# Differential Neutrophil and Eosinophil Infiltrations in the Sub-Lining Compartment of Rheumatoid Versus Osteoarthritic Synovium

**Authors:** Maria Sakkou, Anastasios Mourikis, Ilias Fanourgiakis, Alkiviadis Vossos, Maria Tektonidou, George E. Fragoulis, Petros P. Sfikakis

PMC · DOI: 10.31138/mjr.050225.hre · 2025-12-31

## TL;DR

This study finds that neutrophils and eosinophils are more active in the sub-lining synovial tissue of rheumatoid arthritis patients compared to osteoarthritis patients, suggesting a role in joint inflammation.

## Contribution

The study identifies distinct patterns of neutrophil and eosinophil infiltration in rheumatoid arthritis synovium, highlighting their potential role in disease progression.

## Key findings

- Neutrophils are increased five-fold in the sub-lining compartment of rheumatoid arthritis synovium.
- Eosinophils are present exclusively in the sub-lining compartment of rheumatoid arthritis synovium.
- Neutrophils and eosinophils are found near sub-lining fibroblasts in rheumatoid arthritis but not in osteoarthritis.

## Abstract

The role of innate immunity in the perpetuation of synovial inflammation may have been overlooked in rheumatoid arthritis (RA). Herein, we compared and quantified neutrophil and eosinophil infiltrations in lining and sub-lining compartments of RA versus osteoarthritis (OA) synovium.

Synovia were obtained from consecutive RA and OA patients (n=8, each) with destructive knee arthritis who underwent arthroplasty. Histological stainings and fluorescence immune-stainings were performed on paraffin tissue sections. Neutrophils and eosinophils were imaged with a confocal microscopy using the pan-leukocyte marker anti-CD45 combined with anti-CD14 and anti-CD294 specific antibodies, respectively. Antibodies against CD90 were used for neutrophil-fibroblast and/or eosinophil- sub-lining fibroblast tissue co-localisation analysis.

In both RA and OA patients, higher numbers of leukocytes were quantified in the sub-lining vs lining synovial compartment. In RA, the numbers of neutrophils were higher in the sub-lining vs lining compartment, being increased by 5-fold, which was not the case in OA. On the other hand, eosinophils could be exclusively found in the sub-lining compartment of either RA or OA-derived synovium, being increased in RA. Concerning their possible function we found that both neutrophils and eosinophils could be found in proximity with sub-lining fibroblasts in RA-derived synovia, but not in OA, indicating a crosstalk between these leukocytes and RA synovial fibroblasts.

Increased neutrophilic infiltrations and the presence of eosinophils in synovial sub-lining compartment discriminate RA from OA. Studies to elucidate the contribution of innate immunity cells to the pathophysiology of joint destruction in RA through interactions with fibroblasts are warranted.

## Linked entities

- **Proteins:** PTPRC (protein tyrosine phosphatase receptor type C), CD14 (CD14 molecule), PTGDR2 (prostaglandin D2 receptor 2), THY1 (Thy-1 cell surface antigen)
- **Diseases:** rheumatoid arthritis (MONDO:0008383), osteoarthritis (MONDO:0005178)

## Full-text entities

- **Genes:** CD68 (CD68 molecule) [NCBI Gene 968] {aka GP110, LAMP4, SCARD1}, THY1 (Thy-1 cell surface antigen) [NCBI Gene 7070] {aka CD90, CDw90}, PTGDR2 (prostaglandin D2 receptor 2) [NCBI Gene 11251] {aka CD294, CRTH2, DL1R, DP2, GPR44}, TLR9 (toll like receptor 9) [NCBI Gene 54106] {aka CD289}, Thy1 (thymus cell antigen 1, theta) [NCBI Gene 21838] {aka CD90, T25, Thy-1, Thy-1.2, Thy1.1, Thy1.2}, Ptprc (protein tyrosine phosphatase receptor type C) [NCBI Gene 19264] {aka B220, CD45R, Cd45, L-CA, Ly-5, Lyt-4}, Pdpn (podoplanin) [NCBI Gene 14726] {aka E11, Gp38, OTS-8, RANDAM-2, T1-alpha, T1a}, CD14 (CD14 molecule) [NCBI Gene 929], RNASE3 (ribonuclease A family member 3) [NCBI Gene 6037] {aka ECP, RAF1, RNS3}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, MOK (MOK protein kinase) [NCBI Gene 5891] {aka RAGE, RAGE-1, RAGE1, STK30}
- **Diseases:** Rheumatoid (MESH:D011695), arthritis (MESH:D001168), articular inflammation (MESH:D007249), bone loss (MESH:D001847), joint damage (MESH:D007592), NETs (MESH:C536657), RA (MESH:D001172), rheumatoid arthritic synovial membrane (MESH:D015433), synovitis (MESH:D013585), cartilage damage (MESH:D002357), Eosinophilia (MESH:D004802), rheumatologic conditions (MESH:D020763), autoimmune disease (MESH:D001327), OA (MESH:D010003), synovial infiltration (MESH:D017254), degenerative disorder (MESH:D019636), destruction of the joints (MESH:D008105)
- **Chemicals:** haematoxylin (MESH:D006416), PBS (MESH:D007854), paraffin (MESH:D010232), LPS (MESH:D008070), H&amp;E (MESH:D006371), O (MESH:D010100), eosin (MESH:D004801), Alexa Fluor  594 (-), Alexa Fluor  647 (MESH:C569686), Sodium Citrate (MESH:D000077559), N (MESH:D009584), Alexa Fluor  488 (MESH:C000711379), DAPI (MESH:C007293)
- **Species:** Homo sapiens (human, species) [taxon 9606], Ovis aries (domestic sheep, species) [taxon 9940], Mus musculus (house mouse, species) [taxon 10090]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12835918/full.md

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Source: https://tomesphere.com/paper/PMC12835918