{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T05:56:44Z","timestamp":1776405404644,"version":"3.51.2"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"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:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Vestibular and oculomotor abnormalities have been widely identified in Fabry disease (FD), with inflammation potentially playing an important role. We aim to investigate the expression of inflammatory cytokines (ICs) in FD patients and their relationship with the vestibular\/oculomotor dysfunctions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This prospective observational study enrolled 40 FD patients. All 40 patients underwent the visuo-oculomotor examination, and 22 of them received the vestibulo-oculomotor examination. Plasma concentrations of 14 ICs were detected, including interferon-\u03b3, interleukin (IL)-1\u03b2, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-17F, IL-22, tumor necrosis factor (TNF)-\u03b1, and TNF-\u03b2. Statistical analyses were made between different subgroups of patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>(1) In the visuo-oculomotor examination, TNF-\u03b2 was significantly higher in patients with prolonged saccade latency (1.61\u00a0\u00b1\u00a00.38 VS 1.14\u00a0\u00b1\u00a00.39, p=0.001) and hypometria (1.46\u00a0\u00b1\u00a00.39 VS 1.18\u00a0\u00b1\u00a00.48, p=0.043) than in patients without those abnormalities. The average saccade latency was positively correlated with the level of TNF-\u03b2 (r=0.378, p=0.021), while the average saccadic accuracy was negatively correlated with the level of TNF-\u03b2 (r=-0.333, p=0.044). IL-12p70 was significantly elevated in patients with defective pursuit compared to patients with normal pursuit (1.63\u00a0\u00b1\u00a00.20 VS 1.21\u00a0\u00b1\u00a00.54, p=0.040). (2) In the patients with vestibulo-oculomotor dysfunction, the plasma levels of IL-2 (3.40\u00a0\u00b1\u00a01.00 VS 2.13\u00a0\u00b1\u00a00.91, p=0.007), IL-17A (6.42\u00a0\u00b1\u00a03.59 VS 3.05\u00a0\u00b1\u00a02.13, p=0.021) and TNF-\u03b2 (1.55\u00a0\u00b1\u00a00.41 VS 1.21\u00a0\u00b1\u00a00.37, p=0.030) were significantly elevated compared to the patients with normal vestibulo-oculomotor function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Inflammation-mediated pathological mechanism, especially TNF-\u03b2-related pathways, is associated to both central and peripheral vestibular dysfunction in FD patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1658002","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T05:20:38Z","timestamp":1776403238000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multiple inflammatory cytokines correlate with the vestibular and oculomotor dysfunction in Fabry disease: a prospective, longitudinal study"],"prefix":"10.3389","volume":"17","author":[{"given":"Yinglin","family":"Leng","sequence":"first","affiliation":[{"name":"Department of Neurology, Peking University First Hospital","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujing","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University First Hospital","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yawen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University First Hospital","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University First Hospital","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University First Hospital","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University First Hospital","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University First Hospital","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongjun","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University First Hospital","place":["Beijing, China"]},{"name":"Department of Neuroimmunity, Peking University First Hospital","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guiping","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University First Hospital","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University First Hospital","place":["Beijing, China"]},{"name":"Beijing Key Laboratory of Neurovascular Diseases","place":["Beijing, China"]},{"name":"Rare Disease Medical Center, Peking University First Hospital","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1590\/1806-9282.66.s1.10","article-title":"Fabry disease: genetics, pathology, and treatment","volume":"66","author":"Bernardes","year":"1992","journal-title":"Rev Assoc Med Bras"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102872","article-title":"Plasma globotriaosylsphingosine in relation to phenotypes of Fabry disease","volume":"52","author":"Smid","year":"2015","journal-title":"J Med Genet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1111\/j.1651-2227.2003.tb00219.x","article-title":"Auditory and vestibular findings in Fabry disease: a study of hemizygous males and heterozygous females","volume":"92","author":"Conti","year":"2003","journal-title":"Acta Paediatr"},{"key":"B4","first-page":"87","article-title":"Inner ear involvement in Anderson-Fabry disease: long-term follow-up during enzyme replacement therapy","volume":"30","author":"Sergi","year":"2010","journal-title":"Acta Otorhinolaryngol Ital"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.4081\/audiores.2017.176","article-title":"Neuro-otological and peripheral nerve involvement in Fabry disease","volume":"7","author":"Carmona","year":"2017","journal-title":"Audiol Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.ra120000909","article-title":"Assessing the role of glycosphingolipids in the phenotype severity of Fabry disease mouse model","volume":"61","author":"Jabbarzadeh-Tabrizi","year":"2020","journal-title":"J Lipid Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.anl.2009.08.005","article-title":"Inner ear pathology of alpha-galactosidase A deficient mice, a model of Fabry disease","volume":"37","author":"Sakurai","year":"2010","journal-title":"Auris Nasus Larynx"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1789.2008.00883.x","article-title":"An autopsy case of Fabry disease with neuropathological investigation of the pathogenesis of associated dementia","volume":"28","author":"Okeda","year":"2008","journal-title":"Neuropathology"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2025.2453626","article-title":"The vestibular and oculomotor dysfunction in Fabry disease: a cohort study in China","volume":"57","year":"2025","journal-title":"Ann Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/cells13080654","article-title":"Inflammation and exosomes in Fabry disease pathogenesis","volume":"13","year":"2024","journal-title":"Cells"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1367252","article-title":"Inflammatory cytokine expression in Fabry disease: impact of disease phenotype and alterations under enzyme replacement therapy","volume":"15","author":"Yuan","year":"2024","journal-title":"Front Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/agm2.12165","article-title":"Expert consensus for diagnosis and treatment of Fabry disease in China (2021)","volume":"60","year":"2021","journal-title":"Zhonghua Nei Ke Za Zhi"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.2184","article-title":"The differential diagnostic value of a battery of oculomotor evaluation in Parkinson's Disease and Multiple System Atrophy","volume":"11","author":"Zhou","year":"2021","journal-title":"Brain Behav"},{"key":"B14","doi-asserted-by":"crossref","DOI":"10.1093\/med\/9780199969289.001.0001","volume-title":"The Neurology of Eye Movements","author":"Leigh","year":"2015"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-002-3025-7","article-title":"Proinflammatory cytokine expression in the endolymphatic sac during inner ear inflammation","volume":"4","author":"Satoh","year":"2003","journal-title":"J Assoc For Res Otolaryngol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"49","DOI":"10.21053\/ceo.2021.00920","article-title":"Cytokines and inflammation in Meniere disease","volume":"15","author":"Frejo","year":"2022","journal-title":"Clin Exp Otorhinolaryngology"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3390\/biom13091429","article-title":"Functional, morphological and molecular changes reveal the mechanisms associated with age-related vestibular loss","volume":"13","author":"Paplou","year":"2023","journal-title":"Biomolecules"},{"key":"B18","article-title":"Effect of piperphentonamine hydrochloride on expressions of interleukin-1\u03b2 and TNF-\u03b1 mRNA and Fas protein in Guinea pigs with cochlear ischemia\/reperfusion injury","volume":"33","author":"Li","year":"2013","journal-title":"J South Med Univ"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/118.4.869","article-title":"Vascular changes and demyelination induced by the intraneural injection of tumour necrosis factor","volume":"118","author":"Redford","year":"1995","journal-title":"Brain: A J Neurol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"41","DOI":"10.2139\/ssrn.4829374","article-title":"Quantitative assessments of white matter hyperintensities and plasma biomarkers can predict cognitive impairment and cerebral microbleeds in cerebral small vessel disease patients","volume":"564","author":"Fang","year":"2025","journal-title":"Neuroscience"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1177\/0271678x221106956","article-title":"Cohort study on the differential expression of inflammatory and angiogenic factors in thrombi, cerebral and peripheral plasma following acute large vessel occlusion stroke","volume":"42","author":"cott","year":"2022","journal-title":"J Cereb Blood Flow metabolism: Off J Int Soc Cereb Blood Flow Metab"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1111\/ene.16443","article-title":"Causal relationship of inflammatory cytokines and serum metabolites in cerebral small vessel disease: a two-step Mendelian randomization study","volume":"31","author":"Li","year":"2024","journal-title":"Eur J Neurol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/b978-0-12-374279-7.10003-7","article-title":"Lymphotoxin and TNF: how it all began-a tribute to the travelers","volume":"25","author":"Ruddle","year":"2014","journal-title":"Cytokine Growth factor Rev"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12727","article-title":"Mass cytometry reveals atypical immune profile notably impaired maturation of memory CD4 T with Gb3-related CD27 expression in CD4 T cells in Fabry disease","volume":"47","author":"Mauhin","year":"2024","journal-title":"J Inherited Metab Dis"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.147.9.3165","article-title":"The T cell activation antigen CD27 is a member of the nerve growth factor\/tumor necrosis factor receptor gene family","volume":"147","author":"Camerini","year":"1991","journal-title":"J Immunol (Baltimore Md: 1950)"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202149698","article-title":"Agonistic anti-CD27 antibody ameliorates EAE by suppressing IL-17 production","volume":"52","year":"2022","journal-title":"Eur J Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1097\/00054725-199911000-00009","article-title":"Th1\/Th2 cells","volume":"5","author":"Romagnani","year":"1999","journal-title":"Inflammatory bowel Dis"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2014.10.004","article-title":"Upregulation of immunomodulatory molecules by matrine treatment in experimental autoimmune encephalomyelitis","volume":"97","author":"Liu","year":"2014","journal-title":"Exp Mol Pathol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2022.155963","article-title":"IL-33 attenuates renal fibrosis via group2 innate lymphoid cells","volume":"157","year":"2022","journal-title":"Cytokine"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105492","article-title":"(+)-trans-Cannabidiol-2-hydroxy pentyl is a dual CB1R antagonist\/CB2R agonist that prevents diabetic nephropathy in mice","volume":"169","author":"Gonza\u0301lez-Mariscal","year":"2021","journal-title":"Pharmacol Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-024-12617-5","article-title":"Systematic assessment of square-wave jerks in progressive supranuclear palsy: a video-oculographic study","volume":"271","year":"2024","journal-title":"J Neurol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.visres.2004.05.009","article-title":"Characteristics of saccadic intrusions","volume":"44","year":"2004","journal-title":"Vision Res"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajoc.2022.101444","article-title":"CRB1-associated retinal dystrophy presenting as self-resolving opsoclonus and posterior uveitis","volume":"26","author":"Nguyen","year":"2022","journal-title":"Am J Ophthalmol Case Rep"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2020-240254","article-title":"Tinnitus as a presenting symptom of neurosarcoidosis with ocular involvement","volume":"14","author":"Freedman","year":"2021","journal-title":"BMJ Case Rep"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.753856","article-title":"Ocular motor abnormalities in anti-IgLON5 disease","volume":"12","author":"Macher","year":"2021","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1658002\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T05:20:40Z","timestamp":1776403240000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1658002\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,17]]},"references-count":35,"alternative-id":["10.3389\/fimmu.2026.1658002"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1658002","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,17]]},"article-number":"1658002"}}