# Decreased serum TIMP4 levels in patients with rheumatoid arthritis

**Authors:** Jinyu Chen, Yanyan Fan, Shengyu Cui, Haiping Zhang, Ziliang Yu, Yali Jiang, Xiaogang Zhou

PMC · DOI: 10.1515/biol-2022-1037 · 2025-04-25

## TL;DR

This study found that decreased TIMP4 levels in the blood could help diagnose rheumatoid arthritis and are linked to increased inflammation markers.

## Contribution

The study identifies TIMP4 as a novel potential diagnostic marker for rheumatoid arthritis with downregulated expression.

## Key findings

- TIMP4 levels were significantly decreased in rheumatoid arthritis patients compared to healthy individuals.
- TIMP4 showed negative correlations with inflammatory markers IL-6 and IL-1β in RA patients.
- TIMP4 has potential diagnostic value for rheumatoid arthritis based on ROC curve analysis.

## Abstract

The current study was designed to explore the clinical significance of serum tissue inhibitor of metalloproteinase 4 (TIMP4) levels in rheumatoid arthritis (RA). The GSE1919 chip was analyzed, differentially expressed genes (DEGs) were identified, and gene ontology as well as Kyoto Encyclopedia of Genes and Genomes analyses of the identified DEGs were conducted. Patients with RA (n = 96) and healthy individuals (n = 96) were enrolled in this study. Serum from the participants was collected, and RT-qPCR as well as WB have been conducted to examine TIMP4 levels; additionally, interleukin (IL)-6 and IL-1β levels were determined using the ELISA method. Pearson’s correlation analysis was conducted for evaluating relationships between the expression levels of TIMP4 and those of IL-6 or IL-1β. A receiver operating characteristic (ROC) curve was drawn to determine the potential diagnostic value of serum TIMP4 for RA. TIMP4 was identified as a markedly downregulated gene involved in RA development. TIMP4 levels were significantly decreased in patients with RA, and the results of the ROC analysis showed that TIMP4 may be a potential diagnostic marker. Furthermore, the concentrations of IL-6 and IL-1β were markedly elevated in patients with RA. Finally, TIMP4 levels showed negative correlation with the levels of either IL-6 or IL-1β. TIMP4 is downregulated in RA and is a reliable serum marker for RA diagnosis.

## Linked entities

- **Genes:** TIMP4 (TIMP metallopeptidase inhibitor 4) [NCBI Gene 7079]
- **Proteins:** TIMP4 (TIMP metallopeptidase inhibitor 4), IL6 (interleukin 6), IL1B (interleukin 1 beta)
- **Diseases:** rheumatoid arthritis (MONDO:0008383)

## Full-text entities

- **Genes:** IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, TIMP4 (TIMP metallopeptidase inhibitor 4) [NCBI Gene 7079] {aka TIMP-4}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}
- **Diseases:** RA (MESH:D001172)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12032977/full.md

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Source: https://tomesphere.com/paper/PMC12032977