{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:28:34Z","timestamp":1760146114662,"version":"build-2065373602"},"reference-count":15,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T00:00:00Z","timestamp":1728604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Reports"],"abstract":"<jats:p>Background\u00a0and Clinical Significance: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but may underlie diverse and potentially life-threatening immune-related adverse events (irAEs). They may cause various conditions leading to respiratory failure, including myasthenic syndromes and myositis. However, diaphragmatic paralysis (DP) has rarely been reported. To describe patients with diaphragmatic paralysis in a pharmacovigilance registry, we searched the prospective REISAMIC registry at the Gustave Roussy Cancer Center (Villejuif, France) for cases of diaphragmatic palsy (DP) occurring from September 2014 to December 2021. Case Presentation: We identified three patients, in whom DP was confirmed by diaphragmatic ultrasonography, pulmonary function tests, and\/or diaphragmatic electroneuromyogram. Diaphragmatic palsy was life-threatening in all patients, as it caused respiratory failure requiring mechanical ventilation. In all cases, a pre-existing subclinical paraneoplastic syndrome was detected. Onconeural antibodies (anti-titin and anti-VGCC) were detected in these patients before and after the initiation of ICI therapy, suggesting a mixed paraneoplastic syndrome with features overlapping those of myasthenic syndrome (myasthenia gravis in one patient and Lambert\u2013Eaton syndrome in another) and myositis. Conclusions: Diaphragmatic palsy is a severe irAE potentially resulting from different mechanisms, including myositis and neuromuscular junction involvement (myasthenia gravis, Lambert\u2013Eaton). Antineuronal antibodies associated with such conditions were already present in our patients prior to immunotherapy initiation, suggesting ICIs could trigger flare-ups of pre-existing silent paraneoplastic autoimmune conditions.<\/jats:p>","DOI":"10.3390\/reports7040084","type":"journal-article","created":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T03:53:47Z","timestamp":1728618827000},"page":"84","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diaphragmatic Palsy Due to a Paraneoplastic Autoimmune Syndrome Revealed by Checkpoint Inhibitors"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4899-4378","authenticated-orcid":false,"given":"Jean-Baptiste","family":"Destival","sequence":"first","affiliation":[{"name":"Service de M\u00e9decine Interne et Immunologie Clinique, H\u00f4pital Bic\u00eatre, Assistance Publique\u2014H\u00f4pitaux de Paris, Groupe Hospitalier Universitaire Paris Saclay, 94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3482-3331","authenticated-orcid":false,"given":"Jean-Marie","family":"Michot","sequence":"additional","affiliation":[{"name":"D\u00e9partement d\u2019Innovation Th\u00e9rapeutique et des Essais Pr\u00e9coces (DITEP), Institut de Canc\u00e9rologie Gustave Roussy, 94800 Villejuif, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9cile","family":"Cauquil","sequence":"additional","affiliation":[{"name":"Assistance Publique\u2014H\u00f4pitaux de Paris, Service de Neurologie, Groupe Hospitalier Universitaire Paris Saclay, H\u00f4pital Bic\u00eatre, 94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4055-617X","authenticated-orcid":false,"given":"Nicolas","family":"No\u00ebl","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine Interne et Immunologie Clinique, H\u00f4pital Bic\u00eatre, Assistance Publique\u2014H\u00f4pitaux de Paris, Groupe Hospitalier Universitaire Paris Saclay, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"Facult\u00e9 de m\u00e9decine, Universit\u00e9 Paris Saclay, National Institute of Health and Medical Research (INSERM) UMR-1184, Atomic Energy and Alternative Energies Commission (CEA), 94270 Le Kremlin Bic\u00eatre, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salima","family":"Hacein-Bey-Abina","sequence":"additional","affiliation":[{"name":"Assistance Publique\u2014H\u00f4pitaux de Paris, Service d\u2019Immunologie Biologique, Groupe Hospitalier Universitaire Paris Saclay, H\u00f4pital Bic\u00eatre, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"Unit of Chemical and Biological Technologies for Health (UTCBS), National Center for Scientific Research (CNRS) UMR-8258, INSERM U1267, Facult\u00e9 de Pharmacie de Paris, Universit\u00e9 Paris Cit\u00e9, 75006 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5792-5552","authenticated-orcid":false,"given":"Pascale","family":"Chr\u00e9tien","sequence":"additional","affiliation":[{"name":"Assistance Publique\u2014H\u00f4pitaux de Paris, Service d\u2019Immunologie Biologique, Groupe Hospitalier Universitaire Paris Saclay, H\u00f4pital Bic\u00eatre, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"Unit of Chemical and Biological Technologies for Health (UTCBS), National Center for Scientific Research (CNRS) UMR-8258, INSERM U1267, Facult\u00e9 de Pharmacie de Paris, Universit\u00e9 Paris Cit\u00e9, 75006 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivier","family":"Lambotte","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine Interne et Immunologie Clinique, H\u00f4pital Bic\u00eatre, Assistance Publique\u2014H\u00f4pitaux de Paris, Groupe Hospitalier Universitaire Paris Saclay, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"Facult\u00e9 de m\u00e9decine, Universit\u00e9 Paris Saclay, National Institute of Health and Medical Research (INSERM) UMR-1184, Atomic Energy and Alternative Energies Commission (CEA), 94270 Le Kremlin Bic\u00eatre, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1186\/s40425-019-0821-8","article-title":"Worsening and newly diagnosed paraneoplastic syndromes following anti-PD-1 or anti-PD-L1 immunotherapies, a descriptive study","volume":"7","author":"Manson","year":"2019","journal-title":"J. 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Case Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.2337\/dbi18-0002","article-title":"Collateral Damage: Insulin-Dependent Diabetes Induced with Checkpoint Inhibitors","volume":"67","author":"Stamatouli","year":"2018","journal-title":"Diabetes"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1097\/CJI.0000000000000313","article-title":"Brief Communication: Immune Checkpoint Inhibitor-induced Diaphragmatic Dysfunction: A Case Series","volume":"43","author":"Archibald","year":"2020","journal-title":"J. Immunother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1186\/s40425-019-0774-y","article-title":"Immune checkpoint inhibitor related myasthenia gravis: Single center experience and systematic review of the literature","volume":"7","author":"Safa","year":"2019","journal-title":"J. Immunother. 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