{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:59:01Z","timestamp":1753891141176,"version":"3.41.2"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T00:00:00Z","timestamp":1738540800000},"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>In 2013, a young woman during her early pregnancy was repeatedly hospitalized due to respiratory and swallowing difficulties. The pregnancy was terminated due to recurrent severe lung infections. She was later diagnosed with myasthenia gravis (MG) based on positive acetylcholine receptor antibodies. Her muscle weakness was subsequently well-controlled with pyridostigmine bromide, azathioprine, and prednisone. Notably, in the seventh year after her MG diagnosis (2021), the patient developed severe anemia (hemoglobin: 44 g\/L). Bone marrow analysis revealed a rare combination of pure red cell aplasia (PRCA) with clonal expansion of large granular cells. Further examinations excluded thymoma. Considering the possibility of drug-induced PRCA, azathioprine was replaced with tacrolimus. Remarkably, the anemia resolved within 1 month, and her MG remained well-controlled. It is well-established that abnormal thymic hyperplasia within thymomas can alter the distribution and function of peripheral T lymphocytes, leading to the development of autoimmune diseases such as MG and PRCA. In this unique case without thymoma, we discussed the mechanisms and associations of PRCA with MG, medication, and clonal large granular T cells. This unique case highlights the unprecedented association of MG and PRCA without thymoma, underscoring the complexity of the disease spectrum. The patient\u2019s subsequent successful delivery in June 2023 adds another dimension to the multifaceted clinical course, warranting attention and exploration into potential connections between these conditions.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1367409","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T06:36:30Z","timestamp":1738564590000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Myasthenia gravis complicated by pure red cell aplasia with clonal large granular lymphocytosis in the absence of thymoma: a rare case report and literature review"],"prefix":"10.3389","volume":"16","author":[{"given":"Lijun","family":"Du","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiaolin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1602678","article-title":"Myasthenia gravis","volume":"375","author":"Gilhus","year":"2016","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-05-717140","article-title":"Pure red cell aplasia","volume":"128","author":"Means","year":"2016","journal-title":"Blood"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1080\/20009666.2020.1770019","article-title":"Pure red cell aplasia and seronegative myasthenia gravis in association with thymoma","volume":"10","author":"Lee","year":"2020","journal-title":"J Community Hosp Intern Med Perspect"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.21037\/gs-22-218","article-title":"Huge thymoma combined with pure red cell aplasia: a case report and literature review","volume":"11","author":"Wang","year":"2022","journal-title":"Gland Surg"},{"key":"B5","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.autrev.2015.09.005","article-title":"Thymoma associated with autoimmune diseases: 85 cases and literature review","volume":"15","author":"Bernard","year":"2016","journal-title":"Autoimmun Rev"},{"key":"B6","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1093\/jjco\/28.11.696","article-title":"Pure red cell aplasia and myasthenia gravis with thymoma: a case report and review of the literature","volume":"28","author":"Mizobuchi","year":"1998","journal-title":"Jpn J Clin Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2020.09.015","article-title":"Myasthenia gravis and pregnancy","volume":"177","author":"Roche","year":"2021","journal-title":"Rev Neurol (Paris)"},{"key":"B8","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/s0003-4975(10)65164-8","article-title":"Thymus and myasthenia gravis","volume":"13","author":"Thomas","year":"1972","journal-title":"Ann Thorac Surg"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-2-44","article-title":"Myasthenia gravis","volume":"2","author":"Juel","year":"2007","journal-title":"Orphanet J Rare Dis"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s100720300019","article-title":"Myasthenia gravis with thymoma and autoimmune haemolytic anaemia. A case report","volume":"24","author":"Tuncer Elmaci","year":"2003","journal-title":"Neurol Sci"},{"key":"B11","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s41983-023-00636-4","article-title":"Myasthenia gravis with achalasia secondary to thymoma: a case report and literature review","volume":"59","author":"Haridy","year":"2023","journal-title":"Egypt J Neurol Psychiatr Neurosurg"},{"key":"B12","article-title":"Megaesophagus associated with Myasthenia Gravis: a rare condition in humans","volume":"11","author":"Desuter","year":"2015","journal-title":"B-ENT"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2013.12.005","article-title":"The co-existence of myasthenia gravis in patients with myositis: a case series","volume":"43","author":"Paik","year":"2014","journal-title":"Semin Arthritis Rheum"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.175810","article-title":"Rational management approach to pure red cell aplasia","volume":"103","author":"Balasubramanian","year":"2018","journal-title":"Haematologica"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/j.1875-9114.1996.tb03025.x","article-title":"Drug-induced pure red cell aplasia","volume":"16","author":"Thompson","year":"1996","journal-title":"Pharmacotherapy"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/S1387-2656(04)10008-2","article-title":"Drug-induced and antibody-mediated pure red cell aplasia: a review of literature and current knowledge","volume":"10","author":"Smalling","year":"2004","journal-title":"Biotechnol Annu Rev"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-009-1113-2","article-title":"Isoniazid-triggered pure red cell aplasia in systemic lupus erythematosus complicated with myasthenia gravis","volume":"30","author":"Nakamura","year":"2010","journal-title":"Rheumatol Int"},{"key":"B18","doi-asserted-by":"publisher","first-page":"bcr2017220188","DOI":"10.1136\/bcr-2017-220188","article-title":"Pure red cell aplasia and myasthenia gravis: a patient having both autoimmune conditions in the absence of thymoma","volume":"2017","author":"Aquilina","year":"2017","journal-title":"BMJ Case Rep"},{"key":"B19","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1002\/(SICI)1096-8652(199704)54:4<343::AID-AJH19>3.0.CO;2-C","article-title":"Concomitant association of myasthenia gravis and pure red cell aplasia after chemotherapy for Hodgkin\u2019s disease","volume":"54","author":"Mohri","year":"1997","journal-title":"Am J Hematol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.7.3000.bloodjournal8773000","article-title":"Pure red cell aplasia: association with large granular lymphocyte leukemia and the prognostic value of cytogenetic abnormalities","volume":"87","author":"Lacy","year":"1996","journal-title":"Blood"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.47.7.676","article-title":"Pure red cell aplasia associated with Malignant thymoma, myasthenia gravis, polyclonal large granular lymphocytosis and clonal thymic T cell expansion","volume":"47","author":"Handa","year":"1994","journal-title":"J Clin Pathol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/91.1.112a","article-title":"Azathioprine as possible explanation of etiology of pure red cell aplasia in myasthenics","volume":"91","author":"Smith","year":"1989","journal-title":"Am J Clin Pathol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.4103\/0253-7613.174569","article-title":"Pure red cell aplasia due to azathioprine therapy for Crohn\u2019s disease","volume":"48","author":"Kamath","year":"2016","journal-title":"Indian J Pharmacol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-013-1779-0","article-title":"Azathioprine-associated pure red cell aplasia in renal transplant recipients: a report of two cases","volume":"93","author":"Koduri","year":"2014","journal-title":"Ann Hematol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1978.03290060054014","article-title":"Azathioprine-induced pure red blood cell aplasia","volume":"240","author":"Old","year":"1978","journal-title":"JAMA"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.1993.tb00654.x","article-title":"Azathioprine-associated pure red cell aplasia","volume":"233","author":"Creemers","year":"1993","journal-title":"J Intern Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1136\/gut.34.8.1081","article-title":"Bone marrow toxicity caused by azathioprine in inflammatory bowel disease: 27 years of experience","volume":"34","author":"Connell","year":"1993","journal-title":"Gut"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e7112","DOI":"10.7759\/cureus.7112","article-title":"Isoniazid induced pure red blood cell aplasia","volume":"12","author":"Azhar","year":"2020","journal-title":"Cureus"},{"key":"B29","doi-asserted-by":"publisher","first-page":"bcr2018226134","DOI":"10.1136\/bcr-2018-226134","article-title":"Isoniazid-induced pure red cell aplasia","volume":"2018","author":"Holla","year":"2018","journal-title":"BMJ Case Rep"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.8379-16","article-title":"Isoniazid-induced pure red cell aplasia in a patient with sarcoidosis: A patient summary and review of the literature","volume":"56","author":"Saito","year":"2017","journal-title":"Intern Med"},{"key":"B31","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1016\/s0022-3476(98)70330-0","article-title":"Isoniazid-induced pure red cell aplasia in two siblings","volume":"132","author":"Marseglia","year":"1998","journal-title":"J Pediatr"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/s0954-6111(08)80025-x","article-title":"A case of isoniazid-induced red cell aplasia","volume":"84","author":"Johnsson","year":"1990","journal-title":"Respir Med"},{"key":"B33","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/s00432-020-03440-2","article-title":"Peripheral blood T lymphocytosis in thymoma: an insight into immunobiology","volume":"147","author":"Mishra","year":"2021","journal-title":"J Cancer Res Clin Oncol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/89.5.687","article-title":"Myasthenia gravis with thymoma and pure red blood cell aplasia","volume":"89","author":"Bailey","year":"1988","journal-title":"Am J Clin Pathol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.12.3872","article-title":"Thymomas alter the T-cell subset composition in the blood: a potential mechanism for thymoma-associated autoimmune disease","volume":"96","author":"Hoffacker","year":"2000","journal-title":"Blood"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e3182708edf","article-title":"Pharmacokinetics of tacrolimus during pregnancy","volume":"34","author":"Zheng","year":"2012","journal-title":"Ther Drug Monit"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1367409\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T06:36:32Z","timestamp":1738564592000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1367409\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,3]]},"references-count":36,"alternative-id":["10.3389\/fimmu.2025.1367409"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1367409","relation":{},"ISSN":["1664-3224"],"issn-type":[{"type":"electronic","value":"1664-3224"}],"subject":[],"published":{"date-parts":[[2025,2,3]]},"article-number":"1367409"}}