# Predicting Therapeutic Response to Molecular Hydrogen in Autoimmune Diseases via Immunophenotyping.
> 免疫表現型解析による自己免疫疾患への分子状水素応答予測指標の開発


## Abstract

This observational study enrolled 25 patients with autoimmune diseases—14 with rheumatoid arthritis (RA), 7 with systemic lupus erythematosus (SLE), and 4 with other conditions—who received hydrogen-enriched coral calcium (170 mg/day orally for three months). An additional 15 untreated RA patients served as controls. Flow cytometry was used to characterize immune cell subsets before and after the intervention. Of 108 subsets examined, 15 showed statistically significant shifts, comprising 11 T cell and 4 B cell populations. RA patients displayed a distinctive pattern: elevated proportions of PD-1-positive T cells and Fas-positive B cells alongside a marked decline in type 1 regulatory T (Tr1) cells, differing from SLE and other disease groups. Combining baseline immunophenotype data with percent changes in fatigue scores (Brief Fatigue Inventory), a Hydrogen-assisted Treatment Response Prediction Index (HRPI) was constructed. The index achieved an ROC of 0.9375 (p = 0.0118), with HRPI values below −0.3 associated with favorable clinical outcomes and values near zero linked to poor responses, suggesting its utility as a personalized biomarker.

### Mechanism

Molecular hydrogen is proposed to exert immunomodulatory effects by selectively scavenging mitochondrial reactive oxygen species and suppressing NLRP3 inflammasome activation, thereby reducing chronic inflammatory signaling.

## Bibliographic

- **Authors**: Lui SW, Hsieh TY, Lu J, Ho YJ, Liu FT
- **Journal**: APMIS
- **Year**: 2025
- **PMID**: [40590161](https://pubmed.ncbi.nlm.nih.gov/40590161/)
- **DOI**: [10.1111/apm.70040](https://doi.org/10.1111/apm.70040)
- **Study type**: human observational study
- **Delivery route**: hydrogen-rich water
- **Effect reported**: mixed

## Delivery context

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 40590161. https://h2-papers.org/en/papers/40590161
> **Source**: PubMed PMID [40590161](https://pubmed.ncbi.nlm.nih.gov/40590161/)