# Association of the Reduced Levels of Monocyte Chemoattractant Protein-1 with Herpes Zoster in Rheumatoid Arthritis Patients Treated with Janus Kinase Inhibitors in a Single-Center Cohort

**Authors:** Po-Ku Chen, Yi-Ming Chen, Hsin-Hua Chen, Tsai-Ling Liao, Shih-Hsin Chang, Kai-Jieh Yeo, Po-Hao Huang, Der-Yuan Chen

PMC · DOI: 10.3390/microorganisms12050974 · 2024-05-12

## TL;DR

This study found that lower levels of a protein called MCP-1 are linked to herpes zoster in rheumatoid arthritis patients taking JAK inhibitors, and high levels of anti-IFN-γ antibodies may indicate severe cases.

## Contribution

The study identifies reduced MCP-1 levels as a novel potential biomarker for herpes zoster in JAKi-treated rheumatoid arthritis patients.

## Key findings

- Patients with herpes zoster had significantly lower MCP-1 levels compared to those without.
- High-titer anti-IFN-γ autoantibodies were associated with severe herpes zoster cases.
- No significant differences were found in IFN-γ or IP-10 levels between patients with and without herpes zoster.

## Abstract

Anti-interferon (IFN)-γ autoantibodies are linked to varicella zoster virus (VZV) infection. Given the elevated risks of herpes zoster (HZ) in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKis), we aimed to examine the relationship between anti-IFN-γ autoantibodies with HZ development in JAKi-treated patients. Serum titers of anti-IFN-γ autoantibodies, plasma levels of IFN-γ, monocyte chemoattractant protein-1 (MCP-1), and IFN-γ-inducible protein-10 (IP-10) were measured by ELISA. Among the 66 enrolled RA patients, 24 developed new-onset HZ. Significantly lower MCP-1 levels were observed in patients with HZ compared to those without (median, 98.21 pg/mL, interquartile range (IQR) 77.63–150.30 pg/mL versus 142.3 pg/mL, IQR 106.7–175.6 pg/mL, p < 0.05). There was no significant difference in anti-IFN-γ titers, IFN-γ levels, or IP-10 levels between patients with and without HZ. Three of 24 patients with HZ had severe HZ with multi-dermatomal involvement. Anti-IFN-γ titers were significantly higher in patients with severe HZ than in those with non-severe HZ (median 24.8 ng/mL, IQR 21.0–38.2 ng/mL versus 10.5 ng/mL, IQR 9.9–15.0 ng/mL, p < 0.005). Our results suggest an association between reduced MCP-1 levels and HZ development in JAKi-treated RA patients. High-titer anti-IFN-γ autoantibodies may be related to severe HZ in these patients.

## Linked entities

- **Proteins:** CCL2 (C-C motif chemokine ligand 2), IFNG (interferon gamma), CXCL10 (C-X-C motif chemokine ligand 10)
- **Diseases:** rheumatoid arthritis (MONDO:0008383), herpes zoster (MONDO:0005609)

## Full-text entities

- **Genes:** IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}
- **Diseases:** HZ (MESH:D006562), RA (MESH:D001172), varicella zoster virus (VZV) infection (MESH:D000073618)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11124047/full.md

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Source: https://tomesphere.com/paper/PMC11124047