# Diagnostic performance of serum 14-3-3η protein versus conventional serological markers in early rheumatoid arthritis

**Authors:** Tiantian Liu, Wenbin Guo

PMC · DOI: 10.3389/fimmu.2026.1746239 · Frontiers in Immunology · 2026-02-12

## TL;DR

A new protein called 14-3-3η is highly effective at detecting early rheumatoid arthritis, outperforming traditional tests in sensitivity.

## Contribution

14-3-3η protein is shown as a novel, highly sensitive biomarker for early RA diagnosis.

## Key findings

- 14-3-3η achieved an AUC ≥0.85 for both early and established RA diagnosis.
- 14-3-3η had the highest sensitivity (88.1%) and lowest negative likelihood ratio (0.14) in early RA.
- 14-3-3η showed no significant correlation with traditional RA markers like anti-CCP and RF.

## Abstract

Conventional biomarkers for rheumatoid arthritis (RA) only have a ~70% sensitivity, making early diagnosis difficult. With its high concentration in synovial fluid, the 14-3-3η protein is a promising new biomarker for the early identification of RA in Chinese people.

In this case-control study, 90 disease controls, 110 healthy controls, 72 established RA patients, and 56 early RA patients were enrolled. The 14-3-3η protein’s diagnostic performance was evaluated utilizing ROC curve analysis in comparison to anti-CCP antibodies, RF, CRP, IgM, and ESR. To control for confounding variables, multivariable logistic regression models that were adjusted for sex and age were used.

14-3-3η showed exceptional diagnostic performance, with AUC ≥0.85 for both early and developed RA. In early RA, anti-CCP demonstrated better specificity (96.4%) and a positive likelihood ratio (21.2%), while 14-3-3η had the highest sensitivity (88.1%) and the lowest negative likelihood ratio (0.14). There were no significant associations between 14-3-3η and traditional markers (P>0.05) according to Spearman correlation analysis.

14-3-3η protein serves as an independent and highly sensitive biomarker for early RA diagnosis, particularly valuable for ruling out disease. These biomarkers, combined with the high specificity of anti-CCP, provide supplementary diagnostic benefits for complete early RA assessment.

## Linked entities

- **Diseases:** rheumatoid arthritis (MONDO:0008383)

## Full-text entities

- **Genes:** IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, TNFSF11 (TNF superfamily member 11) [NCBI Gene 8600] {aka CD254, ODF, OPGL, OPTB2, RANKL, TNLG6B}, MAPK9 (mitogen-activated protein kinase 9) [NCBI Gene 5601] {aka JNK-55, JNK2, JNK2A, JNK2ALPHA, JNK2B, JNK2BETA}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, YWHAH (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta) [NCBI Gene 7533] {aka YWHA1}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, CD79A (CD79a molecule) [NCBI Gene 973] {aka IGA, IGAlpha, MB-1, MB1}
- **Diseases:** hyperplasia (MESH:D006965), joint destruction (MESH:D008105), RA (MESH:D001172), death (MESH:D003643), joint deformity (MESH:D016916), synovial hypertrophy (MESH:D013585), infections (MESH:D007239), joint damage (MESH:D007592), joint bone destruction (MESH:D001847), autoimmune diseases (MESH:D001327), tumorigenesis (MESH:D063646), SLE (MESH:D008180), hepatic dysfunction (MESH:D008107), bone and skeletal muscle atrophy (MESH:D009133), inflammation (MESH:D007249), pain (MESH:D010146), pSS (MESH:D012859), cancer (MESH:D009369), inflammatory joint damage (MESH:D018746), swelling (MESH:D004487)
- **Chemicals:** sodium citrate (MESH:D000077559)
- **Species:** Bos taurus (bovine, species) [taxon 9913], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

30 references — full list in the complete paper: https://tomesphere.com/paper/PMC12935600/full.md

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Source: https://tomesphere.com/paper/PMC12935600