Refining synovial inflammation assessment: A modified General Synovitis Score for active rheumatoid arthritis

Wu,Dengfeng; Deng,Yihan; Huang,Yiping; Zhao,Jun; Long,Wei; Peng,Yilin; Xiong,Zhenfang; Wu,Rui

doi:10.3892/etm.2025.12808

Refining synovial inflammation assessment: A modified General Synovitis Score for active rheumatoid arthritis

Authors:
- Dengfeng Wu
- Yihan Deng
- Yiping Huang
- Jun Zhao
- Wei Long
- Yilin Peng
- Zhenfang Xiong
- Rui Wu
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Affiliations: Department of Rheumatology and Immunology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China, First Clinical Medical School, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China, Department of Pathology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
Published online on: January 24, 2025 https://doi.org/10.3892/etm.2025.12808
Article Number: 58
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The General Synovitis Score (GSS) is a well‑established method for scoring synovial inflammation. Despite its widespread use, the GSS does not fully capture the inflammatory manifestations characteristic of the synovium in rheumatoid arthritis (RA). To address this limitation, the modified GSS (mGSS) was developed. The present study compared the correlation of the mGSS and the GSS with clinical disease activity. The aim was to provide a more precise histopathological scoring system based on hematoxylin and eosin (H&E) staining for assessing synovial inflammation in patients with active RA. In this cross‑sectional study, synovial tissues were obtained from 60 patients with RA using a novel synovial biopsy device. Sections from synovial tissues were stained with H&E, and were assessed using the GSS and the mGSS. Neovascularization was observed in 56 patients (93.3%) and was significantly correlated with disease activity score in 28 joints‑C‑reactive protein (DAS28‑CRP) (ρ=0.49; P<0.001), erythrocyte sedimentation rate (ESR) (ρ=0.44; P<0.001) and CRP (ρ=0.51; P<0.001). In addition, patients with severe neovascularization had significantly higher DAS28‑CRP, ESR and CRP levels than those with mild‑to‑moderate neovascularization (P<0.05). Synoviocyte detachment, which occurred in nine patients (15.0%), was associated with higher DAS28‑CRP, ESR and CRP levels than in the patients with synoviocyte proliferation (P<0.05). Furthermore, the mGSS was more strongly correlated with DAS28‑CRP (ρ=0.62; P<0.001) than the GSS (ρ=0.37; P=0.003). These findings indicated that neovascularization and synoviocyte detachment, which are critical yet often overlooked aspects in the traditional GSS, are important in RA. Incorporating these elements into the mGSS may enhance the assessment of disease activity, providing a more precise and accurate evaluation of the synovial histopathology in patients with RA.

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1	Smolen JS, Aletaha D and Mcinnes IB: Rheumatoid arthritis. Lancet. 388:2023–2038. 2016.PubMed/NCBI View Article : Google Scholar
2	Radu AF and Bungau SG: Management of rheumatoid arthritis: An overview. Cells. 10(2857)2021.PubMed/NCBI View Article : Google Scholar
3	Krenn V, Perino G, Rüther W, Krenn VT, Huber M, Hügle T, Najm A, Müller S, Boettner F, Pessler F, et al: 15 years of the histopathological synovitis score, further development and review: A diagnostic score for rheumatology and orthopaedics. Pathol Res Pract. 213:874–881. 2017.PubMed/NCBI View Article : Google Scholar
4	Schmidt T, Najm A, Mussawy H, Burghardt R, Oehler N, Krenn V, Rüther W and Niemeier A: General synovitis score and immunologic synovitis score reflect clinical disease activity in patients with advanced stage rheumatoid arthritis. Sci Rep. 9(8448)2019.PubMed/NCBI View Article : Google Scholar
5	Slansky E, Li J, Häupl T, Morawietz L, Krenn V and Pessler F: Quantitative determination of the diagnostic accuracy of the synovitis score and its components. Histopathology. 57:436–443. 2010.PubMed/NCBI View Article : Google Scholar
6	Szekanecz Z, Besenyei T, Szentpétery A and Koch AE: Angiogenesis and vasculogenesis in rheumatoid arthritis. Curr Opin Rheumatol. 22:299–306. 2010.PubMed/NCBI View Article : Google Scholar
7	Leblond A, Allanore Y and Avouac J: Targeting synovial neoangiogenesis in rheumatoid arthritis. Autoimmun Rev. 16:594–601. 2017.PubMed/NCBI View Article : Google Scholar
8	Henderson B, Revell PA and Edwards JC: Synovial lining cell hyperplasia in rheumatoid arthritis: Dogma and fact. Ann Rheum Dis. 47:348–349. 1988.PubMed/NCBI View Article : Google Scholar
9	Orr C, Vieira-Sousa E, Boyle DL, Buch MH, Buckley CD, Cañete JD, Catrina AI, Choy EHS, Emery P, Fearon U, et al: Synovial tissue research: A state-of-the-art review. Nat Rev Rheumatol. 13:463–475. 2017.PubMed/NCBI View Article : Google Scholar
10	Wang B, Li J, Huang Y and Wu R: Synoviocyte detachment: An overlooked yet crucial histological aspect in rheumatoid arthritis. BMC Musculoskelet Disord. 25(829)2024.PubMed/NCBI View Article : Google Scholar
11	Aletaha D and Smolen JS: Diagnosis and management of rheumatoid arthritis: A review. JAMA. 320:1360–1372. 2018.PubMed/NCBI View Article : Google Scholar
12	Van Riel PL and Renskers L: The disease activity score (DAS) and the disease activity score using 28 joint counts (DAS28) in the management of rheumatoid arthritis. Clin Exp Rheumatol. 34 (Suppl 5):S40–S44. 2016.PubMed/NCBI
13	Krenn V, Morawietz L, Burmester GR, Kinne RW, Mueller-Ladner U, Muller B and Haupl T: Synovitis score: Discrimination between chronic low-grade and high-grade synovitis. Histopathology. 49:358–364. 2006.PubMed/NCBI View Article : Google Scholar
14	Tak PP, Thurkow EW, Daha MR, Kluin PM, Smeets TJ, Meinders AE and Breedveld FC: Expression of adhesion molecules in early rheumatoid synovial tissue. Clin Immunol Immunopathol. 77:236–242. 1995.PubMed/NCBI View Article : Google Scholar
15	De Bois MH, Arndt JW, Tak PP, Kluin PM, van der Velde EA, Pauwels EK and Breedveld FC: 99Tcm-labelled polyclonal human immunoglobulin G scintigraphy before and after intra-articular knee injection of triamcinolone hexacetonide in patients with rheumatoid arthritis. Nucl Med Commun. 14:883–887. 1993.PubMed/NCBI View Article : Google Scholar
16	Szekanecz Z, Besenyei T, Paragh G and Koch AE: Angiogenesis in rheumatoid arthritis. Autoimmunity. 42:563–573. 2009.PubMed/NCBI View Article : Google Scholar
17	Taylor PC and Sivakumar B: Hypoxia and angiogenesis in rheumatoid arthritis. Curr Opin Rheumatol. 17:293–298. 2005.PubMed/NCBI View Article : Google Scholar
18	Konisti S, Kiriakidis S and Paleolog EM: Hypoxia-a key regulator of angiogenesis and inflammation in rheumatoid arthritis. Nat Rev Rheumatol. 8:153–162. 2012.PubMed/NCBI View Article : Google Scholar
19	Pober JS and Sessa WC: Evolving functions of endothelial cells in inflammation. Nat Rev Immunol. 7:803–815. 2007.PubMed/NCBI View Article : Google Scholar
20	Bottini N and Firestein GS: Duality of fibroblast-like synoviocytes in RA: Passive responders and imprinted aggressors. Nat Rev Rheumatol. 9:24–33. 2013.PubMed/NCBI View Article : Google Scholar
21	Lee SS, Joo YS, Kim WU, Min DJ, Min JK, Park SH, Cho CS and Kim HY: Vascular endothelial growth factor levels in the serum and synovial fluid of patients with rheumatoid arthritis. Clin Exp Rheumatol. 19:321–324. 2001.PubMed/NCBI
22	Ballara S, Taylor PC, Reusch P, Marmé D, Feldmann M, Maini RN and Paleolog EM: Raised serum vascular endothelial growth factor levels are associated with destructive change in inflammatory arthritis. Arthritis Rheum. 44:2055–2064. 2001.PubMed/NCBI View Article : Google Scholar
23	Zhao H, Duan S, Shi Y, Zhang M, Zhang L, Jin Z, Fu W, Xiao W, Bai T, Zhang X and Wang Y: Naru-3 inhibits inflammation, synovial hyperplasia and neovascularization in collagen-induced arthritis in rats. J Ethnopharmacol. 311(116350)2023.PubMed/NCBI View Article : Google Scholar
24	Tsubaki T, Arita N, Kawakami T, Shiratsuchi T, Yamamoto H, Takubo N, Yamada K, Nakata S, Yamamoto S and Nose M: Characterization of histopathology and gene-expression profiles of synovitis in early rheumatoid arthritis using targeted biopsy specimens. Arthritis Res Ther. 7:R825–R836. 2005.PubMed/NCBI View Article : Google Scholar
25	Liu H, Zhu Y, Gao Y, Qi D, Zhao L, Zhao L, Liu C, Tao T, Zhou C, Sun X, et al: NR1D1 modulates synovial inflammation and bone destruction in rheumatoid arthritis. Cell Death Dis. 11(129)2020.PubMed/NCBI View Article : Google Scholar
26	Federico A, Morgillo F, Tuccillo C, Ciardiello F and Loguercio C: Chronic inflammation and oxidative stress in human carcinogenesis. Int J Cancer. 121:2381–2386. 2007.PubMed/NCBI View Article : Google Scholar
27	Varela ML, Mogildea M, Moreno I and Lopes A: Acute inflammation and metabolism. Inflammation. 41:1115–1127. 2018.PubMed/NCBI View Article : Google Scholar
28	Liu F, Feng XX, Zhu SL, Huang HY, Chen YD, Pan YF, June RR, Zheng SG and Huang JL: Sonic hedgehog signaling pathway mediates proliferation and migration of fibroblast-like synoviocytes in rheumatoid arthritis via MAPK/ERK signaling pathway. Front Immunol. 9(2847)2018.PubMed/NCBI View Article : Google Scholar
29	Ma C, Wang J, Hong F and Yang S: Mitochondrial dysfunction in rheumatoid arthritis. Biomolecules. 12(1216)2022.PubMed/NCBI View Article : Google Scholar
30	Fearon U, Hanlon MM, Floudas A and Veale DJ: Cellular metabolic adaptations in rheumatoid arthritis and their therapeutic implications. Nat Rev Rheumatol. 18:398–414. 2022.PubMed/NCBI View Article : Google Scholar
31	Firestein GS and Mcinnes IB: Immunopathogenesis of rheumatoid arthritis. Immunity. 46:183–196. 2017.PubMed/NCBI View Article : Google Scholar
32	Firestein GS, Nguyen K, Aupperle KR, Yeo M, Boyle DL and Zvaifler NJ: Apoptosis in rheumatoid arthritis: p53 overexpression in rheumatoid arthritis synovium. Am J Pathol. 149:2143–2151. 1996.PubMed/NCBI
33	Taghadosi M, Adib M, Jamshidi A, Mahmoudi M and Farhadi E: The p53 status in rheumatoid arthritis with focus on fibroblast-like synoviocytes. Immunol Res. 69:225–238. 2021.PubMed/NCBI View Article : Google Scholar