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This paper aims to define immunological characteristics related to PCD. In this cross-sectional observational study, we enrolled 20 healthy controls and 39 CD patients. Blood samples were obtained for the detection of plasma cytokines and lipopolysaccharides (LPS). Peripheral blood mononuclear cells (PBMCs) were phenotyped by flow cytometry. Leukocytes were stimulated with LPS or anti-CD3\/anti-CD28 antibodies. Our results show that CD patients had augmented plasma interleukin (IL)-6 and LPS. However, their PBMC was characterized by decreased IL-6 production, while patients with a history of PCD produced higher IL-6, IL-8, and interferon-\u03b3, along with decreased tumor necrosis factor alpha (TNF). CD patients had augmented FoxP3 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) regulatory markers, though the PCD subjects presented a significant reduction in CTLA-4 expression. CTLA-4 as well as IL-6 and TNF responses were able to distinguish the PCD patients from those who did not present perianal complications. In conclusion, IL-6, TNF, and CTLA-4 exhibit a distinct expression pattern in CD patients with a history of PCD, regardless of disease activity. These findings clarify some mechanisms involved in the development of the perianal manifestations and may have a great impact on the disease management.<\/jats:p>","DOI":"10.1093\/cei\/uxae027","type":"journal-article","created":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T20:15:44Z","timestamp":1710965744000},"page":"78-88","source":"Crossref","is-referenced-by-count":2,"title":["Leukocyte dysfunction and reduced CTLA-4 expression are associated with perianal Crohn\u2019s disease"],"prefix":"10.1093","volume":"217","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4790-5574","authenticated-orcid":false,"given":"Murillo","family":"Duarte-Silva","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo , Ribeir\u00e3o Preto, SP ,","place":["Brazil"]},{"name":"Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo , Ribeir\u00e3o Preto, SP ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rog\u00e9rio Serafim","family":"Parra","sequence":"additional","affiliation":[{"name":"Department of Surgery and Anatomy, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo , Ribeir\u00e3o Preto, SP ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marley Ribeiro","family":"Feitosa","sequence":"additional","affiliation":[{"name":"Department of Surgery and Anatomy, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo , Ribeir\u00e3o Preto, SP ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viviani","family":"Nardini","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo , Ribeir\u00e3o Preto, SP ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra Regina","family":"Maruyama","sequence":"additional","affiliation":[{"name":"Department of Genetics and Evolution, Federal University of S\u00e3o Carlos , S\u00e3o Carlos, SP ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Joaquim Ribeiro","family":"da Rocha","sequence":"additional","affiliation":[{"name":"Department of Surgery and Anatomy, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo , Ribeir\u00e3o Preto, SP ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar","family":"Feres","sequence":"additional","affiliation":[{"name":"Department of Surgery and Anatomy, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo , Ribeir\u00e3o Preto, SP ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina Ribeiro","family":"de Barros Cardoso","sequence":"additional","affiliation":[{"name":"Department of Genetics and Evolution, Federal University of S\u00e3o Carlos , S\u00e3o Carlos, SP ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,3,22]]},"reference":[{"key":"2026041420241111500_CIT0001","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nri3661","article-title":"Cytokines in inflammatory bowel disease","volume":"14","author":"Neurath","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"2026041420241111500_CIT0002","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41572-020-0156-2","article-title":"Crohn\u2019s disease","volume":"6","author":"Roda","year":"2020","journal-title":"Nat Rev Dis Primers"},{"key":"2026041420241111500_CIT0003","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1093\/ecco-jcc\/jjz180","article-title":"ECCO guidelines on therapeutics in Crohn\u2019s disease: medical 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