title: 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.
authors.affiliation: Department of Neurology, Hospital Clinic, Institut d'Investigació Augustí Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain Department of Systemic Autoimmune Disease, Vasculitis Research Unit, Hospital Clinic, Institut d'Investigació Augustí Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain Confocal Microscopy Unit, Faculty of Medicine, University of Barcelona, Barcelona, Spain Department of Internal Medicine, Hospital Clinic, Institut d'Investigació Augustí Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Casanova-Molla
authors.forename: Merche
authors.initials: M
authors.lastname: Morales
authors.forename: Ester
authors.initials: E
authors.lastname: Planas-Rigol
authors.forename: Anna
authors.initials: A
authors.lastname: Bosch
authors.forename: Maria
authors.initials: M
authors.lastname: Calvo
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Grau-Junyent
authors.forename: Josep
authors.initials: J
authors.lastname: Valls-Solé
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007801:Langerhans Cells / Q000378:metabolism / Q000473:pathology*; D037181:Lectins, C-Type / Q000378:metabolism; D008297:Male; D037241:Mannose-Binding Lectins / Q000378:metabolism; D008875:Middle Aged; D009437:Neuralgia / Q000378:metabolism / Q000473:pathology*; D010147:Pain Measurement; D011115:Polyneuropathies / Q000378:metabolism / Q000473:pathology*; D012867:Skin / Q000294:innervation* / Q000378:metabolism / Q000473:pathology; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C121916:CD207 protein, human; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase