Molecular hydrogen is associated with immunophenotypic modulation and changes in T-cell exhaustion markers in refractory primary Sjögren's syndrome-associated interstitial lung disease: A case report.

Sjögren's syndrome-associated interstitial lung disease is a severe systemic complication that often proves refractory to conventional immunosuppressive and biologic therapies. 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 Sjögren's syndrome-associated interstitial lung disease. A 72-year-old female with refractory primary Sjögren's 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 years 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.