{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T08:03:18Z","timestamp":1762070598760,"version":"build-2065373602"},"reference-count":71,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University Hospital Essen (UMEA &amp; ELAN program)"},{"name":"German Research Foundation (DFG) Furthermore"},{"name":"German Society for Strabismus, Neuro-Ophthalmology"},{"name":"Pediatric Ophthalmology (Bielschowsky Foundation)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Non-specific orbital inflammation (NSOI) and IgG4-related orbital disease (IgG4-ROD) are currently treated with non-specific immunosuppressive agents based on non-randomized, uncontrolled studies. Therefore, relapses and prolongated courses are common and remain challenging. For a more specific therapy, a better understanding of the underlying pathophysiology is crucial. Therefore, we aimed to analyze signaling pathways to expand the knowledge on the pathophysiology and possibly identify specific targets in the future, as occurred recently in Graves\u2019 orbitopathy with the IGF-1 receptor. Furthermore, we analyzed potential mechanisms for the described potential progression to orbital MALT (mucosa-associated lymphoid tissue) lymphoma. The investigation cohort for this screening study comprised of 12 patients with either typical NSOI (n = 6), IgG4-ROD or MALT lymphoma (n = 3 each). Mean age was 56.4 \u00b1 17 years. MALT samples, in contrast with IgG4-ROD and NSOI, showed overall upregulation for extracellular matrix receptor interaction (ECM) and adipocytokine signaling. Investigating signaling compounds for MALT samples, differentially expressed genes were re-identified as targets with relevant expression. Even though pathway analysis showed differentially altered products when comparing IgG4-ROD with MALT, main conductors of differentiation in B- and T-cell signaling were commonly altered when observing the microenvironment of examined tissues. Our data reveal the characteristic differences and similarities in genetic-expression-based pathway profiles between MALT lymphoma, IgG4-ROD and NSOI, which may be useful for elucidating the associated pathogenic mechanisms and developing specific treatments for these orbital diseases.<\/jats:p>","DOI":"10.3390\/life12101660","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T22:49:46Z","timestamp":1666306186000},"page":"1660","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Novel Insights into Pathophysiology of Orbital Inflammatory Diseases and Progression to Orbital Lymphoma by Pathway Enrichment Analysis"],"prefix":"10.3390","volume":"12","author":[{"given":"Karim","family":"Al-Ghazzawi","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University Hospital Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabian D.","family":"Mairinger","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roman","family":"Pf\u00f6rtner","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, University of Duisburg-Essen, Kliniken-Essen-Mitte, 45136 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mareike","family":"Horstmann","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolaos","family":"Bechrakis","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Mohr","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, University of Duisburg-Essen, Kliniken-Essen-Mitte, 45136 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Eckstein","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0807-7689","authenticated-orcid":false,"given":"Michael","family":"Oeverhaus","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1210\/jc.2016-1315","article-title":"TSH\/IGF-1 Receptor Cross Talk in Graves\u2019 Ophthalmopathy Pathogenesis","volume":"101","author":"Krieger","year":"2016","journal-title":"J. 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