# Individualized diagnosis of rheumatoid arthritis: A rank-based qualitative T cell-related signature

**Authors:** Hang Su, Xingyi Li, Yawei Li, Wan-Tien Chiang, Wan-Tien Chiang, Wan-Tien Chiang, Wan-Tien Chiang

PMC · DOI: 10.1371/journal.pone.0326027 · 2025-06-26

## TL;DR

This paper introduces a new diagnostic signature for rheumatoid arthritis based on two genes, which helps distinguish RA from healthy individuals with high accuracy.

## Contribution

The study proposes a novel rank-based gene signature (IOS) for individualized RA diagnosis with high sensitivity and specificity.

## Key findings

- The ICAM2-OSTF1 signature (IOS) achieved 87.39% sensitivity and 86.79% specificity in the training dataset.
- IOS demonstrated 91.07% accuracy in an independent validation dataset with 280 samples.
- Transcriptome analysis showed RA-related pathways are enriched in immune microenvironment processes like T cell activation.

## Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease with persistent synovitis and joint destruction, leading to a huge economic and physical burden on patients. The detection of RA is important for the individual’s guiding therapeutic. However, current signatures lacked enough effects for the diagnosis of RA. Here, a pariwise signature, including genes ICAM2 and OSTF1, was derived based on a rank-based method, which was called ICAM2-OSTF1 signature (IOS). The sensitivity and specificity of IOS in the training dataset were 87.39% and 86.79%, respectively. The accuracy of IOS was 91.07% in the validation dataset that contained a total of 280 samples from two independent datasets. Besides, when using eight methods, such as ssGSEA, xCell and TIMER, to quantitate the immune infiltration characteristics in RA. We found that RA presented elevated pro-inflammation immune infiltration and immune score. In addition, transcriptome analysis demonstrated that the consistent transcriptional differences between RA and healthy control were significantly enriched in some pathways typically related to the immune microenvironments, such as T cell activation. Finally, network analysis demonstrated that ICAM2, CXCL16, CKLF and SLPI may be related to the occurrence of RA. In brief, IOS can individually distinguish RA from healthy controls measured by different laboratories, and be an auxiliary test for diagnosing RA.

## Linked entities

- **Genes:** ICAM2 (intercellular adhesion molecule 2) [NCBI Gene 3384], OSTF1 (osteoclast stimulating factor 1) [NCBI Gene 26578], CXCL16 (C-X-C motif chemokine ligand 16) [NCBI Gene 58191], CKLF (chemokine like factor) [NCBI Gene 51192], SLPI (secretory leukocyte peptidase inhibitor) [NCBI Gene 6590]
- **Diseases:** rheumatoid arthritis (MONDO:0008383), RA (MONDO:0005272)

## Full-text entities

- **Genes:** CXCL16 (C-X-C motif chemokine ligand 16) [NCBI Gene 58191] {aka CXCLG16, SR-PSOX, SRPSOX}, OSTF1 (osteoclast stimulating factor 1) [NCBI Gene 26578] {aka OSF, SH3P2, bA235O14.1}, ICAM2 (intercellular adhesion molecule 2) [NCBI Gene 3384] {aka CD102}, CKLF (chemokine like factor) [NCBI Gene 51192] {aka C32, CKLF1, CKLF2, CKLF3, CKLF4, HSPC224}, SLPI (secretory leukocyte peptidase inhibitor) [NCBI Gene 6590] {aka ALK1, ALP, BLPI, HUSI, HUSI-1, HUSI-I}
- **Diseases:** inflammation (MESH:D007249), joint destruction (MESH:D008105), synovitis (MESH:D013585), RA (MESH:D001172), autoimmune disease (MESH:D001327)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12200850/full.md

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Source: https://tomesphere.com/paper/PMC12200850