{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:21:57Z","timestamp":1760955717410,"version":"3.38.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The aim of this study was to identify molecules that trigger complement activation in rheumatic joints. C4d, the final cleavage product of C4 activation, is found in the diseased joint and can bind covalently to complement-activating molecules. By using a highly specific Ab against a cleavage neoepitope in C4d, several molecules that were specifically bound to C4d were identified from pooled synovial fluid (SF) from four rheumatoid arthritis (RA) patients. One of these molecules, pigment epithelium\u2013derived factor (PEDF), is a broadly expressed multifunctional member of the serine proteinase inhibitor family. Using ELISA, we confirmed the presence of various amounts of complexes between PEDF and C4d in the SF from 30 RA patients, whereas none were detected in SF from control subjects. Correlation analyses suggested that, in arthritis patients, C4d\u2013PEDF complexes found in sera arise from the joints, as well as from other tissues, and levels of the complexes did not differ in sera of RA patients and healthy controls. When immobilized, recombinant PEDF expressed in eukaryotic cells activated the classical complement pathway but not the alternative or lectin pathways. C1q protein was demonstrated to bind immobilized PEDF, and PEDF was shown to bind to immobilized C1q, in particular its head regions, which are known to interact with other activators of the classical pathway. Our results call for further investigation into the role of PEDF in inflammatory processes in the joint, which, in combination with classical complement activation, appears to be part of a (patho-)physiologic response.<\/jats:p>","DOI":"10.4049\/jimmunol.1700018","type":"journal-article","created":{"date-parts":[[2017,6,22]],"date-time":"2017-06-22T00:30:32Z","timestamp":1498091432000},"page":"1113-1121","source":"Crossref","is-referenced-by-count":7,"title":["Activation of Complement by Pigment Epithelium\u2013Derived Factor in Rheumatoid Arthritis"],"prefix":"10.1093","volume":"199","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2843-9002","authenticated-orcid":false,"given":"Leonie M","family":"Vogt","sequence":"first","affiliation":[{"name":"Division of Medical Protein Chemistry, Department of Translational Medicine, Lund University, Sk\u00e5ne County Council , S-20502 Malm\u00f6,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Talens","sequence":"additional","affiliation":[{"name":"Division of Medical Protein Chemistry, Department of Translational Medicine, Lund University, Sk\u00e5ne County Council , S-20502 Malm\u00f6,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"Kwasniewicz","sequence":"additional","affiliation":[{"name":"Division of Medical Protein Chemistry, Department of Translational Medicine, Lund University, Sk\u00e5ne County Council , S-20502 Malm\u00f6,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten","family":"Scavenius","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Aarhus University , 8000 Aarhus,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4289-1393","authenticated-orcid":false,"given":"Andr\u00e9","family":"Struglics","sequence":"additional","affiliation":[{"name":"Section of Orthopaedics, Department of Clinical Sciences Lund, Lund University , SE-21184 Lund,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9292-9172","authenticated-orcid":false,"given":"Jan J","family":"Enghild","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Aarhus University , 8000 Aarhus,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tore","family":"Saxne","sequence":"additional","affiliation":[{"name":"Section of Rheumatology, Department of Clinical Sciences Lund, Lund University , S-22185 Lund,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1348-1734","authenticated-orcid":false,"given":"Anna M","family":"Blom","sequence":"additional","affiliation":[{"name":"Division of Medical Protein Chemistry, Department of Translational Medicine, Lund University, Sk\u00e5ne County Council , S-20502 Malm\u00f6,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2017,8,1]]},"reference":[{"key":"2025030614223047200_r1","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1016\/S0140-6736(16)30173-8","article-title":"Rheumatoid arthritis","volume":"388","author":"Smolen","year":"2016","journal-title":"Lancet"},{"key":"2025030614223047200_r2","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1056\/NEJMra1004965","article-title":"The pathogenesis of rheumatoid arthritis","volume":"365","author":"McInnes","year":"2011","journal-title":"N. 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