{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T23:15:37Z","timestamp":1789773337030,"version":"4.0.1"},"reference-count":32,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T00:00:00Z","timestamp":1683072000000},"content-version":"unspecified","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2023,3,31]]},"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Aim of this study was to investigate the expression of interleukin (IL)-40, a new cytokine associated with B cells homoeostasis and immune response, in primary Sj\u00f6gren syndrome (pSS) and in pSS-associated lymphomas.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>29 patients with pSS and 24 controls were enrolled. Minor salivary gland (MSG) biopsies from patients, controls and parotid gland biopsies from pSS-associated lymphoma were obtained. Quantitative gene expression analysis by TaqMan real-time PCR and immunohistochemistry for IL-40 were performed on MSG. MSG cellular sources of IL-40 were determined by flow-cytometry and immunofluorescence. Serum concentration of IL-40 was assessed by ELISA and cellular sources of IL-40 were determined by flow-cytometry. An in vitro assay with recombinant IL-40 (rIL-40) was performed to detect the effect on cytokine production from peripheral blood mononuclear cells (PBMCs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      IL-40 was significantly increased in the lymphocytic infiltrated MSG of patients with pSS and correlated with focus score and with IL-4 and transforming growth factor-\u03b2 expression. In addition, IL-40 was increased in the serum of pSS and its levels correlated with the EULAR Sj\u00f6gren\u2019s Syndrome Disease Activity Index score. B cells from patients were shown to be the major source of IL-40 at both tissue and peripheral level. PBMCs from patients, exposed to rIL-40 in vitro, released proinflammatory cytokines, specifically interferon-\u03b3 from B cells and T-CD8\n                      <jats:sup>+<\/jats:sup>\n                      and tumour necrosis factor-\u03b1 and IL-17 from both T-CD4\n                      <jats:sup>+<\/jats:sup>\n                      and T-CD8\n                      <jats:sup>+<\/jats:sup>\n                      . IL-40 expression in parotid glands of pSS-associated lymphomas was also increased. Moreover, IL-40-driven NETosis was evidenced in neutrophils obtained from pSS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results suggest that IL-40 may play a role in pSS pathogenesis and pSS-associated lymphomas.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2022-002738","type":"journal-article","created":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T11:01:19Z","timestamp":1683111679000},"page":"e002738","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Possible role for IL-40 and IL-40-producing cells in the lymphocytic infiltrated salivary glands of patients with primary Sj\u00f6gren\u2019s syndrome"],"prefix":"10.1136","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2479-6958","authenticated-orcid":false,"given":"Giuliana","family":"Guggino","sequence":"first","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Rheumatology section - \u201cP. Giaccone\u201d, University of Palermo, Palermo, Sicilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Rheumatology section - \u201cP. Giaccone\u201d, University of Palermo, Palermo, Sicilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"Mohammadnezhad","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostic, Immunology Section, University of Palermo, Palermo, Sicilia, Italy"},{"name":"Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, Palermo, Sicilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Lo Pizzo","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostic, Immunology Section, University of Palermo, Palermo, Sicilia, Italy"},{"name":"Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, Palermo, Sicilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo Luca","family":"Lentini","sequence":"additional","affiliation":[{"name":"Pathology Unit, Villa Sofia Cervello United Hospitals, Palermo, Sicilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Di Liberto","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostic, Immunology Section, University of Palermo, Palermo, Sicilia, Italy"},{"name":"Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, Palermo, Sicilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"La Barbera","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Rheumatology section - \u201cP. Giaccone\u201d, University of Palermo, Palermo, Sicilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Raimondo","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics, Section of Biology and Genetics, University of Palermo, Palermo, Sicilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mojtaba","family":"Shekarkar Azgomi","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Rheumatology section - \u201cP. Giaccone\u201d, University of Palermo, Palermo, Sicilia, Italy"},{"name":"Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, Palermo, Sicilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ornella","family":"Urz\u00ec","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics, Section of Biology and Genetics, University of Palermo, Palermo, Sicilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onorina","family":"Berardicurti","sequence":"additional","affiliation":[{"name":"Unit of Allergology, Immunology, Rheumatology, Campus Bio-Medico University Hospital, Roma, Lazio, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Campisi","sequence":"additional","affiliation":[{"name":"Department of Surgical, Oncological and Oral Sciences - \u201cP. 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