{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T19:03:50Z","timestamp":1789758230708,"version":"4.0.1"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T00:00:00Z","timestamp":1598227200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T00:00:00Z","timestamp":1598227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004418","name":"Vrije Universiteit Brussel","doi-asserted-by":"publisher","award":["SRP55"],"award-info":[{"award-number":["SRP55"]}],"id":[{"id":"10.13039\/501100004418","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004744","name":"Innoviris","doi-asserted-by":"publisher","award":["UZBrussel 2013-PFS-EH-16"],"award-info":[{"award-number":["UZBrussel 2013-PFS-EH-16"]}],"id":[{"id":"10.13039\/501100004744","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virchows Arch"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Insulitis is a characteristic inflammatory lesion consisting of immune cell infiltrates around and within the pancreatic islets of patients with recent-onset type 1 diabetes (T1D). The infiltration is typically mild, both in terms of the number of infiltrating cells and the number of islets affected. Here, we present an unusual histopathological case study of a 66-year-old female patient with long-standing T1D, insulitis, and islet-associated lymphoid tissue. Most islets in the head of the pancreas of this patient were insulin-deficient, whereas the islets in the tail appeared normal. Insulitis was present in 0.84% of the insulin-containing islets and three islets had large lymphocytic infiltrates resembling tertiary lymphoid structures (TLS). Of note, this is the first description of potential TLS in the endocrine pancreas of a patient with T1D. Their association with a marked residual beta cell mass is of interest and may hint at new insights into disease progression and regulation of autoimmunity.<\/jats:p>","DOI":"10.1007\/s00428-020-02915-4","type":"journal-article","created":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T12:03:35Z","timestamp":1598270615000},"page":"1209-1214","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Insulitis and lymphoid structures in the islets of Langerhans of a 66-year-old patient with long-standing type 1 diabetes"],"prefix":"10.1007","volume":"478","author":[{"given":"Silke","family":"Smeets","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem","family":"Staels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert","family":"Stang\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Gillard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico","family":"De Leu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5596-7129","authenticated-orcid":false,"given":"Peter","family":"in\u2019t Veld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,24]]},"reference":[{"key":"2915_CR1","doi-asserted-by":"publisher","first-page":"2449","DOI":"10.1016\/S0140-6736(18)31320-5","volume":"391","author":"LA DiMeglio","year":"2018","unstructured":"DiMeglio LA, Evans-Molina C, Oram RA (2018) Type 1 diabetes. Lancet 391:2449\u20132462. https:\/\/doi.org\/10.1016\/S0140-6736(18)31320-5","journal-title":"Lancet"},{"key":"2915_CR2","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1007\/s00281-014-0438-4","volume":"36","author":"P In\u2019t Veld","year":"2014","unstructured":"In\u2019t Veld P (2014) Insulitis in human type 1 diabetes: a comparison between patients and animal models. Semin Immunopathol 36:569\u2013579. https:\/\/doi.org\/10.1007\/s00281-014-0438-4","journal-title":"Semin Immunopathol"},{"key":"2915_CR3","doi-asserted-by":"publisher","first-page":"2541","DOI":"10.1007\/s00125-013-3043-5","volume":"56","author":"ML Campbell-Thompson","year":"2013","unstructured":"Campbell-Thompson ML, Atkinson MA, Butler AE, Chapman NM, Frisk G, Gianani R, Giepmans BN, von Herrath MG, Hy\u00f6ty H, Kay TW, Korsgren O, Morgan NG, Powers AC, Pugliese A, Richardson SJ, Rowe PA, Tracy S, in\u2019t Veld PA (2013) The diagnosis of insulitis in human type 1 diabetes. Diabetologia 56:2541\u20132543. https:\/\/doi.org\/10.1007\/s00125-013-3043-5","journal-title":"Diabetologia"},{"key":"2915_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2018.01952","volume":"9","author":"E Pipi","year":"2018","unstructured":"Pipi E, Nayar S, Gardner DH, Colafrancesco S, Smith C, Barone F (2018) Tertiary lymphoid structures: autoimmunity goes local. Front Immunol 9:1\u201321. https:\/\/doi.org\/10.3389\/fimmu.2018.01952","journal-title":"Front Immunol"},{"key":"2915_CR5","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.it.2012.04.006","volume":"33","author":"K Neyt","year":"2012","unstructured":"Neyt K, Perros F, GeurtsvanKessel CH et al (2012) Tertiary lymphoid organs in infection and autoimmunity. Trends Immunol 33:297\u2013305. https:\/\/doi.org\/10.1016\/j.it.2012.04.006","journal-title":"Trends Immunol"},{"key":"2915_CR6","doi-asserted-by":"publisher","first-page":"5643","DOI":"10.4049\/jimmunol.178.9.5643","volume":"178","author":"PL Kendall","year":"2007","unstructured":"Kendall PL, Yu G, Woodward EJ, Thomas JW (2007) Tertiary lymphoid structures in the pancreas promote selection of B lymphocytes in autoimmune diabetes. J Immunol 178:5643\u20135651. https:\/\/doi.org\/10.4049\/jimmunol.178.9.5643","journal-title":"J Immunol"},{"key":"2915_CR7","doi-asserted-by":"publisher","first-page":"3359","DOI":"10.4049\/jimmunol.1001836","volume":"185","author":"E Astorri","year":"2010","unstructured":"Astorri E, Bombardieri M, Gabba S, Peakman M, Pozzilli P, Pitzalis C (2010) Evolution of ectopic lymphoid neogenesis and in situ autoantibody production in autoimmune nonobese diabetic mice: cellular and molecular characterization of tertiary lymphoid structures in pancreatic islets. 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