Lesional Skin Specimens Research Articles

Expression of JAK/STAT signalling in bullous pemphigoid.

In the present study, we characterise the expression of JAK/STAT signalling in Bullous Pemphigoid (BP). Punch biopsy specimens of normal skin, lesional and perilesional skin of patients diagnosed with biopsy proven BP were utilised for immunoperoxidase labelling with commercially available antibodies for Phosphorylated STAT 1,2,3,5A and 6 (Genesearch, USA). Quantitative analysis demonstrated that in comparison to normal skin, phosphorylated STAT 2, 3, 5A and 6 were overexpressed in BP.

Profibrotic Subsets of SPP1+ Macrophages and POSTN+ Fibroblasts Contribute to Fibrotic Scarring in Acne Keloidalis

Acne keloidalis is a primary scarring alopecia characterized by longstanding inflammation in the scalp causing keloid-like scar formation and hair loss. Histologically, acne keloidalis is characterized by mixed leukocytic infiltrates in the acute stage followed by a granulomatous reaction and extensive fibrosis in the later stages. To further explore its pathogenesis, bulk RNA sequencing, single-cell RNA sequencing, and spatial transcriptomics were applied to occipital scalp biopsy specimens of lesional and adjacent no-lesional skin in patients with clinically active disease. Unbiased clustering revealed 19 distinct cell populations, including 2 notable populations: POSTN+ fibroblasts with enriched extracellular matrix signatures and SPP1+ myeloid cells with an M2 macrophage phenotype. Cell communication analyses indicated that fibroblasts and myeloid cells communicated by SPP1 signaling networks in lesional skin. A reverse transcriptomics in silico approach identified corticosteroids as possessing the capability to reverse the gene expression signatures of SPP1+ myeloid cells and POSTN+ fibroblasts. Intralesional corticosteroid injection greatly reduced SPP1 and POSTN gene expression as well as acne keloidalis disease activity. Spatial transcriptomics and immunofluorescence staining verified microanatomic specificity of SPP1+ myeloid cells and POSTN+ fibroblasts with disease activity. In summary, the communication between POSTN+ fibroblasts and SPP1+ myeloid cells by SPP1 axis may contribute to the pathogenesis of acne keloidalis.

Cutaneous Toll-like Receptor 9 Pre-Defines Hydroxychloroquine Dosage in Patients with Both Discoid and Subacute Lupus Erythematosus.

Background and Objectives: Cutaneous lupus erythematosus (CLE) presents clinically heterogeneous manifestations, partially explained by the different expression of Toll-like receptors (TLRs) type 8 and 9, located to endosomal compartments where they are poised to recognize microbial nucleic acids. This disease is empirically treated with hydroxychloroquine (HCQ), which is hallmarked with a safe and effective profile, but induces a slow and sometimes clinically insufficient therapeutic response. Currently, no biomarkers predictive of response are validated or even proposed in the scientific literature. We aimed to evaluate endosomal TLR type 7, 8 and 9 as predictive biomarkers of HCQ efficacy. Materials and Methods: We conducted a case-control study comparing CLE patients retrospectively assigned to three subgroups based on 3-6-month Cutaneous LE Disease Area and Severity Index (CLASI) reduction upon treatment with HCQ (I = <40% vs. II = 40-80% vs. III = >80%). Before HCQ, lesional skin specimens were collected in untreated CLE and through immunohistochemistry; TLR-7, -8 and -9 expression was evaluated in the epidermis and the lymphocytic infiltrate was evaluated in the dermis. Results: Sixty-six lesional skin biopsies were compared with healthy controls. CLE patients displayed lower epidermal expression of total TLR 8 and 9 as well as infiltrating TLR-8, TLR9 + lymphocytes compared to controls. High HCQ responders differed from low responders for TLR-9 positivity (high vs. low) and for the lymphocytic dermal infiltrate (high vs. low). Conclusions: TLR9 could be envisaged as a possible biomarker to predict HCQ response level and dosage in CLE patients.

Lymphocyte-predominant lesional inflammatory infiltrates of the skin are associated with mucosal-dominant phenotype in pemphigus.

Pemphigus is a potentially life-threatening autoimmune blistering disease. To date, studies assessing the association of histopathology with clinical phenotype are lacking. We sought to evaluate the main histopathologic findings and, also, the potential links between cutaneous inflammatory infiltrates and clinical characteristics in pemphigus. We conducted a retrospective cohort study in patients diagnosed with pemphigus vulgaris (PV) and pemphigus foliaceus (PF) in a referral center for autoimmune blistering diseases. A total of 124 patients were included in the study (97 had PV and 27 had PF). On biopsy specimens, PV was more frequently associated with the "row of tombstones" feature (36.1% vs. 11.1%, p=0.013), and PF was associated with acanthosis (44.4% vs. 23.7%, p=0.034). Acantholysis was found in the upper half of the epidermis in PF (96.3% vs. 5.15%, p < 0.001), as opposed to the lower half in PV (75.2% vs. 0%, p=0.002). Patients with lymphocyte-predominant inflammatory infiltrates in lesional skin specimens presented with a higher frequency of the mucosal-dominant phenotype (25.5% vs. 9.1%, p=0.014), higher-density cellular infiltrate (100% vs. 41.6%, p < 0.001), and more frequent acantholytic cells (42.6% vs. 23.4%, p=0.025). Neutrophil-predominant infiltrates in specimens from lesional skin were linked to a milder disease based on median Pemphigus Disease Area Index (38.9% vs. 13.2%, p=0.036) and Autoimmune Bullous Skin Disorder Intensity Score (20.2 vs. 36.3, p=0.019), while eosinophil-predominant inflammatory infiltrates were more often associated with eosinophilic spongiosis (100% vs. 23.1%, p=0.014). Lymphocyte-predominant infiltrates in lesional skin specimens of pemphigus patients predict a mucosal-dominant phenotype, while neutrophil-predominant infiltrates are associated with a milder disease.

Metabolic Disorders/Obesity Is a Primary Risk Factor in Hidradenitis Suppurativa: An Immunohistochemical Real-World Approach

Background: Hidradenitis suppurativa (HS) is an inflammatory, potentially scarring disease of the hair follicle, affecting the apocrine gland-bearing skin areas. The major comorbid disorders associated with the occurrence or the aggravation of the disease are obesity and smoking. Numerous efforts to dissociate these factors led to controversial results. Objectives: To assess the importance of metabolic disorders/obesity, smoking/environmental toxins, and inflammation in HS by utilizing the differential expression of major relevant protein markers in lesional skin of obese/smoking versus non-obese/non-smoking HS patients. Methods: Lesional skin specimens deriving from two groups of HS patients (BMI >30 and smokers, n = 12 vs. BMI <30 and non-smokers, n = 10) were stained with antibodies raised against irisin, PPARγ, and IGF-1R, which correlate with metabolic disorders/obesity, EGFR and AhR, associated with smoking, and IL-17, IL-17R, and S100A8, as markers of inflammation. Results: Metabolic disorders/obesity-related markers exhibited marked differential expression between the two groups, while smoking-associated markers a limited one. IL-17R expression was stronger in obese/smokers, and S100A8 staining exhibited intense strong immunoreactivity in both groups without significant difference. Conclusions: The notion that obesity plays a role in HS development appears to be supported by the prominent regulation of the associated lesional biomarkers. Tobacco smoking might contribute less to HS than previously suspected.

The impact of lesional inflammatory cellular infiltrate on the phenotype of bullous pemphigoid

The influence of cutaneous cellular infiltration on the phenotype of bullous pemphigoid (BP) remains to be established. To evaluate the main histopathological characteristics of patients with BP and to assess the association between the composition of lesional inflammatory infiltrate and the various clinical, immunological and immunopathological aspects of the disease. Retrospective study encompassing patients diagnosed with BP throughout the years 2009-2020 in a specialized tertiary referral centre. The study encompassed 136 patients with BP, of whom 27 (19.9%) demonstrated a cell-poor inflammatory infiltrate in lesional skin specimens. Overall, 78 (57.4%), 71 (52.2%) and 5 (3.7%) specimens were found to include eosinophil-predominant, lymphocyte-predominant and neutrophil-predominant inflammatory infiltrates, respectively. Relative to the remaining patients with BP, those with an eosinophil-predominant inflammatory infiltrate had higher (90.8% vs. 77.2%; P=0.030) whilst those with a cell-poor inflammatory infiltrate lower (70.3% vs. 88.7%; P=0.017) seropositivity of anti-BP180 NC16A IgG. The latter subgroup presented with higher prevalence of mucosal involvement (25.9% vs. 8.3%; P=0.011) and a non-inflammatory clinical phenotype (50.0% vs. 17.1%; P=0.041). Patients with lymphocyte-predominant inflammatory infiltrate manifested with higher severity BPDAI scores and a lower frequency of the non-inflammatory subtype (11.1% vs. 36.4%; P=0.035), whilst those with a neutrophilic infiltrate presented with lower mean (SD) levels of anti-BP180 NC16A IgG [269.3 (227.6) vs. 722.7 (1499.6) U/mL; P=0.003]. Eosinophil-predominance and high cellularity in the lesional inflammatory infiltrate of BP skin are associated with increased seropositivity of anti-BP180 NC16A IgG. Lymphocyte-predominant infiltrates predict a more severe phenotype, pointing towards a pathogenic role of autoreactive lymphocytes.

Presence of Cutaneous Complement Deposition Distinguishes between Immunological and Histological Features of Bullous Pemphigoid-Insights from a Retrospective Cohort Study.

The practical implications of complement deposition in direct immunofluorescence (DIF) microscopy and its influence on the disease phenotype are poorly understood. We aimed to investigate whether the presence of complement deposition in DIF microscopy gives rise to differences in the morphological, immunological, and histological characteristics of patients with BP (bullous pemphigoid). We performed a retrospective study encompassing patients with BP in a specialized tertiary referral center. Logistic regression model was utilized to identify variables independently associated with complement deposition. The study included 233 patients with BP, of whom 196 (84.1%) demonstrated linear C3 deposition along the dermal-epidermal junction (DEJ) in DIF analysis. BP patients with C3 deposition had higher mean (SD) levels (645.2 (1418.5) vs. 172.5 (243.9) U/mL; p < 0.001) and seropositivity rate (86.3% vs.64.9%; p = 0.002) of anti-BP180 NC16A and less prevalent neutrophilic infiltrate in lesional skin specimens (29.8% vs. 52.4%; p = 0.041). C3 deposition was found positively associated with the detection of anti-BP180 NC16A autoantibodies (OR, 4.25; 95% CI, 1.38–13.05) and inversely associated with the presence of neutrophils in lesional skin (OR, 3.03; 95% CI, 1.09–8.33). To conclude, complement deposition influences the immunological and histological features of BP. These findings are in line with experimental data describing the pathogenic role of complement in BP.

Immunohistochemical Nucleocytoplasmic Localization of Light Chain3 in the Keratinocytes of Psoriatic Skin

Background: Light chain3 is a sensitive autophagy-related protein distributed within the mammalian tissues. The role of LC3 localization in psoriasis pathogenesis is still poorly understood. Objective: This study aimed to investigate, for the first time up to our knowledge, the localization of Light chain3 (LC3) in the keratinocytes of psoriatic skin by immunohistochemical study. Materials and methods: This prospective case case-control study was carried out on 30 patients presented with chronic plaque psoriasis versus 30 age and gender-matched apparently healthy volunteers. Clinical data were collected and Psoriasis Area and Severity Index (PASI) was assessed. From all controls and cases (lesional and perilesional), skin biopsies were taken and the epidermis was assessed for histopathological changes and LC3 immunoreaction. Results: There was a highly significant difference (P<0.001) between the control skin and psoriatic skin (lesional and perilesional) regarding the epidermal LC3 localization. Nucleocytoplasmic LC3 localization was dominant in lesional skin specimens. Conclusion: Nucleocytoplasmic localization of LC3 in the keratinocytes of the psoriatic skin might play a pivotal role in psoriasis pathogenesis. This can open a new gate for target therapy in psoriasis.

Temporal Correlations of Skin and Blood Metabolites with Clinical Outcomes of Biologic Therapy in Psoriasis.

Psoriasis is an inflammatory skin disease causing multisystem effects. Introduction of biologic drugs has led to promising results in treatment of this disease. Here, we carry out time-dependent profiling of psoriasis-related putative metabolic biomarkers. Skin excretion specimens were collected from 17 patients with psoriasis treated with biologics for 7 months. Blood specimens were obtained from the same patients at intervals of 1-3 months. A hydrogel micropatch sampling technique was implemented to collect lesional (L) and nonlesional (NL) skin specimens. The collected skin and blood specimens were analyzed by mass spectrometric methods. The metabolites present on L skin-in particular, choline, and citrulline-showed greater dynamics, corresponding to the resolution of psoriasis than the metabolites present in NL skin or blood. Choline levels in L skin and blood correlated positively, while citrulline correlated negatively with the severity of individual psoriasis plaques and general disease severity, respectively. Nevertheless, the correlations between the metabolite levels in blood and general disease severity were weaker than those between the metabolite levels on L skin and severity of individual plaques. The changes of these skin metabolites were more prominent in the responders to the treatment than in the nonresponders. The results support the feasibility of characterizing dynamic changes in psoriatic skin metabolic profiles with the hydrogel micropatch probes and mass spectrometric tests. The study represents one of few attempts to explore relationships between skin and blood metabolite concentrations. However, practical use of the methodology in close clinical monitoring is yet to be demonstrated.

Immunohistochemical expression of human β-defensin-2 in verruca vulgaris

Background Verruca vulgaris is the commonest viral cutaneous infection that is caused by human papilloma virus. There are more than 150 genotypically different types of human papilloma virus. Types 1, 2, 4, 27, and 57 were found with verruca vulgaris. Human β-defensins (hBDs), a family of small antimicrobial peptides, are important effector molecules of innate immunity, possessing antimicrobial, anti-inflammatory, and immunomodulatory activities. Aim The aim of this work was to investigate the immunohistochemical expression of hBD-2 in verruca vulgaris lesion in a trial to elucidate its possible role in the pathogenesis of the disease. Patients and methods This study included 15 lesional skin specimens of 15 patients with typical clinically and histopathologically diagnosed verruca vulgaris (group I). Seven specimens of nonlesional normal skin of contralateral sides of seven of these patients (group II) in addition to other seven normal skin specimens from seven healthy subjects of matched age and sex (group III) served as controls. All specimens were studied histopathologically using hematoxylin and eosin stain and immunohistochemically for detection of hBD-2 expression. Results All lesional skin specimens (group I) showed positive expression of hBD-2. Twelve (80%) specimens showed positive expression in all epidermal layers [immunoreactivity (IR) 3]. Two (13.3%) specimens showed positive expression in the stratum corneum only (IR 1), and one (6.7%) specimen showed positive expression in the stratum corneum and stratum granulosum (IR 2). Groups II and III showed no expression of hBD-2 (IR 0). There was highly significant difference between patients and controls (P Conclusion There was positive immunohistochemical expression of hBD-2 in lesional skin specimens taken from patients with verruca vulgaris, whereas there was no expression in normal skin specimens taken from the patients and the volunteers. This may indicate a possible role of hBD-2 in the pathogenesis of verruca vulgaris and also in the immunity against it.

459 Resident memory CD8 T cells in both lesional and non- lesional skin of psoriasis patients have a potential of producing IL-17

IL-17-producing T cells are known to be one of the causes of psoriasis. Contribution of CD4 T cells to disease manifestation has been investigated in details. However the role of CD8 T cells has been poorly established. In our present study, T cells were isolated from fifteen lesional and non-lesional skin specimens in psoriasis patients and twelve normal skin specimens and their phenotypical differences were compared. Both psoriatic lesional skin and non-lesional skin included more CD8 T cells compared to normal skin. In CD8 T cell population, CD69+CD103+ resident memory T cells, which stay in skin for a long time instead of recirculating and are reported to be distributed mainly in epidermis, were dominant both in lesional and non-lesional skin. This difference was not detected in CD4 fraction. CD8 T cells both in psoriatic lesional and non-lesional skin included more IL-17-producing cells compared to those from normal skin. Furthermore, the ratio of IL-17-producing cells in CD69+CD103+ resident memory CD8 T cells was higher both in lesional and non-lesional skin of psoriasis than in normal skin. On the other hand, the ratio of IL-17 producing cells in CD4 T cells from non-lesional skin of psoriasis and normal skin were comparable, even though the total number of skin-infiltrating IL-17-producing CD4 T cells was higher in psoriatic non-lesional skin than in normal skin. These results suggest that CD69+CD103+ CD8 resident memory T cells with the potential of producing IL-17 already exist in non-lesional skin of psoriasis and may contribute to disease manifestation.

Regulatory T-cell cytokines in patients with nonsegmental vitiligo.

In the etiopathogenesis of vitiligo, the role of suppressor cytokines, such as transforming growth factor-β (TGF-β) and interleukin-10 (IL-10), associated with regulatory T-cells (Treg) is not completely known. In this study, the role of Treg-cell functions in the skin of patients with nonsegmental vitiligo was investigated. Lesional and nonlesional skin samples from 30 adult volunteers ranging in age from 18 to 36 years with nonsegmental vitiligo were compared with normal skin area excision specimens of 30 benign melanocytic nevus cases as controls. All samples were evaluated staining for forkhead box P3 (Foxp3), TGF-β, and IL-10 using the standardized streptavidin-biotin immunoperoxidase immunohistochemistry method. Foxp3 expression was lower in lesional vitiligo skin specimens compared to controls; it was also lower in lesional vitiligo specimens than nonlesional vitiligo specimens. IL-10 levels were lower in lesional vitiligo specimens compared to the controls, whereas IL-10 expression was significantly lower in lesional specimens compared with nonlesional specimens. TGF-β expression was higher in both lesional and nonlesional skin specimens of patients with vitiligo compared to controls. TGF-β expression was lower in lesional skin specimens than nonlesional skin specimens. In addition, there was no significant correlation between Foxp3 expression with TGF-β and IL-10 expressions in lesional skin specimens in the vitiligo group. In this study, results supporting the contribution of Treg cells and IL-10 deficiency to the autoimmune process were obtained. Therefore, future studies are necessary to demonstrate the definitive role of Treg-cell functions in the etiopathogenesis of vitiligo.

Reduced immunohistochemical expression of adhesion molecules in vitiligo skin biopsies

Because defects in adhesion impairment seem to be involved in the etiopathogenesis of vitiligo, this study aimed to compare the immunohistochemical expression of several adhesion molecules in the epidermis of vitiligo and non lesional vitiligo skin.Sixty-six specimens of lesional and non lesional skin from 33 volunteers with vitiligo were evaluated by immunohistochemistry using anti-beta-catenin, anti-E-cadherin, anti-laminin, anti-beta1 integrin, anti-collagen IV, anti-ICAM-1 and anti-VCAM-1 antibodies. Biopsies of vitiligo skin demonstrated a significant reduction in the expression of laminin and integrin. The average value of the immunohistochemically positive reaction area of the vitiligo specimens was 3053.2μm2, compared with the observed value of 3431.8μm2 in non vitiligo skin (p=0.003) for laminin. The immuno-positive area was 7174.6μm2 (vitiligo) and 8966.7μm2 (non lesional skin) for integrin (p=0.042). A reduction in ICAM-1 and VCAM-1 expression in the basal layer of the epidermis in vitiligo samples was also observed (p=0.001 and p<0.001, respectively). However, no significant differences were observed with respect to the expression of beta-catenin, E-cadherin, and collagen IV between vitiligo and non lesional skin.Our results suggest that an impairment in adhesion exists in vitiligo skin, which is supported by the diminished immunohistochemical expression of laminin, beta1 integrin, ICAM-1 and VCAM-1.

Detection of Langerhans cells and plasmacytoid dendritic cells in condyloma acuminatum lesions of patients

Objective To investigate the possible roles of Langerhans cells (LCs) and plasmacytoid dendritic cells (pDCs) in the pathogenesis of condyloma acuminatum (CA). Methods Tissue specimens were obtained from the lesions of 23 patients with CA and from perilesional normal skin of 13 of the 23 patients. The expressions and distribution of CD1a, CD2AP and CD123 were analyzed using the streptavidin-peroxidase (SP) immunohistochemical method. Statistical analysis was carried out to compare the density and percentage of CD1a+ LCs, CD2AP+ pDCs and CD123+ pDCs between lesional skin and perilesional normal skin. Results Most CD1a+ LCs were observed in the prickle cell layer of the epidermis, and a few in the papillary layer of the dermis. There was no significant difference in the density or percentage of CD1a+ LCs in the epidermis or dermis between the lesional and perilesional skin specimens (all P>0.05). CD2AP+ pDCs and CD123+ pDCs were distributed mainly in the papillary layer of the dermis, and their density and percentage were significantly higher in the lesional than in the perilesional skin specimens (all P<0.05). Conclusion Human papillomavirus infection may affect the quantity of pDCs but not LCs in local mucous membranes. Key words: Condylomata acuminata; Langerhans cells; Dendritic cells; Immunohistochemistry; Human papillomavirus

Expressions of nerve growth factor and its high-affinity receptor, tyrosine kinase A, as well as low-affinity common receptor, p75 neurotrophin receptor, in the lesions of lichen planus and their clinical significance

Objective To detect the expressions of nerve growth factor (NGF) and its receptors tyrosine kinase A (TrkA) as well as p75 neurotrophin receptor (p75NTR) in the lesions of lichen planus.Methods Biopsy specimens were collected from the lesions of 32 patients with lichen planus and normal skin of 12 healthy human controls and subjected to paraffin embedding.Immunohistochemical avidin-biotin complex (ABC) method was used to detect the expressions of NGF,TrkA and p75NTR.Results NGF and TrkA,which were located in the cytoplasm of keratinocytes,were strongly or moderately expressed in the lesional skin specimens,but absent or weakly expressed in the normal skin specimens (both P ＜ 0.01).No significant differences were observed in the expression of p75NTR between the lesional and normal skin specimens,or in the expressions of NGF,TrkA or p75NTR among specimens from patients in different age groups,patients of different gender or lesions at different sites (all P ＞ 0.05).There was a positive correlation between the expression of NGF and TrkA in the lesions of lichen planus (R2 =0.535,P ＜ 0.01).Conclusion NGF may play a certain role in the development of lichen planus via its highaffinity receptor TrkA. Key words: Lichen planus; Nerve growth factor, Protein-tyrosine kinases; p75NTR

Identification by SNP Analysis of a Major Role for Cayetana Blanca in the Genetic Network of Iberian Peninsula Grapevine Varieties

AIMS: To measure Langerhans9 cells in skin of patients treated by bone marrow transplantation who developed chronic graft versus host disease (GvHD); to determine whether the reduction in Langerhans9 cells resulted directly from the GvHD or from other factors, such as the immunosuppressive regimens used in bone marrow transplant patients. PATIENTS AND METHODS: Lesional and nonlesional skin specimens from nine patients with lichen planus-like lesions and three patients with sclerodermoid lesions were studied. Control skin specimens were taken from three patients undergoing breast reduction surgery. The number of Langerhans9 cells/mm2 and the area of Langerhans9 cells as a percentage of total epidermis were measured by counting cells labelled with antihuman CD1a. RESULTS: A significant reduction in Langerhans9 cell area and number were found in specimens with lesions (area 3.5%; number 507/mm2) compared with specimens without lesions (8.42%; 2375/mm2). In contrast, Langerhans9 cell area and number in skin without lesions were similar to controls (10.26%; 2968/mm2). CONCLUSIONS: Langerhans9 cells were significantly reduced in skin with lesions of chronic GvHD but not in skin without lesions from the same patient, suggesting that the reduction is a direct consequence of GvHD and not linked to immunosuppressive drugs or late effects of conditioning regimens. In long term bone marrow transplant recipients, Langerhans9 cells are derived mainly from the donor cells; therefore, this result suggests the occurrence of autoreactive phenomenon in chronic GvHD.

Expression of innate defense antimicrobial peptides in hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder of apocrine gland-bearing skin. It is associated with alterations in innate immunity and frequent bacterial infections. We investigated the expression of innate defense antimicrobial peptides in patients with HS and different grades of severity. Skin biopsy specimens and sweat were collected from 36 patients with HS and 57 healthy control subjects for analysis of epithelial antimicrobial peptides by real-time reverse transcription-polymerase chain reaction, immunohistochemistry, enzyme-linked immunosorbent assay, and surface-enhanced laser desorption ionization time-of-flight mass spectrometry. We provide evidence that human β-defensin-3 expression is induced in lesional HS skin on transcriptional and protein levels, yet, this up-regulation was not detectable in patients with severe HS (Hurley grade III). In contrast, messenger RNA expression of ribonuclease 7 was significantly diminished in lesional HS skin specimens irrespective of HS severity. Overall levels of dermcidin/dermcidin-derived peptides in sweat and messenger RNA expression of psoriasin in skin biopsy specimens did not differ between patients with HS and healthy control subjects. The relatively small number of samples, in particular in the group of patients with HS and Hurley grade III, is a limitation. Deficient constitutive production of ribonuclease 7 and, in severe HS, reduced human β-defensin-3 induction may contribute to impaired immunity within the hair follicle and thereby boost HS inflammation and severity.

Clonal T-cell populations are frequent in the skin and blood of patients with systemic sclerosis

Pilot studies were suggestive for a role of clonal T cells in the pathogenesis of systemic sclerosis (SSc). To investigate the presence of clonal T cells in both peripheral blood and skin of a large collection of patients with SSc. Polymerase chain reaction and high-resolution capillary electrophoresis for detecting T-cell clonality were performed in a series of 126 patients with SSc. Seventy-seven (61%) of 126 patients had clonal T cells in their peripheral blood. In contrast, a clonal T-cell population was present in only four of 29 (14%) age-matched healthy controls (P = 0.03). Older patients were more likely to have clonal T cells than younger patients with SSc (P < 0.0001). Clonal T cells were more commonly detected in the blood of patients with limited cutaneous SSc (48 of 65 patients, 74%) than in those with diffuse cutaneous disease (29 of 61, 48%; P = 0.0002). Lesional skin specimens from 20 of 44 patients (45%) had detectable clonal T-cell populations. There was no correlation between the presence of circulating clonal T cells and lesional clonal T cells, sex, disease duration, extent of skin sclerosis, digital ulcers, organ involvement (e.g. interstitial lung disease, kidney disease, oesophagus involvement), treatment of SSc, or autoantibody profile. Many patients with SSc have expanded clonal T cells in their peripheral blood and skin. These clonal T cells could play a critical role in the pathogenesis of SSc, especially in limited cutaneous disease.

Effects of tacrolimus ointment on the expression of substance P, nerve growth factor, and neurotrophin‐3 in atopic dermatitis

There is increasing evidence that neuropeptides may be involved in the pathogenesis of atopic dermatitis (AD). Objectives To investigate the effects of tacrolimus on the neuropeptides substance P (SP), nerve growth factor (NGF), and neurotrophin-3 (NT-3) in the skin, and SP and NGF in the serum, of patients with AD. Lesional skin specimens were obtained from eight AD patients and eight normal controls. For 8 weeks, AD patients applied 0.03% tacrolimus ointment to all affected areas twice daily. Blood samples and skin biopsies were then repeated. The participants' serum SP and NGF levels, as well as the SP, NGF, and NT-3 immunoreactive cell counts, were evaluated in the epidermal, dermal, and perivascular areas of lesional skin before and after treatment. The immunoreactive cell counts of SP, NGF, and NT-3 in skin were higher in AD patients than in normal controls. Most cell counts decreased significantly after treatment; however, the change in serum SP and NGF was not statistically significant. We demonstrated semiquantitative differences in neuropeptides in the skin of AD patients. In addition, topical tacrolimus reduced the levels of neuropeptides in the tissues of AD patients.

Overexpression of CXCL16 in lesional psoriatic skin

Psoriasis is characterized as an autoimmune disease resulting in an exaggerated innate immune response. The CXC-chemokine ligand 16 (CXCL16) is described to function as an adhesion molecule, a scavenger receptor or as a soluble molecule it acts as a chemoattractant. CXCL16 has been reported to be expressed in a variety of inflammatory diseases. However, no information has been reported in the literature about the expression of CXCL16 in psoriatic skin. The present study was designed to analyze the expression and localization of CXCL16 in human psoriatic skin tissues. In normal skin, cytpoplasmic expression of CXCL16 was increased in keratinocytes of upper epidermal cell layers as compared to the lower epidermal cell layers. In lesional psoriatic skin, CXCL16 immunoreactivity was increased in the cytoplasm of keratinocytes of lower epidermal layer kerartinocytes as compared to the normal epidermis. Cytoplasmic CXCL16 expression was increased in the capillary endothelial cells of psoriatic dermis as compared to capillary endothelial cells of the normal dermis. Notably, almost all inflammatory cells in the dermis were negative for CXCL16. Ten paraffinized specimens of human lesional psoriatic skin and five paraffinized specimens of normal skin were studied using an immunohistochemical streptavidinperoxidase technique. We here report for the first time alterations in the immunohistochemical staining pattern of CXCL16 in lesional psoriatic skin compared to the normal skin. These results suggest that CXCL16 may play a role in the pathogenesis of psoriasis.