Cargando…

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

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 patien...

Descripción completa

Detalles Bibliográficos
Autores principales: Ratneswaran, Anusha, Rockel, Jason S., Antflek, Daniel, Matelski, John J., Shestopaloff, Konstantin, Kapoor, Mohit, Baltzer, Heather
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814933/
https://www.ncbi.nlm.nih.gov/pubmed/35126358
http://dx.doi.org/10.3389/fimmu.2021.794792
_version_ 1784645179533164544
author Ratneswaran, Anusha
Rockel, Jason S.
Antflek, Daniel
Matelski, John J.
Shestopaloff, Konstantin
Kapoor, Mohit
Baltzer, Heather
author_facet Ratneswaran, Anusha
Rockel, Jason S.
Antflek, Daniel
Matelski, John J.
Shestopaloff, Konstantin
Kapoor, Mohit
Baltzer, Heather
author_sort Ratneswaran, Anusha
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8814933
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-88149332022-02-05 Investigating Molecular Signatures Underlying Trapeziometacarpal Osteoarthritis Through the Evaluation of Systemic Cytokine Expression Ratneswaran, Anusha Rockel, Jason S. Antflek, Daniel Matelski, John J. Shestopaloff, Konstantin Kapoor, Mohit Baltzer, Heather Front Immunol Immunology 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. Frontiers Media S.A. 2022-01-20 /pmc/articles/PMC8814933/ /pubmed/35126358 http://dx.doi.org/10.3389/fimmu.2021.794792 Text en Copyright © 2022 Ratneswaran, Rockel, Antflek, Matelski, Shestopaloff, Kapoor and Baltzer https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Ratneswaran, Anusha
Rockel, Jason S.
Antflek, Daniel
Matelski, John J.
Shestopaloff, Konstantin
Kapoor, Mohit
Baltzer, Heather
Investigating Molecular Signatures Underlying Trapeziometacarpal Osteoarthritis Through the Evaluation of Systemic Cytokine Expression
title Investigating Molecular Signatures Underlying Trapeziometacarpal Osteoarthritis Through the Evaluation of Systemic Cytokine Expression
title_full Investigating Molecular Signatures Underlying Trapeziometacarpal Osteoarthritis Through the Evaluation of Systemic Cytokine Expression
title_fullStr Investigating Molecular Signatures Underlying Trapeziometacarpal Osteoarthritis Through the Evaluation of Systemic Cytokine Expression
title_full_unstemmed Investigating Molecular Signatures Underlying Trapeziometacarpal Osteoarthritis Through the Evaluation of Systemic Cytokine Expression
title_short Investigating Molecular Signatures Underlying Trapeziometacarpal Osteoarthritis Through the Evaluation of Systemic Cytokine Expression
title_sort investigating molecular signatures underlying trapeziometacarpal osteoarthritis through the evaluation of systemic cytokine expression
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814933/
https://www.ncbi.nlm.nih.gov/pubmed/35126358
http://dx.doi.org/10.3389/fimmu.2021.794792
work_keys_str_mv AT ratneswarananusha investigatingmolecularsignaturesunderlyingtrapeziometacarpalosteoarthritisthroughtheevaluationofsystemiccytokineexpression
AT rockeljasons investigatingmolecularsignaturesunderlyingtrapeziometacarpalosteoarthritisthroughtheevaluationofsystemiccytokineexpression
AT antflekdaniel investigatingmolecularsignaturesunderlyingtrapeziometacarpalosteoarthritisthroughtheevaluationofsystemiccytokineexpression
AT matelskijohnj investigatingmolecularsignaturesunderlyingtrapeziometacarpalosteoarthritisthroughtheevaluationofsystemiccytokineexpression
AT shestopaloffkonstantin investigatingmolecularsignaturesunderlyingtrapeziometacarpalosteoarthritisthroughtheevaluationofsystemiccytokineexpression
AT kapoormohit investigatingmolecularsignaturesunderlyingtrapeziometacarpalosteoarthritisthroughtheevaluationofsystemiccytokineexpression
AT baltzerheather investigatingmolecularsignaturesunderlyingtrapeziometacarpalosteoarthritisthroughtheevaluationofsystemiccytokineexpression