{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:04:47Z","timestamp":1792789487244,"version":"4.5.0"},"reference-count":28,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Committee of Science of the Ministry of Science and Higher Education of the Republic of Kazakhstan","award":["AP25795047"],"award-info":[{"award-number":["AP25795047"]}],"id":[{"id":"https:\/\/ror.org\/05tyne317","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Thyroid eye disease (TED) is an autoimmune inflammatory disorder of the orbit closely associated with thyroid dysfunction. Total thyroidectomy is traditionally expected to attenuate the autoimmune cascade, yet some patients continue to progress after surgery, which challenges this paradigm and points to a potentially autonomous orbital immune response. To investigate this, we performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from a 47-year-old woman with severe, glucocorticoid-refractory TED, four years after total thyroidectomy, and compared her immune landscape with that of an age- and sex-matched healthy control. The patient\u2019s peripheral blood showed a clear shift toward an active, stress-associated inflammatory state: pro-inflammatory mediators, immediate-early response transcription factors (FOS, JUNB, FOSB, TNFAIP3), and survival-related genes (CXCR4, DDIT4) were all upregulated. Gene Set Enrichment Analysis (GSEA) pointed to different mechanisms across cell types\u2014myeloid cells were enriched for IL-6\/JAK\/STAT3 and TNF-\u03b1 signaling, activated T cells for oxidative phosphorylation and mTORC1 signaling\u2014while B lymphocytes and NK cells showed the opposite pattern, with reduced inflammatory and metabolic activity. One possible explanation is a \u201ctissue-drainage\u201d effect, where the most pathogenic lymphocytes leave the bloodstream and migrate into the inflamed orbital tissue along chemokine gradients. Together, these findings point to the CXCR4\/CXCL12 axis and cellular stress pathways as candidate therapeutic targets, though as a single-case observation this remains preliminary and requires validation in larger cohorts, at the protein level, and in functional in vitro\/in vivo studies.<\/jats:p>","DOI":"10.3390\/genes17091143","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T08:03:47Z","timestamp":1789977827000},"page":"1143","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single-Cell Transcriptomic Profiling of Peripheral Blood in a Patient with Progressive Thyroid Eye Disease Following Total Thyroidectomy"],"prefix":"10.3390","volume":"17","author":[{"given":"Ainura","family":"Mussakulova","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Genetics, Institute of Genetics and Physiology, Almaty 050060, Kazakhstan"},{"name":"Faculty of Medicine and Health Care, Al-Farabi Kazakh National University, Almaty 050040, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zarina","family":"Zhalgasbaeva","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Institute of Genetics and Physiology, Almaty 050060, Kazakhstan"},{"name":"Faculty of Biology and Biotechnology, Al-Farabi Kazakh National University, Almaty 050040, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vyacheslav","family":"Korobeynikov","sequence":"additional","affiliation":[{"name":"Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk 634009, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8642-9577","authenticated-orcid":false,"given":"Gulnur","family":"Zhunussova","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Institute of Genetics and Physiology, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"ref_1","first-page":"477","article-title":"The epidemiologic characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmsted County, Minnesota","volume":"92","author":"Bartley","year":"1994","journal-title":"Trans. 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