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Molecular hydrogen has recently emerged as a novel therapeutic agent known for its selective antioxidant, anti-inflammatory, and immunomodulatory properties. This report evaluates the therapeutic potential of hydrogen in a patient with progressive Sj\u00f6gren\u2019s syndrome-associated interstitial lung disease. A 72-year-old female with refractory primary Sj\u00f6gren\u2019s syndrome-associated interstitial lung disease presented with worsening dyspnea, anemia, and progressive pulmonary fibrosis despite prior treatment with corticosteroids, synthetic disease-modifying antirheumatic drugs, and rituximab. The patient initiated oral molecular hydrogen capsule therapy as an adjunctive treatment. Follow-up assessments revealed marked clinical stabilization: pulmonary function tests demonstrated significant objective improvement in gas exchange capacity, anti-Ro antibody titers significantly decreased, and high-resolution computed tomography showed no further progression of fibrosis. Notably, flow cytometric analysis indicated changes associated with the normalization of immunophenotypic markers suggestive of improved immune homeostasis, evidenced by observed alterations in effector T-cell subsets and a shift in previously aberrant regulatory T-cell populations toward levels comparable to healthy controls. No adverse events were observed. Although the patient had received multiple immunosuppressive therapies, including a single dose of rituximab nearly 3\u2009years prior, these outcomes require a cautious interpretation of causality. While the observed clinical and immunophenotypic changes may represent delayed effects of prior therapies or natural disease fluctuation, the extended timeframe makes a solely delayed effect unlikely, strengthening the potential association with hydrogen therapy. These findings suggest hydrogen therapy as a safe and potentially beneficial adjunctive strategy for refractory autoimmune fibrotic diseases, supporting further clinical validation.<\/jats:p>","DOI":"10.1177\/2050313x261454858","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T06:44:48Z","timestamp":1780641888000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular hydrogen is associated with immunophenotypic modulation and changes in T-cell exhaustion markers in refractory primary Sj\u00f6gren\u2019s syndrome-associated interstitial lung disease: A case report"],"prefix":"10.1177","volume":"14","author":[{"given":"Wei-Hung","family":"Hsu","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan, R.O.C."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2128-2046","authenticated-orcid":false,"given":"Jeng-Wei","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan, R.O.C."},{"name":"Biotech Research and Innovation Centre, University of Copenhagen, Denmark"},{"name":"The Finsen Laboratory, Faculty of Health and Medical Sciences, Rigshospitalet\/National University Hospital, University of Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Jung","family":"Ho","sequence":"additional","affiliation":[{"name":"School of Pharmacy, National Defense Medical University, Taipei, Taiwan, R.O.C."},{"name":"Graduate Institute of Life Sciences, National Defense Medical University, Taipei, Taiwan, R.O.C."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan-Wen","family":"Lui","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Linkou Chang-Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Yu","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuang-Yih","family":"Wang","sequence":"additional","affiliation":[{"name":"Rheumatology\/Immunology and Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan, R.O.C."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7978-8309","authenticated-orcid":false,"given":"Feng-Cheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Rheumatology\/Immunology and Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan, R.O.C."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.47"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-216114"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-021-00605-2"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp1702514"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2020.10.011"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0210-2022"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2009.10.004"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12115"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-208659"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.731122"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.163030"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1127704"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13618-015-0035-1"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/apm.70040"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.70194"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1577"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116802"},{"key":"e_1_3_2_19_2","article-title":"Hydrogen therapy promotes macrophage polarization to the M2 subtype in radiation lung injury by inhibiting the NF-\u03baB signalling pathway","volume":"10","author":"Gao X","year":"2024","unstructured":"Gao X, Niu S, Li L, et al. 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