Monocyte phenotype as a predictive marker for wound healing in diabetes-related foot ulcers

Danqing Min; Vanessa Nube; Anh Tao; Xin Yuan; Paul F Williams; Belinda A Brooks; Jencia Wong; Stephen M Twigg; Susan V McLennan

doi:10.1016/j.jdiacomp.2021.107889

Monocyte phenotype as a predictive marker for wound healing in diabetes-related foot ulcers

J Diabetes Complications. 2021 May;35(5):107889. doi: 10.1016/j.jdiacomp.2021.107889. Epub 2021 Feb 16.

Authors

Danqing Min¹, Vanessa Nube², Anh Tao³, Xin Yuan³, Paul F Williams³, Belinda A Brooks², Jencia Wong², Stephen M Twigg², Susan V McLennan⁴

Affiliations

¹ Diabetes Centre, Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Greg Brown Diabetes and Endocrinology Research Laboratory, Sydney Medical School (Central), Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia. Electronic address: danqing.min@sydney.edu.au.
² Diabetes Centre, Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Greg Brown Diabetes and Endocrinology Research Laboratory, Sydney Medical School (Central), Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
³ Greg Brown Diabetes and Endocrinology Research Laboratory, Sydney Medical School (Central), Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
⁴ Diabetes Centre, Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Greg Brown Diabetes and Endocrinology Research Laboratory, Sydney Medical School (Central), Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; NSW Health Pathology, Sydney, NSW, Australia.

PMID: 33642146
DOI: 10.1016/j.jdiacomp.2021.107889

Abstract

Aims: Delayed healing of diabetes-related foot ulcers (DRFUs) is associated with increased macrophage and matrix metalloproteinases (MMPs) at the wound site. Whether circulating monocyte phenotype and/or MMPs are altered in association with wound healing outcome is unknown, and was investigated in this study.

Methods: Blood was obtained from 21 participants with DRFU, at initial visit (V1), week-4 (V2), and week-8 (V3) for measurement of monocyte number (CD14⁺), phenotype (CD16, CD163) and chemokine receptors (CCRs) by flow cytometry, and circulating MMPs and TIMP-1 by ELISA.

Results: Six wounds healed during the study. At V1, non-classical CD16⁺⁺ monocytes and MMP-3 were higher in healed vs unhealed (both p < 0.05). At V3, the increased %CD16⁺⁺ persisted and %CCR2⁺ was decreased in healed, but no other monocyte markers nor MMP/TIMP differed between groups. Increased wound closure rate (WCR) at V3 correlated with increased %CD16⁺⁺ monocytes and decreased MMP-2 at V1 or V1 + V2. Receiver operating characteristic (ROC) curves yielded an area-under-the-curve of %CD16⁺⁺ at V1 of 0.78 to predict ulcer healing at V3.

Conclusions: These results indicate that circulating monocyte phenotype and MMPs alter as DRFUs heal. The relationship of %CD16⁺⁺ monocytes with WCR and ROC curve suggest a predictive role of %CD16⁺⁺ monocytes for ulcer healing.

Keywords: Biomarker; Diabetes-related foot ulcers; Inflammation; Matrix metalloproteinases; Monocyte phenotype; Wound healing.

Publication types

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

MeSH terms

Biomarkers
Diabetes Mellitus*
Diabetic Foot* / complications
Humans
Matrix Metalloproteinases
Monocytes / cytology*
Phenotype
Ulcer
Wound Healing*

Substances

Biomarkers
Matrix Metalloproteinases