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

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.

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.

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.

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.