{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T22:33:51Z","timestamp":1788993231239,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,4,14]],"date-time":"2020-04-14T00:00:00Z","timestamp":1586822400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Ankylosing spondylitis (AS) is associated with autoantibody production to class II MHC\u2010associated invariant chain peptide, CD74\/CLIP. In this study, we considered that anti\u2010CD74\/CLIP autoantibodies present in sera from AS might recognize CD74 degradation products that accumulate upon deficiency of the enzyme signal peptide peptidase\u2010like 2A (SPPL2a). We analyzed monocytes from healthy controls (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a042), psoriatic arthritis (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a025), rheumatoid arthritis (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a016), and AS patients (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a015) for SPPL2a enzyme activity and complemented the experiments using SPPL2a\u2010sufficient and \u2010deficient THP\u20101 cells. We found defects in SPPL2a function and CD74 processing in a subset of AS patients, which culminated in CD74 and HLA class II display at the cell surface. These findings were verified in SPPL2a\u2010deficient THP\u20101 cells, which showed expedited expression of MHC class II, total CD74 and CD74 N\u2010terminal degradation products at the plasma membrane upon receipt of an inflammatory trigger. Furthermore, we observed that IgG anti\u2010CD74\/CLIP autoantibodies recognize CD74 N\u2010terminal degradation products that accumulate upon SPPL2a defect. In conclusion, reduced activity of SPPL2a protease in monocytes from AS predisposes to endosomal accumulation of CD74 and CD74 N\u2010terminal fragments, which, upon IFN\u2010\u03b3\u2010exposure, is deposited at the plasma membrane and can be recognized by anti\u2010CD74\/CLIP autoantibodies.\n                  <\/jats:p>","DOI":"10.1002\/eji.201948502","type":"journal-article","created":{"date-parts":[[2020,3,21]],"date-time":"2020-03-21T09:08:21Z","timestamp":1584781701000},"page":"1209-1219","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Impaired proteolysis by SPPL2a causes CD74 fragment accumulation that can be recognized by anti\u2010CD74 autoantibodies in human ankylosing spondylitis"],"prefix":"10.1002","volume":"50","author":[{"given":"Tessa S.","family":"van Kempen","sequence":"first","affiliation":[{"name":"Department of Rheumatology &amp; Clinical Immunology University Medical Center Utrecht  Utrecht The Netherlands"},{"name":"Center for Translational Immunology University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmerik F.A.","family":"Leijten","sequence":"additional","affiliation":[{"name":"Department of Rheumatology &amp; Clinical Immunology University Medical Center Utrecht  Utrecht The Netherlands"},{"name":"Center for Translational Immunology University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marthe F.S.","family":"Lindenbergh","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology University Medical Center Utrecht  Utrecht The Netherlands"},{"name":"Department of Biochemistry and Cell Biology Faculty of Veterinary Medicine Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel Olde","family":"Nordkamp","sequence":"additional","affiliation":[{"name":"Department of Rheumatology &amp; Clinical Immunology University Medical Center Utrecht  Utrecht The Netherlands"},{"name":"Center for Translational Immunology University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Driessen","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hematology Cantonal Hospital St. Gallen  St. Gallen Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert\u2010Jan","family":"Lebbink","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Baerlecken","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Rheumatology Medical University Hannover  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Witte","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Rheumatology Medical University Hannover  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R.D.J.","family":"Radstake","sequence":"additional","affiliation":[{"name":"Department of Rheumatology &amp; Clinical Immunology University Medical Center Utrecht  Utrecht The Netherlands"},{"name":"Center for Translational Immunology University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Boes","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology University Medical Center Utrecht  Utrecht The Netherlands"},{"name":"Department of Pediatrics University Medical Center Utrecht  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1406182"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2015.147"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2015.60"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.873"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.582"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80249-6"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200526323"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200202)32:2<467::AID-IMMU467>3.0.CO;2-Y"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80020-5"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121076"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121072"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121069"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202208"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-018-1535-x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202177"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00574"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2006.04.011"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1070925"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005980200"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200009)30:9<2604::AID-IMMU2604>3.0.CO;2-6"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(95)00287-J"},{"key":"e_1_2_7_23_1","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.4049\/jimmunol.132.3.1249","article-title":"Interferons as modulators of human monocyte\u2010macrophage differentiation. I. Interferon\u2010gamma increases HLA\u2010DR expression and inhibits phagocytosis of zymosan","volume":"132","author":"Becker S.","year":"1984","journal-title":"J. Immunol."},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032712-095910"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00421-4"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b01371"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.9b00044"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00017a002"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2009.01024.x"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep28973"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005701"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.037"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201970107"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00038-14"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Feji.201948502","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.201948502","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/eji.201948502","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.201948502","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T05:19:48Z","timestamp":1693891188000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.201948502"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,14]]},"references-count":33,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["10.1002\/eji.201948502"],"URL":"https:\/\/doi.org\/10.1002\/eji.201948502","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/EJI.201948502\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948502\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948502\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948502\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948502\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948502\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948502\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,14]]},"assertion":[{"value":"2019-12-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}