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Updated: Jul 14, 2025
Author Spotlight: Enhancing Rheumatoid Arthritis Research Through HR-pQCT Imaging Analysis
Published on: October 6, 2023
Identification of biomarkers in patients with rheumatoid arthritis responsive to DMARDs but with progressive bone
Emiliano Marasco1,2, Gianluigi Fabbriciani3, Laura Rotunno3
1Division of Rheumatology, Ospedale Pediatrico Bambino Gesù IRCCS, Roma, Italy.
Introduction:
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that may cause joint destruction and disability. The pharmacological treatment of RA aims at obtaining disease remission by effectively ceasing joint inflammation and arresting progressive bone erosions. Some patients present bone lesions accrual even after controlling joint inflammation with current therapies. Our study aimed to analyze lymphocyte subsets and levels of circulating cytokines in patients with RA with progressive bone erosions.
Methods:
We enrolled 20 patients with a diagnosis of RA and 12 healthy donors (HD). Patients with RA were divided into patients with bone erosions (RA-BE+) and without bone erosions (RA-BE-). Lymphocyte subsets in peripheral blood were evaluated by flow cytometry. Circulating cytokines levels were evaluated by protein array.
Results:
The distribution of lymphocyte subsets was not able to separate HD from AR patients and RA-BE+ and RA-BE- in cluster analysis. We observed a significant expansion of CXCR5- PD1+ T peripheral helper cells (Tph cells) and a reduction in both total memory B cells and switched memory B cells in RA patients compared to HD. We observed an expansion in the frequency of total B cells in RA-BE+ patients compared to RA-BE- patients. Unsupervised hierarchical clustering analysis of 39 cytokines resulted in a fairly good separation of HD from RA patients but not of RA-BE+ patients from RA-BE- patients. RA-BE+ patients showed significantly higher levels of IL-11 and IL-17A than RA-BE- patients.
Conclusion:
We show that patients with progressive erosive disease are characterized by abnormalities in B cells and in cytokines with a proven role in bone reabsorption. Understanding the role played by B cells and the cytokine IL-11 and IL-17A in progressive erosive disease can help identify novel biomarkers of erosive disease and design treatment approaches aimed at halting joint damage in RA.
Insights
Patients with rheumatoid arthritis (RA) and progressive bone erosion show altered B cell populations and elevated IL-11 and IL-17A cytokines. These findings may lead to new biomarkers and treatments for halting joint damage in RA.
Area of Science:
- Immunology
- Rheumatology
- Autoimmune Diseases
Background:
- Rheumatoid arthritis (RA) is an autoimmune disease causing joint inflammation, destruction, and disability.
- Current RA treatments aim for remission but some patients develop progressive bone erosions despite controlled inflammation.
Purpose of the Study:
- To investigate lymphocyte subsets and circulating cytokine levels in RA patients with progressive bone erosions.
- To identify potential biomarkers and therapeutic targets for halting joint damage in RA.
Main Methods:
- Flow cytometry to analyze lymphocyte subsets in 20 RA patients and 12 healthy donors (HD).
- Protein array to evaluate circulating cytokine levels.
- RA patients were categorized into groups with (RA-BE+) and without (RA-BE-) bone erosions.
Main Results:
- RA patients exhibited reduced memory B cells and expanded T peripheral helper (Tph) cells compared to HD.
- RA-BE+ patients showed increased total B cells compared to RA-BE- patients.
- Significantly higher levels of IL-11 and IL-17A were observed in RA-BE+ patients versus RA-BE- patients.
Conclusions:
- Progressive bone erosion in RA is associated with B cell abnormalities and elevated cytokines (IL-11, IL-17A) involved in bone resorption.
- Understanding these factors can aid in developing novel biomarkers and treatments to prevent joint damage in RA.
