{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T03:17:56Z","timestamp":1784085476767,"version":"3.55.0"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T00:00:00Z","timestamp":1623283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Current literature regarding systemic autoimmune diseases in X-chromosome aneuploidies is scarce and limited to case reports. Our aim was to evaluate the frequency of anti-nuclear (ANAs), extractable nuclear (ENA), anti-double-stranded DNA (dsDNAs), anti-smooth muscle (ASMAs) and anti-mitochondrial (AMAs) antibodies in a large cohort of adults with Klinefelter's syndrome (KS, 47,XXY) and rare higher-grade sex chromosome aneuploidies (HGAs) for the first time. Sera from 138 X-chromosome aneuploid patients [124 adult patients with 47,XXY KS and 14 patients with HGA (six children, eight adults)] and 50 age-matched 46,XY controls were recruited from the Sapienza University of Rome (2007\u201317) and tested for ANAs, ENAs, anti-dsDNAs, ASMAs and AMAs. Non-organ-specific immunoreactivity was found to be significantly higher in patients with 47,XXY KS (14%) than in the controls (2%, p\u00a0=\u00a00.002). Among all the antibodies investigated, only ANAs were observed significantly more frequently in patients with 47,XXY KS (12.1%) than in the controls (2%, p\u00a0=\u00a00.004). No anti-dsDNA immunoreactivity was found. Stratifying by testosterone replacement therapy (TRT), non-organ-specific autoantibody frequencies were higher in TRT-naive (p\u00a0=\u00a00.01) and TRT-treated groups than in controls. No patients with HGA were found positive for the various autoantibodies. Non-organ-specific autoantibodies were significantly present in 47,XXY adult patients. Conversely, HGAs did not appear to be target of non-organ-specific immunoreactivity, suggesting that KS and HGAs should be considered as two distinct conditions. The classification and diagnosis of systemic autoimmune diseases is frequently difficult. To support a correct clinical evaluation of KS disease and to prevent eventual secondary irreversible immune-mediated damages, we highlight the importance of screening for non-organ-specific autoimmunity in Klinefelter's syndrome.<\/jats:p>","DOI":"10.1111\/cei.13616","type":"journal-article","created":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T10:41:16Z","timestamp":1620816076000},"page":"316-325","source":"Crossref","is-referenced-by-count":25,"title":["Non-organ-specific autoimmunity in adult 47,XXY Klinefelter patients and higher-grade X-chromosome aneuploidies"],"prefix":"10.1093","volume":"205","author":[{"given":"Francesca","family":"Panimolle","sequence":"first","affiliation":[{"name":"Center of Rare Diseases, Section of Medical Pathophysiology, Department of Experimental Medicine, Sapienza University of Rome, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Tiberti","sequence":"additional","affiliation":[{"name":"Center of Rare Diseases, Section of Medical Pathophysiology, Department of Experimental Medicine, Sapienza University of Rome, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Spaziani","sequence":"additional","affiliation":[{"name":"Center of Rare Diseases, Section of Medical Pathophysiology, Department of Experimental Medicine, Sapienza University of Rome, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Riitano","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Lucania","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Anzuini","sequence":"additional","affiliation":[{"name":"Center of Rare Diseases, Section of Medical Pathophysiology, Department of Experimental Medicine, Sapienza University of Rome, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Lenzi","sequence":"additional","affiliation":[{"name":"Center of Rare Diseases, Section of Medical Pathophysiology, Department of Experimental Medicine, Sapienza University of Rome, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Gianfrilli","sequence":"additional","affiliation":[{"name":"Center of Rare Diseases, Section of Medical Pathophysiology, Department of Experimental Medicine, Sapienza University of Rome, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3534-1502","authenticated-orcid":false,"given":"Maurizio","family":"Sorice","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, Roma, 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