{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T14:13:57Z","timestamp":1774880037079,"version":"3.50.1"},"reference-count":18,"publisher":"Walter de Gruyter GmbH","issue":"5","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_cclm-2025-1499_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Diagnosing atypical IgG4-mediated anti-glomerular basement membrane (anti-GBM) disease is challenging because conventional serological assays poorly detect IgG4 antibodies. Here we study which commercial assays are affected and we describe proof-of-concept of improved IgG4\u00a0anti-GBM detection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2025-1499_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To investigate the scope of the diagnostic dilemma detecting IgG4\u00a0anti-GBM antibodies, serum from a patient with atypical IgG4-mediated anti-GBM was distributed to 36 laboratories participating in the Dutch External Quality Assessment (EQA) program. To improve IgG4\u00a0anti-GBM detection in the fluorescent enzyme immunoassay (FEIA), the standard anti-IgG conjugate was replaced with anti-IgG4 conjugate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2025-1499_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We report the diagnostic delay of a patient with atypical anti-GBM disease who presented with an indolent disease course. Histopathology comprised hallmarks of classic anti-GBM disease including bright linear IgG deposits along the GBM but without the typical findings of diffuse crescentic and necrotizing glomerulonephritis. IgG anti-GBM test results were repeatedly negative. Histopathological subclass analysis demonstrated that the linear IgG deposits were predominantly IgG4. All 36 Dutch EQA-participants reported negative anti-GBM test results, demonstrating that the diagnostic challenge of detecting IgG4\u00a0anti-GBM is broadly applicable across multiple diagnostic assays. A minor modification to the manufacturer\u2019s standard protocol of the FEIA anti-GBM dramatically improved the assay\u2019s performance for measuring antibodies of the IgG4 isotype. Using the modified IgG4-GBM test, we were able to diagnose and monitor one more patient with atypical IgG4-mediated anti-GBM disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2025-1499_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Here we demonstrate proof-of-concept of a modified IgG4\u00a0anti-GBM blood test allowing serological confirmation of atypical anti-GBM disease and sensitive monitoring of therapy response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/cclm-2025-1499","type":"journal-article","created":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T13:02:19Z","timestamp":1769950939000},"page":"1102-1108","source":"Crossref","is-referenced-by-count":0,"title":["Laboratory solution to diagnose and monitor atypical IgG4-mediated anti-GBM disease"],"prefix":"10.1515","volume":"64","author":[{"given":"Joannes F.M.","family":"Jacobs","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Laboratory Medical Immunology , Radboudumc , Nijmegen , The Netherlands"},{"name":"Humoral Immunology, Dutch Foundation for Quality Assessment in Medical Laboratories (SKML) , Nijmegen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annechien J.A.","family":"Lambeck","sequence":"additional","affiliation":[{"name":"Humoral Immunology, Dutch Foundation for Quality Assessment in Medical Laboratories (SKML) , Nijmegen , The Netherlands"},{"name":"Department of Laboratory Medicine , University Medical Center Groningen , Groningen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa G.M.","family":"Lammerts","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine , University Medical Center Groningen , Groningen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne-Els","family":"van de Logt","sequence":"additional","affiliation":[{"name":"Department of Nephrology , Radboudumc , Nijmegen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan-Stephan","family":"Sanders","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology , University Medical Center Groningen , Groningen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Lenssen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology , University Medical Center Groningen , Groningen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Eijgelsheim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology , University Medical Center Groningen , Groningen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingeborg","family":"Bajema","sequence":"additional","affiliation":[{"name":"Department of Pathology , University Medical Center Groningen , Groningen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric J.","family":"Steenbergen","sequence":"additional","affiliation":[{"name":"Department of Pathology , Radboudumc , Nijmegen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wibe","family":"Hoefsloot","sequence":"additional","affiliation":[{"name":"Department of Nephrology , Radboudumc , Nijmegen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilbert A.G.","family":"van der Meijden","sequence":"additional","affiliation":[{"name":"Department of Nephrology , Radboudumc , Nijmegen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renate G.","family":"van der Molen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Laboratory Medical Immunology , Radboudumc , Nijmegen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"2026033013262440186_j_cclm-2025-1499_ref_001","doi-asserted-by":"crossref","unstructured":"Kuang, H, Liu, J, Jia, XY, Cui, Z, Zhao, MH. 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