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Current therapeutic strategies\u2014including corticosteroids, immunosuppressants, and biologics\u2014often exhibit variable efficacy and are associated with potential adverse effects. Molecular hydrogen, recognized for its ability to scavenge mitochondrial reactive oxygen species and inhibit the NLRP3 inflammasome, has emerged as a promising adjunctive treatment. However, its immunomodulatory effects remain insufficiently defined. This study aimed to evaluate the immunological effects of molecular hydrogen\u2010assisted therapy (MHAT) on immune cell subsets and to identify potential predictive biomarkers of treatment efficacy. A total of 25 patients with autoimmune diseases who received MHAT were included (RA:\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200914; SLE:\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20097; others:\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094, including one each with psoriatic arthritis, primary Sj\u00f6gren's syndrome, immune\u2010related interstitial lung disease, and diffuse idiopathic skeletal hyperostosis). An additional 15 untreated RA patients served as controls for the assessment of MHAT\u2010induced changes in lymphocyte profiles and type 1 regulatory T (Tr1) cells. MHAT was administered orally at a daily dose of 170\u2009mg hydrogen\u2010enriched coral calcium for three months. Immune phenotyping of T cells, B cells, and regulatory T cells was performed using flow cytometry before and after treatment. Among the 108 immune subsets analyzed, 15 exhibited significant changes, including 11 T cell and 4 B cell subsets. Disease\u2010specific immune modulation was observed in RA patients, particularly characterized by increased proportions of programmed cell death protein 1 (PD\u20101\n                    <jats:sup>+<\/jats:sup>\n                    ) T cells and Fas\n                    <jats:sup>+<\/jats:sup>\n                    B cells, and a marked reduction in Tr1 cells compared to patients with SLE or other autoimmune diseases. Based on baseline immune profiles and the percent change in fatigue scores (assessed by the Brief Fatigue Inventory, BFI\u2010T), a Hydrogen\u2010assisted Treatment Response Prediction Index (HRPI) was developed, demonstrating strong predictive performance (ROC\u2009=\u20090.9375,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0118). HRPI values below \u22120.3 predicted favorable clinical responses, whereas values near zero were associated with poor outcomes. HRPI shows potential as a predictive biomarker for MHAT efficacy and guides personalized autoimmune treatment.\n                  <\/jats:p>","DOI":"10.1111\/apm.70040","type":"journal-article","created":{"date-parts":[[2025,7,13]],"date-time":"2025-07-13T12:47:09Z","timestamp":1752410829000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Predicting Therapeutic Response to Molecular Hydrogen in Autoimmune Diseases via Immunophenotyping"],"prefix":"10.1111","volume":"133","author":[{"given":"Shan\u2010Wen","family":"Lui","sequence":"first","affiliation":[{"name":"Department of Medical Education Linkou Chang\u2010Gung Memorial Hospital  Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting\u2010Yu","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Medical Education Taichung Veterans General Hospital  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2128-2046","authenticated-orcid":false,"given":"Jeng\u2010Wei","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology National Taiwan Ocean University  Keelung Taiwan"},{"name":"Biotech Research and Innovation Centre University of Copenhagen  Copenhagen Denmark"},{"name":"The Finsen Laboratory, Rigshospitalet\/National University Hospital, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Jung","family":"Ho","sequence":"additional","affiliation":[{"name":"School of Pharmacy National Defense Medical Center  Taipei Taiwan"},{"name":"Graduate Institute of Life Science National Defense Medical Center  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1291-8946","authenticated-orcid":false,"given":"Feng\u2010Cheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Rheumatology\/Immunology and Allergy, Department of Internal Medicine, Tri\u2010Service General Hospital National Defense Medical Center  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.03.007"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.148965.3"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2024.102019"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8384742"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612825666190506123038"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28237785"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-024-05685-7"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12122062"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox14010111"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.789507"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpainsymman.2005.12.019"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.12677\/ACM.2021.1110648"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25147726"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-013-9718-8"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/apm.13341"},{"key":"e_1_2_8_17_1","first-page":"301","article-title":"Hydrogen Gas Restores Exhausted CD8+ T Cells in Patients With Advanced Colorectal Cancer to Improve Prognosis","volume":"41","author":"Akagi J.","year":"2019","journal-title":"Oncology Reports"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00422"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-016-1803-z"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2011.03470.x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2478(00)00316-3"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2414"},{"key":"e_1_2_8_23_1","article-title":"Effector Memory CD4(+) T Cells Induce Damaging Innate Inflammation and Autoimmune Pathology by Engaging CD40 and TNFR on Myeloid Cells","volume":"7","author":"McDaniel M. 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