Enhanced serum interferon-lambda 1/interleukin-29 levels in patients with psoriasis vulgaris

Abstract Background: Interferon (IFN)-λ1, also named Interleukin (IL)-29, is a new member of the Type III IFN or IFN-λ family. IL-29 plays an important role in the pathogenesis of many types of autoimmune and inflammatory diseases. Objective: To study the role of IL-29 in the pathogenesis of psoriasis vulgaris. Methods: The authors detected the serum levels of IL-29 in forty-one patients with psoriasis vulgaris, twenty-three patients with atopic dermatitis and thirty-eight age and gender-matched controls by sandwich Enzyme-Linked Immunosorbent Assay (ELISA). The effects of IL-29 on the expression of cytokines, such as IL-6, IL-17, IL-8, IL-4, IL10, Interferon (IFN-γ) and Tumor Necrosis Factor-α (TNF-α), in PBMCs and HaCat cells were determined by real-time quantitative PCR. Results: Our data indicated that serum IL-29 levels were significantly elevated in patients with psoriasis vulgaris when compared with atopic dermatitis patients and the control group. Moreover, Serum levels of IL-29 were closely associated with the severity of psoriasis vulgaris. Furthermore, IL-29 up-regulated the mRNA expression levels of IL-6, IL-17 and TNF-α in PBMCs from psoriasis vulgaris patients. In addition, IL-29 enhanced the IL-6 and IL-8 expression from the HaCat cells. Conclusion: This study provides the first observations on the association of IL-29 and psoriasis vulgaris and showed elevated IL-29 serum levels. The authors suggest that IL-29 may play a role in the pathogenesis of psoriasis vulgaris.

Enhanced serum interferon-lambda 1 interleukin-29 levels in patients with psoriasis vulgaris.

BACKGROUND: Interferon (IFN)-λ1, also named Interleukin (IL)-29, is a new member of the Type III IFN or IFN-λ family. IL-29 plays an important role in the pathogenesis of many types of autoimmune and inflammatory diseases. OBJECTIVE: To study the role of IL-29 in the pathogenesis of psoriasis vulgaris. METHODS: The authors detected the serum levels of IL-29 in forty-one patients with psoriasis vulgaris, twenty-three patients with atopic dermatitis and thirty-eight age and gender-matched controls by sandwich Enzyme-Linked Immunosorbent Assay (ELISA). The effects of IL-29 on the expression of cytokines, such as IL-6, IL-17, IL-8, IL-4, IL10, Interferon (IFN-γ) and Tumor Necrosis Factor-α (TNF-α), in PBMCs and HaCat cells were determined by real-time quantitative PCR. RESULTS: Our data indicated that serum IL-29 levels were significantly elevated in patients with psoriasis vulgaris when compared with atopic dermatitis patients and the control group. Moreover, Serum levels of IL-29 were closely associated with the severity of psoriasis vulgaris. Furthermore, IL-29 up-regulated the mRNA expression levels of IL-6, IL-17 and TNF-α in PBMCs from psoriasis vulgaris patients. In addition, IL-29 enhanced the IL-6 and IL-8 expression from the HaCat cells. CONCLUSION: This study provides the first observations on the association of IL-29 and psoriasis vulgaris and showed elevated IL-29 serum levels. The authors suggest that IL-29 may play a role in the pathogenesis of psoriasis vulgaris.

Interleukin-35 inhibited the production of histamine and pro-inflammatory cytokines through suppression MAPKs pathway in HMC-1 cells.

BACKGROUND: IL-35 is a newly anti-inflammatory cytokine that belongs to the IL-12 family. Mast cells, as one of the major effector cells in the immune response system, plays an important role in the pathogenesis of chronic spontaneous urticarial (CSU). Our study aims to explore the inhibited role of IL-35 in HMC-1. METHODS: The effects of IL-35 on cell proliferation, cytokine expression, and histamine release in a human mast cell line (HMC-1) were investigated by CCK8, ELISA, or RT-PCR. The phosphorylation levels of ERK1/2, p38, and JNK1/2, in PMA plus A23187 induced HMC-1 cells was detected by Western Blot. RESULTS: We found that IL-35 significantly inhibited the proliferation of HMC-1 cells stimulated by PMA and A23187. IL-35 also down-regulates the release of histamine and the mRNA expression of IL-6 and IL-17 in activated HMC-1. Furthermore, IL-35 markedly inhibited the phosphorylation levels of ERK1/2, p38, and JNK1/2, in PMA plus A23187 induced HMC-1 cells. CONCLUSIONS: This study provides the first observations on the inhibitory and anti-inflammatory effect of IL-35 in activated HMC-1 cells. We suggest that IL35 may play an inhibited role in the pathogenesis of CSU.

Secukinumab demonstrates high efficacy and a favorable safety profile over 52 weeks in Chinese patients with moderate to severe plaque psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis. METHODS: This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12. RESULTS: A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P < 0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; P < 0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period. CONCLUSION: Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03066609; https://clinicaltrials.gov/ct2/show/record/NCT03066609.

Etanercept biosimilar (recombinant human tumor necrosis factor-α receptor II: IgG Fc fusion protein) and methotrexate combination therapy in Chinese patients with moderate-to-severe plaque psoriasis: a multicentre, randomized, double-blind, placebo-controlled trial.

Etanercept biosimilar recombinant human tumour necrosis factor-α receptor II: IgG Fc fusion protein (rhTNFR-Fc, trade name Yisaipu) has shown good efficacy in the treatment of moderate-to-severe plaque psoriasis. To compare the efficacy and safety of rhTNFR-Fc plus methotrexate (MTX) and rhTNFR-Fc plus placebo in Chinese patients with moderate-to-severe plaque psoriasis. In this multicentre, randomized, placebo-controlled trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned in a 1:1 ratio to receive rhTNFR-Fc plus MTX or rhTNFR-Fc plus placebo. The primary endpoint was the proportion of patients achieving Psoriasis Area and Severity Index improvement of at least 75% (PASI 75) from baseline at week 24. Adverse events (AEs) were recorded to evaluate safety. Efficacy analysis was performed using the intent-to-treat principle. A total of 466 patients were enrolled and randomly received rhTNFR-Fc plus MTX (combination group, n = 233) or rhTNFR-Fc plus placebo (monotherapy group, n = 233). PASI 75 at week 24 was significantly higher in the combination group than in the monotherapy group (81.86% vs. 65.50%, p < 0.001). Similar results were observed in other PASI improvement scores at week 12 [PASI 75, 62.39% vs. 44.54% (p < 0.001); PASI 50, 87.17% vs. 75.55% (p = 0.001); and PASI 90, 34.07% vs. 18.78% (p < 0.001)] and week 24 [PASI 50, 92.48% vs. 85.59% (p = 0.019); and PASI 90, 64.16% vs. 42.36% (p < 0.001)]. Significantly more patients had a static Physicians' Global Assessment of clear or almost clear in the combination group than in the monotherapy group at week 12 (26.46% vs. 12.50%, p < 0.001) and week 24 (62.38% vs. 40.83%, p < 0.001). The most common AEs in the two groups were upper respiratory tract infection and abnormal liver function. The combination therapy of rhTNFR-Fc plus MTX was an effective therapy for moderate-to-severe plaque psoriasis with an acceptable safety and tolerability profile, indicating that it was feasible and well tolerated for patients.

[Expression of TWEAK and Its Receptor CD163 in Peripheral Blood of Psoriasis Vulgaris (PV)].

OBJECTIVE: To investigate serum levels and mRNA expressions of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor CD163 from the patients with psoriasis vulgaris (PV). METHODS: Peripheral blood samples were obtained from 28 patients with PV and 15 healthy control subjects. Serum levels of TWEAK and CD163 were detected by ELISA, mRNA expressions of TWEAK and CD163 in peripheral blood were analyzed by real time-PCR, and protein expressions of TWEAK and CD163 were determined by flow cytometry. RESULTS: All the 28 PV patients were in progressive stage at the beginning of this study, 10 patients then recovered in convalescent stage after treatment. Compared to healthy controls, PV patients had higher serum TWEAK levels and lower serum CD163 levels. Serum TWEAK level in progressive stage was significantly higher than that in convalescent stage. Serum CD163 level were elevated significantly in convalescent stage compared with those in progressive stage. TWEAK mRNA expression in PV patients were significantly lower than that in healthy controls, but there was no significant differences of CD163 mRNA expression. TWEAK expression in monocytes in progressive stage and convalescent stage were significantly higher than that of controls, CD163 expression in monocytes in progressive stage and convalescent stage significantly lower than that in controls. No correlations wene found between psoriasis area and severity index (PASI) score and expression of TWEAK and CD163. CONCLUSION: TWEAK/CD163 pathway may play a role in PV.

Increased serum soluble vascular endothelial cadherin levels in patients with chronic spontaneous urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common skin disease characterized by recurrent itchy wheals with or without angioedema that lasts longer than 6 weeks. Vascular endothelial (VE)-cadherin is an endothelial cell-specific adhesion molecule that plays critical roles in angiogenesis and endothelial permeability. OBJECTIVE: To investigate serum levels of soluble VE (sVE)-cadherin in patients with CSU. METHODS: Serum levels of sVE-cadherin in patients with CSU, patients with atopic dermatitis, and healthy controls were determined by enzyme-linked immunosorbent assay. In addition, changes in sVE-cadherin serum levels were compared in patients with CSU before and after H1 antihistamine treatment. Furthermore, the effects of histamine on sVE-cadherin release by HMEC-1 cells were determined by enzyme-linked immunosorbent assay. The inhibition effects of H1 antihistamine and H2 antihistamine on sVE-cadherin release, VE-cadherin phosphorylation, and VE-cadherin disruption were evaluated in histamine-treated HMEC-1 cells by western blot and immunofluorescence. RESULTS: Serum levels of sVE-cadherin in patients with CSU were significantly higher than those in patients with atopic dermatitis and healthy controls. Serum sVE-cadherin levels in patients with CSU were correlated with the severity of CSU according to Urticaria Activity Scores. Furthermore, serum sVE-cadherin levels in patients with CSU at pretreatment decreased after H1 antihistamine treatment. In addition, histamine markedly induced sVE-cadherin release in HMEC-1 cells. Moreover, H1 antihistamine, but not H2 antihistamine, significantly inhibited sVE-cadherin release in histamine-treated HMEC-1 cells. Western blot data showed that histamine induced phosphorylation of VE-cadherin in HMEC-1 cells, which was blocked by H1 antihistamine. CONCLUSION: The present data showed serum levels of sVE-cadherin are increased in patients with CSU. Histamine-induced sVE-cadherin release from endothelial cells could play a role in the pathogenesis of CSU.

Involvement of high mobility group box-1 in imiquimod-induced psoriasis-like mice model.

In the previous work, we have indicated that HMGB1, a pro-inflammatory cytokine, is closely associated with the pathogenesis of psoriasis. To further clarify the role of HMGB1 in the pathogenesis of psoriasis, we investigated the direct function of HMGB1 application and HMGB1 blockade in imiquimod (IMQ)-induced psoriatic mouse model in this study. Mice were treated with imiquimod (IMQ) to induce psoriasis-like inflammation, and consecutively injected with recombinant HMGB1 or phosphate-buffered saline (PBS) i.d. Abundant cytoplasmic expression of HMGB1 was observed in lesional skin from IMQ-treated skin. The injection of HMGB1 into the IMQ-treated skin further aggravated the psoriasis-like disease, enhanced the infiltration of CD3+ T cells, myeloperoxidase+ neutrophils and CD11c+ dendritic cells, increased the number of γδ T cells, and upregulated the mRNA expression of interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IL-17 compared with the PBS injection. Finally, by using anti-HMGB1 monoclonal antibody or HMGB1 inhibitor glycyrrhizin, we indicated that HMGB1 blockade reduced the number of γδ T cells, suppressed the mRNA expression of IL-6, TNF-α, IFN-γ and IL-17, and moderated clinical and histological evolvement in the IMQ-treated skin. Our data suggest that HMGB1 may act as a pro-inflammatory cytokine, and contribute to the development of IMQ-induced psoriasis-like inflammation. HMGB1 blockade may represent a new direction in the suppression of psoriasis.

Clinical Features of Adult/Adolescent Atopic Dermatitis and Chinese Criteria for Atopic Dermatitis.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin disease characterized by chronic recurrent dermatitis with profound itching. Most patients have personal and/or family history of atopic diseases. Several criteria have been proposed for the diagnosis of AD. Although the clinical features of childhood AD have been widely studied, there has been less large-scale study on adult/adolescent AD. The aim of this study was to investigate the clinical features of adult/adolescent patients with chronic symmetrical eczema/AD and to propose Chinese diagnostic criteria for adult/adolescent AD. METHODS: A hospital-based study was performed. Forty-two dermatological centers participated in this study. Adult and adolescent patients (12 years and over) with chronic symmetrical eczema or AD were included in this study. Questionnaires were completed by both patients and investigators. The valid questionnaires were analyzed using EpiData 3.1 and SPSS 17.0 software. RESULTS: A total of 2662 valid questionnaires were collected (1369 male and 1293 female). Of all 2662 patients, 2062 (77.5%) patients had the disease after 12 years old, while only 600 (22.5%) patients had the disease before 12 years old, suggesting late-onset eczema/AD is common. Two thousand one hundred and thirty-nine (80.4%) patients had the disease for more than 6 months. One thousand one hundred and forty-four (43.0%) patients had a personal and/or family history of atopic diseases. One thousand five hundred and forty-eight (58.2%) patients had an elevated total serum IgE and/or eosinophilia and/or positive allergen-specific IgE. Based on these clinical and laboratory features, we proposed Chinese criteria for adult/adolescent AD. Of all 2662 patients, 60.3% were satisfied with our criteria, while only 48.2% satisfied with Hanifin Rajka criteria and 32.7% satisfied with Williams criteria, suggesting a good sensitivity of our criteria in adult/adolescent AD patients. CONCLUSION: Late-onset of eczema or AD is common. The clinical manifestations of AD are heterogeneous. We have proposed Chinese diagnostic criteria for adolescent and adult AD, which are simple and sensitive for diagnosis of adult/adolescent AD.

Monoammonium glycyrrhizate suppresses tumor necrosis factor-α induced chemokine production in HMEC-1 cells, possibly by blocking the translocation of nuclear factor-κB into the nucleus.

Monoammonim glycyrrhizate (MAG) derived from licorice has been shown to have anti-inflammatory properties. Chemokines are vital inflammatory mediators that are involved with endothelial damage from leukocyte infiltrates in various inflammatory skin diseases. In this study, we investigated the anti-inflammatory effects and mechanisms of MAG on tumor necrosis factor-α (TNF-α) induced chemokine production in a human dermal microvascular endothelial cell line (HMEC-1). HMEC-1 cells were treated with TNF-α, with or without MAG. The results showed that MAG suppressed TNF-α-induced chemokine (including CXCL8, CX3CL1, and CXCL16) mRNA expression in HMEC-1 cells, in a dose-dependent manner, and reduced the secretion of these chemokines in culture supernatant. Moreover, endothelial activation in the presence of MAG blocked the chemotactic activities of TNF-α-stimulated HMEC-1 cell supernatant on the migration of primary neutrophils and primary monocytes. In addition, Western blot and immunofluorescence data revealed that MAG inhibited nuclear translocation of nuclear factor-κB p65 (NF-κB p65). It is the first report to demonstrate that MAG suppresses TNF-α-induced chemokine production in HMEC-1 cells, and that the mechanism may be inhibiting the translocation of NF-κB p65 into the nucleus to prevent the starting of inflammatory signaling pathway. Our results revealed that MAG is a potential anti-inflammatory agent capable of improving inflammatory skin diseases.

Elevated serum levels of visfatin in patients with henoch-schönlein purpura.

BACKGROUND: Henoch-Schönlein purpura (HSP) is an immune complex-mediated disease predominantly characterized by the deposition of circulating immune complexes containing immunoglobulin A (IgA) on the walls of small vessels. Although the pathogenesis of HSP is not yet fully understood, some researchers proposed that B-cell activation might play a critical role in the development of this disease. OBJECTIVE: To investigate the serum levels of visfatin (pre-B-cell colony-enhancing factor), B-cell-activating factor (BAFF), and CXCL13, and to analyze their association with disease severity. METHODS: The serum levels of visfatin, BAFF, and CXCL13 were measured by using a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) in 43 patients with HSP and 45 controls. The serum levels of IgA anticardiolipin antibodies (ACA) were detected by using a double-antigen sandwich ELISA. RESULTS: Levels of visfatin but not BAFF and CXCL13 were significantly elevated in the sera of patients with HSP in the acute stage, and restored to normal levels in the convalescent stage. Furthermore, serum levels of visfatin were significantly higher in patients with HSP having renal involvement than in those without renal involvement. Serum levels of visfatin were correlated with the severity of HSP and serum concentration of ACA-IgA. CONCLUSION: We show for the first time that the serum levels of visfatin are abnormally elevated in patients with HSP. Visfatin may be associated with the pathogenesis of HSP.

Increased serum HMGB1 levels in patients with Henoch-Schönlein purpura.

High-mobility group box-1 (HMGB1) has been implicated as a pro-inflammatory cytokine in the pathogenesis of various inflammatory and autoimmune diseases. However, information about HMGB1 in Henoch-Schönlein purpura (HSP) is still unclear. Herein, we investigated the role of HMGB1 in patients with HSP and the pro-inflammatory effects of HMGB1 on human dermal microvascular endothelial cell line (HMEC-1). Serum HMGB1 levels in patients with HSP together with patients with allergic vasculitis (AV) and urticarial vasculitis (UV) were detected by enzyme-linked immunosorbent assay (ELISA). HMEC-1 cells were treated with HMGB1 at concentrations ranging from 4 ng/ml to 100 ng/ml. Serum HMGB1 levels were significantly increased in patients with HSP, AV and UV, when compared with those in control group. Moreover, abundant cytoplasmic expression of HMGB1 was observed in endothelial cells in lesional skin of HSP patients. Using membrane cytokine antibody array, we indicate that HMGB1 markedly induced TNF-α and IL-6 release in cultured supernatant. Furthermore, by real-time quantitative PCR and ELISA, the effects of HMGB1 on these cytokines production in HMEC-1 cells were established. Finally, Western blot data revealed that HMGB1 can induce phosphorylation of inhibitor of κB-α (IκBα) and the nuclear translocation of nuclear factor-κB (NF-κB) p65 in HMEC-1 cells. In conclusion, this study provides first observations on the association of HMGB1 with HSP. We suggest that HMGB1 may be an important mediator of endothelial inflammation through the induction of TNF-α and IL-6 production and may play a crucial role in the pathogenesis of HSP.

Increased serum levels of soluble vascular endothelial-cadherin in patients with systemic vasculitis.

Henoch-Schönlein purpura (HSP) is a commonest systemic vasculitis (SV) in childhood characterized by an inflammatory reaction directed at vessels. Endothelial damage and perivascular leukocyte infiltrates are vital in the development of HSP. Vascular endothelial (VE)-cadherin is an endothelial cell-specific adhesion molecule, which plays critical roles in angiogenesis and endothelial integrity. Herein, we investigated the serum levels of soluble VE-cadherin (sVE-cadherin) in patients with HSP and other forms of SV. The serum levels of sVE-cadherin in 30 patients with HSP, together with patients with urticarial vasculitis, allergic vasculitis, Behcet disease, psoriasis vulgaris (PV) and atopic dermatitis (AD) and 26 health controls were measured by enzyme-linked immunosorbent assay. Serum levels of sVE-cadherin were significantly increased in patients with HSP in acute stage and patients with other forms of SV but not in patients with PV or AD. Moreover, Serum sVE-cadherin levels in HSP patients were correlated with the severity of this disease and serum concentrations of IgA anticardiolipin antibodies and vascular endothelial growth factor. Taken together, we show firstly that serum sVE-cadherin is abnormally increased in HSP patients. Increased serum levels of sVE-cadherin might be a novel biomarker for evaluating the severity of HSP and useful for identifying the presence of SV in inflammatory skin conditions.

Paeoniflorin suppresses vascular damage and the expression of E-selectin and ICAM-1 in a mouse model of cutaneous Arthus reaction.

Paeoniflorin (PF) extracted from the root of Paeonia lactiflora pall, displays anti-inflammation properties in several animal models. Adhesion molecules are important for the recruitment of leucocyte to the vessel wall and involved in the pathogenesis of various autoimmune and inflammatory diseases. Herein, we investigate the effects of PF on adhesion molecule expression in a mouse model of cutaneous Arthus reaction and cultured human dermal microvascular endothelial cells (HDMECs). We showed that PF significantly ameliorated the immune complex (IC) induced vascular damage, leucocyte infiltrates and adhesion molecules expression. Furthermore, PF markedly blocked tumor necrosis factor-α (TNF-α)-induced E-selectin and intercellular adhesion molecule-1 (ICAM-1) expression in HDMECs at both mRNA and protein levels. PF also suppressed TNF-α-induced adhesion of polymorphonuclear leucocytes (PMNs) to HDMECs. Finally, western blot data revealed that PF can inhibit the phosphorylation of p38, JNK in TNF-α-treated HDMECs. These data suggest that PF, as an anti-inflammatory agent, can downregulate adhesion molecules expression. PF may be a candidate medicine for the treatment of IC-induced inflammatory response.

TWEAK enhances E-selectin and ICAM-1 expression, and may contribute to the development of cutaneous vasculitis.

Our previous work indicated that TWEAK is associated with various types of cutaneous vasculitis (CV). Herein, we investigate the effects of TWEAK on vascular injury and adhesion molecule expression in CV mice. We showed that TWEAK priming in mice induced a local CV. Furthermore, TWEAK priming also increased the extravasation of FITC-BSA, myeloperoxidase activity and the expression of E-selectin and ICAM-1. Conversely, TWEAK blockade ameliorated the LPS-induced vascular damage, leukocyte infiltrates and adhesion molecules expression in LPS-induced CV. In addition, TWEAK treatment of HDMECs up-regulated E-selectin and ICAM-1 expression at both mRNA and protein levels. TWEAK also enhanced the adhesion of PMNs to HDMECs. Finally, western blot data revealed that TWEAK can induce phosphorylation of p38, JNK and ERK in HDMECs. These data suggest that TWEAK acted as an inducer of E-selectin and ICAM-1 expression in CV mice and HDMECs, may contribute to the development of CV.

Increased HMGB1 serum levels and altered HMGB1 expression in patients with psoriasis vulgaris.

High mobility group box-1 (HMGB1) has been implicated as a pro-inflammatory cytokine in the pathogenesis of various inflammatory and autoimmune diseases. However, information about HMGB1 in inflammatory skin diseases is unknown. Herein, we investigated the serum HMGB1 levels and tissue HMGB1 expression in patients with psoriasis vulgaris (PV) and atopic dermatitis (AD). Serum levels of HMGB1 in patients with PV and AD were detected by enzyme-linked immunosorbent assay (ELISA). The expression of HMGB1 in lesional skin was evaluated by immunohistochemistry and immunofluorescence. Protein levels of HMGB1 in the nuclear fraction and cytoplasmic fraction were determined by western blot. Serum levels of HMGB1 in patients with PV but not AD were significantly higher than those in nornal controls. Moreover, serum HMGB1 levels were correlated with the severity of PV according to PASI socres. Furthermore, by immunohistochemistry and immunofluorescence, we showed that the expression of HMGB1 in normal skin was almost completely restricted to the nucleus. However, abundant cytoplasmic expression of HMGB1 was observed in the epidermis in lesional skin of PV patients. In addition, western blot data indicated that HMGB1 expression was in the nucleus protein and was absent in the cytoplasm protein in control group. In contrast, HMGB1 expression in the cytoplasmic fraction was detectable in AD patients and more distinct in PV patients. Taken together, this study provides first observations on the association of HMGB1 with PV, and showed the elevated HMGB1 serum levels and altered HMGB1 distribution in lesional skin in patients with PV. We suggest that HMGB1 might be involved in the pathogenesis of PV.

Elevated serum interleukin-33 levels in patients with Henoch-Schönlein purpura.

Henoch-Schönlein purpura (HSP) is the most common systemic vasculitis and is known as an immunoglobulin (Ig) A related immune complex-mediated disease. However, the molecular mechanisms in the development of HSP are not yet fully understood. Herein, we investigated the serum levels of Interleukin (IL)-33 and soluble ST2 (sST2) in HSP patients and their association with disease severity and IgA autoantibodies production. The serum levels of IL-33 and sST2 were measured by double antibody sandwich enzyme-linked immunosorbent assay (ELISA) in the serum of 33 patients with HSP and 22 controls. Serum levels of IgA anti-endothelial cell antibodies (AECA) and IgA anticardiolipin antibodies (ACA) in HSP patients were detected by double antigen sandwich ELISA. Our results indicated that serum levels of IL-33 but not sST2 were significantly elevated in patients with HSP in acute stage and restored to normal levels in convalescent stage. Moreover, serum IL-33 levels were correlated with the severity of HSP and serum concentrations of AECA-IgA and ACA-IgA. Taken together, we show firstly that serum IL-33 is abnormally elevated in HSP patients. IL-33 might be associated with the IgA autoantibodies production in the pathogenesis of HSP.

Treatment of psoriasis with recombinant human LFA3-antibody fusion protein: a multi-center, randomized, double-blind trial in a Chinese population.

To evaluate clinical efficacy and safety of injectable recombinant human LFA3-antibody fusion protein (rhLFA3-IgFP), a multi-center, randomized, double-blind, double-dummy, parallel-controlled clinical trial was performed in 212 cases of moderate to severe psoriasis. Intramuscular injection of rhLFA3-IgFP (15 mg/week) and oral administration of blank dummy methotrexate at the dose of 7.5 mg/week was performed in the patients in the experimental group, and control patients were orally administered with methotrexate at the dose of 7.5 mg/week and intramuscularly injected with the blank dummy rhLFA3-IgFP (15 mg/week). PASI was determined prior to and at 2, 4, 6, 8, 12, 16, 20 weeks after the treatment. The efficacy evaluation was carried out on 192 patients, and no significant differences were found in PASI50, PASI75 & PASI90 between the two groups after twelve weeks' treatment (p>0.05). After discontinuation, PASI scores continued to decrease drastically in the experiment group, whereas they increased in the control group. At 8 weeks after discontinuation, PASI scores were decreased by 62.32% (p<0.05) and 52.67% (p<0.05) in the experimental and control groups, respectively. No serious adverse reactions were observed. In conclusion, the results of our investigation demonstrated that rhLFA3-IgFP was an effective therapy for chronic plaque psoriasis with lasting action and low incidence of adverse reactions.