Subepidermal Schwann cell counts correlate with skin innervation – an exploratory study

Abstract

Introduction/Aims: Schwann cell clusters have been described at the murine dermisepidermis border. We quantified dermal Schwann cells in the skin of patients with small-fiber neuropathy (SFN) compared with healthy controls to correlate with the clinical phenotype.Methods: Skin punch biopsies from the lower legs of 28 patients with SFN (11 men, 17 women; median age, 54 [range, years) and 9 healthy controls (five men, four women, median age, 34 [range, 25-69] years) were immunoreacted for S100 calcium-binding protein B as a Schwann cell marker, protein-gene product 9.5 as a pan-neuronal marker, and CD207 as a Langerhans cell marker. Intraepidermal nerve fiber density (IENFD) and subepidermal Schwann cell counts were determined. Results: Skin samples of patients with SFN showed lower IENFD (P < .05), fewer Schwann cells per millimeter (P < .01), and fewer Schwann cell clusters per millimeter (P < .05) than controls. When comparing SFN patients with reduced (n = 13; median age, 53 [range, 19-73] years) and normal distal (n = 15, median age, 54 [range, 43-68] years) IENFD, the number of solitary Schwann cells per millimeter (p < .01) and subepidermal nerve fibers associated with Schwann cell branches (P < .05) were lower in patients with reduced IENFD. All three parameters correlated positively with distal IENFD (P < .05 to P < .01), whereas no correlation was found between Schwann cell counts and clinical pain characteristics. Discussion: Our data raise questions about the mechanisms underlying the interdependence of dermal Schwann cells and skin innervation in SFN. The temporal course and functional impact of Schwann cell presence and kinetics need further investigation.

Structural changes in Schwann cells and nerve fibres in type 1 diabetes: relationship with diabetic polyneuropathy

“…2f; Table 2), and post hoc analysis showed declines of SSCP density in the T1DPN and P-T1DPN groups compared with the healthy control and T1D groups after adjusting for confounders (all p adj <0.01; Table 3). We also quantified solitary and total SSCS number density and SSCP density per length using the methods published in the aforementioned study [25], and the results pointed to the same conclusion (data not shown).…”

“…Post hoc analysis showed reduced SNF density per volume in the T1DPN and P-T1DPN groups compared with the healthy control and T1D groups (all p adj <0.05), while there was no difference between the T1DPN and P-T1DPN groups (p adj =1.000, Table 3). Lastly, quantifying SNF density per length using the previously published method was also performed [25] and the results pointed towards the same conclusion (data not shown).…”

“…Comparison between methods A significant difference in SNF density per volume (a method modified from a published study [25]) was seen between the groups (p<0.001, p adj <0.001; Fig. 3i; Table 2).…”

“…To compare the results with previously published methods, we analysed the expression of subepidermal SCs (including the subepidermal SC process [SSCP]) and subepidermal SC soma [SSCS]) and subepidermal nerve fibres (SNFs) using a method optimised from a published study [ 25 ]. Here, we quantified the solitary and total SSCS number density, SSCP density and SNF density per volume within 40 µm from the border (for details see ESM Methods ), and per length within 40 µm from the border (the original method [ 25 ]).…”

Transient immune activation without loss of intraepidermal innervation and associated Schwann cells in patients with complex regional pain syndrome

“…Cutaneous Schwann cells were documented in the leg from healthy humans—though without quantification [ 22 ]. In another study processes of Schwann cells accompanying IENFs were not detected in human hairy skin from the leg; instead subepidermal Schwann cell somata and their branches associated with IENFs in the dermis were quantified [ 40 ]. So, different skin areas might harbour different numbers of intraepidermal Schwann cells.…”