{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T23:06:48Z","timestamp":1792364808563,"version":"4.4.0"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T00:00:00Z","timestamp":1726444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Corticosteroids and immunosuppressive drugs can alleviate the symptoms of most autoimmune diseases and induce remission by restraining the autoimmune attack and limiting the damage to the target tissues. However, four autoimmune non-degenerative diseases\u2014adult advanced type 1 diabetes mellitus, Hashimoto\u2019s thyroiditis, Graves\u2019 disease, and advanced primary biliary cholangitis\u2014are refractory to these drugs. This article suggests that the refractoriness of certain autoimmune diseases is due to near-total loss of secreting cells coupled with the extremely low regenerative capacity of the affected tissues. The near-complete destruction of cells responsible for secreting insulin, thyroid hormones, or biliary HCO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    diminishes the protective effects of immunosuppressants against further damage. The slow regeneration rate of these cells hinders tissue recovery, even after drug-induced immune suppression, thus preventing remission. Although the liver can fully regenerate after injury, severe primary biliary cholangitis may impair this ability, preventing liver recovery. Consequently, these four autoimmune diseases are resistant to immunosuppressive drugs and corticosteroids. In contrast, early stages of type 1 diabetes and early primary biliary cholangitis, where damage to secreting cells is partial, may benefit from immunosuppressant treatment. In contrast to these four diseases, chronic degenerative autoimmune conditions like multiple sclerosis may respond positively to corticosteroid use despite the limited regenerative potential of the affected tissue (the central nervous system). The opposite is true for acute autoimmune conditions like Guillain\u2013Barr\u00e9 syndrome.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2024.1447337","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T00:37:07Z","timestamp":1726447027000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Autoimmune diseases refractory to corticosteroids and immunosuppressants"],"prefix":"10.3389","volume":"15","author":[{"given":"Zeev","family":"Elkoshi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.4187\/respcare.06314","article-title":"Clinical pharmacology of corticosteroids","volume":"63","author":"Williams","year":"2018","journal-title":"Respir Care"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2021.101757","article-title":"Immunosuppressive drugs modes of action","author":"Meneghini","year":"2021","journal-title":"Best Pract Res Clin Gastroenterol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2023.103451","article-title":"Low-dose intravenous immunoglobulin (IVIg) in different immune-mediated conditions","volume":"22","author":"Danieli","year":"2023","journal-title":"Autoimmun Rev"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-1-60761-720-4_1","article-title":"Pathogenesis and spectrum of autoimmunity","volume":"900","author":"Perl","year":"2012","journal-title":"Methods Mol Biol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1339714","article-title":"Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis","volume":"15","author":"Shirafkan","year":"2024","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1136\/ard-2023-224762","article-title":"EULAR recommendations for the management of systemic lupus erythematosus: 2023 update","volume":"83","author":"Fanouriakis","year":"2024","journal-title":"Ann Rheum Dis"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/acr.24596","article-title":"2021 American college of rheumatology guideline for the treatment of rheumatoid arthritis","volume":"73","author":"Fraenkel","year":"2021","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2020.07.087","article-title":"Joint AAD-NPF Guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures","volume":"84","author":"Elmets","year":"2021","journal-title":"J Am Acad Dermatol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2020.02.044","article-title":"Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies","volume":"82","author":"Menter","year":"2020","journal-title":"J Am Acad Dermatol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.2337\/dci21-0043","article-title":"The management of type 1 diabetes in adults. 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