Investigating Molecular Signatures Underlying Trapeziometacarpal Osteoarthritis Through the Evaluation of Systemic Cytokine Expression

Anusha Ratneswaran; Jason S Rockel; Daniel Antflek; John J Matelski; Konstantin Shestopaloff; Mohit Kapoor; Heather Baltzer

doi:10.3389/fimmu.2021.794792

Investigating Molecular Signatures Underlying Trapeziometacarpal Osteoarthritis Through the Evaluation of Systemic Cytokine Expression

Front Immunol. 2022 Jan 20:12:794792. doi: 10.3389/fimmu.2021.794792. eCollection 2021.

Authors

Anusha Ratneswaran^{1

2

3}, Jason S Rockel^{2

3}, Daniel Antflek^{1

3}, John J Matelski⁴, Konstantin Shestopaloff^{2

3}, Mohit Kapoor^{2

3

5}, Heather Baltzer^{1

3

6}

Affiliations

¹ Hand Program, Schroeder Arthritis Institute, University Health Network, Toronto, ON, Canada.
² Division of Orthopedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, ON, Canada.
³ Krembil Research Institute, University Health Network, Toronto, ON, Canada.
⁴ Biostatistics Research Unit, University Health Network, Toronto, ON, Canada.
⁵ Department of Surgery and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
⁶ Division of Plastic and Reconstructive Surgery, University of Toronto, Toronto, ON, Canada.

Abstract

Purpose: Non-operative management of trapeziometacarpal osteoarthritis (TMOA) demonstrates only short-term symptomatic alleviation, and no approved disease modifying drugs exist to treat this condition. A key issue in these patients is that radiographic disease severity can be discordant with patient reported pain, illustrating the need to identify molecular mediators of disease. This study characterizes the biochemical profile of TMOA patients to elucidate molecular mechanisms driving TMOA progression.

Methods: Plasma from patients with symptomatic TMOA undergoing surgical (n=39) or non-surgical management (n=44) with 1-year post-surgical follow-up were compared using a targeted panel of 27 cytokines. Radiographic (Eaton-Littler), anthropometric, longitudinal pain (VAS, TASD, quick DASH) and functional (key pinch, grip strength) data were used to evaluate relationships between structure, pain, and systemic cytokine expression. Principal Component Analysis was used to identify clusters of patients.

Results: Patients undergoing surgery had greater BMI as well as higher baseline quick DASH, TASD scores. Systemically, these patients could only be distinguished by differing levels of Interleukin-7 (IL-7), with an adjusted odds ratio of 0.22 for surgery for those with increased levels of this cytokine. Interestingly, PCA analysis of all patients (regardless of surgical status) identified a subset of patients with an "inflammatory" phenotype, as defined by a unique molecular signature consisting of thirteen cytokines.

Conclusion: Overall, this study demonstrated that circulating cytokines are capable of distinguishing TMOA disease severity, and identified IL-7 as a target capable of differentiating disease severity with higher levels associated with a decreased likelihood of TMOA needing surgical intervention. It also identified a cluster of patients who segregate based on a molecular signature of select cytokines.

Keywords: cytokine; inflammation; molecular factors; osteoarthritis; trapeziometacarpal osteoarthritis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Biomarkers*
Clinical Decision-Making
Cytokines / genetics*
Cytokines / metabolism
Disease Management
Disease Susceptibility*
Female
Gene Expression*
Hand Strength
Humans
Male
Middle Aged
Osteoarthritis / diagnosis
Osteoarthritis / etiology*
Osteoarthritis / metabolism*
Osteoarthritis / surgery
Pain
Symptom Assessment
Treatment Outcome
Wrist Joint / pathology*

Substances

Biomarkers
Cytokines

Grants and funding

CIHR/Canada