Abstract
Aims | Neuroinflammation is a crucial phenomenon that precedes and potentially elucidates the complications of peripheral diabetic neuropathy. Here we attempt to describe innate lymphoid blood cells natural killers (NK) and common glia chemokine receptor espression CX3CR1 on circulating blood cells in diabetic patients (DM2) with clinical neuropathy without foot lesions (N), with foot lesions without (N1), and with (NV) peripheral distal ischemia.
Methods | We examined 149 DM2 patients: 39 N, 42 N1, and 43 NV diagnosed with neuropathy by Toronto criteria. A control group consisted of 25 younger subjects (C). In these patients, we use ELISA and flow cytometry to characterize the following cluster of differentiation: CD45, CD3, CD4, CD8, CD16, CD56, CD14, CD11c, SLAN, CX3CR1, and HLA, which identify different blood cell subpopulations. We assessed: 1) the frequency of circulating B-, CD4+, and CD8+ T-cells, total NKs, dendritic and inflammatory monocytes using a flow cytometry (FC)-based diagnostic kits. 2) circulating and membrane-bound activation markers possibly associated with inflammatory blood cells such as natural killer cells.
Results Using age and sex-adjusted logistic multivariate models, we observed increased frequency of NKs in diabetic patients with neuropathy N. Classic Dendritic cells (CDC) were reduced and inflammatory monocytes elevated in N1 and NV versus N. (p<002 for both). % SLAN/CD16 HLA positive monocytes were particularly elevated with significant progression in N1 and NV versus N and C (p<0,001 C vs. N,N1,NV and N vs N1, NV). In these inflammatory cells we found similar incremental behavior of CX3CR1 expression, receptor of the ligand fractalkine, constitutionally espressed in different tissues, but also in arterial endothelium, glia and neuron membrane. NK morphology and CX3CR1 espression in circulating dendritic cells were correlated ( p<0,01 R2=.371).
Conclusions Diabetic neuropathy contributes to an inflammatory condition and may play a significant role in infected diabetic foot complications. Further research is needed to determine how neuropathy could lead to peripheral distal ischemia and infection. NK and CX3CR1 positive cells might represent early markers of pathogenesis, potentially helping to prevent minor and major leg amputations.
