{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:50:29Z","timestamp":1791618629696,"version":"4.3.4"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2018,10,11]],"date-time":"2018-10-11T00:00:00Z","timestamp":1539216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Australian National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1041900"],"award-info":[{"award-number":["1041900"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Australian National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1090759"],"award-info":[{"award-number":["1090759"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,11,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Anti-double-stranded (ds)DNA autoantibodies are prototypical serological markers of systemic lupus erythematosus (SLE), but little is known about their immunoglobulin variable (IgV) region composition at the level of the secreted (serum) proteome. Here, we use a novel proteomic workflow based on de novo mass spectrometric sequencing of anti-dsDNA precipitins to analyse IgV subfamily expression and mutational signatures of high-affinity, precipitating anti-dsDNA responses. Serum anti-dsDNA proteomes were oligoclonal with shared (public) expression of immunoglobulin (Ig)G heavy chain variable region (IGHV) and kappa chain variable region (IGKV) subfamilies. IgV peptide maps from eight subjects showed extensive public and random (private) amino acid replacement mutations with prominent arginine substitutions across heavy (H)- and light (L)-chains. Shared sets of L-chain complementarity determining region 3 (CDR3) peptides specified by arginine substitutions were sequenced from the dominantly expressed IGKV3-20 subfamily, with changes in expression levels of a clonal L-chain CDR3 peptide by quantitative multiple reaction monitoring (MRM) paralleling the rise and fall of anti-dsDNA levels by Farr radioimmunoassays (RIA). The heavily mutated IgV peptide signatures of precipitating anti-dsDNA autoantibody proteomes reflect the strong selective forces that shape humoral anti-dsDNA responses in germinal centres. Direct sequencing of agarose gel precipitins using microlitre volumes of stored sera streamlines the antibody sequencing workflow and is generalizable to other precipitating serum antibodies.<\/jats:p>","DOI":"10.1111\/cei.13197","type":"journal-article","created":{"date-parts":[[2018,8,7]],"date-time":"2018-08-07T16:28:43Z","timestamp":1533659323000},"page":"273-282","source":"Crossref","is-referenced-by-count":24,"title":["Precipitating anti-dsDNA peptide repertoires in lupus"],"prefix":"10.1093","volume":"194","author":[{"given":"J J","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Immunology, Flinders Medical Centre and Flinders University, SA Pathology, Bedford Park, SA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A D","family":"Colella","sequence":"additional","affiliation":[{"name":"Department of Immunology, Flinders Medical Centre and Flinders University, SA Pathology, Bedford Park, SA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Beroukas","sequence":"additional","affiliation":[{"name":"Department of Immunology, Flinders Medical Centre and Flinders University, SA Pathology, Bedford Park, SA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T K","family":"Chataway","sequence":"additional","affiliation":[{"name":"Flinders Proteomics Facility, Flinders University, Bedford Park, SA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T P","family":"Gordon","sequence":"additional","affiliation":[{"name":"Department of Immunology, Flinders Medical Centre and Flinders University, SA Pathology, Bedford Park, SA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,10,11]]},"reference":[{"key":"2021120808501143100_cei13197-bib-0001","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1002\/art.1780251101","article-title":"The 1982 revised criteria for the classification of systemic lupus erythematosus","volume":"25","author":"Tan","year":"1982","journal-title":"Arthritis Rheum"},{"key":"2021120808501143100_cei13197-bib-0002","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1002\/art.34473","article-title":"Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus","volume":"64","author":"Petri","year":"2012","journal-title":"Arthritis Rheum"},{"key":"2021120808501143100_cei13197-bib-0003","doi-asserted-by":"crossref","first-page":"939","DOI":"10.12688\/f1000research.6875.1","article-title":"Anti-dsDNA antibodies are one of the many autoantibodies in systemic lupus erythematosus","volume":"4","author":"Fu","year":"2015","journal-title":"F1000Res"},{"key":"2021120808501143100_cei13197-bib-0004","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.semnephrol.2015.08.005","article-title":"The role of anti-DNA antibodies in the development of lupus nephritis: a complementary, or alternative, viewpoint?","volume":"35","author":"Goilav","year":"2015","journal-title":"Semin Nephrol"},{"key":"2021120808501143100_cei13197-bib-0005","first-page":"530","article-title":"The anti-DNA antibody: origin and impact, dogmas and controversies. 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