{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:12:27Z","timestamp":1776903147075,"version":"3.51.2"},"reference-count":65,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T00:00:00Z","timestamp":1768089600000},"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>Acute Appendicitis (AA) is the commonest abdominal digestive surgical emergency, but its etiology is not clarified. Based on histologic observations, an allergic cause has been proposed. In a type I hypersensitivity allergic reaction, there is a Th2 immune response characterized by Th2 cells, eosinophils, basophils, IgE, IL-4, IL-5, and IL-13 serum elevation. Recent studies showed a local appendicular endoluminal and parietal Th2 immune response in acute phlegmonous appendicitis. We performed a prospective single-center study where we evaluated the Th2 blood immune response in 38 patients with acute phlegmonous appendicitis, 27 patients with acute gangrenous appendicitis, and 18 patients with the clinical picture of AA, who underwent appendectomy but had negative histology for AA (negative appendectomy group). Higher levels of basophils were found in phlegmonous appendicitis (p = 0.03), and higher levels of eosinophils were found in the control group (p = 0.003). Effector memory CD4 T cells re-expressing CD45RA were higher in gangrenous (p = 0.020) and central memory CD4 T cells in phlegmonous appendicitis (p = 0.004). The number of Th2 circulating cells was higher in gangrenous appendicitis (p = 0.037), while Th1 circulating cells were higher in phlegmonous appendicitis (p = 0.028). IL-4 blood concentrations were elevated in acute gangrenous appendicitis (p = 0.029). No significant differences were found in the levels of IgE, IL-5, or IL-13 in any of the groups. Thus, a Th2 response was not detected in patients\u2019 serum with phlegmonous appendicitis. Serum levels of IgE, IL-5, and IL-13 were not different among patients with acute phlegmonous appendicitis, acute gangrenous appendicitis, and the negative appendectomy group. These findings are in contrast to our previous work in which we evaluated the Th2 response at the local level, at the appendicular luminal aspect and appendicular wall, in phlegmonous appendicitis and control groups, and we unequivocally showed a Th2 response in phlegmonous appendicitis. Thus, in patients with phlegmonous appendicitis, the local Th2 response is not reflected in the serum levels of immune cells and cytokines.<\/jats:p>","DOI":"10.3390\/ijms27020733","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T09:13:01Z","timestamp":1768209181000},"page":"733","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Characterization of Th2 Serum Immune Response in Acute Appendicitis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9325-0145","authenticated-orcid":false,"given":"Nuno","family":"Carvalho","sequence":"first","affiliation":[{"name":"Servi\u00e7o Cirurgia Geral, Hospital Garcia de Orta, Unidade Local de Sa\u00fade Almada-Seixal, 2805-267 Almada, Portugal"},{"name":"Faculdade Medicina, Universidade Lisboa, 1649-028 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2024-0434","authenticated-orcid":false,"given":"Jani-Sofia","family":"Almeida","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Oncology, Center for Neuroscience and Cell Biology [CNC], University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Institute of Immunology, Faculty of Medicine [FMUC], University of Coimbra, 3000-504 Coimbra, Portugal"},{"name":"Center of Investigation in Environment, Genetics and Oncobiology [CIMAGO], Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research [iCBR], Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovation in Biomedicine and Biotechnology [CIBB], University of Coimbra, 3000-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra [CACC], 3004-561 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4165-7052","authenticated-orcid":false,"given":"Elisabete","family":"Carolino","sequence":"additional","affiliation":[{"name":"H&TRC\u2014Health & Technology Research Center, ESTeSL\u2014Escola Superior de Tecnologia da Sa\u00fade, Instituto Polit\u00e9cnico de Lisboa, 1990-096 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2108-0616","authenticated-orcid":false,"given":"Francisco","family":"Lopes","sequence":"additional","affiliation":[{"name":"Servi\u00e7o Cirurgia Geral, Hospital Garcia de Orta, Unidade Local de Sa\u00fade Almada-Seixal, 2805-267 Almada, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2723-8070","authenticated-orcid":false,"given":"Susana","family":"Henriques","sequence":"additional","affiliation":[{"name":"Servi\u00e7o Cirurgia Geral, Hospital Garcia de Orta, Unidade Local de Sa\u00fade Almada-Seixal, 2805-267 Almada, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8343-0780","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Vaz","sequence":"additional","affiliation":[{"name":"Servi\u00e7o Cirurgia Geral, Hospital Garcia de Orta, Unidade Local de Sa\u00fade Almada-Seixal, 2805-267 Almada, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5342-8081","authenticated-orcid":false,"given":"H\u00e9lder","family":"Coelho","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Anatomia Patol\u00f3gica, Hospital Garcia de Orta, Unidade Local de Sa\u00fade Almada-Seixal, 2805-267 Almada, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7519-1620","authenticated-orcid":false,"given":"Paulo Rodrigues","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Oncology, Center for Neuroscience and Cell Biology [CNC], University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Institute of Immunology, Faculty of Medicine [FMUC], University of Coimbra, 3000-504 Coimbra, Portugal"},{"name":"Center of Investigation in Environment, Genetics and Oncobiology [CIMAGO], Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research [iCBR], Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovation in Biomedicine and Biotechnology [CIBB], University of Coimbra, 3000-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra [CACC], 3004-561 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0789-8637","authenticated-orcid":false,"given":"Manuel Santos","family":"Rosa","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Faculty of Medicine [FMUC], University of Coimbra, 3000-504 Coimbra, Portugal"},{"name":"Center of Investigation in Environment, Genetics and Oncobiology [CIMAGO], Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research [iCBR], Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovation in Biomedicine and Biotechnology [CIBB], University of Coimbra, 3000-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra [CACC], 3004-561 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0707-315X","authenticated-orcid":false,"given":"Lu\u00eds","family":"Moita","sequence":"additional","affiliation":[{"name":"Innate Immunity and Inflammation Lab, Instituto Gulbenkian de Ci\u00eancia Oeiras, 2780-156 Oeiras, Portugal"},{"name":"Instituto de Histologia e Biologia do Desenvolvimento, Faculdade Medicina [FMUC], Universidade Lisboa, 1649-028 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2363-9670","authenticated-orcid":false,"given":"Carlos","family":"Luz","sequence":"additional","affiliation":[{"name":"Servi\u00e7o Cirurgia Geral, Hospital Garcia de Orta, Unidade Local de Sa\u00fade Almada-Seixal, 2805-267 Almada, Portugal"},{"name":"Faculdade Medicina, Universidade Lisboa, 1649-028 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7550-8285","authenticated-orcid":false,"given":"Paulo Matos","family":"da Costa","sequence":"additional","affiliation":[{"name":"Faculdade Medicina, Universidade Lisboa, 1649-028 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1001\/jama.2021.20502","article-title":"Diagnosis and Management of Acute Appendicitis in Adults: A Review","volume":"326","author":"Moris","year":"2021","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17352","DOI":"10.1038\/s41598-020-73798-3","article-title":"An observational study of innate immune responses in patients with acute appendicitis","volume":"10","author":"Peeters","year":"2020","journal-title":"Sci. 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