Serum LL-37 Research Articles

Circulating Antimicrobial Peptide LL-37 Status in Type 1 Diabetes Mellitus and its Relation with Glycemic Control

Antimicrobial-peptides are important molecules of constitutive innate immunity. Though patients with diabetes mellitus are generally prone to infections, there is limited information on their antimicrobialpeptide status. We assessed the circulating LL-37 antimicrobial peptide (also referred as cathelicidin) levels in patients with type 1 diabetes mellitus and its relation with their glycemic status. The LL-37 mRNA expression was assessed in the peripheral blood mononuclear cells (PBMC) by quantitative RT-PCR usingβ-actin and cytochrome-C1 as the reference genes in 154 subjects (Type 1 diabetes, n=111 and healthy subjects, n=43). Serum LL-37 was quantified using sandwich-ELISA. Average HbA1c over last 2 years and current HbA1c were used to determine long-term and short-term glycemic status. LL-37 mRNA expression and serum LL-37 levels were correlated with the glycemic status. The LL-37 mRNA copies were comparable between type 1 diabetes and healthy subjects [median (IQR) = 6.7 (1.8–15.28) vs. 7.2 (2.23–21.86), respectively, P = 0.42]. There was no significant difference in serum LL-37 levels between the two groups [median (IQR) = 3.9 (2.88–7.52) vs. 5.0 (3.19–9.05) ng/ml, respectively, P = 0.52]. The LL-37 mRNA and its protein concentration showed no significant correlation with the average or current HbA1c values. The constitutive circulating antimicrobial peptide LL-37 status is not significantly altered in patients with type 1 diabetes mellitus and also not affected by their glycemic status.

Cathelicidin (LL-37) and its correlation with pro-oxidant, antioxidant balance and disease activity in systemic lupus erythematosus: a cross-sectional human study

Background Cathelicidin (LL-37), an endogenous antimicrobial peptide, has recently been involved in the pathogenesis of autoimmune diseases. To assess whether LL-37 reflects disease activity, we measured serum levels of it in systemic lupus erythematosus (SLE) patients with active and inactive disease compared to healthy controls. LL-37 was also compared between new and old cases. Moreover, the correlation of LL-37 and pro-oxidant, antioxidant balance (PAB) was measured. Methods The study population consisted of 50 SLE patients and 28 healthy controls. Of those, 39 patients had active and 11 patients had inactive disease. Serum levels of LL-37 were measured by ELISA and PAB values by a special method. Results There was no difference in levels of LL-37 between patients and healthy controls (50.9 ± 20.8 vs. 67.7 ± 43.3 ng/ml, P = 0.31). LL-37 did not correlate with SLEDAI and its items in total patients. LL-37 had a positive correlation with SLEDAI in active patients ( P = 0.01, r = 0.4). In active patients (78% of patients), multivariate regression analysis showed significant negative correlation between LL-37 and C3 ( P = 0.01, standardized beta -0.50). No difference was found in levels of PAB between patients and controls (90.4 ± 34.1 vs. 86.9 ± 25.6 HK, P = 0.4).There was no difference in the levels of PAB between patients with active and inactive disease (93.2 ± 34.1 vs. 80.2 ± 33.7 HK, P = 0.27). No correlation was found between levels of PAB and SLEDAI items and total score. However, a positive correlation between the levels of LL-37 and PAB in SLE patients was found ( r = 0.3, P < 0.01). Conclusion Based on this study, serum LL-37 and PAB did not increase in lupus compared with healthy individuals. LL-37 serum values rose in parallel with SLEDAI in active disease. Positive correlation between serum PAB and LL-37 could be a great achievement of this study that may suggest the role of antioxidants in controlling NETosis.

Implication of vitamin D-associated factors in patients with non-tuberculous mycobacterial lung disease.

Little information is available regarding vitamin D-associated factors in patients with non-tuberculous mycobacteria (NTM) lung disease. To determine the association between vitamin D-related factors and susceptibility to NTM lung disease. The relative gene expression levels of cathelicidin (CAMP), defensin (DEFB4), vitamin D receptor (VDR) and 1-hydroxylase (CYP27B1), as well as the serum levels of 25-hydroxyvitamin D (25[OH]D), cathelicidin (LL-37), defensin (hBD-2) and vitamin D-binding protein (DBP) from 82 patients with NTM lung disease and 28 control subjects were analysed. Gene expression of CAMP and DEFB4 was significantly higher, and gene expression of VDR and CYP27B1 was significantly lower, in NTM patients than controls. Serum LL-37 and hBD-2 levels were not significantly different between NTM patients and controls; however, the serum DBP level was higher in NTM patients than controls. The serum vitamin D status of patients did not correlate with serum LL-37, hBD-2, or DBP concentration or gene expression of CAMP, DEFB4, VDR or CYP27B1. A higher level of gene expression for antimicrobial peptide is more likely to be associated with NTM lung disease than serum vitamin D status.

A potential contribution of antimicrobial peptide LL-37 to tissue fibrosis and vasculopathy in systemic sclerosis.

LL-37 is an antimicrobial peptide with pleiotropic effects on the immune system, angiogenesis and tissue remodelling. These are cardinal pathological events in systemic sclerosis (SSc). To elucidate the potential role of LL-37 in SSc. The expression of target molecules was evaluated by immunostaining and quantitative reverse-transcription real-time polymerase chain reaction in human and murine skin. The mechanisms regulating LL-37 expression in endothelial cells were examined by gene silencing and chromatin immunoprecipitation. Serum LL-37 levels were determined by enzyme-linked immunosorbent assay. In SSc lesional skin, LL-37 expression was increased in dermal fibroblasts, perivascular inflammatory cells, keratinocytes and, particularly, dermal small vessels. Expression positively correlated with interferon-α expression, possibly reflecting LL-37-dependent induction of interferon-α. In SSc animal models, bleomycin-treated skin exhibited the expression pattern of CRAMP, a murine homologue of LL-37, similar to that of LL-37 in SSc lesional skin. Furthermore, Fli1+/- mice showed upregulated expression of CRAMP in dermal small vessels. Fli1 binding to the CAMP (LL-37 gene) promoter and Fli1 deficiency-dependent induction of LL-37 were also confirmed in human dermal microvascular endothelial cells. In the analysis of sera, patients with SSc had serum LL-37 levels significantly higher than in healthy controls. Furthermore, serum LL-37 levels positively correlated with skin score and the activity of alveolitis and were significantly elevated in patients with digital ulcers compared with those without. LL-37 upregulation, induced by Fli1 deficiency at least in endothelial cells, potentially contributes to the development of skin sclerosis, interstitial lung disease and digital ulcers in SSc.

Pathogenesis of antimicrobial peptides LL-37 and CpG-ODN in ANCA associated vasculitis.

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) are a group of systemic autoimmune disorders characterized by necrotizing inflammation of small- to medium-sized blood vessels. The pathogenesis of patients with AAV are still in investigation. In this study, we explored the involvement of LL-37 and nucleic acids in AAV. 15 patients with AAV diagnosed according to the Chapel Hill definition between October 2014 and July 2015 in the department of Nephrology of Huangdao, affiliated Hospital of Qingdao University were enrolled. 16 patients with chronic bronchitis (CB) were selected as disease control group. 15 cases of healthy people from Medical Healthy Center were as healthy control group. Peripheral blood mononuclear cells (PBMCs) were collected from these groups and stimulated by LL-37and (or) two types ofCpG-ODN for 7days. The IFN-α and ANCA in vitro were measured by ELISA. The serum IFN-α, LL-37 and ANCA were measured also. The serum level of IFN-α in AAV group was much higher than that in CB group (692.13±407.28 vs 397.07±211.62pg/ml, p=0.019), and that in healthy control group (692.13±407.28 vs 251.54±190.46pg/ml, p<0.001). The serum level of LL-37 in AAV group was much higher than that in CB group (101.18±66.59 vs 40.23±13.51ng/ml, p<0.001, and that in healthy control group (101.18±66.59 vs 27.80±16.86ng/ml, p<0.001). Also the level of IFN-α showed a significant positive relationship with ANCA in AAV group both in serum and in supernatant of cultured PBMCs stimulated by LL-37 and (or) CpG-ODN (r=0.783, p=0.001; r=0.575, p=0.064; r=0.649, p=0.031; r=0.806, p=0.003). In patients with AAV, the supernatant levels of IFN-α in cultured PBMCs stimulated by LL-37 and (or) CpG-ODN were higher than that without stimulating factor (p<0.05). The supernatant level of IFN-α in cultured PBMC stimulated by LL-37 alone was lower than that stimulated by CpGA alone (699.57±476.26 vs 2342.63±2025.11pg/ml, p=0.001). But the supernatant level of IFN-α in cultured PBMCs stimulated by LL-37 alone was higher than in that stimulated by CpGB alone (699.57±476.26 vs 153.35±78.08pg/ml, p<0.001). The supernatant level of IFN-α in cultured PBMCs stimulated by both LL-37 and CpG-ODN was higher than that stimulated by LL-37 or CpG-ODN alone (2550.57±2217.41 vs 699.57±476.26pg/ml, p=0.003; 2550.57±2217.41 vs 153.35±78.08pg/ml, p=0.001; 2660.95±391.31 vs 699.57±476.26pg/ml, p<0.001; 2660.95±391.31 vs 153.35±78.08pg/ml, p<0.001). Either it is stimulated by LL-37 or CpG-ODN or both, the supernatant level of IFN-α in cultured PBMCs in AAV patients wasthe highest, that in healthy controls was the lowest. Either stimulated by LL-37 or CPG-ODN, or both, the levels of ANCA production in vitro in AAV groups were statistically significantly higher than those in CB group and healthy control group. There were higherserum levels of LL-37and IFN-α in patients with AAV. IFN-α could reach a higher level stimulated by LL-37 and nucleic acidsboth of which are related to infection. Patients with AAV have ANCA-producing B lymphocytes in the circulation even in remission stage. Infections could induce the relapse of AAV.

Cathelicidin (LL-37) and human β2-defensin levels of children with post-infectious bronchiolitis obliterans.

The antimicrobial peptides (AMPs) human β-defensins and cathelicidin (LL-37) are key factors in innate and adaptive immune responses of the respiratory tract and play an important role in many respiratory diseases. No data are available in the literature about the levels of these AMPs in paediatric patients with post-infectious bronchiolitis obliterans (BO). This study aimed to determine human β-defensin 2 (hBD2) and LL-37 levels and compare between post-infectious BO patients and the control group. The patients diagnosed with post-infectious BO between September 2012 and 2013 and age- and-gender matched healthy controls were enrolled in this multi-center study. Serum hBD2 and LL37 levels were determined with the enzyme-linked immunosorbent assay method. Sixty-three post-infectious BO patients and 65 healthy children (median age 73 ± 55 and 78.74 ± 36.32 months, respectively) were enrolled in the study. The mean of hBD2 levels in patients and the control group were 1.06 ± 0.24 and 0.67 ± 0.72 ng/mL, respectively (P < 0.001). The mean of LL-37 levels in patients and the control group were 72.13 ± 29.06 and 50.10 ± 21.98 ng/mL, respectively (P < 0.001). No correlation was found between these AMPs levels and chronological age, age at the time of diagnosis, gender, Z-scores of weight and length, hospitalization numbers, the disease history before diagnosis and 25-OH D vitamin levels. This is the first study to demonstrate the higher levels of serum hBD2 and LL-37 levels in paediatric post-infectious BO patients. These AMPs may have important roles in the immune systems and pathogenesis of these patients.

Decrease of LL-37 in systemic sclerosis: a new marker for interstitial lung disease?

Interstitial lung disease (ILD) is the leading cause of systemic sclerosis (SSc) related morbidity and mortality. LL-37 peptide is the only cathelicidin of the human antimicrobial peptide family with antimicrobial effects and immunomodulatory activity. LL-37 has anti-fibrotic effects and anti-apoptotic effects on SSc dermal fibroblasts. The aim of the study was to investigate the circulating levels of LL-37 in SSc patients and its association with clinical, laboratory, and instrumental parameters. Fifty-eight SSc patients (30 with and 28 without pulmonary involvement) and 28 healthy controls were enrolled in the study. Pulmonary involvement was defined when ILD was found at HRCT (ground glass, reticular, and honeycombing pattern). Circulating LL-37 levels were measured with ELISA test. In SSc patients with ILD serum, LL-37 concentrations were remarkably lower (1.36 mg/ml) than those in SSc patients without ILD (4.62 ng/ml, p = 0.035) and controls (5.53 ng/ml, p = 0.009). In SSc patients without ILD, serum LL-37 levels were not different from controls (p = 0.812). No significant association or correlation was found between LL-37 levels and any other clinical, serological, or instrumental features. Serum LL-37 levels are significantly lower in patients with SSc ILD. Our results may suggest that lower LL-37 levels may be associated with the development of ILD. Whether circulating levels of LL-37 might be used as an indirect marker of ILD remains to be determined in larger SSc cohorts.

Vitamin D Status and Its Association with the SCORAD Score and Serum LL-37 Level in Korean Adults and Children with Atopic Dermatitis.

BackgroundVitamin D insufficiency could be associated with the prevalence of atopic dermatitis (AD).ObjectiveTo examine vitamin D status and the relations between serum 25-hydroxyvitamin D levels, SCORAD score, serum LL-37 level, and body mass index (BMI) in Korean AD patients, and to explore whether these associations differ between adults and children.MethodsSerum 25-hydroxyvitamin D levels, serum LL-37, and clinical features were analyzed in a total of 72 Korean patients with AD (39 adults and 33 children) and 140 healthy control subjects (70 adults and 70 children).ResultsSerum 25-hydroxyvitamin D levels were significantly reduced in children with AD (15.06±4.64 ng/ml) compared with normal children in the control group (16.25±6.60 ng/ml) (p=0.036). Significant inverse correlations were found between BMI and 25-hydroxyvitamin D level (r=-0.315, p=0.007) and between the SCORAD score and serum LL-37 level (r=-0.3, p=0.011) in the total AD patients.ConclusionThe results showed that serum vitamin D levels were lower in children with AD than in healthy children; however, the same relation was not observed between adults with AD and healthy adults. Serum 25-hydroxyvitamin D concentration was not significantly correlated with AD severity or serum LL-37 levels in our study population.

No evidence of pathogenic involvement of cathelicidins in patient cohorts and mouse models of lupus and arthritis.

Apart from their role in the immune defence against pathogens evidence of a role of antimicrobial peptides (AMPs) in autoimmune diseases has accumulated in the past years. The aim of this project was to examine the functional impact of the human cathelicidin LL-37 and the mouse cathelicidin-related AMP (CRAMP) on the pathogenesis of lupus and arthritis. Serum LL-37 and anti-LL-37 levels were measured by ELISA in healthy donors and patients with Systemic Lupus Erythematosus (SLE) and Rheumatoid arthritis (RA). Pristane-induced lupus was induced in female wild type (WT) and cathelicidin-deficient (CRAMP−/−) mice. Serum levels of anti-Sm/RNP, anti-dsDNA, and anti-histone were determined via ELISA, cytokines in sera and peritoneal lavages were measured via Multiplex. Expression of Interferon I stimulated genes (ISG) was determined by real-time PCR. Collagen-induced arthritis (CIA) was induced in male WT and CRAMP−/− mice and arthritis severity was visually scored and analysed histomorphometrically by OsteoMeasure software. Serum levels of anti-LL-37 were higher in SLE-patients compared to healthy donors or patients with RA. However, no correlation to markers of disease activity or organ involvement was observed. No significant differences of autoantibody or cytokine/chemokine levels, or of expression of ISGs were observed between WT and CRAMP−/− mice after pristane-injection. Furthermore, lung and kidney pathology did not differ in the absence of CRAMP. Incidence and severity of CIA and histological parameters (inflammation, cartilage degradation, and bone erosion) were not different in WT and CRAMP−/− mice. Although cathelicidins are upregulated in mouse models of lupus and arthritis, cathelicidin-deficiency did not persistently affect the diseases. Also in patients with SLE, autoantibodies against cathelicidins did not correlate with disease manifestation. Reactivity against cathelicidins in lupus and arthritis could thus be an epiphenomenon caused by extensive overexpression in blood and affected tissues. In addition, other cationic AMPs could functionally compensate for the deficiency of cathelicidins.

AB0042 Human Host Defense Peptide Cathelicidin (LL37) Serum Levels Are Increased in Anti-Cyclical Citrullinated Peptide Positive Patients with Recent Onset Inflammatory Arthritis

BackgroundDisruption of normal innate immune responses to pathogens and toxins may contribute to Rheumatoid Arthritis (RA) pathogenesis. The host defense peptide cathelicidin (LL37) is produced as part of the innate...

Serum antimicrobial peptides in patients with familial Mediterranean fever

Familial Mediterranean fever (FMF) is characterized by recurrent inflammation of serosal and synovial membranes. Despite the fact that it is a genetic disease, environmental factors, including infections, are shown to be triggering factors associated with the precipitation of attacks in FMF. Antimicrobial peptides (AMPs) are components of innate immunity which exert antimicrobial activity against many microorganisms. Human AMPs; cathelicidin (LL37) and defensins have immunomodulatory properties and are involved in the pathogenesis of many inflammatory disorders. Hence, we investigated serum AMPs in 23 newly diagnosed FMF patients. Blood samples were obtained at baseline, 6 months after initiation of colchicine and during an attack. Twenty-four healthy individuals constituted the control group. The concentrations of LL37, alpha-1, beta-1 and beta-2 defensins were determined by ELISA. Serum AMPs did not change during attacks and did not correlate with acute phase reactants. However, serum LL37 and defensins were found to be remarkably higher in FMF patients compared to healthy individuals both at baseline and 6 months after initiation of colchicine therapy which suggest that AMPs might have a role in the pathogenesis of FMF.

A3.7 No evidence of cathelicidin being involved in the pathogenesis of lupus and arthritis

Background and ObjectivesAntimicrobial peptides (AMPs) such as cathelicidins have a well known role in the immune defence against pathogens. In the last years a contributory impact of AMPs was also...

Effect of Narrowband Ultraviolet B Therapy on Serum Vitamin D and Cathelicidin (LL-37) in Patients with Chronic Plaque Psoriasis

Narrowband ultraviolet B (NB-UVB) has been widely used in the treatment of psoriasis. It has been shown that vitamin D is a major regulator of the expression of human antimicrobial peptide cathelicidin LL-37, which has a critical role in inflammatory cascade in psoriasis. To evaluate the effect of NB-UVB therapy on serum levels of cathelicidin LL-37 and 25-hydroxyvitamin D [25(OH)D] in psoriasis patients. Ninety-three psoriasis patients and 50 controls were included in the study. For psoriasis patients, serum levels of 25(OH)D and cathelicidin LL-37 were estimated before and after NB-UVB therapy. Before treatment, serum 25(OH)D levels were significantly lower in psoriasis patients (31.5 ± 14.41 nmol/L) compared to controls (53.5 ± 19.6 nmol/L), p = .015. In contrast, serum LL-37 was significantly higher in psoriasis patients (13.24 ± 3.2 ng/mL) than in controls (7.92 ± 5.33 ng/mL), p < .001. After NB-UVB treatment, there was a highly significant elevation of serum 25(OH)D to reach 56.85 ± 5.2 nmol/L (p < .001) and further elevation of serum LL-37 to reach 29.4 ± 4.2 (p = .02). The elevation of serum 25(OH)D and cathelicidin LL-37 could be an additional possible mechanism of action of NB-UVB therapy in the treatment of psoriasis.

The influence of cathelicidin LL37 in human anti-neutrophils cytoplasmic antibody (ANCA)-associated vasculitis

IntroductionAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterised by the autoinflammation and necrosis of blood vessel walls. The renal involvement is commonly characterised by a pauci-immune crescentic glomerulonephritis (PiCGN) with a very rapid decline in renal function. Cathelicidin LL37, an endogenous antimicrobial peptide, has recently been implicated in the pathogenesis of autoimmune diseases. To assess whether serum LL37 reflects renal crescentic formation, we measured the serum levels of LL37 in AAV patients with and without crescentic glomerulonephritis (crescentic GN) as compared to healthy controls (HCs). We also analysed the correlation of the serum levels of LL37 and interferon-α (IFN-α) with the clinical characteristics of the patients.MethodsThe study population consisted of 85 AAV patients and 51 HCs. In 40 ANCA-positive patients, a parallel analysis was performed, including the assessment of LL37 and IFN-α levels in the serum and renal biopsies. Of those studied, 15 AAV patients had biopsy-proven crescentic GN, and 25 AAV patients lacked crescent formation. The serum levels of cathelicidin LL37 and IFN-α were both measured by ELISA, and the clinical and serological parameters were assessed according to routine procedures. Immunofluorescence staining was performed on frozen sections of kidney needle biopsies from AAV patients with crescentic GN.ResultsThe serum levels of LL37 and IFN-α were significantly increased in AAV patients with crescentic GN compared to AAV patients without crescentic formation and HCs, and patients with high LL37 and IFN-α levels were more likely to be in the crescentic GN group. The LL37 levels were positively correlated with the IFN-α levels, and both LL37 and IFN-α levels showed a positive correlation with serum creatinine and no correlation with complement C3. The renal tissue of crescentic GN patients showed expression of LL37 and IFN-α at the Bowman’s capsule and extracellular sites, suggesting the active release of LL37 and IFN-α.ConclusionsSignificantly higher levels of LL-37 and IFN-α were observed in AAV patients, particularly those with crescentic formation, and LL37 and IFN-α were expressed in the renal tissue of patients with crescentic GN. These data suggest that serum levels of LL37 and IFN-α may reflect both local renal inflammation and systemic inflammation.

Decreased serum LL-37 and vitamin D3 levels in atopic dermatitis: relationship between IL-31 and oncostatin M

BACKGROUND: Patients with atopic dermatitis (AD) are susceptible to cutaneous infection with Staphylococcus aureus or herpes simplex virus, which may be related to the reduced expression of antimicrobial peptides. Skin lesions with AD are associated with dysregulated expression of LL-37 and enhanced expression of IL-22, thymic stromal lymphopoietin (TSLP), IL-25, IL-31, and oncostatin M. Vitamin D3 enhances LL-37 production in keratinocytes. This study aimed to examine the serum levels of LL-37 and vitamin D3 and their regulation of cytokine production in patients with AD.

Decreased serum LL‐37 and vitamin D3 levels in atopic dermatitis: relationship between IL‐31 and oncostatin M

Skin lesions with atopic dermatitis (AD) are associated with dysregulated expression of LL-37 and enhanced expression of IL-22, thymic stromal lymphopoietin (TSLP), IL-25, IL-31, and oncostatin M. Vitamin D3 enhances LL-37 production in keratinocytes. This study aimed to examine the serum levels of LL-37 and vitamin D3 and their regulation of cytokine production in patients with AD. Serum levels of LL-37 and 25-hydroxyvitamin D3 were analyzed by ELISA. The effects of 1,25-dihydroxyvitamin D3 or LL-37 on cytokine production in T cells or keratinocytes were analyzed by ELISA and real-time PCR. Serum levels of LL-37 and 25-hydroxyvitamin D3 were decreased in patients with AD compared to normal donors and were correlated in both groups. Serum levels of LL-37 correlated with those of oncostatin M and IL-31 in normal donors and patients with AD, while 25-hydroxyvitamin D3 levels did so only in normal donors. 1,25-dihydroxyvitamin D3 increased LL-37 production in human keratinocytes and neutrophils. 1,25-dihydroxyvitamin D3 and LL-37 enhanced the oncostatin M and IL-31 production in CD3/28-stimulated T cells, but did not alter IL-25 and TSLP production in TNF-α-stimulated keratinocytes. In CD3/28-stimulated T cells, 1,25-dihydroxyvitamin D3 reduced the IL-22 production, while LL-37 enhanced it. These effects of 1,25-dihydroxyvitamin D3 and LL-37 were suppressed by vitamin D receptor antagonist and pertussis toxin, respectively. Systemic vitamin D3 levels are reduced in patients with AD, which may contribute to decreased systemic LL-37 levels. LL-37 may systemically potentiate the oncostatin M and IL-31 production in normal donors and patients with AD, while vitamin D3 may do so only in normal donors.

Serum levels of antimicrobial peptides and proteins do not correlate with psoriasis severity and are increased after treatment with fumaric acid esters

Overexpression of antimicrobial peptides and proteins (AMPs) such as human β-defensin-2 (hBD2), LL37, and psoriasin has frequently been observed in lesional skin of psoriasis patients. We aimed to evaluate whether circulating AMP levels correlate with disease severity, and change under therapy with fumaric acid esters (FAE). We studied psoriasis patients who underwent systemic therapy using oral FAE (Fumaderm(®)). An enzyme-linked immunosorbent assay for the detection of serum protein expression of hBD2, LL37, and psoriasin was performed at baseline and after 12-week therapy. After 12-week FAE treatment of 28 patients, the median PASI significantly (P < 0.0001) decreased from 27.1 to 12.5. In psoriasis patients, mean ± SD serum hBD2, psoriasin, and LL37 levels at baseline were 295.6 ± 93.5 pg/ml, 79.4 ± 32.7 ng/ml, and 106.3 ± 90 ng/ml, respectively, which were significantly increased when compared to healthy controls (110 ± 53.7 pg/ml, P ≤ 0.0001; 3.1 ± 0.7 ng/ml, P ≤ 0.0001; 3.8 ± 0.9 ng/ml, P = 0.0004, respectively). After 12-week FAE treatment, a significant increase of serum hBD2 (339.7 ± 74.3 pg/ml; P = 0.0046), psoriasin (106 ± 58.9 ng/ml; P = 0.0014), and LL37 (136.6 ± 115.1 ng/ml; P = 0.0035) was observed. Correlation studies did not reveal significant relationships between serum AMP levels and PASI (r < 0.1; P > 0.05). In contrast to AMP expression in psoriatic skin serum, AMP levels seem not to correlate with disease severity. Increased serum AMP protein levels in psoriasis resolution are an unexpected observation that needs to be investigated more in detail in future studies.

Steroid requirements and immune associations with vitamin D are stronger in children than adults with asthma

The effects of serum vitamin D status on atopy, steroid requirement, and functional responsiveness to corticosteroids in children versus adults with asthma have not been studied systematically. We sought to explore the age-specific effects of vitamin D in asthmatic patients. Serum vitamin D levels were examined in a prospective study of adults and children (102 healthy control subjects and 103 asthmatic patients). PBMCs were cultured for 3 hours with or without 100 nmol/L dexamethasone, and the expression of corticosteroid-regulated genes was detected by using real-time PCR. Serum IgE levels were measured, and information about asthmatic patients' steroid requirements was collected. Deficient serum vitamin D levels (<20 ng/mL) were found in 47.6% of asthmatic patients and 56.8% of healthy control subjects, with means ± SDs of 20.7 ± 9.8 and 19.2 ± 7.7 ng/mL, respectively. In multivariate regression models a significant positive correlation between serum vitamin D levels and the expression of vitamin D-regulated targets, cytochrome P450, family 24, subfamily a (cyp24a) expression by PBMCs (P = .0084, pediatric asthma group only) and serum LL-37 levels (P = .0006 in the pediatric group but P = .0067 in the adult asthma group), was found. An inverse association between vitamin D and serum IgE levels was observed in the pediatric (P = .006) asthma group. Serum vitamin D level (P = .05), as well as PBMC cyp24a expression (P = .0312), demonstrated a significant inverse relationship with daily inhaled corticosteroid dose in the pediatric asthma group only. Cyp24a expression in PBMCs correlated positively with in vitro suppression of TNF-α by dexamethasone (P = .05) and IL-13 (P = .0094) in PBMCs in the pediatric asthma group only. This study demonstrated significant associations between serum vitamin D status and steroid requirement and in vitro responsiveness to corticosteroids in the pediatric but not the adult asthma group. Vitamin D was also related to IgE levels in children but not in adults.

E1-6 Decreased serum LL-37 and vitamin D3 levels in atopic dermatitis : relationship between IL-31 and oncostatin M(English Session 1)

E1-6 Decreased serum LL-37 and vitamin D3 levels in atopic dermatitis : relationship between IL-31 and oncostatin M(English Session 1)

Circulating LL‐37 is a biomarker for eczema severity in children

Eczema lesions are characterized by impaired expression of antimicrobial peptides such as cathelicidin, which play crucial roles in the innate immune defence against cutaneous infections. LL-37 corresponds to amino acids 134-170 of human cathelicidin and is a multifunctional host defence molecule essential for normal immune responses to infection and tissue injury. The aim of this study was to investigate the relationship between childhood eczema and circulating LL-37 levels. One hundred and forty-four eczema children and 36 controls were recruited. Eczema severity was assessed by SCORing Atopic Dermatitis (SCORAD) and serum LL-37 concentration measured using enzyme immunoassay. Patients' skin hydration and transepidermal water loss at forearms were measured using Corneometer and Tewameter. Patients' mean SCORAD was 49.2 and their disease was classified as mild (n=28; 12.8%), moderate (n=95; 43.6%) and severe (n=95; 43.6%). Serum LL-37 concentrations did not differ between eczema patients and controls (mean: 832 pg/mL vs. 952 pg/mL, P=0.471). However, serum LL-37 concentrations increased with increasing eczema severity among the patients (P=0.005 for trend). This biomarker shows weakly positive correlation with patients' objective SCORAD (r=0.207, P=0.013) and age (r=0.170, P=0.041), but not skin hydration or transepidermal water loss (P>0.09). Linear regression confirmed significant association between objective SCORAD and serum LL-37 when adjusted for age and gender as covariates (β=0.171, P=0.038). On the other hand, serum LL-37 did not differ between patients with and without heavy growth of staphylococci (P=0.151). Circulating LL-37 may be a biomarker for severity of childhood eczema, which supports the importance of innate immunity in eczema pathogenesis.