{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T03:47:26Z","timestamp":1775792846108,"version":"3.50.1"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T00:00:00Z","timestamp":1699920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>mRNA-based vaccines against SARS-CoV-2 have been proven to be very efficient in preventing severe COVID-19. Temporary lymphadenopathy (LA) has been observed as a common adverse event following immunization. Here we describe a case series of three female patients with prominent local to generalized LA after SARS-CoV-2 mRNA-1273 vaccination, which led to lymph node biopsy due to the suspicion of lymphoma or metastasis. All three patients morphologically showed similar patterns of follicular hyperplasia and especially extrafollicular blast activation. Two of the three patients only had short-lasting humoral immune responses to the vaccination. Gene expression profiling (GEP) using the HTG <jats:italic>Immune response panel<\/jats:italic> revealed that all three patients clustered together and clearly differed from the GEP-patterns of COVID-19, infectious mononucleosis and non-specific follicular hyperplasia. The closest similarities were seen with lymph nodes showing extrafollicular activation of B-blasts as well as hemophagocytosis. The GEP of the vaccination-induced LA was reminiscent of an immune response with little potential of immunologic memory. mRNA-1273 vaccination-induced LA may to a certain extend reflect disordered immune response with potentially poor immunologic memory in affected individuals.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1285168","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T13:13:15Z","timestamp":1699967595000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Case Report: Gene expression profiling of COVID-19 vaccination-related lymphadenopathies reveals evidence of a dominantly extrafollicular immune response"],"prefix":"10.3389","volume":"14","author":[{"given":"Thomas","family":"Menter","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carl P.","family":"Zinner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph T.","family":"Berger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Went","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandar","family":"Tzankov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9580","article-title":"Using lymph node swelling as a potential biomarker for successful vaccination","volume":"7","author":"Brewer","year":"2016","journal-title":"Oncotarget"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(196804)21:4<632::aid-cncr2820210415>3.0.co;2-o","article-title":"Postvaccinial lymphadenitis. Hyperplasia of lymphoid tissue that simulates Malignant lymphomas","volume":"21","author":"Hartsock","year":"1968","journal-title":"Cancer"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2996","DOI":"10.1016\/j.vaccine.2023.03.072","article-title":"Evaluation of mortality risk after COVID-19 vaccination, Utah 2021","volume":"41","author":"Payne","year":"2023","journal-title":"Vaccine"},{"key":"B4","unstructured":"Our world in data 2023"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2034577","article-title":"Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine","volume":"383","author":"Polack","year":"2020","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2035389","article-title":"Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine","volume":"384","author":"Baden","year":"2021","journal-title":"N Engl J Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2110475","article-title":"Safety of the BNT162b2 mRNA Covid-19 vaccine in a nationwide setting","volume":"385","author":"Barda","year":"2021","journal-title":"N Engl J Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-022-03400-w","article-title":"Atypical follicular hyperplasia with light chain-restricted germinal centers after COVID-19 booster: a diagnostic pitfall","volume":"482","author":"Patil","year":"2023","journal-title":"Virchows Arch"},{"key":"B9","doi-asserted-by":"publisher","first-page":"6292","DOI":"10.3390\/jcm11216290","article-title":"Pathological Findings in COVID-19 and non-COVID-19 vaccine-associated lymphadenopathy: A systematic review","volume":"11","author":"Chua","year":"2022","journal-title":"J Clin Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/ccr3.5398","article-title":"Extrafollicular proliferation of B-blasts: Morphologic correlate to Spikevax-induced lymphadenopathy","volume":"10","author":"Tzankov","year":"2022","journal-title":"Clin Case Rep"},{"key":"B11","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1111\/j.1365-2559.2005.02173.x","article-title":"Extrafollicular proliferation of B cells in the absence of follicular hyperplasia: a distinct reaction pattern in lymph nodes correlated with primary or recall type responses","volume":"47","author":"Brighenti","year":"2005","journal-title":"Histopathology"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.763098","article-title":"Vascular damage, thromboinflammation, plasmablast activation, T-Cell dysregulation and pathological histiocytic response in pulmonary draining lymph nodes of COVID-19","volume":"12","author":"Haslbauer","year":"2021","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1111\/his.14134","article-title":"Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction","volume":"77","author":"Menter","year":"2020","journal-title":"Histopathology"},{"key":"B14","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.anai.2022.10.009","article-title":"Patients with coronavirus disease 2019 characterized by dysregulated levels of membrane and soluble cluster of differentiation 48","volume":"130","author":"Pahima","year":"2023","journal-title":"Ann Allergy Asthma Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"100182","DOI":"10.1016\/j.rpth.2023.100182","article-title":"Von Willebrand factor and the thrombophilia of severe COVID-19: in situ evidence from autopsies","volume":"7","author":"van den Berg","year":"2023","journal-title":"Res Pract Thromb Haemost"},{"key":"B16","doi-asserted-by":"publisher","first-page":"w30188","DOI":"10.4414\/SMW.2022.w30188","article-title":"Multifocal lymphadenopathies with polyclonal reactions primed after EBV infection in a mRNA-1273 vaccine recipient","volume":"152","author":"Girardin","year":"2022","journal-title":"Swiss Med Wkly"},{"key":"B17","doi-asserted-by":"publisher","first-page":"696","DOI":"10.3390\/vaccines11030696","article-title":"Immune response related to lymphadenopathy post COVID-19 vaccination","volume":"11","author":"Ho","year":"2023","journal-title":"Vaccines (Basel)"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.23822\/EurAnnACI.1764-1489.273","article-title":"Kikuchi-Fujimoto disease and COVID-19 vaccination: pharmacovigilance approach","volume":"55","author":"Rodriguez-Ferreras","year":"2022","journal-title":"Eur Ann Allergy Clin Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/nature09121","article-title":"Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR\/IL-1R signalling","volume":"465","author":"Lin","year":"2010","journal-title":"Nature"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12967-016-1111-6","article-title":"Adjuvant effects of a sequence-engineered mRNA vaccine: translational profiling demonstrates similar human and murine innate response","volume":"15","author":"Edwards","year":"2017","journal-title":"J Transl Med"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e21","DOI":"10.4110\/in.2020.20.e21","article-title":"TLR10 and its unique anti-inflammatory properties and potential use as a target in therapeutics","volume":"20","author":"Fore","year":"2020","journal-title":"Immune Netw"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4781(00)00289-X","article-title":"Identification of hTLR10: a novel human Toll-like receptor preferentially expressed in immune cells","volume":"1518","author":"Chuang","year":"2001","journal-title":"Biochim Biophys Acta"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/apa.15720","article-title":"Toll-like receptor 10 rs10004195 variation may be protective against Bacillus Calmette-Guerin osteitis after newborn vaccination","volume":"110","author":"Korppi","year":"2021","journal-title":"Acta Paediatr"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1285168\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T13:13:20Z","timestamp":1699967600000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1285168\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,14]]},"references-count":23,"alternative-id":["10.3389\/fimmu.2023.1285168"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1285168","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,14]]},"article-number":"1285168"}}