Search

© 2022 Elsevier Inc.Background/objectives: Long-term efficacy and safety of tocilizumab (TCZ) in adult-onset Still's disease (AOSD) mostly derive from small case series. Herein we report a registry-based study investigating TCZ efficacy and safety in a cohort of patients with AOSD evaluated by clinical and serum inflammatory markers as well as drug retention rate analysis. Methods: This is an international multicentre study analyzing data from patients with AOSD regularly enrolled in the AIDA registry. TCZ efficacy was evaluated between baseline and last follow-up assessment in terms of changes in the Pouchot score and laboratory findings. Drug-retention rate was estimated by the Kaplan-Meier method, while Cox-regression analysis was employed to detect potential predictive factors of treatment withdrawal. Results: Data from 31 patients (15 men, 16 women) refractory to the conventional therapies and treated with TCZ were extracted from the AIDA registry. Mean ± SD time of treatment duration with TCZ was 24.32 ± 20.57 months. Median (IRQ) Pouchot score significantly decreased throughout the study period (p=0.001) with a significant difference between baseline [2.00 (4.00)] and 6 month-follow-up [0.00 (0.00)] (p=0.003) and between baseline and last follow-up assessment [0.00 (0.00)] (p=0.032), while no differences were observed between 6 month-evaluation and last follow-up assessment (p=0.823). Similarly, laboratory parameters significantly decreased from baseline to the last follow-up visit. With regard to drug survival, cumulative TCZ retention rate at 12-, 24-, and 36-month follow-up visit were 83.1%, 71.7% and 63.7%, respectively, without significant differences between biologic naïve patients and those previously treated with other biologics (p=0.329). Likewise, no significant differences were observed between chronic articular course of AOSD and other types of disease course (p=0.938) or between patients co-administered with conventional immunosuppressants and patients receiving TCZ as monotherapy (p=0.778). Cox-regression analysis identified no variable associated with a higher hazard of treatment withdrawal. Treatment was discontinued in 9 patients due to long-term remission (n=4), adverse events (n=2), loss of efficacy (n=1), non-medical reason (n=1) and unspecified cause (n=1). Mean glucocorticosteroids daily dose significantly decreased from baseline (18.36 ± 24.72 mg) to the last follow-up assessment (4.02 ± 4.99 mg, p=0.003). Conclusions: TCZ allows control of disease activity as well as normalization of serum inflammatory markers in both systemic and chronic articular form of AOSD. Additionally, TCZ displays an excellent drug retention rate while minimizing the risk of long-term exposure to corticosteroids.

Idiopathic inflammatory myopathies (IIM) are rare connective tissue diseases, which can lead to internal organ involvement. IL-33/ST2 pathway is involved in the pathogenesis of numerous diseases including autoimmune disorders. IL-33 fulfils cardioprotective function, while soluble ST2 (sST2) is a decoy receptor that reduces protective impact of IL-33. The aim of the study was to evaluate the concentrations of sST2 and IL-33 in sera of patients with IIM and evaluate its associations with the clinical course of the disease. Patients with IIM as well as age- and sex-matched healthy controls were recruited. Concentrations of sST2 and IL-33 were assessed with ELISA in sera of both patients and controls. Patients were asked to fill in the questionnaires concerning clinical symptoms and physical functioning. Concentrations of sST2 and IL-33 were correlated with the results of laboratory tests and clinical symptoms. Concentrations of sST2 were significantly higher in IIM group than in healthy subjects (median sST2 in IIM 26.51 vs in healthy controls 21.39; p = 0.03). In the majority of patients, IL-33 concentrations did not exceed the detection limit. Anti-SRP-positive patients presented significantly higher concentrations of sST2 as compared to anti-SRP-negative patients (p = 0.04). In patients with anti-Ro52 antibodies, sST2 concentrations were significantly lower than in anti-Ro52-negative patients (p = 0.02). Concentrations of sST2 correlated with the degree of disability evaluated with Health Assessment Questionnaire. sST2 is increased in patients with IIM and its concentration correlates with the degree of disability. In patients with anti-SRP antibodies, levels of sST2 are exceptionally high. Electronic supplementary material The online version of this article (10.1007/s00296-020-04554-z) contains supplementary material, which is available to authorized users.

Biological agents such as monoclonal antibodies and fusion proteins are widely used for the treatment of patients with various rheumatic disorders, influencing the quality of life, disability and even mortality in patients. However, biological agents can evoke adverse reactions of different grades of severity. Although drug avoidance remains a gold standard in the care of patients hypersensitive to medication, in certain clinical situations the culprit drug is the drug of choice and cannot be replaced by another equally effective compound. In such cases, desensitization can allow the patient to be treated within current guidelines and with the most effective treatment. The authors searched Medline and Scopus databases for English-language sources using the following key words: hypersensitivity, desensitization, biologicals, adalimumab, etanercept, adalimumab, certolizumab, golimumab, rituximab, infliximab, ixekizumab, tocilizumab, anakinra and canakinumab. The aim of our review is to present the current knowledge about desensitization to biological agents and some guidelines according to patient inclusion, contraindications, procedures, and safety requirements. Drug desensitization is a new issue in rheumatology, and the solution to the problem of allergic reactions to biological drugs, which gives patients with rheumatic diseases the opportunity to extend and prolong their therapy. The present article is one of the first widely discussing this topic in the biological treatment of rheumatic diseases.

RANTES is implicated in allergic asthma and in T cell-dependent clearance of infection. RANTES receptor family comprises CCR1, CCR3, and CCR5, which are G-protein-coupled receptors consisting of seven transmembrane helices. Infections with respiratory viruses like Rhinovirus cause induction of RANTES production by epithelial cells. Here, we studied the role of RANTES in the peripheral blood mononuclear cells in cohorts of children with and without asthma and validated and extended this study to the airways of adults with and without asthma. We further translated these studies to a murine model of asthma induced by house dust mite allergen in wild-type RANTES and CCR5-deficient mice. Here we show an unpredicted therapeutic role of RANTES in the resolution of allergen-induced asthma by orchestrating the transition of effector GATA-3+CD4+ T cells into immune-regulatory-type T cells and inflammatory eosinophils into resident eosinophils as well as increased IL-10 production in the lung.

BackgroundANCA associated vasculitides (AAV) are a heterogeneous group of rare diseases with unknown etiology. In the most severe cases AAV can lead to end stage kidney disease or death. Since etiology and detailed pathogenesis of AAV is not known, the prediction of disease outcome at the time of diagnosis is challenging. Thus, there is an unmet need for tools to identify patients with the highest risk of organ dysfunction and death and apply effective personalized therapy.ObjectivesThe aim of this work was to search for tools allowing outcome prediction at the time of AAV diagnosis. Early identification of patients, who are likely to develop severe organ dysfunction and death is crucial for appropriate disease management. Induction therapy in AAV relays on immunosuppressive drugs characterized by a high risk of severe side effects. Thus, their administration in high doses should be limited only to individual patients with an especially high risk of poor outcome.MethodsWe applied here two methods of identification of AAV patients at risk to develop severe organ dysfunction and death. First method (latent class analysis [LCA] followed by logistic regression) was meant to subcategorize patients and identify a subgroup at subjects at risk to develop chronic renal replacement therapy (CRRT) and death [1]. Second, served to assess individual poor outcome risk and was based on two machine learning (ML) classifiers, which by analyzing clinical information allow assigning computed risk for CRRT and death in an individual patient allowing to identify subjects with high risk of chronic replacement therapy (CRRT) and death. We have evaluated a number of different approaches to build the ML models (including logistic regression, support vector machines, random forests), and obtained the best results for the gradient boosting algorithm implementation called LightGBM [2]. It works as a sequential ensemble of so-called weak learners (decision trees) finally combined in a one prediction model. Both analyses were based on retrospective data from Polish national AAV registry (POLVAS) [3] including presently 565 GPA and 135 MPA patients. The parameters used were: demographic data and laboratory parameters, specific organ involvement, ANCA specificity and time between selected stages of the disease.ResultsLCA used on our AAV cohort identified four subphenotypes – three already previously proposed - and revealing a fourth clinically relevant subphenotype. This new subphenotype includes only GPA patients, usually diagnosed at a younger age as compared to other groups, and characterized by multiorgan involvement, high relapse rate, relatively high risk of death, but no end-stage kidney disease. Logistic regression analysis revealed significant differences in the risk of CRRT and death between those subphenotypes – the worst prognosis was found for severe MPO AAV. On the other hand, using ML approach we obtained an individual prediction model with potentially relevant clinical performance (ROC AUC of 0.85 for CRRT and 0.82 for death).ConclusionWe consider results obtained encouraging. They may offer a new insight into AAV course based on data available at diagnosis, and create a solid foundation for potential clinical decision support system.References[1]Wójcik K et al. Subphenotypes of ANCA-associated vasculitis identified by latent class analysis. Clin Exp Rheumatol. 2021 Mar-Apr;39 Suppl 129(2):62-68.[2]Ke G, at al. Light GBM: A Highly Efficient Gradient Boosting Decision Tree. Advances in Neural Information Processing Systems 30 (NIPS 2017), pp. 3149-3157.[3]Wójcik K et al. Clinical characteristics of Polish patients with ANCA-associated vasculitides-retrospective analysis of POLVAS registry. Clin Rheumatol. 2019 Sep;38(9):2553-2563.AcknowledgementsThis work was supported by a grant from Polish National Science Center UMO-2018/31/B/NZ6/03898Disclosure of InterestsNone declared

Fractional exhaled nitric oxide (FeNO) is a non-invasive marker for eosinophilic airway inflammation and has been used for monitoring asthma. Here, we assess the characteristics of FeNO from preschool to school age, in parallel with asthma activity. A total of 167 asthmatic children and 66 healthy, age-matched controls were included in the 2-year prospective PreDicta study evaluating wheeze/asthma persistence in preschool-aged children. Information on asthma/rhinitis activity, infections and atopy was recorded at baseline. Follow-up visits were performed at 6-month intervals, as well as upon exacerbation/cold and 4&ndash, 6 weeks later in the asthmatic group. We obtained 539 FeNO measurements from asthmatics and 42 from controls. At baseline, FeNO values did not differ between the two groups (median: 3.0 ppb vs. 2.0 ppb, respectively). FeNO values at 6, 12, 18 and 24 months (4.0, CI: 0.0&ndash, 8.6, 6.0, CI: 2.8&ndash, 12.0, 8.0, CI: 4.0&ndash, 14.0, 8.5, CI: 4.4&ndash, 14.5 ppb, respectively) increased with age (correlation p &le, 0.001) and atopy (p = 0.03). FeNO was non-significantly increased from baseline to the symptomatic visit, while it decreased after convalescence (p = 0.007). Markers of disease activity, such as wheezing episodes and days with asthma were associated with increased FeNO values during the study (p &lt, 0.05 for all). Age, atopy and disease activity were found to be important FeNO determinants in preschool children. Longitudinal and individualized FeNO assessment may be valuable in monitoring asthmatic children with recurrent wheezing or mild asthma.

Fractional exhaled nitric oxide (FeNO) is a non-invasive marker for eosinophilic airway inflammation and has been used for monitoring asthma. Here, we assess the characteristics of FeNO from preschool to school age, in parallel with asthma activity. A total of 167 asthmatic children and 66 healthy, age-matched controls were included in the 2-year prospective PreDicta study evaluating wheeze/asthma persistence in preschool-aged children. Information on asthma/rhinitis activity, infections and atopy was recorded at baseline. Follow-up visits were performed at 6-month intervals, as well as upon exacerbation/cold and 4–6 weeks later in the asthmatic group. We obtained 539 FeNO measurements from asthmatics and 42 from controls. At baseline, FeNO values did not differ between the two groups (median: 3.0 ppb vs. 2.0 ppb, respectively). FeNO values at 6, 12, 18 and 24 months (4.0, CI: 0.0–8.6; 6.0, CI: 2.8–12.0; 8.0, CI: 4.0–14.0; 8.5, CI: 4.4–14.5 ppb, respectively) increased with age (correlation p ≤ 0.001) and atopy (p = 0.03). FeNO was non-significantly increased from baseline to the symptomatic visit, while it decreased after convalescence (p = 0.007). Markers of disease activity, such as wheezing episodes and days with asthma were associated with increased FeNO values during the study (p < 0.05 for all). Age, atopy and disease activity were found to be important FeNO determinants in preschool children. Longitudinal and individualized FeNO assessment may be valuable in monitoring asthmatic children with recurrent wheezing or mild asthma. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Introduction Low-level laser therapy is used in managing chronic wounds including pressure ulcers. Less is known about its impact on the healing process if an inhibitive agent e.g. bacterial infection takes place. Modulating non-specific immunity processes might eliminate bacteria if laser therapy is applied. Aim To investigate the impact of low-level laser therapy on pressure ulcer dynamics considering an infectious agent and cathelicidin LL-37 concentration. Material and methods The study comprised 6 patients with pressure ulcers ranging from stage II to III in Torrance classification and 12 patients without pressure ulcers. Venous blood sample and decubitus wound swab were taken - in study groups A at baseline and after 2 weeks; in control group B once - at a specific point of time. The swabs served for species identification. Drug susceptibility of isolated pathogens and cathelicidin LL-37 in serum concentration were measured. Results In study group A, the following bacteria predominantly occurred: S. aureus, E. faecalis, P. mirabilis, P. aeruginosa, while in control group B, excluding one MRSA case, S. hominis, S. epidermidis, D. nishinomiyaensis, A. haemolyticus (physiological flora) were present. HLGR resistance mechanisms were detected when analyzing drug susceptibility panels. Study group A findings demonstrated a statistically significant difference between the levels of cathelicidin LL-37 concentration at baseline and at the end. Conclusions There is insufficient information to accurately determine the effect of LLLT on pressure ulcer dynamics considering an infectious agent. These effects may occur if innate immunity processes are modulated so that laser therapy might eliminate bacteria indirectly.

Marek L. Kowalski was a dedicated scientist and clinician, dynamic leader and organizer, as well as committed educator and mentor for many students, researchers and doctors. His discoveries in human immunology, his empirical and implementation works made a significant contribution to modern medical knowledge and practice in the field of pathogenesis, diagnosis and treatment of allergic diseases, bronchial asthma, and hypersensitivity to non-steroidal anti-inflammatory drugs.

Psoriatic arthritis is an autoimmune, chronic disease, which often le- ading to disability. It affects 44 thousand people in Poland and consti- tute 24-41% of all patients with psoriasis. Usually, psoriasis precedes the occurrence of PsA. Psoriatic arthritis symptoms are joint stiffness in the morning which disappears after physical activity and pain in joints and spine. The difference between PsA and other rheumatic diseases is tendonitis and dactylitis. The etiology of the psoriatic arthritis is not fully understood. It is suggested that the onset of PsA may be caused by genetic susceptibility, severe stress, bacterial or viral infections or mechanical trauma. For years, the impact of microtrauma and trauma on the onset of PsA has been proven in research. The aim of this study was to review the latest literature to confirm the thesis, that trauma can cause the psoriatic arthritis and to collect case reports in which trauma was the probable factor causing the PsA

Background One of the hypothesis of RA pathogenesis is that autoimmune process in rheumatoid arthritis starts within the airways. The factors leading to increased antiCCP antibodies formation within the airways are not fully understood. People with allergies to inhaled allergens suffer from chronic inflammation within upper and lower airways. Objectives The aim of this study was study was to assess the prevalence of symptoms of upper and lower airways allergic diseases in patients with rheumatoid arthritis as compared to general population prevalence. Methods The study group consisted of 96 patients with RA (age years – 46,69±15,70 women-93%, men – 7%). Control group consist 1685 subjects from Lodz population (47,89±15,11 women-55%, men-45%). All responders completed a screening test for allergy symptoms, 60 of RA and all controls were asked to complete a detailed survey consisting of 30 questionnaires based on GA2LEN Global Allergy and Asthma Network protocol include diagnoses and separate symptoms of allergic diseases. Results In screening questionnaire 16,84% of RA patients and 7,24% control declare that suffer from asthma (p 0,05), however the coexistence of dyspnoea and wheezing was more frequent in the group of patients with RA (44,83% vs 14,01%; p The symptoms of upper airway chronic inflammation were also more prevalent in patients with RA as compared to controls. Chronic sinusitis was declared by 26,67% of patients and 10,62% controls (p Conclusion Increased prevalence of symptoms of upper and lower allergic diseases in patients with RA requires further investigation as chronic inflammation within airways can lead to posttranslational modification of proteins and autoantigen formation. Disclosure of Interests None declared

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder with not fully elucidate pathogenesis. Rheumatoid arthritis patients have increased risk of developing lymphomas. One of the possible mechanisms of this predisposition is increased genomic instability and impaired DNA repair. It is unclear how this genomic instability contributes to diseases pathogenesis. Objectives: The aim of this study was to analyze the sensitivity and repair efficiency of mononuclear cells isolated from RA patients to DNA damaging agents. Methods: The study group consisted of 22 patients with RA (age years - 60,77±13,00 women-17, men - 5) hospitalized in the Department of Rheumatology between 2017 and 2018 and 10 healthy controls without autoimmune and oncological diseases in clinical history (age 44,09±16,56; women-5, men-6). The peripheral blood mononuclear cells (PBMC) from all subjects were isolated. Using comet assay the degree of intracellular DNA damage as a result of exposure to standard damage factors: tert-butyl hydroperoxide (TBH), bleomycin, methyl methanesulfonate (MMS) and UV radiation was assessed. Results: RA patients show a statistically significant higher level of endogenous damage in PBMC DNA than controls (mean RA- 8,64% vs 4,68% in control; p Conclusion: DNA of people with rheumatoid arthritis is significantly more susceptible to damage in baseline and induced. The kinetics of DNA repair from RA patients after the introduction (TBH and bleomycin) was statistically less effective as compared to healthy control. Understanding the ethology of this phenomenon in RA may provide insight into disease pathogenesis and explain the increased susceptibility of patients to malignancies. Acknowledgement: The project is financed under the funds of the National Science Center (2017/25/B/NZ6/01358) Disclosure of Interests: None declared

Introduction. Impaired repair of airway epithelium may lead to persistence of inflammation and remodelling. Regeneration of injured epithelium is a complex phenomenon and the role of toll-like receptors (TLRs) and respiratory virus products in this process have not been established. Aim of the study. In this study we aimed to test if wound repair in nasal epithelial cells is modulated by microbial products and if this process was different in patients with allergic rhinitis and in healthy subjects. Materials and methods. Injured human nasal epithelial cells (hNECs) monolayers were incubated with the toll-like receptors agonists: poly (I:C) and lipopolisacharide (LPS); allergen Der p1, and supernatants from virus-infected epithelial cells. Regeneration of injured epithelium was assessed by measuring changes in the area of epithelial damage. Results. Addition of either poly (I:C) or LPS induced a dose depen-dant inhibition of wound repair in hNECs monolayers. Supernatants from RV1b-infected cells decreased epithelial cell regeneration after mechanical injury only in allergic patients. At baseline conditions the dynamics of epithelial repair was similar in allergic and non-allergic epithelium. However, inhibitory effects of innate stimuli on epithelial repair was stronger in patients with allergic rhinitis as compared to healthy individuals. Conclusions. This study showed that microbial products may affect regeneration of the nasal epithelium, and allergic patients are more susceptible to suppression of epithelial regeneration

Background Treatment with acetylsalicylic acid (ASA) after desensitization may be a therapeutic option in patients with nonsteroidal anti-inflammatory drug exacerbated respiratory disease (NERD). The mechanisms that lead to improvement in rhinosinusitis and asthma symptoms remain unknown. Aim To attribute the documented clinical effects of ASA treatment of chronic rhinosinusitis and/or asthma to the release of eicosanoid metabolites in urine. Methods Fourteen patients with NERD were successfully desensitized, and, eventually, eight patients were treated with 650 mg of ASA daily for 3 months. In addition to clinical assessments, nuclear magnetic resonance imaging and smell test were performed before and after treatment with ASA. Venous blood and urine were collected before desensitization and after 1 and 3 months of treatment. The levels of urinary leukotrienes (LT) (cysteinyl LT and LTE4) and tetranor PGDM (metabolite of prostaglandin D2) were measured by enzyme-linked immunosorbent assay. Results Treatment with ASA after desensitization alleviated symptoms of rhinosinusitis, improved nasal patency (mean, 50% decrease in peak nasal inspiratory flow) and sense of smell (fourfold increase in smell test score) in as early as 4 weeks. Clinical improvements were not accompanied by any change in sinonasal mucosa thickness as assessed with nuclear magnetic resonance. Urinary cysteinyl LTs, LTE4, and prostaglandin D2 metabolite remained relatively stable during ASA treatment and did not correlate with clinical improvements. Desensitization was associated with a progressive decrease of urinary creatinine. Conclusion Clinical improvement in rhinosinusitis and/or asthma after ASA desensitization was not related to concentrations of urinary eicosanoid metabolites. A decrease of urinary creatinine requires further study to determine the renal safety of long-term treatment with ASA after desensitization.

Purpose Respiratory viral infection and nonsteroidal anti-inflammatory drugs (NSAIDs) may affect arachidonic acid (AA) metabolism in the airway epithelium, however their joint effect has not been studied. We hypothesized, that alternations of AA metabolism in human airway epithelial cells (ECs) – induced by Parainfluenza virus type 3 (PIV3) – may be modified by concomitant treatment with NSAIDs. Materials and methods Nasal (RPMI 2650) and bronchial (BEAS-2B) epithelial cells were cultured into confluence and then infected with PIV3. Prostaglandin E2 (PGE2) and 15-hydroxyeicosatetraenoic acid (15-HETE) levels in cell supernatants were measured by ELISA and expression of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LO) and 15-lipoxygenase (15-LO) mRNA in cells was evaluated after reverse transcription with real-time polymerase chain reactions. Results PGE2 generation was decreased by PIV3 infection in the upper airway epithelial cells, and increased in the lower airway epithelial cells. Both naproxen and celecoxib induced significant reduction in PGE2 release in both infected and non-infected upper and lower airway epithelial cells. However, in PIV3-infected epithelial cells celecoxib inhibited PGE2 release and COX-2 expression to significantly higher degree as compared to non-infected cells. 15-HETE generation or COX-1, 5-LO and 15-LO expression were not affected by the virus infection or by NSAIDs. Conclusion Virus infection in airway epithelial cells enhances inhibitory effect of NSAIDs on prostaglandin E2 generation.

RATIONALE: Rhinoviruses are major triggers of common cold and acute asthma exacerbations; Rhinovirus species A, B and C may have distinct clinical impact; however, little is known regarding RV species-specific antibody responses in health and asthma.OBJECTIVES: To describe and compare total and rhinovirus species-specific antibody levels in healthy and asthmatic children, away from an acute event.METHODS: Serum samples from 163 preschool children with mild to moderate asthma and 72 healthy controls from the multinational Predicta cohort were analysed using the recently developed PreDicta rhinovirus antibody chip.MAIN RESULTS: Rhinovirus antibody levels varied, with rhinovirus C and rhinovirus A being higher than rhinovirus B in both groups. Compared to controls, asthma was characterised by significantly higher levels of antibodies to rhinovirus A and rhinovirus C, but not rhinovirus B. Rhinovirus antibody levels positively correlated with the number of common colds over the previous year in healthy children, and wheeze episodes in asthmatics. Antibody levels also positively correlated with asthma severity but not with current asthma control.CONCLUSIONS: The variable humoral response to rhinovirus species in both groups, suggests a differential infectivity pattern between rhinovirus species. In healthy pre-schoolers, rhinovirus antibodies accumulate with colds. In asthma, rhinovirus A and rhinovirus C antibodies are much higher and further increase with disease severity and wheeze episodes. Higher antibody levels in asthma may be due to a compromised innate immune response, leading to increased exposure of the adaptive immunity to the virus. Importantly, there is no apparent protection with increasing levels of antibodies.

Background: Impaired regeneration of airway epithelium may lead to persistence of inflammation and remodelling. Regeneration of injured epithelium is a complex phenomenon and the role of toll-like receptors (TLRs) in the stimulation of respiratory virus products in this process has not been established. Objective: This study was undertaken to test the hypothesis that the wound repair process in airway epithelium is modulated by microbial products via toll-like receptors. Methods: Injured and not-injured bronchial epithelial cells (ECs) (BEAS-2B line) were incubated with the TLR agonists poly(I:C), lipopolisacharide (LPS), allergen Der p1, and supernatants from virus-infected epithelial cells, either alone or in combination with TLR inhibitors. Regeneration and immune response in injured and not-injured cells were studied. Results: Addition of either poly(I:C) or LPS to ECs induced a marked inhibition of wound repair. Supernatants from RV1b-infected cells also decreased regeneration. Preincubation of injured and not-injured ECs with TLR inhibitors decreased LPS and poly(I:C)-induced repair inhibition. TGF-&beta, and RANTES mRNA expression was higher in injured ECs and IFN-&alpha, IFN-&beta, IL-8, and VEGF mRNA expression was lower in damaged epithelium as compared to not-injured. Stimulation with poly(I:C) increased IFN-&alpha, and IFN-&beta, mRNA expression in injured cells, and LPS stimulation decreased interferons mRNA expression both in not-injured and injured ECs. Conclusion: Regeneration of the airway epithelium is modulated by microbial products via toll-like receptors.

Background Idiopathic inflammatory myopathies (IIM) being one of the connective tissue diseases are a group of diseases with not fully understood pathology. The common features are production of autoantibodies, abnormal immune response against self-antigens and inflammatory process leading to destruction of muscle cells and internal organ involvement. Patients with inflammatory myopathies have higher risk of developing cancers. One of the processes that can attribute to increased risk of cancers can be genomic instability and impaired DNA repair. Objectives The aim of the study was to assess the processes of endogenous and exogenous DNA damage and its repair in patients with IIM as compared to healthy controls. Methods The study included 10 patients (9 men and 1 woman, mean age 46,6±16,5) with idiopathic inflammatory myopathies (dermatomyositis or polymyositis) as well as 7 healthy control individuals (4 men and 3 women, mean age 33,8±9,8). DNA damage and repair were investigated by the comet assay. To perform the comet assay human peripheral blood mononuclear cells (PBMCs) were isolated and incubated with tert-butyl hydroperoxide (t-BOOH) or bleomycin. Both compounds are common DNA damaging agents – t-BOOH induces oxidative DNA lesions whereas bleomycin induces also DNA double strand breaks (DSBs). To test the DNA repair capability, PBMCs were allowed to recover for 2 hour. The level of endogenous DNA lesions was also investigated. Results The levels of endogenous DNA damage were not statistically significantly different between tested groups (IIM-3,3±3,6% vs 3,2±3,8% in control; p=0,648). The extent of the DNA damage induced by bleomycin (IIM-23,3±19,5% vs 9,8±5,9% in control) as well as oxidative stress (IIM-14,7±16,2% vs 10,4±7,4% in control) was significantly higher in PBMS derived from IIM patients than in healthy counterparts (p Conclusions Understanding the etiology of this phenomena in these diseases may provide insight into disease pathogenesis and explain the increased susceptibility of patients to malignancies. Finding the patients with increased DNA instability could potentially serve as a biomarker and indicate the group of patients who should be carefully screened for neoplasmatic disorder. Disclosure of Interest None declared

Background Psoriatic arthritis (PsA) is affecting up to 40% of the patients with psoriasis. The pathogenesis of PsA in not completely understood. One of the hypothesis suggest that repeated micro injuries and trauma and lack of proper inhibition of inflammation lead to chronic inflammation spreading to surrounding tissue and other joints and ligaments. One of the mediators which lead to inhibition of inflammation in healthy conditions are derivatives of arachidonic acid – lipoxins. Objectives The aim of the study was to assess if the influence of lipoxin A4 on inhibition of synthesis of pro-inflammatory cytokines by peripheral blood mononuclear cells (PBMNCs) of patients with psoriatic arthritis. Methods The study group consisted of 10 patients with psoriatic arthritis and 5 healthy controls. The peripheral blood mononuclear cells from patients with PsA and healthy controls were isolated and were stimulated with lipopolisacharide (LPS) with or without 200 nM of lipoxin A4 for 24 hours. The supernatants were collected after 24 hour stimulation. The levels of IL-1b, IFN-gamma, TNF alfa, MCP-1, IL-6, IL-8 and IL-33 were assessed by cytometric bead array system. Results Incubation of cells with LPS, increased production of all cytokines assessed either in patients with psoriatic arthritis or in healthy controls. In PBMCs from healthy controls incubation of cells with lipoxine A4 decrease production of proinflammatory cytokines (IL-1b, MCP-1, IL-8, IL-6, IL-33 and TNF-alfa; p Conclusions Our study demonstrated that modulation of Inflammation by lipid mediatiors in patients with psoriatic arthritis is dysregulated. Disclosure of Interest None declared

BACKGROUND The PreDicta cohort was designed to prospectively evaluate wheeze/asthma persistence in preschoolers in association with viral/microbial exposures and immunological responses. We present the cohort design and demographic/disease characteristics and evaluate unsupervised and predefined phenotypic subgroups at inclusion. METHODS PreDicta is a 2-year prospective study conducted in five European regions, including children 4-6 years with a diagnosis of asthma as cases and healthy age-matched controls. At baseline, detailed information on demographics, asthma and allergy-related disease activity, exposures, and lifestyle were recorded. Lung function, airway inflammation, and immune responses were also assessed. Power analysis confirmed that the cohort is adequate to answer the initial hypothesis. RESULTS A total of 167 asthmatic children (102 males) and 66 healthy controls (30 males) were included. Groups were homogeneous in respect to most baseline characteristics, with the exception of male gender in cases (61%) and exposure to tobacco smoke. Comorbidities and number and duration of infections were significantly higher in asthmatics than controls. 55.7% of asthmatic children had at least one positive skin prick test to aeroallergens (controls: 33.3%, P = .002). Spirometric and exhaled nitric oxide values were within normal limits; only baseline FEV0.5 and FEV1 reversibility values were significantly different between groups. Viral infections were the most common triggers (89.2%) independent of severity, control, or atopy; however, overlapping phenotypes were also common. Severity and control clustered together in an unsupervised analysis, separating moderate from mild disease. CONCLUSIONS The PreDicta cohort presented no differences in non-asthma related measures; however, it is well balanced regarding key phenotypic characteristics representative of "preschool asthma".

Rationale: Rhinoviruses (RVs) are major triggers of common cold and acute asthma exacerbations. RV species A, B, and C may have distinct clinical impact; however, little is known regarding RV species-specific antibody responses in health and asthma. Objectives: To describe and compare total and RV species-specific antibody levels in healthy children and children with asthma, away from an acute event. Methods: Serum samples from 163 preschool children with mild to moderate asthma and 72 healthy control subjects from the multinational Predicta cohort were analyzed using the recently developed PreDicta RV antibody chip. Measurements and Main Results: RV antibody levels varied, with RV-C and RV-A being higher than RV-B in both groups. Compared with control subjects, asthma was characterized by significantly higher levels of antibodies to RV-A and RV-C, but not RV-B. RV antibody levels positively correlated with the number of common colds over the previous year in healthy children, and wheeze episodes in children with asthma. Antibody levels also positively correlated with asthma severity but not with current asthma control. Conclusions: The variable humoral response to RV species in both groups suggests a differential infectivity pattern between RV species. In healthy preschoolers, RV antibodies accumulate with colds. In asthma, RV-A and RV-C antibodies are much higher and further increase with disease severity and wheeze episodes. Higher antibody levels in asthma may be caused by a compromised innate immune response, leading to increased exposure of the adaptive immune response to the virus. Importantly, there is no apparent protection with increasing levels of antibodies. Copyright © 2018 by the American Thoracic Society.