-8411(24)00012-X [pii] AID - 10.1016/j.jaut.2024.103178 [doi] PST - ppublish SO - J Autoimmun. 2024 Apr;144:103178. doi: 10.1016/j.jaut.2024.103178. Epub 2024 Feb 17.