Epidermal Langerhans cells in small fiber neuropathies

Abstract

We quantified the immune histiocytic Langerhans cells (LCs) in skin biopsy samples of patients with distal small fiber neuropathy (SFN). Patients were divided according to the presence or absence of neuropathic pain (burning pain) assessed by a visual analogue scale (VAS). We studied 13 diabetic patients (pain-DSFN), 7 nondiabetic patients (pain-SFN) who reported relevant neuropathic pain (VAS ≥ 3), and 6 nondiabetic patients without neuropathic pain (no-pain-SFN). Using double immunofluorohistochemistry with the PGP 9.5 and the langerin/CD207, we quantified the intraepidermal nerve fibers density (IENFD) and LCs per square millimeter in the epidermis. A group of 10 skin samples from healthy subjects served as controls. Confocal analysis was performed to evaluate LC PGP 9.5-immunoreactivity. We found a mean value of 334.3LC/mm(2) in controls, 310.2LC/mm(2) in no-pain-SFN, 329.6LC/mm(2) in pain-SFN and 484.3LC/mm(2) in pain-DSFN (analysis of variance; P=.01). In patients, analysis of covariance adjusted by different covariables showed that the presence of diabetes (F=5.2, P=.03) was associated with an increased number of LC/mm(2). There was a negative correlation between the IENFD and the number of LCs (r(2)=-0.13, P=.03). No statistically significant differences were found among groups of subjects either for the co-localization or for the number of LCs that were PGP 9.5-immunoreactive (analysis of variance; P>.05). These results indicate that patients with neuropathic pain in the context of SFN, specially those who had diabetes (DSFN), had an increased number of LCs in the epidermis that may play a role in the generation or maintenance of neuropathic pain.

Corneal confocal microscopy in chronic inflammatory demyelinating polyneuropathy

“…The infiltrates of cells without dendrites detected in this study may be involved in this scenario. There are recent data that show increased epidermal Langerhans cells in patients with painful small fiber neuropathy58 and Langerhans cell activation in diabetic mice with mechanical allodynia 59. In this study, differentiation of infiltrating cells was based on morphology, therefore we can only speculate regarding the involvement of specific immunological subtypes of cells.…”

Vascular endothelial growth factor-A165b prevents diabetic neuropathic pain and sensory neuronal degeneration

“…Activated caspase-3 coexpression with NF200 in DRG neurons is also consistent with this interpretation. Concurrent small fibre neuropathy in these animals is also indicated by the increased epidermal recruitment of Langerhans cells [30], and AC3 expression in the smaller diameter neurons. Langerhans cells are dendritic cells that increase their expression of PGP9.5 following denervation and inflammation [36].…”

“…4B). Langerhans cells, inflammatory cells reported to increase in number in diabetic patients [30], were also increased in the epidermis of diabetic rats at week 7 (Fig. 4A, arrowheads) and this was also significantly reduced by VEGF-A 165 b treatment (Fig.…”

Molecular and cellular mechanisms that initiate pain and itch

“…Skin DCs can be divided into two major populations: epidermal Langerhans cells (LCs) and dermal dendritic cells. LCs reside in the basal and suprabasal epidermis, where they form a network between keratinocytes and contribute to the generation of painful hypersensitivity after peripheral tissue or nerve injury [66]. On the other hand, LC-deficient mice also display enhanced contact hypersensitivity [67], suggesting different roles of LCs in neuropathic pain and contact hypersensitivity.…”