Histologic and transcriptional evidence of subclinical synovial inflammation in rheumatoid arthritis patients in clinical remission

Patients with rheumatoid arthritis (RA) in clinical remission may have subclinical synovial inflammation. Here, we sought to determine the proportion of patients in remission or low disease activity at the time of arthroplasty that have histologic or transcriptional evidence of synovitis, as well as clinical features that distinguish patients with subclinical synovitis.

We compared disease activity scores with 28 joint counts (DAS28) to synovial histology features in 135 patients with RA undergoing arthroplasty. We also compared DAS28 to RNA-Seq data on a subset of 35 patients.

14% of patients met DAS28 criteria for clinical remission (DAS28<2.6) and another 15% met criteria for low disease activity (DAS28<3.2). Histologic analysis of synovium revealed synovitis in 27% and 31% of samples from patients in remission and low disease activity respectively. Patients with low disease activity (DAS28<3.2) and synovitis also exhibited increased CRP and anti-citrullinated peptide antibody (CCP) levels compared to those without synovitis. 183 genes were differentially expressed in synovium of patients with subclinical synovitis compared to those with low inflammatory synovium. 86% of these genes were also differentially expressed in synovium of patients who were clinically active (DAS28≥3.2).

31% of patients with low clinical disease activity exhibit histologic evidence of subclinical synovitis, which was associated with increased CRP and CCP levels. Synovial gene expression signatures of clinical synovitis are present in patients with subclinical synovitis. This article is protected by copyright. All rights reserved.

 2019 Mar 5. doi: 10.1002/art.40878.

Other Contributors

Orange DE1,2, Agius P3, DiCarlo EF4, Mirza S1, Pannellini T4, Szymonifka J1, Jiang CS5, Figgie MP6, Frank MO2, Robinson WH7,8, Donlin LT1, Rozo C1, Gravallese EM9, Bykerk VP1, Goodman SM1.

Author information
1 Rheumatology, Hospital for Special Surgery, New York, NY.
2 Laboratory of Molecular Neuro-Oncology & Howard Hughes Medical Institute, The Rockefeller University, New York, NY.
3 Bioinformatics, New York Genome Center, New York, NY.
4 Pathology, Hospital for Special Surgery, New York, NY.
5 Biostatistics, Rockefeller University Hospital, New York, NY.
6 Orthopedic Surgery, Hospital for Special Surgery, New York, NY.
7 Division of Immunology and Rheumatology, Stanford University, Stanford, CA.
8 VA Palo Alto Health Care System, Palo Alto, CA.
9 Division of Rheumatology, University of Massachusetts Memorial Medical Center, Worcester, MA.