Keratinocyte-derived circulating microRNAs in extracellular vesicles: a novel biomarker of psoriasis severity and potential therapeutic target.

BACKGROUND: Psoriasis is a chronic inflammatory disorder characterized by pathogenic hyperproliferation of keratinocytes and immune dysregulation. Currently, objective evaluation tools reflecting the severity of psoriasis are insufficient. MicroRNAs in extracellular vesicles (EV miRNAs) have been shown to be potential biomarkers for various inflammatory diseases. Our objective was to investigate the possibility of plasma-derived EV miRNAs as a marker for the psoriasis disease severity. METHODS: EVs were extracted from the plasma of 63 patients with psoriasis and 12 with Behçet's disease. We performed next-generation sequencing of the plasma-derived EV miRNAs from the psoriasis patients. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the level of EV miRNA expression. In situ hybridization was used to discern the anatomical location of miRNAs. qRT-PCR, western blotting, and cell counting kits (CCKs) were used to investigate IGF-1 signaling in cells transfected with miRNA mimics. RESULTS: We identified 19 differentially expressed EV miRNAs and validated the top three up-and down-regulated EV miRNAs. Among these, miR-625-3p was significantly increased in patients with severe psoriasis in both plasma and skin and most accurately distinguished moderate-to-severe psoriasis from mild-to-moderate psoriasis. It was produced and secreted by keratinocytes upon stimulation. We also observed a significant intensification of IGF-1 signalling and increased cell numbers in the miR-625-3p mimic transfected cells. CONCLUSIONS: We propose keratinocyte-derived EV miR-625-3p as a novel and reliable biomarker for estimating the severity of psoriasis. This biomarker could objectively evaluate the severity of psoriasis in the clinical setting and might serve as a potential therapeutic target. Trial registration None.

All-cause and cause-specific mortality in patients with Behçet disease versus the general population.

BACKGROUND: The comparative risk of cause-specific mortality in patients with Behçet disease (BD) vs. the general population is not known. OBJECTIVES: To compare the risk of all-cause and cause-specific mortality in patients with BD vs. the general population. METHODS: Using data from the Korea National Health Insurance Service database for the period 2002-20, we conducted a cohort study comparing patients with BD with the general population, matched according to age and sex (1 : 4 ratio). We used Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality. Subgroup analyses by age and sex were done. RESULTS: We included 24 669 patients with BD and 98 676 age- and sex-matched controls [mean (SD) age 40.5 (12.9) years; 34% male]. During a mean follow-up of 11.9 years, the incidence rate (IR) of death per 100 person-years was 0.36 in patients with BD and 0.29 in controls [hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.20-1.38]. The risk of mortality was highest in the first year after BD diagnosis (HR 2.66, 95% CI 2.09-3.40). Patients with BD died more often in this period as a result of malignancy (HR 1.96, 95% CI 1.30-2.98); cardiovascular (HR 2.68, 95% CI 1.45-4.97), gastrointestinal (HR 3.50, 95% CI 1.35-9.07) and respiratory disease (HR 5.00, 95% CI 1.34-18.62); and infection (HR 3.33, 95% CI 1.02-10.92). Mortality as a result of neurological (HR 1.58, 95% CI 1.06-2.35) or genitourinary disease (HR 2.20, 95% CI 1.43-3.37) was also more common in patients with BD during the overall follow-up. Subgroup analyses showed consistent results. The risk of cardiovascular mortality vs. the general population was higher in younger patients (P = 0.006) and the risk of gastrointestinal mortality was increased in women vs. men (P = 0.04). CONCLUSIONS: This population-based cohort study revealed that the first year after diagnosis is the highest risk period for excess mortality in people with BD. The mortality burden in BD derives from a wide spectrum of organ involvement and should serve as a warning to clinicians about the systemic nature of the disease.

Behçet disease (BD) is a multisystem vasculitis (inflammation of the blood vessels) of unknown origin that commonly results in oral and genital ulcers, uveitis (eye inflammation) and skin lesions. BD is most prevalent in people from the Mediterranean to East Asia, affecting 0.4% of people in this area. Most lesions go away with time, but more severe forms that involve the cardiovascular and neurological systems can lead to death. It is estimated that people with BD have 1.4 times the risk of dying than the general population. Using large insurance databases in Korea, we investigated the risk of death in people with BD versus age- and sex-matched controls (i.e. people without the disease) from the general population. We found that patients with BD had a 28% greater risk of death than controls over 11.9 years of follow-up, with the highest risk being in first year after diagnosis. Top causes of death in people with BD included cancer, and cardiovascular, gastrointestinal, neurological, genitourinary, respiratory and infectious disease. Further analyses of the data showed that the risk of death in BD is affected by age and sex. In particular, younger patients were more susceptible to death as a result of cardiovascular disease and women were more susceptible to dying of gastrointestinal disease. Our study suggests that there could be an increased risk of death within the first year of being diagnosed with BD and highlights how BD is a systemic disease (i.e. the involvement of any internal organ system could lead to an increase in mortality). Finally, there were unique patterns of cause-specific deaths across subgroups of people with BD.

No Association Between First Exposure to General Anaesthesia and Atopic Dermatitis in the Paediatric Population.

General anaesthesia could affect various immune responses, including Th1 and Th2 immunity, which might also affect cells that play an important role in the pathogenesis of atopic dermatitis. However, the relationship between general anaesthesia exposure and atopic dermatitis remains unknown. The aim of this study was to investigate the risk of developing atopic dermatitis after first exposure to general anaesthesia in the paediatric population (18 years or under). A retrospective cohort study, including those exposed (n = 7,681) and unexposed (n = 38,405; control participants) to general anaesthesia (1:5 ratio), was conducted using national sample cohort data from 2002 to 2015. All participants were followed up for 2 years after cohort entry. The 2-year cumulative incidences of atopic dermatitis in the exposed and unexposed groups were 2.3% and 2.2%, respectively. In the subgroup analysis by age, the cumulative incidence was not significantly different between these cohorts. The risks of atopic dermatitis were not significant in the exposed group in the univariate model (hazard ratio 1.05; confidence interval 0.88-1.24) and in the multivariate model, wherein all covariates were adjusted (adjusted hazard ratio, 1.03; 95% confidence interval 0.87-1.23). The results suggest that children's exposure to general anaesthesia was not associated with increased or decreased risk of atopic dermatitis.

Differential expression of novel genes and signalling pathways of senescent CD8+ T cell subsets in Behçet's disease.

OBJECTIVES: Behçet's disease (BD) is a rare disease characterised by recurrent mucocutaneous ulceration and chronic multi-systemic inflammation; however, its pathogenic mechanisms and biomarkers have not been fully discovered. Previously, we found that peripheral blood CD8+CD27-CD28- T cell frequency was higher in patients with BD than in healthy controls (HCs). In this study, we used global gene expression analysis to identify candidate genes that might be related to pathogenesis or developed as biomarkers in two CD8+ T cell subsets from BD patients and HCs. METHODS: We performed RNA sequencing analysis in CD8+CD27-CD28- and CD8+CD27+CD28+ T cell subsets isolated from 18 patients with BD and healthy controls. Real time qPCR was used to validate the differential expression of genes in five patients with BD and healthy controls. RESULTS: We found that 1,103 genes and 652 genes were differentially expressed in the CD8+CD27-CD28- and CD8+CD27+CD28+ T cell subsets of patients with BD, respectively. We validated the differential expression of COL5A1 in CD8+CD27-CD28- T cells and TRPV3 and ARHGEF10 in CD8+CD27+CD28+ T cells. Furthermore, Ingenuity Pathway Analysis indicated that eleven pathways were more active in BD CD8+CD27-CD28- T cells and more suppressed in BD CD8+ CD27+CD28+ T cells than in the HCs. CONCLUSIONS: Our study is the first transcriptome analysis of CD8+ T cell subsets in patients with BD and our results provide novel genes that might be related to BD pathogenesis.

Histopathological Features of Riehl Melanosis.

Histological features of Riehl melanosis have rarely been compared between lesional and perilesional normal skin and have not been precisely described using quantitative or immunohistochemical analysis or electron microscopic findings. To investigate the histopathological and immunohistochemical features of lesional and perilesional normal skin of patients with Riehl melanosis, we retrospectively evaluated the electronic medical records and skin biopsy specimens of 48 patients with Riehl melanosis. In addition, electron microscopy was performed on 1 case. Fontana-Masson staining for melanin and immunohistochemical staining for Melan-A, NKI/beteb, tyrosinase, and microphthalmia-associated transcription factor were performed. Although the difference was statistically insignificant, melanin pigment was increased in the epidermis of lesional skin compared with that of perilesional normal skin in patients. The number of melanocytes and their activity were significantly increased in lesional epidermal skin. Melanin pigment was also significantly increased in the lesional dermis. Pigmentary incontinence, basal cell liquefaction, dilated vessels, epidermal spongiosis, and colloid bodies were found in the lesional skin as well as in the perilesional normal skin to a lesser extent. Under electron microscopy of 1 randomly selected subject, many fibrocytes contained numerous melanosome particles in the cytoplasm of the lesional dermis. In perilesional normal skin, fibroblasts also contained melanosome particles; however, the number of melanosome-containing cells was less than that in lesional skin. Riehl melanosis is characterized by increased epidermal melanocytes and pigmentation, primarily involving the dermis, with histologically typical changes at the interface. Unlike that in other pigmentary diseases, most perilesional normal-appearing skin in Riehl melanosis also shows typical histopathological changes, although to a lesser extent.

The role of CCR1 and therapeutic effects of anti-CCL3 antibody in herpes simplex virus-induced Behçet's disease mouse model.

Behçet's disease (BD) is a chronic systemic inflammatory disease with unclear etiopathogenesis. Although gene variants of CC chemokine receptor type 1 (CCR1) have been reported, the protein expression of CCR1 in patients with BD remains unclear. The objective of this study was to analyze the frequencies of CCR1+ cells in a herpes simplex virus-induced mouse model of BD. The frequencies of CCR1+ cells on the surface and in the cytoplasm of peripheral blood mononuclear cells and lymph nodes were analyzed by flow cytometry. The CCR1+ cells were significantly down-regulated in BD mice compared with the normal control and symptom-free control mice. Colchicine and pentoxifylline treatment improved the symptoms of BD and increased the frequencies of CCR1+ cells in BD mice. Treatment with chemokine CC motif ligand 3 (CCL3), a ligand of CCR1, caused BD symptoms to deteriorate in 10 of 16 BD mice (62·5%) via down-regulation of CCR1+ cells. Anti-CCL3 antibody treatment ameliorated BD symptoms in 10 of 20 mice (50%) and significantly decreased the disease severity score compared with CCL3-treated BD mice (P = 0·01) via up-regulation of CCR1+ cell frequencies. In patients with BD, plasma levels of CCL3 in an active state were significantly higher than in healthy control individuals (P = 0·02). These results show that the up-regulation of CCR1+ cells was related to the control of systemic inflammation of BD in mouse models.

Frequencies of IL-15Rα+ cells in patients with Behçet's disease and the effects of overexpressing IL-15Rα+ on disease symptoms in mice.

It has been suggested higher serum levels of IL-15 and lower expression levels of IL-15 receptor alpha (IL-15Rα) are correlated with pathogenesis of Behçet's disease (BD). However, whether overexpressing IL-15Rα could be used as a therapeutic candidate for BD is currently unclear. Therefore, the purpose of this study was to determine whether overexpressing IL-15Rα could affect BD symptoms in a mouse model. IL-15/IL-15Rα complex expressing vector or protein complex of IL-15/IL-15Rα-Fc was used to treat BD mice. Frequencies of IL-15Rα+ cells in peripheral blood leukocytes (PBL) and lymph node cells were determined using a flow cytometer. BD symptoms in mice improved after treatment with IL-15/15Rα expression vector or IL-15/IL-15Rα-Fc protein complex. In addition, treatment with pIL-15/15Rα significantly (p = .016) decreased disease severity score of BD mice compared to treatment with control vector. Frequencies of IL-15Rα+ cells were also significantly (p = .01) higher in peritoneal macrophages of pIL-15/15Rα treated BD mice than those of mice treated with control vector. Frequencies of IL-15Rα+ PBL were also significantly higher in BD mice treated with IL-15/IL-15Rα-Fc protein complex than those in the control group. These results suggest up-regulating IL-15Rα+ cells could be used as novel therapeutic strategies to control BD in the future.

Two histopathological patterns of postinflammatory hyperpigmentation: epidermal and dermal.

BACKGROUND: Postinflammatory hyperpigmentation (PIH) commonly occurs, but the histopathological features are not well characterized. METHODS: A total of 21 PIH patients' medical charts were reviewed. Punch biopsies from lesional and perilesional normal skin were performed. Sections were stained with hematoxylin-eosin, Fontana-Masson, NKI/beteb, microphthalmia-associated transcription factor (MITF), CD68, c-kit, factor XIIIa, MMP-2 and MMP-9. RESULTS: Fontana-Masson-stained sections suggested two obvious PIH groups: epidermal (13 cases) and dermal (8 cases) pigmentation. The epidermal pigment group had increased epidermal basal pigmentation. The dermal pigment group had marked pigmentation within the upper dermis and decreased epidermal pigmentation. More intense perivascular lymphocytic infiltration was observed in the dermal pigment group. NKI/beteb levels were increased in lesional skin in both groups. The numbers of MITF+ melanocytes were not different between lesional and perilesional normal skin in either group. The expression of CD68 and c-kit was significantly higher in the dermis of lesional skin than in normal skin in the dermal pigment group. MMP-2 expression was upregulated in lesional skin in both groups. CONCLUSION: PIH patients can be classified into two histopathological groups: epidermal and dermal pigmentation. The dermal pigment group showed decreased levels of epidermal pigmentation. This study provides histopathological information that can improve the treatment of PIH.

MicroRNA-155 regulates the Th17 immune response by targeting Ets-1 in Behçet's disease.

OBJECTIVES: The goal of this study was to investigate whether microRNA-155 might be a potential therapeutic target for Behçet's disease (BD). METHODS: Expression levels of miR-155 were quantified using TaqMan microRNA assays in peripheral blood mononuclear cells and in isolated CD4+ T cells from BD patients and healthy controls. To identify targets of miR-155, luciferase reporter assays and western blotting were performed. The effect of miR-155 on Th17 polarisation was analysed in patients with active BD by using flow cytometry and enzyme-linked immunosorbent assay. RESULTS: The expression of miR-155 and IL-17 was significantly increased in CD4+ T cells of patients with active BD. A luciferase reporter assay and western blot showed that Ets-1 expression was reduced by miR-155 mimics. Furthermore, the expression of Ets-1 was significantly decreased in patients with active BD compared to healthy controls. More importantly, repression of miR-155 in CD4+ T cells from active BD patients increased Ets-1 expression and reduced the number of IL- 17-expressing T cells and overall IL-17 production. CONCLUSIONS: MiR-155 regulates the Th17 immune response by targeting Ets-1. Suppression of miR-155 reduced the amount of pathogenic IL-17-expressing T cells and may be a potential therapeutic strategy for BD.

CD11c is upregulated in CD8+ T cells of patients with Behçet's disease.

OBJECTIVES: Single nucleotide polymorphisms of CD11a and CD11c have been suggested as susceptibility loci in Korean patients with Behçet's disease (BD). As immunoregulatory roles of CD11c+CD8+T cells were previously observed in multiple autoimmune and autoinflammatory diseases, we aimed to investigate CD11a and CD11c in CD4+ and CD8+ subpopulation of BD patients. METHODS: Peripheral-blood mononuclear cells were isolated from 21 patients with active BD, 26 patients with inactive BD, 20 patients with recurrent aphthous ulcers (RAU), and 23 healthy controls (HCs). The surface expression of CD11a and CD11c in CD4+ and CD8+ cell populations was analyzed by flow cytometry, and CD11a and CD11c mRNA and protein levels from puri ed CD8(+) T cells were analyzed using real-time polymerase chain reaction and western blot. RESULTS: The frequencies of CD11a+ and CD11c+ cells were significantly increased in the CD4+ and CD8+ cell populations of active-BD patients, respectively, than that in the HCs. Additionally, both CD11a and CD11c mRNA and protein levels were significantly elevated in the CD8+ T cells of active-BD patients than that in the HCs. CONCLUSIONS: The CD8+ T cells of BD patients exhibited increased CD11c expression levels. Upregulation of CD11c in CD8+ cells may contribute to BD pathogenesis.

Differentiating confluent and reticulated papillomatosis from acanthosis nigricans.

BACKGROUND: Confluent and reticulated papillomatosis (CRP) is an uncommon dermatosis with a reticular pattern. As differentiation between CRP and benign acanthosis nigricans (AN) can be challenging because of their similar clinicopathological features, we aimed to distinguish the two diseases. METHODS: We retrospectively reviewed the clinical characteristics of 60 CRP and 30 AN patients. Histological examinations were conducted on 33 CRP and 30 AN lesions. RESULTS: While CRP was concentrated on the trunk, AN mostly appeared in the axilla. In the AN group, the number of obese patients was higher, and acanthosis and papillomatosis were more evident. In both group, increases in Ki-67 and keratin 16 expression were similar. Bacterial infection was detected at a higher rate in CRP lesions than in AN lesions.AN lesions had greater pigmentation because of a high number of melanocytes than CRP lesions. CONCLUSIONS: The location of skin lesions and body mass index are the main clinical factors that enable differentiation between CRP and AN. The epidermal histological changes in CRP are milder than those in AN. AN lesions also showed a greater degree of pigmentation and melanocytic proliferation.

Fractional carbon dioxide laser-assisted photodynamic therapy for patients with actinic keratosis.

BACKGROUND/PURPOSE: A relatively long incubation time is needed for photosensitizer absorption in conventional photodynamic therapy (PDT) for actinic keratosis (AK). The use of ablative CO2 fractional lasers (AFXLs) to increase drug delivery could shorten the incubation time. Here, we aimed to compare the efficacy between AFXL-assisted PDT with a short incubation time and conventional PDT for AK. METHODS: Patients with histopathologically confirmed facial AK were randomly divided into two groups. The lesions were histopathologically classified into grades I-III. In the AFXL-assisted PDT group, an ablative fractional laser was used for pretreatment, prior to the application of methyl aminolevulinate, with an incubation time of 90 min. Irradiation was performed with a 630-nm light-emitting diode. In the conventional PDT group, the incubation time was 180 min. All the patients received two rounds of PDT at 2-week intervals and underwent clinical or histological evaluation at 10 weeks after the first PDT course. RESULTS: Twenty-two patients underwent conventional PDT and 24 patients underwent AFXL-assisted PDT. Thirty-four AKs were included in the conventional PDT group, and 35 AKs were included in the AFXL-assisted PDT group. The clearance rate was 64.7% in the conventional PDT and 71.4% in the AFXL-assisted PDT group; no significant differences in the clearance rate were noted between the groups (P = 0.55). The clearance rates for each grade also did not significantly differ between the two groups. CONCLUSIONS: The use of AFXL before PDT reduced the incubation time, but yielded similar treatment efficacy as compared to conventional PDT.

Nipple eczema, an indicative manifestation of atopic dermatitis? A clinical, histological, and immunohistochemical study.

Nipple eczema exhibits as a minor manifestation of atopic dermatitis (AD) or occurs as a single skin symptom on the nipple. To characterize the relationship between nipple eczema and AD, a clinical evaluation and an immunohistochemical study were performed. All cases of nipple eczema were confirmed histopathologically. We divided the patients with nipple eczema into 2 groups, namely, those with AD and those without AD, and compared several clinical features. Upon histological examination, the degree of inflammation was subjectively graded as mild, moderate, or severe by 2 separate investigators. Immunohistochemical stainings were performed by using antiinterleukin (IL)-4, anti-IL-13, anti-CD4, and anti-CD8 antibodies, and the results were scored semiquantitatively. In 43 cases evaluated, 12 were nipple eczema with AD. The clinical analysis and histological examination showed no significant differences between the groups. There were consistent findings of IL-4 expressions throughout the epidermis and IL-13 expression mainly in the perivascular area of the dermis. Although CD4 and CD8 were expressed in the cells in the dermis, CD8 expression was detected in the serocrusts of the epidermis. Expression levels of IL-4, IL-13, CD4, and CD8 exhibited no significant differences between the nipple eczema group with AD and the nipple eczema group without AD. Although nipple eczema may accompany AD, we found no definite differences in the degree or pattern of inflammation and cytokine expression level regardless of whether AD was present or not. Serocrust formation seemed to be mainly a collection of CD8-positive cells.

Changes of epidermal thickness in vitiligo.

The stratum corneum and epidermal pigmentation have protective roles against ultraviolet radiation. Because vitiligo skin lacks melanocytes and has no potential to produce pigment, some studies suggested that the epidermis in vitiligo skin is thicker than in normal skin. However, only a few studies investigated epidermal thickness changes in vitiligo, and some of these had relatively small sample sizes. Thus, this study aimed to compare epidermal thickness between vitiligo skin and adjacent normal-appearing skin in a large cohort. Photos of hematoxylin and eosin­stained slides of vitiligo skin and adjacent normal-appearing skin were taken under a microscope. The thicknesses of the stratum corneum, viable epidermis, and full epidermis were then measured by a computerized image analyzer. A total of 206 patients (412 sections) were included. There were significant differences between vitiligo skin and adjacent normal-appearing skin in the thickness of the stratum corneum (P = 0.009), viable epidermis (P = 0.001), and total epidermis (P = 0.001). An analysis comparing skin biopsied from a sun-exposed area versus a sun-protected area showed that the stratum corneum, viable epidermis, and total epidermis were significantly thicker in vitiligo skin than in normal-appearing skin in sun-exposed areas (P < 0.05), but not in sun-protected areas. We revealed that the epidermis was thicker in vitiligo skin than in normal-appearing skin, especially on sun-exposed skin, and that this may represent a photoprotective role compensating for absent pigmentation.

Expression of follicular helper T-cell markers in primary cutaneous T-cell lymphoma.

The follicular helper T cells (TFH) seemed to be expressed in several subsets of T-cell lymphomas. However, their expression in cutaneous T-cell lymphomas (CTCLs) has been rarely described. We investigated the clinical features, histopathological morphology, and expression of TFH markers in CTCLs. Forty-nine patients (24 men and 25 women) diagnosed with CTCL were examined, 25 patients with mycosis fungoides (MF) and 24 with other CTCLs. Immunohistochemical staining for CD10, Bcl-6, inducible costimulator, CXCL13, and PD-1 were performed. Relation between PD-1 and clinical course in MF was evaluated. PD-1 was detected in 21 of 25 (84.0%) MF cases and in 11 of 24 (45.8%) other CTCL cases. Bcl-6, CXCL13, inducible costimulator, and CD10 were occasionally expressed in most T-cell lymphomas, including MF. The staining for PD-1 was negative in all the MF cases with large-cell transformation. No correlation was observed between disease course and PD-1 expression rate in the MF cases. In conclusion, among the TFH markers, PD-1 was most frequently expressed in CTCL. PD-1 was expressed in most MF. PD-1 expression rates were significantly higher in MF than in other CTCLs.

Real-world safety and effectiveness of secukinumab in adult patients with moderate to severe plaque psoriasis: results from postmarketing surveillance in Korea.

Background: Secukinumab, a fully human monoclonal antibody, was approved in Korea for the treatment of moderate to severe psoriasis in September 2015. Objectives: To assess the safety and effectiveness of secukinumab in patients with moderate to severe psoriasis in Korea. Design: Multicenter, real-world, noninterventional study conducted over 6 years. Methods: Adults with moderate to severe psoriasis were enrolled. Safety was assessed by evaluating adverse events (AEs), treatment-related AEs, and serious AEs (SAEs). Effectiveness was assessed using the change in absolute Psoriasis Area and Severity Index (PASI) score, percentage of patients achieving PASI 75/90/100 and PASI ⩽2; at weeks 12 and 24. Results: Overall, 829 and 542 patients were included in the safety and effectiveness sets, respectively. AEs, treatment-related AEs, and SAEs occurred in 29.0%, 9.5%, and 4.1% of patients, with incidence rates of 39.43, 12.98, and 5.59 per 100 patient years, respectively. The absolute PASI score decreased from 16.1 ± 7.1 (baseline) to 1.6 ± 2.4 (week 24), with a similar reduction in biologic-naïve (16.4 ± 7.3 to 1.5 ± 2.2) and biologic-experienced (14.8 ± 5.9 to 2.4 ± 3.2) groups. At week 24, PASI 75/90/100 was achieved by 95.1%, 62.4%, and 24.9% of patients. At week 24, PASI 75/90 were higher in biologic-naïve (96.6%/65.8%) than biologic-experienced patients (88.3%/48.6%), whereas PASI 100 was similar in both cohorts (24.1% and 28.6%). A similar trend in PASI ⩽ 2 was observed in both cohorts. Conclusion: Secukinumab showed sustained effectiveness and favorable safety profile in adult patients with moderate to severe psoriasis in Korea.

Up-regulation of Th17 and related cytokines in Behçet's disease corresponding to disease activity.

OBJECTIVES: The IL-23/IL-17 pathway is implicated in the development of certain inflammatory diseases. The aim of the present study was to investigate the expression of Th17 and related cytokines according to clinical activity in Behçet's disease (BD). METHODS: Peripheral blood mononuclear cells (PBMCs) from eleven patients with active BD, eleven patients with inactive BD, ten patients with recurrent aphthous ulcers, and ten healthy controls were cultured and stained with the appropriate fluorescent antibodies for analysis by flow cytometry. ELISA assays were utilized to determine the concentrations of IL-17, IFN-γ, IL-23, and IL-12/23p40 in serum and culture supernatants. IL-12p35, IL-12/23p40, and IL-23p19 transcript levels in PBMCs were measured by real-time PCR. RESULTS: Significantly higher frequencies of IL-17 and IFN-γ expressing CD4(+) T cells were observed in patients with active BD compared with control groups. Similarly, levels of IL-17, IL-23, IL-12/23p40, and IFN-γ in serum and supernatants were significantly elevated in patients with BD despite the fact that IL-12p35 and IL-12/23p40 mRNA expression in PBMCs was up-regulated in the inactive BD group. In the same patient, the frequency of IL-17 expressing cells decreased when the BD disease activity was stabilised. CONCLUSIONS: The results of this study suggest that up-regulated IL-17 expression may be associated with clinical activity of BD.