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Synovial and Adipose Tissue Composition in Overweight/Obese Patients With Active Rheumatoid Arthritis Under JAK/STAT Inhibition

NCT05767775 · Status: UNKNOWN · Type: OBSERVATIONAL · Enrollment: 30

Last updated 2023-03-14

No results posted yet for this study

Summary

Rheumatoid Arthritis (RA) is a chronic autoimmune disease that affects nearly 1% of the general population worldwide leading to joint inflammation, disability and increate mortality. Several factors are associated with disease activity and treatment outcomes. Among them, overweight/obesity status was demonstrated to be associated with higher risk of RA development and most importantly to different treatment response to biological DMARDs. Moreover, overweight/obese RA patients do show higher degree of synovial inflammation compared to lean RA patients. In this context, adipose tissue accumulation is associated with higher inflammatory burden through the secretion by activated mature adipocytes of adipokines with pro-inflammatory properties on innate and adaptive immune cells. Among them, Leptin is an important adipokine, released by mature adipocytes with multiple activating properties on immune cells as monocytes, macrophages, dendritic cells, T and B lymphocytes acting through the activation of its receptor LEPR via JAK/STAT pathway. In particular, leptin exerts its effects on macrophages populations through the promotion of M1 differentiation with pro-inflammatory phenotype. In our research hypothesis we expect that leptin levels does correlate with immunohistochemical scores of synovial inflammatory cells (CD68+, CD21+, CD20+ and CD3+) and CD31+ synovial vessels. Moreover, we expect that the inhibition of JAK/STAT signal using Tofacitinib may interfere with leptin activation action on resident synovial inflammatory cells expressing LEPR (as CD68+, CD20+ and CD3+) in particular restoring the M1/M2 phenotype ratio within resident macrophages populations. Finally, we expect that the inhibition of JAK/STAT signaling pathway by Tofacitinib will result in a significant reduction of synovitis degree in patients with higher leptin expression due to adipose tissue activation.

Conditions

Interventions

OTHER

Assessment of synovial- and adipose tissue-derived inflammatory biomarkers

Paraffin-embedded synovial tissue (ST) specimens will be stained for H\&E and other sections will be stained for CD68, CD21, CD20, CD3, CD31 and Masson Trichrome Goldner with light green to assess the microanatomical organization of resident synovial inflammatory cells. Some synovial samples will be used for tissue resident macrophages subpopulations analysis using FACS gated on their expression of the CD64+/CD11b+/MHC-ClassII+/CD206+/-/Lineage-. Each RA patient reaching a stable clinical (DAS\<1.6 for at least two different evaluations 6 months apart) and imaging (PDUS negative signal) remission under Tofacitinib treatment will undergo synovial biopsy and each synovial tissue sample will be processed as above. Plasma levels of adipokines will be tested through ELISA method at baseline, 3, 6 and 12 months of follow-up in all patients.

Sponsors & Collaborators

  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS

    lead OTHER

Eligibility

Min Age
18 Years
Max Age
75 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2019-06-01
Primary Completion
2022-08-31
Completion
2023-03-15

Countries

  • Italy

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05767775 on ClinicalTrials.gov