{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T16:35:06Z","timestamp":1775061306877,"version":"3.50.1"},"reference-count":17,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Studies examining IgG subclasses within circulating immune complexes (CICs) in patients with IgG4-related disease remain scarce. A Japanese man in his 50s with a history of diabetes mellitus and chronic pancreatitis was referred to our department because of an increase in serum creatinine levels. Serum IgG and IgG4 levels were markedly high, accompanied by eosinophilia and elevated serum IgE levels. C3 hypocomplementemia and an increase in CICs were also noted, and imaging revealed swollen mediastinal lymph nodes. Renal biopsy revealed extensive tubulointerstitial nephritis with numerous IgG4-positive plasma cells and dense interstitial fibrosis. The patient was diagnosed with IgG4-related disease, and glucocorticoid therapy was initiated; renal function, serological abnormalities, and swelling of the mediastinal lymph nodes improved. Subsequent analyses revealed that the patient\u2019s CICs mainly comprised IgG4 and that there was tubular deposition of complement components C1q, C4d, C3, and C5b-9 in the renal biopsy tissue, suggesting that immune complexes containing IgG4 activated the complement pathway in circulation and locally in the kidneys. Hypocomplementemia and CICs are observed in a subset of patients with IgG4-related diseases; however, the underlying mechanisms remain unclear. Further accumulation of IgG4-related disease cases is required to evaluate the possibility of IgG4-mediated complement activation.<\/jats:p>","DOI":"10.3390\/ijms262110687","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:15:14Z","timestamp":1762175714000},"page":"10687","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Possible Involvement of Circulating Immune Complex Containing IgG4 in the Pathogenesis of IgG4-Related Disease Complicated by Hypocomplementemia: A Case Report"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5852-9690","authenticated-orcid":false,"given":"Takahiro","family":"Uchida","sequence":"first","affiliation":[{"name":"Department of Nephrology and Blood Purification, Kidney Disease Center, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji, Tokyo 193-0998, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuka","family":"Miyake","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Blood Purification, Kidney Disease Center, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji, Tokyo 193-0998, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sachiko","family":"Iwama","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Blood Purification, Kidney Disease Center, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji, Tokyo 193-0998, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Blood Purification, Kidney Disease Center, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji, Tokyo 193-0998, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Blood Purification, Kidney Disease Center, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji, Tokyo 193-0998, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0483-0012","authenticated-orcid":false,"given":"Muneharu","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Blood Purification, Kidney Disease Center, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji, Tokyo 193-0998, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6131-7752","authenticated-orcid":false,"given":"Takashi","family":"Oda","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Blood Purification, Kidney Disease Center, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji, Tokyo 193-0998, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1056\/NEJMra1104650","article-title":"IgG4-related disease","volume":"366","author":"Stone","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.ekir.2023.10.016","article-title":"Improved renal function in initial treatment improves patient survival, renal outcomes, and glucocorticoid-related complications in IgG4-related kidney disease in Japan","volume":"9","author":"Mizushima","year":"2023","journal-title":"Kidney Int. Rep."},{"key":"ref_3","first-page":"73","article-title":"Case of IgG4-related tubulointerstitial nephritis showing the progression of renal dysfunction after a cure for autoimmune pancreatitis","volume":"52","author":"Saida","year":"2010","journal-title":"Nihon Jinzo Gakkai Shi"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000496465","article-title":"Progressive renal dysfunction due to IgG4-related kidney disease refractory to steroid therapy: A case report","volume":"9","author":"Wakabayashi","year":"2019","journal-title":"Case Rep. Nephrol. Dial."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1080\/14397595.2018.1558519","article-title":"The front line of research into immunoglobin G4-related disease\u2014Do autoantibodies cause immunoglobin G4-related disease?","volume":"29","author":"Umehara","year":"2019","journal-title":"Mod. Rheumatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"251","DOI":"10.3109\/14397595.2015.1076924","article-title":"Possible participation of IgG4 in the activation of complement in IgG4-related disease with hypocomplementemia","volume":"26","author":"Sugimoto","year":"2016","journal-title":"Mod. Rheumatol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Fujita, Y., Fukui, S., Umeda, M., Tsuji, S., Iwamoto, N., Nakashima, Y., Horai, Y., Suzuki, T., Okada, A., and Aramaki, T. (2022). Clinical characteristics of patients with IgG4-related disease complicated by hypocomplementemia. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.828122"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s10157-020-01993-7","article-title":"Validation of the diagnostic criteria for IgG4-related kidney disease (IgG4-RKD) 2011, and proposal of a new 2020 version","volume":"25","author":"Saeki","year":"2021","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.humpath.2018.07.008","article-title":"Role of complement system in patients with biopsy-proven immunoglobulin G4-related kidney disease","volume":"81","author":"Wang","year":"2018","journal-title":"Hum. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"F1325","DOI":"10.1152\/ajprenal.00447.2012","article-title":"Protective effects of Rho kinase inhibitor fasudil on rats with chronic kidney disease","volume":"304","author":"Kushiyama","year":"2013","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1080\/14397595.2020.1859710","article-title":"The 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD","volume":"31","author":"Umehara","year":"2021","journal-title":"Mod. Rheumatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1080\/14397595.2019.1709942","article-title":"Hypocomplementemia is related to elevated serum levels of IgG subclasses other than IgG4 in IgG4-related kidney disease","volume":"31","author":"Fujisawa","year":"2021","journal-title":"Mod. Rheumatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1093\/ndt\/gfac317","article-title":"Comparison of clinicopathological features between patients with and without hypocomplementemia in IgG4-related kidney disease","volume":"38","author":"Saeki","year":"2023","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1159\/000330664","article-title":"Immune complex-mediated complement activation in a patient with IgG4-related tubulointerstitial nephritis","volume":"1","author":"Nagamachi","year":"2011","journal-title":"Case Rep. Nephrol. Urol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Konno, N., Sugimoto, M., Takagi, T., Furuya, M., Asano, T., Sato, S., Kobayashi, H., Migita, K., Miura, Y., and Aihara, T. (2018). Changes in N-glycans of IgG4 and its relationship with the existence of hypocomplementemia and individual organ involvement in patients with IgG4-related disease. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0196163"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1097\/01.mpa.0000188308.75043.e4","article-title":"Autoimmune pancreatitis and complement activation system","volume":"32","author":"Muraki","year":"2006","journal-title":"Pancreas"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Oskam, N., Damelang, T., Streutker, M., Ooijevaar-de Heer, P., Nouta, J., Koeleman, C., Van Coillie, J., Wuhrer, M., Vidarsson, G., and Rispens, T. (2023). Factors affecting IgG4-mediated complement activation. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1087532"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10687\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:42:02Z","timestamp":1762177322000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10687"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,3]]},"references-count":17,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ijms262110687"],"URL":"https:\/\/doi.org\/10.3390\/ijms262110687","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,3]]}}}