Density Of Langerhans Cells Research Articles

Comparative analysis of antigen-presenting cells in gingival tissues in healthy and periodontitis patients

AimsMicrobial flora of dental plaque trigger innate and adaptive immune responses. The function of antigen-presenting cells (APCs) is to bridge the innate and adaptive immune systems. The human immune system...

A pilot study on Langerhans cells in keratoconus patients by in vivo confocal microscopy before and after corneal cross-linking and correlation with eye rubbing

PurposeThe aim of this study was to investigate the corneal microstructure and Langerhans cells using in vivo confocal microscopy in keratoconus patients before and after cross-linking, and to correlate the morphologic findings with clinical and patient-reported outcomes, including eye rubbing (ER) behavior. MethodsPatients with progressive keratoconus undergoing iontophoresis-assisted epithelium-on cross-linking (I-CXL) were consecutively enrolled. In vivo confocal microscopy was performed before and 6 months after treatment. Patients were asked to quantify their ER behavior on a Visual Analogue Scale (VAS) and completed the Keratoconus Outcomes Research Questionnaire and the Ocular Surface Disease Index questionnaires at the same time points. Visual acuity, tear osmolarity, topography, aberrometry, and pachymetry of both eyes were assessed. ResultsThirteen patients were included in this pilot study. Preoperatively, the mean Langerhans cells density was 35,615 cells per mm2, and the median morphology was 3. The mean ER VAS before treatment was 7,077 out of 10. The ER VAS showed significant positive correlations with both Langerhans cells density and morphology of the study eye. After treatment, a statistically significant reduction in ER VAS and in Langerhans cells variables was observed. The mean sub-basal plexus nerve density was comparable to pre-operative values 6 months after I-CXL. ConclusionsBased on this preliminary evidence, the presence of high density of mature Langerhans cells in the central cornea of keratoconus patients and its correlation with eye rubbing support the role of inflammation in keratoconus. The reduction in these markers after treatment may suggest a potential of CXL in moderating immune-related inflammation and eye rubbing in the medium term.

Chlamydia trachomatis enhances HPV persistence through immune modulation

Chlamydia trachomatis (CT) is the most common sexually transmitted infections globally, and CT infection can enhance HPV persistence. Epidemiological analysis has shown that patients with CT/HPV coinfection have a higher risk of developing cervical cancer and exhibit more rapid progression to cervical cancer than patients with HPV infection alone. However, the mechanism has not been fully elucidated. Here, we report that CT infection supports HPV persistence by further suppressing the functions of Langerhans cells (LCs); in particular, CT further activates the PI3K pathway and inhibits the MAPK pathways in LCs, and these pathways are frequently involved in the regulation of immune responses. CT/HPV coinfection also impairs LC functions by reducing the antigen-presenting ability and density of LCs. Moreover, CT/HPV coinfection can alter T-cell subsets, resulting in fewer CD4 + and CD8 + T cells and more infiltrating Tregs. Moreover, CT/HPV coinfection decreases the CD4 + /CD8 + T cell ratio to below 1, coinfection also induces greater T lymphocytes’ apoptosis than HPV infection, thus impairing cell-mediated immunity and accelerating the progress to cervical cancer.

Antihyperlipidemic and Histopathological Pancreas Analysis of Muntingia calabura L. Fruit Extract on Alloxan-Induced Diabetic Mice

Hyperlipidemia is clinically manifested by high levels of Total Cholesterol (TC), Triglycerides (TG), Low Density Lipoprotein (LDL) and low levels of High Density Lipoprotein (HDL) in the blood. Antihyperlipidemic drugs available currently have adverse effects. One of the medicine plants with antihyperlipidemic properties with no side effects is Muntingia calabura fruit. The sample used for this research were 30 male mice were divided into 5 groups, i.e., a negative control, a diabetic control, a positive control group, and two treatment groups which were given 100 and 300mg/kg of M. calabura fruit extract every day for 14 days. Examination of TC, TG, HDL, LDL and histopathological pancreas were determined after administration of the extract orally for 14 days. The results demonstrated an administration of glibenclamide and M. calabura fruit could effectively reduce TC, TG and LDL and increase HDL compared to the diabetes control group (P<0.05). In the diabetes control group, the mice given alloxan 150mg/kg showed a decrease in Langerhans islet density, vascularity, and islet injury compared to the normal control group. Mice given M. calabura fruit extract showed a significant increase in pancreatic Langerhans cells granulation and cell density. The conclusion of this research is M. calabura fruit extract showed improvements in lipid profile and pancreatic Langerhans cell regeneration. Therefore, the fruit extract of M. calabura is a potential antihyperlipidemic drug.

Disrupted Neural Regeneration in Dry Eye Secondary to Ankylosing Spondylitis-With a Theoretical Link between Piezo2 Channelopathy and Gateway Reflex, WDR Neurons, and Flare-Ups.

This study aimed at analyzing the corneal neural regeneration in ankylosing spondylitis patients using in vivo corneal confocal microscopy in correlation with Langerhans cell density, morphology, and dry eye parameters. Approximately 24 ankylosing spondylitis subjects and 35 age- and gender-matched control subjects were enrolled. Data analysis showed that all corneal nerve-fiber descriptives were lower in the ankylosing spondylitis group, implicating disrupted neural regeneration. Peripheral Langerhans cell density showed a negative correlation with nerve fiber descriptions. A negative correlation between tear film break-up time and corneal nerve fiber total branch density was detected. The potential role of somatosensory terminal Piezo2 channelopathy in the pathogenesis of dry eye disease and ankylosing spondylitis is highlighted in our study, exposing the neuroimmunological link between these diseases. We hypothesized earlier that spinal neuroimmune-induced sensitization due to this somatosensory terminal primary damage could lead to Langerhans cell activation in the cornea, in association with downregulated Piezo1 channels on these cells. This activation could lead to a Th17/Treg imbalance in dry eye secondary to ankylosing spondylitis. Hence, the corneal Piezo2 channelopathy-induced impaired Piezo2-Piezo1 crosstalk could explain the disrupted neural regeneration. Moreover, the translation of our findings highlights the link between Piezo2 channelopathy-induced gateway to pathophysiology and the gateway reflex, not to mention the potential role of spinal wide dynamic range neurons in the evolution of neuropathic pain and the flare-ups in ankylosing spondylitis and dry eye disease.

Neural Regeneration in Dry Eye Secondary to Systemic Lupus Erythematosus Is Also Disrupted like in Rheumatoid Arthritis, but in a Progressive Fashion.

Our objective in this study was to analyze the aberrant neural regeneration activity in the cornea by means of in vivo confocal microscopy in systemic lupus erythematosus patients with concurrent dry eye disease. We examined 29 systemic lupus erythematosus patients and 29 age-matched healthy control subjects. Corneal nerve fiber density (CNFD, the number of fibers/mm2) and peripheral Langerhans cell morphology were lower (p < 0.05) in systemic lupus erythematosus patients compared to the control group. Interestingly, corneal nerve branch density, corneal nerve fiber length, corneal nerve fiber total branch density, and corneal nerve fiber area showed a negative correlation with disease duration. A negative correlation was also demonstrated between average corneal nerve fiber density and central Langerhans cell density. This is in line with our hypothesis that corneal somatosensory terminal Piezo2 channelopathy-induced impaired Piezo2-Piezo1 crosstalk not only disrupts regeneration and keeps transcription activated, but could lead to Piezo1 downregulation and cell activation on Langerhans cells when we consider a chronic path. Hence, Piezo2 containing mechanosensory corneal nerves and dendritic Langerhans cells could also be regarded as central players in shaping the ocular surface neuroimmune homeostasis through the Piezo system. Moreover, lost autoimmune neuroinflammation compensation, lost phagocytic self-eating capacity, and lost transcription regulation, not to mention autoantibodies against vascular heparin sulfate proteoglycans and phospholipids, could all contribute to the progressive fashion of dry eye disease in systemic lupus erythematosus.

Corneal nerve loss and increased Langerhans cells are associated with disease severity in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a multisystem autoimmune disorder characterized by articular and extra-articular manifestations. Neuropathy is a poorly studied manifestation of RA. The aim of this study was to utilize the rapid non-invasive ophthalmic imaging technique of corneal confocal microscopy to identify whether there is evidence of small nerve fibre injury and immune cell activation in patients with RA. Fifty consecutive patients with RA and 35 healthy control participants were enrolled in this single-centre, cross-sectional study conducted at a university hospital. Disease activity was assessed with the 28-Joint Disease Activity Score and erythrocyte sedimentation rate (DAS28-ESR). Central corneal sensitivity was measured with a Cochet-Bonnet contact corneal esthesiometer. A laser scanning in vivo corneal confocal microscope was used to quantify corneal nerve fibre density (CNFD), nerve branch density (CNBD), nerve fibre length (CNFL), and Langerhans cell (LC) density. Corneal sensitivity (P = 0.01), CNFD (P = 0.02), CNBD (P < 0.001), and CNFL (P < 0.001) were lower, and mature (P = 0.001) and immature LC densities (P = 0.011) were higher in patients with RA compared to control subjects. CNFD (P = 0.016) and CNFL (P = 0.028) were significantly lower in patients with moderate to high (DAS28-ESR > 3.2) compared to mild (DAS28-ESR ≤ 3.2) disease activity. Furthermore, the DAS28-ESR score correlated with CNFD (r = -0.425; P = 0.002), CNBD (ρ = -0.362; P = 0.010), CNFL (r = -0.464; P = 0.001), total LC density (ρ = 0.362; P = 0.010) and immature LC density (ρ = 0.343; P = 0.015). This study demonstrates reduced corneal sensitivity, corneal nerve fibre loss and increased LCs which were associated with the severity of disease activity in patients with RA.

Peritumoural and Intratumoural Distribution of Langerhan Cell in Oral Squamous Cell Carcinoma and its Association with Known Prognostic Factors

Introduction: Oral Squamous Cell Carcinoma (OSCC) accounts for about 2/3rd of the Head and Neck Squamous Cell Carcinomas (HNSCC). It is the sixth most common cancer worldwide and the third most common cancer in developing countries including India. More than half the HNSCC patients have advanced disease at the time of diagnosis and overall long-term survival is low (50%), despite aggressive therapeutic regimens. This has demanded the need for prognostic indicators that can be used to improve the ability to select a more individualised approach for treatment relative to the risks of recurrence, metastases and death. Aim: To study the intratumoural and peritumoural distribution and density of Langerhans Cells (LC) in OSCC using Immunohistochemistry (IHC) markers Cluster of Differentiation1a (CD1a) and Langerin and to study its association with known prognostic factors. Materials and Methods: This was a hospital-based crosssectional study conducted at the Department of Pathology, Amala institute of Medical Sciences, Kerala, India during a period of 18 months, from January 2019 to June 2020. In total, 28 specimens of wide local excision with cervical lymph node dissection done for OSCC were enrolled in the study. Small biopsy samples and cases who had undergone neoadjuvant treatment as well as cases of recurrent OSCC were excluded. Clinical details were obtained from the patients’ case files. The immunohistochemical staining for LCs using CD1a and Langerin was done. The distribution of LCs was compared to the tumour grade and lymph node status along with lymphovascular and perineural invasion. Statistical analysis was performed using sample t-test after identifying normality of distribution. The p-value of &lt;0.05 was taken as significant. Results: Fourteen cases of well differentiated and 14 cases of moderate to poorly differentiated OSCC were selected for the study. The LC distribution in these cases were compared to prognostic factors like histological grade, Lymphovascular Invasion (LVI), perineural invasion, tumour size, depth of invasion, T stage and lymph node status. A significant positive association was observed between the tumour differentiation and peritumoural CD1a positive cell density (p-value: 0.001). Further, a negative association was also established between the lymph node staging and peritumoural CD1a positive cell density (p-value: 0.004). There was no association between the LC density and presence of lymphovascular or perineural invasion in OSCC. Conclusion: A depleted peritumoural LC density in OSCC reflects poor tumour immunity, associated with higher grade and higher stage of lymph node metastasis. LC density may hence be of prognostic value in OSCC.

Corneal Langerhans cells in children with celiac disease

Celiac disease (CeD) is a common small bowel enteropathy characterized by an altered adaptive immune system and increased mucosal antigen presenting cells. This study aims to establish if quantification of corneal Langerhans cells (LCs) using corneal confocal microscopy (CCM) could act as a surrogate marker for antigen presenting cell status and hence disease activity in children with CeD. Twenty children with stable CeD and 20 age-matched controls underwent CCM and quantification of central corneal total, mature and immature LC density. There was no difference in age (11.78 ± 1.7 vs. 12.83 ± 1.91; P = 0.077) or height (1.38 ± 0.14 vs. 1.44 ± 0.13; P = 0.125). BMI (18.81 ± 3.90 vs. 22.26 ± 5.47; P = 0.031) and 25 OHD levels (43.50 ± 13.36 vs. 59.77 ± 22.45; P = 0.014) were significantly lower in children with CeD compared to controls. The total (33.33(16.67–59.37) vs. 51.56(30.21–85.42); P = 0.343), immature (33.33(16.67–52.08) vs. 44.79(29.17–82.29); P = 0.752) and mature (1.56(0–5) vs. 1.56(1.04–8.33); P = 0.752) LC density did not differ between the CeD and control groups. However, immature (r = 0.535, P = 0.015), mature (r = 0.464, P = 0.039), and total (r = 0.548, P = 0.012) LC density correlated with age. Immature (r = 0.602, P = 0.038) and total (r = 0.637, P = 0.026) LC density also correlated with tissue transglutaminase antibody (Anti-TtG) levels assessed in 12/20 subjects with CeD. There was no difference in corneal LC density between children with CeD and controls. However, the correlation between corneal LC density and anti-TtG levels suggests a relationship with disease activity in CeD and requires further study.

Corneal Confocal Analysis after Scleral Lens Wear in Keratoconus Patients: A Pilot Study.

Scleral lenses rely on the scleroconjunctival region without bearing the cornea, which could improve the symptoms and modify the corneal nerve plexus morphology. This study aimed to evaluate symptoms and changes in corneal nerve plexus morphology and density of Langerhans cells in keratoconus patients with and without intrastromal corneal ring before and after scleral lens wear. Sixteen scleral lens wearers with keratoconus were recruited for this short-term experimental pilot study. Subjects were divided into two groups: keratoconus group and intrastromal corneal ring segment group. All subjects were examined in two visits: baseline (before scleral lens wear) and after 6 months of scleral lens wear, after lens removal. The Schirmer I test, the Ocular Surface Disease Index, tear breakup time, and in vivo confocal microscopy were evaluated. The mean age was 42.33 ± 11.27 years. A significant decrease in tear breakup time was found in the total group ( P = .01, Wilcoxon) compared with baseline. Ocular Surface Disease Index score had decreased after 6 months of scleral lens wear in the keratoconus with intrastromal corneal ring segment subgroup ( P = .03, Wilcoxon) and in the total group ( P = .001, Wilcoxon). No statistical changes in nerve density, tortuosity, and ramification were found for either the total group or the subgroup. However, the mean nerve length was higher in all groups, especially in the keratoconus subgroup ( P = .03, Wilcoxon) after 6 months of scleral lens wear. Regarding optical density, the total group showed a significant increase after 6 months of wearing ( P = .02, Wilcoxon). Finally, Langerhans cell density was not statistically different in any group. These results suggest that scleral lens wearing improves the symptoms and increased the mean length nerves after 6 months of wear use in keratoconus patients.

Course and structure of corneal nerve fibers in patients with primary open-angle glaucoma

PURPOSE. T o analyze the course and structure of corneal nerve fibers (CNF) in patients with different stages of primary open-angle glaucoma (POAG), and to determine possible correlations with the available diagnostic indicators of glaucoma progression. METHODS. The study included 48 patients (48 eyes) diagnosed with stages I–IV POAG at the age of 33 to 75 years. In addition to standard examination methods, all patients underwent static perimetry with Humphrey Field Analyzer II, optical coherence tomography (OCT) of the optic disc, measurement of biomechanical properties of the fibrous membrane of the eye, as well as laser confocal microscopy of the cornea on HRT III device with corneal adapter Cornea Rostock. RESULTS. There were positive correlations of medium strength between the indices of basic nerve fiber length (r = 0.64 and r = 0.63; p &lt; 0.05) and density (r = 0.6 and r = 0.65; p &lt; 0.05) with perimetry data (MD and PSD) and retinal nerve fiber thickness measured with OCT of the optic disc (r = 0.65 and r = 0.61; p &lt; 0.05). Nerve fiber anisometry and symmetry coefficients depended on glaucoma stage (r = 0.62 and r = 0.65; p &lt; 0.05). An increase in the number and density of Langerhans cells and an increase in the length of their processes were detected. A reliable correlation (r = 0.63) was found between glaucoma stage and corneal inflammatory response. The immune etiology of the glaucoma process considered by several authors may be a reason of an increase in the number and density of macrophages during the progression of POAG. CONCLUSION. Laser confocal microscopy can be used as an additional diagnostic method for patients with different stages of POAG.

Examination of corneal microstructure in the quiescent phase of vernal keratoconjunctivitis using in vivo confocal microscopy.

This study investigated the morphological characteristics of corneal microstructure in the quiescent phase of vernal keratoconjunctivitis (VKC). Twenty patients with quiescent VKC and 25 healthy subjects were included. In vivo confocal microscopy (IVCM) of the central cornea was performed. Cellular density of each layer and the morphology of subbasal nerve plexus (SBNP) was analysed. Langerhans cell density (LCD), morphology (LCM), and field area (LCF) were also examined. No differences were found either in cell densities nor in SBNP morphology (p > 0.05). LCD, LCM and LCF were significantly higher in the VKC group (p = 0.005, p < 0.001 and p < 0.001, respectively). The severity of papillary hypertrophy had a significant impact on LCD, LCM and LCF (β-coefficient: 19.541, p < 0.001; β-coefficient: 0.283, p < 0.001 and β-coefficient: 595.255, p < 0.001, respectively). In quiescent VKC, LCD, LCM, and LCF were increased, and they were associated with the severity of papillary hypertrophy. Alterations of Langerhans cells indicate a subclinical inflammatory process without ocular symptoms.

Corneal confocal microscopy in the evaluation of immune-related motor neuron disease syndrome

BackgroundTo investigate the sensitivity and specificity of corneal confocal microscopy (CCM) in the diagnosis of immune-related motor neuron disease syndrome and evaluation of the response to immunosuppressive therapy.MethodsSeventy-two patients with clinical manifestations of motor neuron disease (MND) were analysed. According to whether they had concomitant rheumatic immune disease or rheumatic immune antibody abnormalities, they were divided into an MND group (33 patients) and an immune-related MND syndrome group (39 patients). Another 10 healthy adults were selected as the control group. All individuals were examined by CCM.ResultsFor Langerhans cell(LC) density, the area under the receiver operating characteristic(ROC)curve was 0.8, the best cut-off was 67.7 cells/mm2, the sensitivity was 79.5%, and the specificity was 72.7%. For inferior whorl length (IWL), the area under the ROC curve was 0.674, the best cut-off was 17.41 mm/mm2, the sensitivity was 69.2%, and the specificity was 66.7%. After immunosuppressive therapy in 5 patients with immune-related MND syndrome, the LCD was significantly reduced (P < 0.05), and there was no statistically significant change in the IWL (P > 0.05).ConclusionThe LC density and IWL are ideal for distinguishing MND from immune-related MND syndrome. The LC density reflects the immunotherapy response sensitively.

Trauma of Peripheral Innervation Impairs Content of Epidermal Langerhans Cells.

Langerhans cells represent the first immune cells that sense the entry of external molecules and microorganisms at the epithelial level in the skin. In this pilot case-study, we evaluated Langerhans cells density and progression of epidermal atrophy in permanent spinal cord injury (SCI) patients suffering with either lower motor neuron lesions (LMNSCI) or upper motor neuron lesions (UMNSCI), both submitted to surface electrical stimulation. Skin biopsies harvested from both legs were analyzed before and after 2 years of home-based Functional Electrical Stimulation for denervated degenerating muscles (DDM) delivered at home (h-bFES) by large anatomically shaped surface electrodes placed on the skin of the anterior thigh in the cases of LMNSCI patients or by neuromuscular electrical stimulation (NMES) for innervated muscles in the cases of UMNSCI persons. Using quantitative histology, we analyzed epidermal thickness and flattening and content of Langerhans cells. Linear regression analyses show that epidermal atrophy worsens with increasing years of LMNSCI and that 2 years of skin electrostimulation reverses skin changes, producing a significant recovery of epidermis thickness, but not changes in Langerhans cells density. In UMNSCI, we did not observe any statistically significant changes of the epidermis and of its content of Langerhans cells, but while the epidermal thickness is similar to that of first year-LMNSCI, the content of Langerhans cells is almost twice, suggesting that the LMNSCI induces an early decrease of immunoprotection that lasts at least 10 years. All together, these are original clinically relevant results suggesting a possible immuno-repression in epidermis of the permanently denervated patients.

Cornea Confocal Microscopy Study of Patients with Preclinical Keratoconus

Purpose: To report the difference of corneal confocal microscopy examination in patients with preclinical keratoconus or clinical keratoconus. Methods: 8 unilateral keratoconus patients were examined by confocal microscopy before they had cross-linking surgery. As control groups, 23 patients with myopia and 13 patients with keratoconus in both eyes were also examined by confocal microscopy. Then we used Image J to compared the density of epithelium cell, length of cornea nerve fiber, density of Langerhans cell, density of keratocyte in shallow, middle, deep stroma, and the width and grayscale value of fold near Descement membrane for each group. Result: There was differences in corneal epithelial cell count between three groups (4358.27 ± 635.14 cells/mm² versus 4057.81 ± 316.29 cells/mm² versus 3522.65 ± 978.10 cells/mm²). The density of keratocyte in stroma showed a tendency to decrease with increasing depth. The density of keratocyte in keratoconus was less than that in normal eyes. The fold showed much wider and daker in keratoconus eyes than in normal eyes. The density of Langerhans cell was more in keratoconus group than it in normal group. Conclusion: We first report the differences in corneal epithelial cell count and fold near Descement membrane. It might provide a new way to diagnose early keratoconus. The difference of density of Langerhans cell suggested us the possibility of inflammation in keratoconus.

Subclinical Corneal Nerve Fiber Damage and Immune Cell Activation in Systemic Lupus Erythematosus: A Corneal Confocal Microscopy Study.

PurposeThe purpose of this study was to evaluate the utility of corneal confocal microscopy (CCM) in identifying small nerve fiber damage and immune cell activation in patients with systemic lupus erythematosus (SLE).MethodsThis cross-sectional comparative study included 39 consecutive patients with SLE and 30 healthy control participants. Central corneal sensitivity was assessed using a Cochet-Bonnet contact corneal esthesiometer and a laser scanning CCM (Heidelberg, Germany) was used to quantify corneal nerve fiber density (CNFD), nerve branch density (CNBD), nerve fiber length (CNFL), and Langerhans cell (LC) density.ResultsAge was comparable among patients with SLE (33.7 ± 12.7) and controls (35.0 ± 13.7 years, P = 0.670) and the median duration of disease was 3.0 years (2.0–10.0 years). CNBD (P = 0.003) and CNFL (P = 0.019) were lower and mature LC density (P = 0.002) was higher, but corneal sensitivity (P = 0.178) and CNFD (P = 0.198) were comparable in patients with SLE compared with controls. The SELENA-SLEDAI score correlated with CNFD (ρ = −0.319, P = 0.048) and CNFL (ρ = −0.373, P = 0.019), and the total and immature LC densities correlated with CNBD (ρ = −0.319. P = 0.048, and ρ = −0.328, P = 0.041, respectively). Immature LC density was higher (P = 0.025), but corneal sensitivity and nerve fiber parameters were comparable between patients with (33%) and without neuropsychiatric symptoms and SLE.ConclusionsCorneal confocal microscopy identifies distal corneal nerve fiber loss and increased immune cell density in patients with SLE and corneal nerve loss was associated with disease activity.Translational RelevanceCorneal confocal microscopy may enable the detection of subclinical corneal nerve loss and immune cell activation in SLE.

O-PN003. Corneal sub-basal whorl-like nerve plexus: A landmark for early and follow-up evaluation in transthyretin familial amyloid polyneuropathy

Introduction . To evaluate the quantification of corneal sub-basal whorl-like nerve plexus parameters as a sensitive and static marker in early diagnosis of small fiber neuropathy (SFN) and monitor disease progression in familial amyloid polyneuropathy (FAP) patients. Methods . Fifteen FAP patients and fifteen healthy controls underwent neurological evaluation (including clinical scales and electrophysiological tests) and corneal nerve observation. Corneal nerve fiber density (CNFD), Corneal nerve fiber branch density (CNBD), Corneal nerve fiber length (CNFL) were detected in the central cornea (conventional method) and the whorl-like inferocentral cornea (new method). The Langerhans cells (LC) density in each image was calculated. Results . Corneal parameters were significantly reduced with disease progression. Only inferior whorl length (IWL) was significantly reduced in preclinical patients (with normal SSR and CHEPs results) comparing with age matched controls. IWL, CNFL, CNBD and CNFD were significantly lower in early phase patients. LC density was significantly increased around the central whorl in early phase patients than in healthy controls (p = 0.009), and was lower in the progressive patients. Both IWL and CNFL correlated with severity of neuropathy. IWL was more significantly reduced with the progression of disease than CNFL. The area under the ROC curve to distinguish FAP with CNFL and IWL was 88.0% and 89.3%, respectively, exceeding other parameters. The coefficient of variation of the IWL value was significantly (P < 0.0001) smaller than that of the conventional method. Conclusion . The observation of corneal sub-basal whorl-like nerve plexus can detect SFN in preclinical FAP patients earlier than traditional electrophysiological methods. IWL is the most sensitive and reliable parameters and it can best discriminate FAP patients from controls. The clustering of immature LCs at the whorl area might reflect the inflammatory response of small- fiber nerves at the very early stage.

Morphological Alterations and Increased S100B Expression in Epidermal Langerhans Cells Detected in Skin from Patients with Progressive Vitiligo.

The role of Langerhans cells (LCs) in vitiligo pathogenesis remains unclear, with published studies reporting contradictory results regarding the quantity of LCs and no data on the features of LCs in vitiligo. Here, we aimed to analyze the presence, density, and morphological features of LCs in the epidermis of patients with vitiligo. Skin biopsies were stained for LCs using anti-CD1a/anti-langerin antibodies and analyzed by immunocytochemistry with light and electron microscopy. Compared with healthy controls, we detected significantly increased numbers of epidermal LCs in lesional skin from vitiligo in the progressive state. These LCs exhibited striking morphological alterations, including an elevated number of dendrites, with increased length and more branches than dendrites from controls. Ultrastructure examination via immuno-electron microscopy revealed markedly reduced Birbeck granules (BGs) and shorter BG rods in LCs from progressive vitiligo, with higher expression of langerin. Additionally, expression of S100B, the activity biomarker of vitiligo, was increased in these LCs. This work provides new insight on the cellular composition of LCs in vitiliginous skin, revealing altered morphology and increased LC numbers, with elevated S100B expression. Our data suggest LCs might play a critical role in vitiligo pathogenesis and thus may represent a novel therapeutic target for this disease.

Tiroid Oftalmopati Hastalarında In vivo Konfokal Mikroskopi Kullanılarak Langerhans Hücrelerinin Değerlendirilmesi: Retrospektif Bir Çalışma

Objective: To assess corneal Langerhans cell (LC) density in thyroid-associated ophthalmopathy (TAO) patients to evaluate the role of inflammation in ocular surface disease related to TAO by using in vivo confocal microscopy (IVCM). Methods: Thirty-three patients who had inactive disease [(Clinical Activity Score (CAS)&amp;lt;3] and thirty age-matched healthy control subjects were enrolled in the study. All subjects underwent routine ophthalmologic examination including visual acuity levels, intraocular pressure, anterior segment, and posterior segment evaluation. The subjects were evaluated with tear break-up time (BUT). IVCM was performed to assess LC density in the central cornea. Also, correlation analyses of LC density and clinical data were performed. Results: The mean BUT was 9.61±5.01 seconds in the TAO group and 12.70±2.76 seconds in the control group (p=0.003). The median central corneal LC density in the control group was 19.00 (7.00-24.50) whereas it was significantly increased to 68.00 (50.00-92.00) in the TAO patients (p&amp;lt;0.001). In correlation analysis, there was a significant negative correlation between age and CAS of TAO patients (r=-0.348, p=0.047), and the age of TAO patients was not correlated with BUT and LC count (r=0.236, p=0.186 and r=-0.211, p=0.240, respectively). BUT of TAO patients was negatively correlated with LC count and CAS (r=-0.495, p=0.003 and r=-0.644, p&amp;lt;0.001, respectively). The CAS of the patients was not correlated with the LC count of the patients (r=0.261, p=0.143). In the control group, BUT, CAS and LC count was not correlated with each other. Conclusion: TAO patients in the inactive phase suffer from ocular surface inflammation and LC participates in corneal inflammation in TAO.

Small Nerve Fiber Damage and Langerhans Cells in Type 1 and Type 2 Diabetes and LADA Measured by Corneal Confocal Microscopy.

PurposeIncreased corneal and epidermal Langerhans cells (LCs) have been reported in patients with diabetic neuropathy. The aim of this study was to quantify the density of LCs in relation to corneal nerve morphology and the presence of diabetic neuropathy and to determine if this differed in patients with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and latent autoimmune diabetes of adults (LADA).MethodsPatients with T1DM (n = 25), T2DM (n = 36), or LADA (n = 23) and control subjects (n = 23) underwent detailed assessment of peripheral neuropathy and corneal confocal microscopy. Corneal nerve fiber density (CNFD), branch density (CNBD), length (CNFL) and total, immature and mature LC densities were quantified.ResultsLower CNFD (P < 0.001), CNBD (P < 0.0001), and CNFL (P < 0.0001) and higher LC density (P = 0.03) were detected in patients with T1DM, T2DM, and LADA compared to controls. CNBD was inversely correlated with mature (r = –0.5; P = 0.008), immature (r = –0.4; P = 0.02) and total (r = –0.5; P = 0.01) LC density, and CNFL was inversely correlated with immature LC density (r = –0.4; P = 0.03) in patients with T1DM but not in patients with T2DM and LADA.ConclusionsThis study shows significant corneal nerve loss and an increase in LC density in patients with T1DM, T2DM, and LADA. Furthermore, increased LC density correlated with corneal nerve loss in patients with T1DM.