# Immunophenotypic Landscape of synovial tissue in rheumatoid arthritis: Insights from ACPA status

## TL;DR

This study explores how different levels of ACPA antibodies in rheumatoid arthritis patients affect synovial tissue inflammation and immune cell infiltration.

## Contribution

The study introduces a new synovial biopsy tool and reveals a strong link between high ACPA titers and ectopic lymphoid neogenesis in RA patients.

## Key findings

- High-titer ACPA RA patients have significantly more T cells, B cells, and macrophages in synovial tissues.
- Ectopic lymphoid neogenesis is strongly correlated with high ACPA titers (OR = 3.63).
- No significant differences in synovitis grading or matrix activation were found across ACPA groups.

## Abstract

To examine the clinical features and synovial pathologies in rheumatoid arthritis (RA) patients across varying titers of circulating anti-citrullinated protein antibodies (ACPA).

We devised a negative pressure suction and rebound synovial biopsy tool to enhance the yield of synovial biopsies, noted for its ease and safety of use. This research involved a retrospective examination of 60 active RA patients who underwent synovial biopsies with this tool from June to November 2023 at our institution. A range of disease activity markers were collected, including DAS28-CRP, ESR, CRP, count of swollen and tender joints, VAS pain scale, and so forth. Synovial tissue underwent HE staining and immunohistochemistry, including synovitis grading (GSS) and counting of B cells (CD20), T cells (CD3), macrophages (CD68), and plasma cells (CD138).

were categorized into three groups as per ACPA titers: ACPA-negative (0–5U/mL), low-titer (5–20U/mL), and high-titer (above 20U/mL). The study compared the clinical features and synovial pathologies across these groups.

Of the 60 RA patients, they were segregated into three groups based on ACPA titers: 20 in ACPA-negative, 9 in the low-titer group, and 31 in the high-titer group. No significant differences were observed in GSS scores, synovial cell proliferation and loss, matrix activation, inflammatory infiltration, and neovascularization among these groups (P > 0.05). The high-titer ACPA group demonstrated significantly increased counts of CD3+ T cells, CD20+ B cells, and CD68+ macrophages in synovial tissues compared to the ACPA-negative and low-titer groups (p < 0.05), along with a higher incidence of ectopic lymphoid neogenesis (p < 0.05). Ordinal logistic regression revealed that rheumatoid factor (RF), and counts of synovial T cells, B cells, macrophages, and ectopic lymphoid neogenesis correlated with ACPA titers (P < 0.05), particularly lymphoid neogenesis (OR = 3.63, P = 0.023).

RA patients with high-titer ACPA demonstrate elevated levels of inflammatory cell infiltration in synovial tissues, with ectopic lymphoid neogenesis showing a strong correlation with high ACPA positivity.