Synovial Fluid Cell Profiling Identifies Distinct Inflammatory Phenotypes in Late-Onset Rheumatoid Arthritis and...

Area of Science:

• Rheumatology
• Immunology
• Cell Biology

Background:

• Late-onset rheumatoid arthritis (LORA) and polymyalgia rheumatica (PMR) are difficult to differentiate, especially in anti-citrullinated protein antibody (ACPA)-negative cases.
• Understanding synovial fluid immune cell profiles can aid in distinguishing these conditions.

Purpose of the Study:

• To characterize synovial fluid immune cell profiles in ACPA-positive LORA, ACPA-negative LORA, and PMR.
• To explore unbiased patient stratification based on immune cell data.

Main Methods:

• Synovial fluid was collected from 21 patients with ACPA-positive LORA, ACPA-negative LORA, or PMR.
• Immune cell composition was analyzed using mass cytometry.
• Principal component analysis and hierarchical clustering were employed for patient stratification.

Main Results:

• ACPA-positive LORA showed neutrophil predominance, while PMR had a neutrophil-poor profile with more T and NK cells.
• ACPA-negative LORA exhibited heterogeneity, with patients showing either neutrophil-rich or neutrophil-poor patterns.
• Unsupervised clustering separated ACPA-positive LORA and PMR but not ACPA-negative LORA.

Conclusions:

• Late-onset inflammatory arthritis presents at least two distinct synovial inflammatory phenotypes, not fully aligning with current diagnoses.
• ACPA-negative LORA is a heterogeneous condition encompassing these inflammatory states.
• Synovial fluid immunophenotyping can enhance classification and guide therapeutic strategies.