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Abstract Number: 2637

Chaperone-mediated Autophagy in Synovitis Distinguishes Psoriatic Arthritis from Rheumatoid Arthritis

Vincenzo Venerito1, Gerardo Cazzato2, Fabio Cacciapaglia3, Eleonora Ceglie4, Sergio Del Vescovo4, Teresa Caferri4, Giuseppe Lopalco4, Francesco Girolamo5 and Florenzo Iannone1, 1Rheumatology Unit- University of Bari "Aldo Moro", IT, Bari, Italy, 2Pathology Unit - University of Bari "Aldo Moro", IT, Bari, Italy, 3Rheumatology Unit � DiMePRe-J, University and AOU Policlinico of Bari, Italy, Bari, Italy, 4Rheumatology Unit - University of Bari "Aldo Moro", IT, Bari, Italy, 5Human Anatomy Department - University of Bari "Aldo Moro", IT, Bari, Italy

Meeting: ACR Convergence 2024

Keywords: Biomarkers, Inflammation, Synovitis

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Session Information

Date: Monday, November 18, 2024

Title: Abstracts: SpA Including PsA – Diagnosis, Manifestations, & Outcomes II

Session Type: Abstract Session

Session Time: 3:00PM-4:30PM

Background/Purpose: Recent studies have suggested that autophagy may play different roles in the pathogenesis of rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Lysosome-associated membrane protein type 2A (LAMP2A) is a key component of the chaperone-mediated autophagy (CMA) machinery. LAMP2A may be differently regulated in RA and PsA synovial tissue. 

This study aims to evaluate LAMP2A expression in synovial tissue as a potential biomarker to distinguish PsA from RA.

Methods: We included 29 patients  with classified PsA and 11 patients with classified RA who underwent ultrasound-guided synovial biopsy. Synovial specimens were stained with hematoxylin and eosin (H&E) for Krenn’s score, and anti- CD3, CD4, CD8, CD20, CD138, and recombinant anto-LAMP2A antibodies (Abcam, ab125068). Positivity for each marker was quantified using ImageJ software on microphotographs. The density of LAMP2A-positive cells (n/mm2) was counted in the synovial lining layer, synovial stroma, and inflammatory infiltrate, and compared between PsA and RA with t-test, also stratifying by Krenn’s synovitis grading. Logistic regression analysis was performed to evaluate the ability of LAMP2A-positive cell density to discriminate between RA and PsA. The area under the receiver operating characteristic curve (AUROC) was calculated to assess the diagnostic performance.

Results: he study included 29 PsA patients (mean age 50.53 ± 12.02 years) with a mean DAPSA score of 17.25 ± 4.63 at biopsy. Nineteen (65.52%) PsA synovial specimens had high-grade synovitis (Krenn score ≥ 5). The 11 RA patients (mean age of 53.31 ± 9.31 years) had a mean DAS28 score of 4.36 ± 1.05 at biopsy. Six (54.55%) RA synovial specimens showed high-grade synovitis. LAMP2A-positive cell density in the synovial lining layer was similar between PsA and RA patients (p = 0.26), regardless of synovitis grade. In the synovial stroma, LAMP2A-positive cell density trended towards a difference between PsA and RA (p = 0.08). In high-grade synovitis, RA specimens had higher LAMP2A-positive cell density than PsA patients (p=0.03). LAMP2A-positive cell density in the inflammatory infiltrate was significantly different between PsA and RA patients,  with RA specimens displaying higher density than PsA (p=0.0001). This difference was also observed in low-grade synovitis (RA vs. PsA, p=0.008, Figure 1). The density of LAMP2A-positive cells in the inflammatory infiltrate could differentiate RA from PsA (OR 1.02 per point increase, 95% CI 1.01-1.03) with an AUROC of 0.89 (Figure 2).

Conclusion: This study demonstrates that LAMP2A expression in the inflammatory infiltrate of synovial tissue is significantly higher in RA compared to PsA, regardless of the synovitis grade. The density of LAMP2A-positive cells in the inflammatory infiltrate exhibits good diagnostic performance in discriminating RA from PsA, suggesting its potential as a biomarker for differential diagnosis.

Supporting image 1

LAMP2A-positive cell density in the inflammatory infiltrate was significantly different between PsA and RA patients, with RA specimens displaying higher density than PsA (p=0.0001). This difference was also observed in low-grade synovitis (RA vs. PsA, p=0.008, Figure 1). The density of LAMP2A-positive cells in the inflammatory infiltrate could differentiate RA from PsA (OR 1.02 per point increase, 95% CI 1.01_1.03) with an AUROC of 0.89 (Figure 2).


Disclosures: V. Venerito: None; G. Cazzato: None; F. Cacciapaglia: AbbVie/Abbott, 2, 6, Boehringer-Ingelheim, 2, 6, Eli Lilly, 6, Galapagos, 6, Janssen, 2, 6, Pfizer, 6; E. Ceglie: None; S. Del Vescovo: None; T. Caferri: None; G. Lopalco: None; F. Girolamo: None; F. Iannone: AstraZeneca, 2, GSK, 2, Pfizer, 2, UCB, 2.

To cite this abstract in AMA style:

Venerito V, Cazzato G, Cacciapaglia F, Ceglie E, Del Vescovo S, Caferri T, Lopalco G, Girolamo F, Iannone F. Chaperone-mediated Autophagy in Synovitis Distinguishes Psoriatic Arthritis from Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/chaperone-mediated-autophagy-in-synovitis-distinguishes-psoriatic-arthritis-from-rheumatoid-arthritis/. Accessed .
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