The CD163 is a marker of monocyte/macrophage anti-inflammatory function. Its soluble form (sCD163) also exert anti-inflammatory activities including inhibition of T cell proliferation.
To evaluate ...the effect of dexamethasone (Dx) and Dermatophagoides pteronyssinus (Dp) on ex vivo production of sCD163 by peripheral blood mononuclear cells (PBMCs).
PBMCs from 26 allergic asthma patients (AAs) and 12 non-atopic healthy controls (HCs) were cultured with Dp, Dx, Dp + Dx or without any stimulation for up to 144 h (T144). Concentration of sCD163, interleukin (IL) -6 and IL-10 in PMBC culture supernatants was evaluated using ELISA. The mRNA expression of CD163 by PBMCs was estimated using quantitative PCR (qPCR).
At T144 the median concentration of CD163 in unstimulated PBMC cultures of AAs was greater than that in HCs (p = 0.008). Concomitant application of Dp and Dx resulted in a synergistic effect reflected by a dramatic increase of sCD163 concentration both in HCs (p = 0.0002) and AAs (p < 0.0001). Also a synergistic effect of Dp and Dx on CD163 mRNA expression was seen at T24 and T48 but not at T6 or T12. Among asthmatic patients the effect of Dx on sCD163 production was attenuated in severe in comparison to mild-to-moderate AAs (p = 0.0007). Moreover, Dp-induced production of IL-6 but not IL-10 was inhibited by Dx (p < 0.0001). Inhibition of IL-10 decreased sCD163 concentration by more than 50%.
Dx-triggered upregulation of anti-inflammatory CD163 expression by monocytes is synergistic with endogenous mechanisms involved in the resolution of Dp-induced inflammation. This effect is impaired in severe asthma patients.
A proliferation-inducing ligand (APRIL), a member of the tumor necrosis factor (TNF) family, plays a crucial role in the survival of peripheral B cells, and may contribute to the pathogenesis of ...systemic sclerosis (SSc) through upregulation of autoantibody production and maintenance of autoimmune phenomena. We evaluated the capacity of peripheral blood mononuclear cells from patients with SSc (SSc-PBMC) to produce APRIL; and investigated correlations between production of APRIL by SSc-PBMC and clinical and laboratory features of the disease.
PBMC from 20 patients with SSc and 14 healthy subjects were incubated in fetal calf serum-supplemented RPMI medium. APRIL levels were determined in cell culture supernatants by ELISA.
PBMC from patients with SSc produced significantly more APRIL (961 ± 151 pg/ml/10⁵ cells) than control PBMC (798 ± 219 pg/ml/10⁵ cells; p < 0.01). In patients with SSc, increased production of APRIL was associated with the presence of diffuse skin involvement, scleroderma lung disease, peripheral vasculopathy, greater capillary damage on capillaroscopy, and presence of anti-topoisomerase I (anti-topo I) antibodies. Multivariate regression analysis revealed anti-topo I antibodies as the only independent predictor of high production of APRIL by PBMC.
Production of APRIL is increased in SSc-PBMC and is associated with the presence of anti-topo I antibodies and more severe disease. Targeting the APRIL pathway might represent a therapeutic possibility for treatment of patients with SSc, in particular those with anti-topo I antibodies.
The aim of this study was to evaluate the potential of anti-immunoglobulin E (IgE) and/or anti-IgE-IgE immune complexes to release histamine from peripheral blood basophils. In addition, a potential ...modulating effect of anti-IgE-IgE complexes on allergen-induced peripheral blood basophil histamine release was evaluated.
Whole blood basophil histamine release (WBB-HR) tests done by using glass-fiber-based microtiter plates were performed in 62 patients with allergic rhinitis and/or asthma sensitized to perennial allergens. Evaluation of the direct effects of monoclonal anti-IgEs, including E25, E27, and QGE031, on WBB-HR, and the indirect effects of anti-IgE-serum IgE complexes on spontaneous and allergen-induced WBB-HR were conducted. The tests were performed with and without pretreatment of the basophils with interleukin 3, and the results were expressed as the fraction of total histamine content released.
There was no difference between WBB-HR induced by any of the studied anti-IgE antibodies and that induced by isotype antibodies for all blood samples assessed, which, for each patient, was significantly less than that induced by positive anti-IgE control antibodies. Similarly, no effect of any of the studied anti-IgE-IgE complexes on spontaneous or allergen-induced WBB-HR could be demonstrated.
There was no evidence that humanized, monoclonal anti-IgE antibodies E25 (omalizumab), E27, or QGE031 directly or indirectly induced histamine release from peripheral blood basophils.
Allergen immunotherapy (AIT) is effective in treatment of allergic diseases including allergic rhinoconjunctivitis and allergic asthma. The majority of allergic patients are sensitized to at least ...two non-related allergens. Only a few controlled clinical studies report results concerning efficacy of AIT in polysensitized patients. Allergen immunotherapy with a single allergen in polysensitized patients is effective during AIT. In patients sensitized to two non-related allergens AIT with two non-related allergens seems to be more effective than AIT with any allergen alone. Before starting AIT it is very important to establish to which allergens sensitization is clinically important. Making a decision about AIT with two or more allergens one should keep in mind that efficacy of AIT depends on achieving an appropriate dose of major allergens. Further controlled studies are necessary to address the efficacy and safety of AIT in polysensitized patients.
Objective: The optimal use of drug combinations for the management of asthma is providing significant results. This has prompted Interasma (Global Asthma Association) to take a position on inhaled ...triple therapy in asthma.Methods: We performed an extensive literature research to clinical trials, meta-analyses, randomized controlled trials and systematic reviews.Results: Starting from an extensive literature review, Interasma executive committee discussed and approved this Manifesto, developed by Interasma scientific network (INES) members.Conclusions: The manifesto describes the evidence gathered to date and states, advocates, and proposes issues on inhaled corticosteroid (ICS) plus long-acting beta 2 agonist (LABA) and long-acting muscarinic antagonists (LAMA) with the aim of challenging assumptions, fostering commitment, and bringing about change.
Abstract The aim of the study was to find associations between the process of neoplastic transformation and mtDNA mutations/polymorphisms, i.e. factors with potential prognostic significance, and to ...determine their impact on the biochemical properties, as well as structural, and functional properties of proteins. Blood and neoplastic tissue samples were collected from a 9-year-old Labrador dog with a diagnosed malignant mammary tumour. Next-generation genome sequencing (NGS) of the entire mitochondrial genome was performed using Illumina technology, and bioinformatics analyses were carried out. This is the first report demonstrating the application of NGS in the analysis of the canine mtDNA genome in neoplastic disease. The proposed strategy is innovative and promising. For the first time in the literature, the sequence of 29 genes was analysed to determine their association with the prevalence of tumour. In total, 32 polymorphic loci and 15 mutations were identified. For the first time, as many as 24 polymorphisms and all the mutations have been described to be associated with the neoplastic process in dogs. Most polymorphisms/mutations were found in the D-loop (31% of the polymorphisms and 93% of the mutations) and the COX1 gene sequence (16% of the polymorphisms). Blood or cancer heteroplasmy was noted in 93% of the mutations. Four of the 18 polymorphisms detected in the protein-coding genes were non-synonymous polymorphisms that have not been described in the literature so far (m.T7593C in COX2 , m.G8807A in COX3 , m.A9911G in ND4L , and m.T13299A in ND5 ) but resulted in changes in amino acids in proteins. These mutations and polymorphisms can affect mitochondrial functions and may be a result of cell adaptation to the changes in the environment occurring during carcinogenesis. The replacement of “wild type” mtDNA by a mutated molecule may be an important phenomenon accompanying carcinogenesis.
Currently, there are no universally accepted criteria to measure the response to biologics available as treatment for severe asthma. This survey aims to establish consensus criteria to use for the ...evaluation of response to biologics after 4 months of treatment.
Using Delphi methodology, a questionnaire including 10 items was validated by 13 international experts in asthma. The electronic survey circulated within the Interasma Scientific Network platform. For each item, five answers were proposed graduated from 'no importance' to 'very high importance' and by a score (A = 2 points; B = 4 points; C = 6 points; D = 8 points; E = 10 points). The final criteria were selected if the median score for the item was ≥7 and > 60% of responses according 'high importance' and 'very high importance'. All selected criteria were validated by the experts.
Four criteria were identified: reduce daily systemic corticosteroids dose by ≥50%; decrease the number of asthma exacerbations requiring systemic corticosteroids by ≥50%; have no/minimal side effects; and obtain asthma control according validated questionnaires. The consensual decision was that ≥3 criteria define a good response to biologics.
Specific criteria were defined by an international panel of experts and could be used as tool in clinical practice.
Allergic rhinitis (AR) is associated with histamine-mediated physiologic events. The currently used histamine antagonists are all inverse agonists that bind and inactivate histamine H1 receptors. ...Second- generation antihistamines are much more H1-receptor selective with less central nervous system penetration than first-generation agents. Antihistamines typically are more effective in seasonal than perennial AR and do not demonstrate significant relief of nasal congestion. The recent availability of some second-generation antihistamines as over-the-counter products clearly places them as the preferred first-line treatment for mild to moderate AR based on safety when compared with first-generation over-the-counter antihistamines. The remaining prescription-only second-generation antihistamines, fexofenadine, desloratadine, and levocetirizine, all have unique attributes. Antihistamines in oral, intranasal, or intraocular formulations will likely remain among the mainstays of allergy therapeutics.
Systemic sclerosis (SSc) is an autoimmune disease characterized by chronic inflammation, vascular injury and excessive fibrosis. CD163 is a scavenger receptor which affects inflammatory response and ...may contribute to connective tissue remodelling. It has recently been demonstrated that CD163 can bind and neutralize the TNF-like weak inducer of apoptosis (TWEAK), a multifunctional cytokine which regulates inflammation, angiogenesis and tissue remodelling. We aimed to investigate the relationships between serum levels of soluble CD163 (sCD163) and soluble TWEAK (sTWEAK) in relation to disease manifestations in SSc patients.
This study included 89 patients with SSc who had not received immunosuppressive drugs or steroids for at least 6 months and 48 age- and sex-matched healthy controls (HC) from four European centres. Serum concentrations of sTWEAK and sCD163 were measured using commercially available ELISA kits.
The mean serum concentrations of sTWEAK were comparable between SSc patients (mean +/- SD: 270 +/- 171 pg/mL) and HC (294 +/- 147pg/mL, P >0.05). Concentration of sCD163 and sCD163/sTWEAK ratio were significantly greater in SSc patients (984 +/- 420 ng/mL and 4837 +/- 3103, respectively) as compared to HC (823 +/- 331 ng/mL and 3115 +/- 1346 respectively, P <0.05 for both). High sCD163 levels and a high sCD163/sTWEAK ratio (defined as > mean +2SD of HC) were both associated with a lower risk of digital ulcers in SSc patients (OR, 95%CI: 0.09; 0.01, 0.71, and 0.17; 0.06, 0.51, respectively). Accordingly, patients without digital ulcers had a significantly higher sCD163 concentration and sCD163/sTWEAK ratio as compared to SSc patients with digital ulcers (P <0.01 for both) and HC (P <0.05 for both). A high sCD163/sTWEAK ratio, but not high sCD163 levels, was associated with greater skin involvement.
The results of our study indicate that CD163-TWEAK interactions might play a role in the pathogenesis of SSc and that CD163 may protect against the development of digital ulcers in SSc. Further studies are required to reveal whether targeting of the CD163-TWEAK pathway might be a potential strategy for treating vascular disease and/or skin fibrosis in SSc.
The molecular mechanism underlying embryonic implantation is vital to understand the correct communications between endometrium and developing conceptus during early stages of pregnancy. This study’s ...objective was to determine molecular changes in the uterine endometrial proteome during the preimplantation and peri-implantation between 9 days (9D), 12 days (12D), and 16 days (16D) of pregnant Polish Large White (PLW) gilts. 2DE-MALDI-TOF/TOF and ClueGOTM approaches were employed to analyse the biological networks and molecular changes in porcine endometrial proteome during maternal recognition of pregnancy. A total of sixteen differentially expressed proteins (DEPs) were identified using 2-DE gels and MALDI-TOF/TOF mass spectrometry. Comparison between 9D and 12D of pregnancy identified APOA1, CAPZB, LDHB, CCT5, ANXA4, CFB, TTR upregulated DEPs, and ANXA5, SMS downregulated DEPs. Comparison between 9D and 16D of pregnancy identified HP, APOA1, ACTB, CCT5, ANXA4, CFB upregulated DEPs and ANXA5, SMS, LDHB, ACTR3, HP, ENO3, OAT downregulated DEPs. However, a comparison between 12D and 16D of pregnancy identified HP, ACTB upregulated DEPs, and CRYM, ANXA4, ANXA5, CAPZB, LDHB, ACTR3, CCT5, ENO3, OAT, TTR down-regulated DEPs. Outcomes of this study revealed key proteins and their interactions with metabolic pathways involved in the recognition and establishment of early pregnancy in PLW gilts.
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