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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. [ABSTRACT FROM AUTHOR]

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. 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. 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. Virus infection in airway epithelial cells enhances inhibitory effect of NSAIDs on prostaglandin E2 generation. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis is an autoimmune, chronic disease, which often leading to disability. It affects 44 thousand people in Poland and constitute 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. [ABSTRACT FROM AUTHOR]

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 dependant 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. [ABSTRACT FROM AUTHOR]

Check-point inhibitors are becoming a chance for patients with neoplasmatic disorders. The inhibitors of PD-1/PD1L and CTLA4 pathway are used in treatment of such neoplasmatic disorders as melanoma or lung cancer. Unfortunately interference with signaling between antigen presenting cells and T-Lymphocytes can lead to deregulation of immune system, loss of autotolerance and results in occurence of autoimmune diseases symptoms. Immune-related adverse drug reactions affects even 25% of treated patients and in 6% the observed reactions are severe. The most common clinical manifestation of these reactions include cutaneous symptoms, endocrine disturbances, complaints from gastrointestinal and respiratory systems and renal involvement as well. In the recent years it is reported that also "rheumatologic symptoms" like arthritis, polymyalgia or sicca symptoms are often observed in patients treated with check-point inhibitors. The aim of the article is to present the current knowledge on pathogenesis, clinical pattern, prevalence and treatment of immune-related adverse drug reactions evoked by check-point inhibitors. [ABSTRACT FROM AUTHOR]

We are presenting five patients with fish allergy. The diagnosis was based on clear history, positive skin prick tests with fish allergens (cod, salmon, tuna, hake, sole) and presence of specific IgE against cod allergen (Gad c 1) and modified carp allergen (mCyp c 1). Allergy was confirmed with DBPCFD with fish. Four of five patients had been selected for clinical trial of fish-allergen immunotherapy with vaccine developed within the FAST project (EU FP7). [ABSTRACT FROM AUTHOR]

Introduction. Airway epithelium is a mechanical barrier playing a protective role in anti-infectious immunity but also in pathophysiology of bronchial asthma. The epithelium can be damaged by endogenous or environmental factors. Aim. The aim of this study was to develop and standardize experimental model of the epithelial damage and assess the repair of epithelial cells of the upper and lower respiratory tract. Material and methods. Cell lines of epithelial upper (RPMI 2650) and lower airway (BEAS-2B) were employed in this study. The cells were cultured to confluence, damaged mechanically and the repair was evaluated by calculating the percentage of regenerated surface. Simultaneously the assessment of damage and regeneration of tight junction by measuring intraepithelial resistance (TER) was performed. Results. Epithelial cells of the upper respiratory tract (RPMI 2650) underwent regeneration on average after 5±1 days and in cell cultures of lower respiratory tract complete regeneration of the damage was observed after 24±2 hours. The damage of RPMI 2650 cells took 72 hours to repair in 50% and full recovery was observed after 120 hours. Epithelial cells of the lower respiratory tract were much faster to regenerate and 50% of the damaged surface was regenerated within 6 hours from injury and complete recovery took 24 hours. During the regeneration of the cells the increase in the TER was observed. Conclusions. The in vitro model of epithelial damage and repair is suitable for assessment of endogenous and environmental factors affecting regeneration of the respiratory epithelium. [ABSTRACT FROM AUTHOR]

Despite the fact that allergic diseases are less common in the elderly than in patients under 65 years old, allergy should be consider in the differential diagnosis of diseases in geriatric patients, because proper diagnosis and treatment can improve the quality of life of elderly patients. Changes in the immune system, associated with the ageing of the organism known as immunosenescence do not manifest a decrease in the incidence of allergic diseases and asthma. In addition, the weakening of the epidermal and epithelial barrier, facilitates the penetration of allergens, and the immune deviation towards Th2 predominance, may lead to the onset or worsening of existing allergies. Diagnosis and treatment of allergic diseases and asthma is not significantly different from the procedure in younger patients, however, may be more difficult in elderly patients due to polytherapy and comorbidities. This paper discuss the prevalence and management of allergic diseases in the elderly patients. [ABSTRACT FROM AUTHOR]

Introduction: Allergen-induced basophil activation has been associated with the release of several mediators and with an increased expression of CD203c molecules on basophils. Aim: To assess the influence of specific allergens on the generation of 15-hydroxyeicosatetraenoic (15-HETE) from peripheral blood leukocytes in relation to basophil activation, on the basis of CD203c molecule expression and histamine release. Material and methods: The study included 15 patients with clinical symptoms of birch pollen allergy confirmed by a positive skin prick test with the birch allergen, and 6 healthy controls. Leukocytes isolated from peripheral blood were incubated with 3 concentrations of the birch pollen allergen (Betv1), anti-IgE or with ionophore A23187. Results: In vitro challenge of leukocytes from allergic patients with 1 ng/ml of allergen induced a significant increase in 15-HETE generation. An increase above 30% was observed in almost half the allergic patients, with mean values ranging from 40% to 46%, but not in healthy controls. Anti-IgE antibodies increased 15-HETE generation in 5 patients (termed IgE+), and the allergen induced a significant increase in 15-HETE in all patients who reacted to anti-IgE. The mean CD203c expression on basophils of the allergic patients increased after allergen challenge, but a significant increase (> 30%) was observed only in patients who demonstrated an increased expression after anti-IgE exposure. A significant correlation was seen between 15-HETE generation and histamine release induced by the highest concentration of the allergen (r = 0.95; p < 0.01). Conclusions: Allergen-induced, IgE-mediated activation of basophils is associated with a significant increase in 15-HETE generation. [ABSTRACT FROM AUTHOR]

Allergic rhinitis is the most frequent atopic disease and is an important health problem that causes impairment in patients activities, social functioning, sleep, school and work. Asthma prevalence ranges from 5 to 20% of the population in different countries and most patients with asthma have rhinitis supporting the concept of "one airway one disease". Epidemiologic studies have shown that asthma and rhinitis often coexist in the same patient. Moreover, patients with moderate/severe persistent allergic rhinitis may be more likely to suffer from asthma than those with intermittent allergic rhinitis and/or a milder form of the disease. The coexistence of rhinitis with asthma appears to impair asthma control. The presence of allergic rhinitis commonly exacerbates asthma increasing the risk of asthma attacks, emergency visits and hospitalizations for asthma, In April 2008 an Update of ARIA (Allergic Rhinitis and Its Impact on Asthma) guidelines have been published in which classification of rhinitis and management recommendations were validated. In ARIA 2008 document the links between asthma and allergic rhinitis have been confirmed and accented. The epidemiologic evidence and common risk factors were reviewed. The similarities and differences of nasal and bronchial mucosa and mechanisms of allergic inflammation in asthma and rhinitis were presented. In this article, it is aimed to summarize the newly updated and published version of "Allergic Rhinitis and its Impact on Asthma (ARIA) 2008" and to present the diagnostic and therapeutic consequences of ARIA guidelines. According to them patients with allergic rhinitis should be evaluated for asthma, because the treatment of rhinitis reduces asthma severity and optimize asthma control. [ABSTRACT FROM AUTHOR]

Background The mechanism of aspirin (acetylsalicylic acid: ASA) hypersensitivity in asthmatic patients is related to arachidonic acid metabolism abnormalities, and specific triggering by ASA of 15-hydroxyeicosatetraenoic acid (15-HETE) generation was observed in leucocytes from aspirin-sensitive (AS) but not from aspirin-tolerant (AT) asthmatics. Objective The aim of this study was to identify the enzymatic pathway involved in ASA-induced 15-HETE generation in AS asthmatics and to assess the regulatory role of prostaglandin EP receptors. Methods Peripheral blood leucocytes (PBLs) were isolated from AS ( n=18) and AT ( n=20) asthmatics and challenged with ASA, with and without pre-incubation with caffeic acid (CA) [15-lipoxygenase (15-LO) inhibitor] or prostaglandin receptor non-specific (misoprostol, sulprostone) and specific EP1–4 receptors agonists. Eicosanoids were measured in supernatants using specific immunoassays. Results Aspirin triggered 15-HETE generation in PBLs of AS asthmatics (mean increase 292%) but not in AT asthmatics and inhibited prostaglandin2 (PGE2) generation in both groups of patients to the same degree. Leucocytes from AS patients produced less PGE2, both before and after ASA incubation. Pre-incubation of PBLs with CA decreased basal 15-HETE production in all patients and completely inhibited ASA-induced 15-HETE generation in AS asthmatics. CA did not change basal PGE2 production but enhanced induced by ASA inhibition of PGE2. Non-specific agonists of EP receptors (misoprostol and sulprostone) did not affect basal 15-HETE production but inhibited in a dose-dependent manner the ASA-induced increase of 15-HETE generation in AS asthmatics. On the contrary, in AT asthmatics, pre-incubation of PBLs with misoprostol or sulprostone resulted in a significant increase in 15-HETE generation after addition of ASA (200 μm). EP1–3 receptor agonists inhibited (range 72–94%) the ASA-induced 15-HETE production significantly. Conclusion Our study demonstrated that ASA-triggered 15-HETE generation involves the activation of 15-LO and is modulated by prostaglandin EP1–3 receptors. The relevance of these observations to the mechanism of in vivo ASA-induced asthmatic attack remains to be established. [ABSTRACT FROM AUTHOR]

Mast cells constitute a significant proportion of cells infiltrating nasal polyp tissue, and epithelial cells may release stem cell factor (SCF), a cytokine with chemotactic and survival activity for mast cells. We aimed to assess the expression of SCF in human nasal polyp epithelial cells (NPECs) as related to patients’ clinical phenotypes. Nasal polyp tissues were obtained from 29 patients [including nine with aspirin (ASA)-hypersensitivity and 12 with bronchial asthma] undergoing polypectomy for nasal obstruction. Epithelial cells were obtained following 6-week culture of nasal polyps explants. The SCF released into the culture supernatant was assessed by enzyme-linked immunosorbent assay (ELISA) and total SCF mRNA in the polyp tissue was determined by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). For the whole group of patients, the number of polypectomies correlated with expression of SCF mRNA (r = 0.62;P < 0.005), SCF protein in the NPECs supernatants (r = 0.39;P < 0.05) and with density of mast cells in epithelial layer (r = 0.37;P < 0.05) and stromal layer (r = 0.5;P < 0.01) of nasal polyps. The SCF/β-actin mRNA ratios were significantly higher in ASA-hypersensitive (AH) asthmatics (median 0.97, range: 0.8–1.5) when compared with ASA-tolerant (AT) patients (median 0.5, range: 0.1–0.7;P < 0.001). The SCF protein concentration in NPEC supernatants was also significantly higher in AH asthmatics (median 1.10 pg/μg DNA, range: 0.4–1.9) when compared with AT patients (median 0.1 pg/μg DNA, range: 0.02–1.2;P < 0.001). In the subpopulation of ASA-sensitive asthmatics the number of poypectomies correlated also with the density of mast cells and eosinophils in the polyp tissue. [ABSTRACT FROM AUTHOR]

This review provides a detailed examination of original research and previously published reviews regarding cardiovascular involvement in systemic sclerosis (SSc). Our study aims to evaluate the current understanding of SSc-associated heart involvement (SHI), focusing on its most prevalent forms, diagnostic methods and treatment options. A comprehensive search of PUBMED, Medline, Web of science, Scopus and DOAJ databases was conducted, involving articles published between January 2019 and August 2024, available in English, both original research and reviews. Additionally, the authors examined the references cited in the selected articles, reviewed relevant literature, and included key publications dating back to 2010. Systemic Sclerosis (SSc) is an autoimmune connective tissue disease characterized by skin and internal organs fibrosis with accompanying vasculopathy. SHI encompasses both primary and secondary cardiac disease with a prevalence rate of up to 39%. It constitutes one of the leading causes of death among affected individuals. Systemic sclerosis- primary heart involvement comprises a wide range of conditions including arrhythmias, heart failure, pericardial disease, valvular abnormalities, and myocardial inflammation. However, its subclinical course, often misinterpreted as other forms of cardiomyopathy, poses true diagnostic challenges, requiring diagnostic tools like transthoracic echocardiography with tissue Doppler echocardiography and cardiac magnetic resonance imaging. The review underscores the importance of SHI and a holistic approach to managing patients with systemic sclerosis. Furthermore, it emphasizes the need for further investigation into potential pathogenetic mechanisms and biomarkers crucial for targeted treatment to fully optimize recommendations for this patient subgroup. [ABSTRACT FROM AUTHOR]

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-β and RANTES mRNA expression was higher in injured ECs and IFN-α, IFN-β, IL-8, and VEGF mRNA expression was lower in damaged epithelium as compared to not-injured. Stimulation with poly(I:C) increased IFN-α and IFN-β 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. [ABSTRACT FROM AUTHOR]

Vasculitis of the central nervous system can be a localized process, such as primary angiitis of the central nervous system (PACNS), or systemic vasculitis, such as ANCA-associated vasculitis (AAV). Since both conditions share neurological manifestations, the following review will discuss the neurological aspects of both. This review aims to provide a comprehensive comparison of the pathogenesis, clinical manifestation and assessment, diagnostic workup, and treatment protocol for both PACNS and AAV with central nervous system involvement. To provide a comprehensive comparison and update, a literature review was conducted using PubMed and Ovid databases (Embase and Medline). Then, the references were retrieved, screened, and selected according to the inclusion and exclusion criteria. PACNS and AAV share similarities in clinical presentation and neurological symptoms, especially in terms of headache, focal deficits, and cognitive impairment. Additionally, both conditions may exhibit similarities in laboratory and radiological findings, making brain biopsy the gold standard for differentiation between the two conditions. Moreover, the treatment protocols for PACNS and AAV are nearly identical. Comparing PACNS and AAV with CNS involvement highlights the similarities in clinical presentation, radiological findings, and treatment protocols between the two conditions. Further research should focus on establishing a practical diagnostic protocol. [ABSTRACT FROM AUTHOR]

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 nonspecific 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. [ABSTRACT FROM AUTHOR]

The interplay between Psoriatic arthritis and Gout is a current diagnostic challenge faced by many physicians and researchers. We aimed at reviewing the coexistence of gout and its features such as hyperuricemia and deposition of monosodium urate crystals in patients with psoriatic arthritis (PsA). We also focused on a brief presentation of the pathophysiology underneath the interplay between PsA and gout, and ultimately on recommendation of approaches for the differential diagnosis. The literature search for this narrative review was conducted using PubMed and Medline and after retrieving and screening the references, articles were selected according to the inclusion and exclusion criteria. Part of the assessed studies reported the coexistence of PsA and gout (Psout) and its association with several clinical outcomes among affected patients. Other studies stressed incidences of misdiagnosis of gout with PsA and vice versa. Additionally, the presence of hyperuricemia in PsA patients could interfere with the patient’s characteristics and outcomes of their treatment. Further research on the assessment and clinical course of Psout is required to develop an official protocol for its diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of rhinosinusitis in aspirin-exacerbated airway disease is closely linked to the disequilibrium in arachidonic acid metabolism. Although considerable amounts of data concerning impaired eicosanoid production are available, the precise mechanism and pathogenesis of the disease are still unknown. The aim of the present study was to assess the expression of enzymes belonging to the arachidonic acid cascade and receptors for arachidonate derivative metabolites in nasal polyps from aspirin- hypersensitive (AH) and aspirin-tolerant (AT) patients with rhinosinusitis. Methods: Cells expressing cysteinyl leukotriene (CysLT) receptors (CysLT1 and CysLT2), arachidonate 5-lipoxygenase, leukotriene B4 receptor type 1, E-prostanoid receptors (EP2 and EP4), cyclooxygenase (COX)-1 and COX-2 were detected by immunocytochemistry in nasal polyps obtained from 10 AH patients and 18 AT patients. Results: There was a significantly higher density of cells expressing CysLT1 and CysLT2 receptors in nasal polyps from AH patients than from AT patients (p < 0.001). In contrast, the density of cells expressing EP2 receptor and COX-2 was significantly lower in AH patients than in AT patients (p < 0.02). The number of COX-2-positive epithelial cells was significantly reduced in AH polyps (p < 0.04). Conclusions: The elevated number of nasal polyp cells expressing CysLT receptors and lack of cells expressing EP2 receptor and COX-2 may be related to a more severe course of hyperplastic rhinosinusitis in aspirin hypersensitivity. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Cite this as: C. A. Pérez Novo, M. Jedrzejczak-Czechowicz, A. Lewandowska-Polak, C. Claeys, G. Holtappels, P. Van Cauwenberge, M. L. Kowalski and C. Bachert, Clinical & Experimental Allergy, 2010 (40) 1323–1332. Background Staphylococcal superantigens may modulate airway inflammatory disease. Objective We assessed the effect of Staphylococcus aureus enterotoxin B (SEB) on T cell activation in patients with nasal polyps and asthma, and its possible link to aspirin hypersensitivity. Methods Leucocytes were isolated from five healthy subjects (controls), five asthmatics with nasal polyps without (NP-ATA) and five with aspirin-induced asthma (NP-AIA). Cells were incubated with increasing concentrations of SEB for 4 and 18 h. Release of TH1/TH2 cytokines was assessed by Cytometric Bead-Array. Foxp3 and TNFRS18-L expression were analysed by qPCR and flow cytometry. Results After 4 and 18 h, SEB significantly increased IFN-gamma, IL-4, TNF-alpha, IL-5 and IL-2 concentrations in supernatants of both NP polyp groups compared with controls. Baseline Foxp3 was significantly decreased in both NP-asthma groups. Incubation with SEB for 4 h induced a limited up-regulation of Foxp3 in NP-AIA patients, which was switched off consecutively. Foxp3 was significantly up-regulated in the control group after 18 h, but not in the NP-asthmatic groups. In parallel, TNFRS18-L mRNA significantly increased after 18 h in the NP-asthma groups compared with control subjects. This molecule was highly expressed in CD11c+CD14+ cells and its levels increased after 18 and 24 h culture in the NP-asthma patients. Conclusion SEB induces both TH1 and TH2 pro-inflammatory responses in patients with nasal polyps and asthma regardless of the presence of aspirin hypersensitivity. The nature of this response may be linked to a basal deficiency of Foxp3 observed in the NP-asthmatic patients and/or to the up-regulation of TNFRS18-L on monocytes/dendritic cell precursors. [ABSTRACT FROM AUTHOR]

Background: Up to 40% of patients with psoriasis suffer from psoriatic arthritis (PsA), an underrecognized inflammatory arthropathy of incompletely understood pathogenesis. PsA affects axial joints, surrounding ligaments, tendons and entheses. One hypothesis links repeated microinjuries with disorders of inflammation resolution mechanisms that lead to chronic inflammation, which spreads to surrounding tissues. An example of the mediators which lead to resolution of inflammation in physiological conditions are derivatives of arachidonic acid - lipoxins. Objectives: The aim of the study was to compare if the influence of lipoxin A4 on the synthesis of pro-inflammatory cytokines by peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood of patients with PsA and healthy individuals. Methods: 10 patients with PsA and 5 matching healthy controls were enrolled in the study. PBMSc were isolated by gradient-density centrifugation technique and incubated with lipopolysaccharide with or without the addition of lipoxin A4 for 24 hours. The levels of IL-1ß, IFN-α, IFN-β, TNFa, MCP-1, IL-6, IL-8, IL-10, IL-17, IL-12, IL-18, IL-23 and IL-33 in cell culture supernatants were quantified by cytometric bead array system. Results: Incubation of PBMCs 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. However, in patients with psoriatic arthritis addition of lipoxine A4 did not inhibited LPS - induced proinflammatory cytokines release. Conclusions: The anti-inflammatory effect of lipoxin A4 is reversed in PsA PBMCs, supporting the hypothesis of defective resolution of inflammation in the pathogenesis of PsA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: 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”. [ABSTRACT FROM AUTHOR]

Introduction. Psoriasis is a chronic autoimmune disease of skin which may affect around 2% of population and 20-40% of psoriatic patients develop psoriatic arthritis (PsA). It is estimated that cutaneous symptoms are present for about 10 years ahead of the musculoskeletal symptoms. Early diagnosis of arthritis and implementation of treatment are crucial for achieving remission and improved prognosis. Aim. The aim of the study was to assess the musculoskeletal symptoms in patients with psoriasis. Material and methods. 180 subjects with psoriasis of the skin and/or nails were enrolled in the study. The screening questionnaire was developed to assess the frequency of musculoskeletal symptoms and their character. The symptoms reported by the patients were compared with the CASPAR classification criteria and with the screening questionnaire PEST. Results. More than 90% of respondents declared complaints from musculoskeletal system. In 70% of the surveyed, the symptoms were present at the time of completing the questionnaire and in 40% the reported symptoms fulfilled the criteria of inflammatory arthritis. 43% of the surveyed patients reported Achilles tendon pain and 42% reported dactylitis. The examined patients rarely reported back pain of inflammatory character (11%). In the study group nearly 40% of the patients were diagnosed with psoriatic arthritis. About 23% respondents (16/70) who reported symptoms fulfilling the criteria for psoriatic arthritis had not been previously diagnosed with rheumatic disease, and in patients reporting inflammatory back pain this figure amounted to 55% (10/18). Conclusions. Musculoskeletal complaints are frequent among patients with psoriasis. The significant percentage of patients treated by dermatologists do not have any diagnosis of inflammatory joint disease despite the presented symptoms. [ABSTRACT FROM AUTHOR]

Background: Several proangiogenic molecules have been implicated in the pathogenies of asthmatic inflammation and remodeling. The aim of the study was to compare the concentration of proangiogenic factors in the sera of asthmatic patients and in healthy subjects (HS), and to refer the concentrations to both clinical and inflammatory markers of the disease severity. Methods: Serum was collected from 45 patients with severe/refractory asthma (SRA) and 51 patients with nonsevere asthma (nSA). The control group included 30 HS. Serum concentrations of Angiopoietin-1, Angiopoietin-2, vascular endothelial growth factor (VEGF) and osteopontin were assessed by the enzyme-linked immunosorbent assay. Results: The levels of Angiopoietin-1 (68.8 ± 2.7 vs 56.4 ± 9.3 ng/ml; p < 0.05), Angiopoietin-2 (4.9 ± 0.35 vs 1.38 ± 0.14 ng/ml; p < 0.0001) and VEGF were significantly higher in asthmatic patients (n = 94) as compared to HS (255 ± 45.4 vs 424.5 ± 27.8 pg/ml; p < 0.01). The mean serum level of Angiopoietin-2 was found to be significantly higher in patients with SRA as compared to nSA patients (6.04 ± 0.46 vs 3.84 ± 0.43; p < 0.001). Angiopoietin-2 serum level correlated with respiratory function and with parameters of asthma severity: the mean number of asthma exacerbations in the preceding 12 months (R = 0.21; p < 0.05), mean number of emergency visits due to severe asthma exacerbation (R = 0.24; p < 0.04) and mean number of hospitalizations (R = 0.21; p < 0.05) or dose of inhaled glucocorticosteroids taken by the patients (R = 0.36; p < 0.001). Conclusion: Angiopoietin-2 seems to be a crucial proangiogenic cytokine overproduced in patients with SRA characterized by repeated exacerbations and Angiopoietin-2 serum levels can serve as a biomarker of severe asthma. [ABSTRACT FROM AUTHOR]

Introduction. Model of primary bronchial epithelial cells culture has been used to study the innate response to viral infections in patients with bronchial asthma. Aim. The aim of the study was to evaluate the effectiveness of bronchial epithelial cell culture and the influence of parainfluenza virus type 3 (PIV- 3) on cell morphology. Materials and methods. Human Bronchial Epithelial cells (HBECs) were obtained during bronchoscopy from 31 subjects: 12 healthy subjects and 19 patients with bronchial asthma. The cells were grown in BEGM culture medium (Bronchial Epithelial Cell Growth Medium) and were infected with PIV-3 0.1 MOI. Results. Successful cultures were obtained for 61.3% of HBECs. Fungal infection was the main reason for the failure to grow HBECs. No cytopathic effect of PIV3 on epithelial cells was observed for up to 48 hours after infection. Conclusions. The described methodology enables successful culture of primary bronchial epithelial cells and their infection with PIV3. [ABSTRACT FROM AUTHOR]

Background: The FAST (food allergy-specific immunotherapy) project aims at developing safe and effective subcutaneous immunotherapy for fish allergy, using recombinant hypoallergenic carp parvalbumin, Cyp c 1. Objectives: Preclinical characterization and good manufacturing practice (GMP) production of mutant Cyp (mCyp) c 1. Methods:Escherichia coli-produced mCyp c 1 was purified using standard chromatographic techniques. Physicochemical properties were investigated by gel electrophoresis, size exclusion chromatography, circular dichroism spectroscopy, reverse-phase high-performance liquid chromatography and mass spectrometry. Allergenicity was assessed by ImmunoCAP inhibition and basophil histamine release assay, immunogenicity by immunization of laboratory animals and stimulation of patients' peripheral blood mononuclear cells (PBMCs). Reference molecules were purified wild-type Cyp c 1 (natural and/or recombinant). GMP-compliant alum-adsorbed mCyp c 1 was tested for acute toxicity in mice and rabbits and for repeated-dose toxicity in mice. Accelerated and real-time protocols were used to evaluate stability of mCyp c 1 as drug substance and drug product. Results: Purified mCyp c 1 behaves as a folded and stable molecule. Using sera of 26 double-blind placebo-controlled food-challenge-proven fish-allergic patients, reduction in allergenic activity ranged from 10- to 5,000-fold (1,000-fold on average), but with retained immunogenicity (immunization in mice/rabbits) and potency to stimulate human PBMCs. Toxicity studies revealed no toxic effects and real-time stability studies on the Al(OH)3-adsorbed drug product demonstrated at least 20 months of stability. Conclusion: The GMP drug product developed for treatment of fish allergy has the characteristics targeted for in FAST: i.e. hypoallergenicity with retained immunogenicity. These results have warranted first-in-man immunotherapy studies to evaluate the safety of this innovative vaccine. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

He was a board member and treasurer of the European Academy of Allergy and Clinical Immunology (EAACI) and a member of the Board of Directors of the World Allergy Organization (WAO). He was awarded as the Knight's Cross of the Order of Polonia Restituta by Lech Kaczy'nski, President of Poland, for outstanding contributions to the development of allergology and clinical immunology in Poland. GLO:1X5/01oct21:all15055-fig-0001.jpg PHOTO (COLOR): . gl 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. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]