Relationship between CCR5+FoxP3+ Treg cells and forced expiratory volume in 1 s, peak expiratory flow in patients with severe asthma.

INTRODUCTION: Severe asthma is a special clinical problem. CD4+CD25highCD127lowFoxp3+ Tregs play a role in maintaining appropriate immunological response. It is a known fact that Treg cells with CCR5 expression represent strong suppressive activity. It has been shown that a low number or altered function of FoxP3+ Tregs is associated with the inflammatory process and airway obstruction in asthma. AIM: To evaluate whether CCR5 Tregs expression and surface density on FoxP3+ Treg cells depend on the severity of asthma. MATERIAL AND METHODS: The study included 50 patients with asthma (25 with severe and 25 with mild-to-moderate asthma). The control group comprised 25 healthy volunteers. The phenotype of CD4+CD25highCD127lowFoxp3+CCR5+ cells was evaluated by multicolour flow cytometry. The degree of airflow obstruction was assessed by spirometry as forced expiratory volume in 1 s (FEV1) and peak expiratory flow (PEF). RESULTS: The absolute count of FoxP3+ Treg cells in patients with severe asthma was significantly decreased in comparison with the control group. MFI (median fluorescence intensity) of CCR5 expression on FoxP3+ Treg cells was significantly decreased in severe asthma compared to the mild-to-moderate asthma and control groups. CCR5 expression on FoxP3+ Treg cells as MFI positively correlated with lung function parameters FEV1% and PEF% in patients with severe asthma. CONCLUSIONS: High CCR5 Tregs expression as MFI is associated with improved in lung function parameters: FEV1% and PEF% in patients with severe asthma. The measurement of CCR5 expression on the surface of peripheral blood FoxP3+ Treg cells as MFI could be an additional tool to estimate the severity of asthma.

The relationship between peripheral blood mononuclear cells telomere length and diet - unexpected effect of red meat.

BACKGROUND: Repeated nucleotide sequences combined with proteins called telomeres cover chromosome ends and dictate cells lifespan. Many factors can modify telomere length, among them are: nutrition and smoking habits, physical activities and socioeconomic status measured by education level. The aim of the study was to determine the influence of above mentioned factors on peripheral blood mononuclear cells telomere length. METHODS: Study included 28 subjects (seven male and 21 female, age 18-65 years.), smokers and non-smokers without any serious health problems in past and present. Following a basic medical examination, patients completed the food frequency questionnaire with 17 foods and beverages most common groups and gave blood for testing. PBMC telomere length were measured with qualitative real-time Polymerase Chain Reaction (rtPCR) method and expressed as a T/S ratio. RESULTS: Among nine food types (cereal, fruits, vegetables, diary, red meat, poultry, fish, sweets and salty snacks) and eight beverages (juices, coffee, tea, mineral water, alcoholic- and sweetened carbonated beverages) only intake of red meat was related to T/S ratio. Individuals with increased consumption of red meat have had higher T/S ratio and the strongest significant differences were observed between consumer groups: "never" and "1-2 daily" (p = 0.02). Smoking habits, physical activity, LDL and HDL concentrations, and education level were not related to telomere length, directly or as a covariates. CONCLUSIONS: Unexpected correlation of telomere length with the frequency of consumption of red meat indicates the need for further in-depth research and may undermine some accepted concepts of adverse effects of this diet on the health status and life longevity.

Tissue Factor in Dermatitis Herpetiformis and Bullous Pemphigoid: Link between Immune and Coagulation System in Subepidermal Autoimmune Bullous Diseases.

Dermatitis herpetiformis (DH) and bullous pemphigoid (BP) are skin diseases associated with eosinophilic and neutrophilic infiltrations. Although chemokines are critical for the selective accumulation and activation of various leukocyte subsets in the inflammatory process, there are few findings concerning inflammatory cells and production of coagulation factors in blistering diseases. Skin biopsies were taken from 14 patients with DH, 27 with BP, and 20 control subjects. The localization and expression of tissue factor (TF) in skin lesions and perilesional skin were studied by immunohistochemistry and confirmed by Western Blot. Moreover the plasma concentrations of TF were measured by immunoassays. D dimers, fibrinogen, and selected coagulation parameters were measured by routine methods. Expression of TF in the epidermis and in inflammatory influxed cells in dermis was detected in skin biopsies from BP patients. Examined TF expression was detected in perilesional skin of all BP patients too. The expression of TF was not observed in biopsies from healthy people and DH patients. The findings of the study show an increased expression of tissue factor in the lesional and perilesional skin of patients with bullous pemphigoid. The difference in chemokine pattern expression and variations in the cellular infiltration in BP and DH cause variable expression of TF.

The patents on glucocorticosteroids and selected new therapies for the management of asthma in children: update.

Despite the continuous increase in the prevalence of asthma in many developing countries, there have been major advances in understanding and managing this disease. The remarkable role of inflammation in asthma is well known. Current asthma guidelines recommend the use of anti-inflammatory drugs and immunotherapy for long-term management of asthma. The management of asthma in children is a challenge because of their inability to express warning signs and seek medical attention in a timely manner. Unlike adults, asthmatic children must rely on their parents or caregivers for the administration of asthma medications. The inability to carry and self-administer asthma drugs may increase the risk of non-compliance. Glucocorticosteroids, the most important drugs for patients with asthma, are associated with an increased level of side effects and compliance issues mostly in children. In an attempt to solve that dilemma, emphasis is being placed on the modification of current management tactics and the introduction of other drugs. This review presents more recent patents for childhood asthma therapies for the management of asthma in children.

[The use of multi-color flow cytometry for identification of functional markers of nTregs in patients with severe asthma]. / Wykorzystanie wielokolorowej cytometrii przeplywowej do identyfikacji markerów czynnosciowych limfocytów nTreg u chorych na ciezka astme oskrzelowa.

INTRODUCTION: At present, severe asthma is a particular clinical problem. An important role is attributed to dysfunction of nTreg subpopulations of lymphocytes in the pathogenesis of asthma. Therefore, the purpose of this study was to identify markers of nTreg cell function in patients with severe and mild to moderate asthma. MATERIAL AND METHODS: The study included sixty patients with asthma (30 with severe and 30 with mild to moderate asthma). The control group comprised 30 healthy volunteers. The diagnosis of asthma was confirmed accordance with generally accepted recommendations (GINA 2008). nTreg immunophenotype CD4/CD25/CD127/FoxP3/GITR/CD152/CCR5/ /CCR7 was evaluated by multicolor flow cytometry. RESULTS: We showed a significant reduction in the percentage of nTreg (76%) cells and the expression of CD152 (46.2%) in patients with severe asthma compared with mild-moderate asthma (85.5% and 86.7%; p 〈 0.05). It was observed that the transcription factor FoxP3 expression in nTreg cells positively correlated with FEV1 in patients with severe asthma (r = 0.53; p 〈 0.05). It was also found that the ratio nTregCCR5∗/TeffCCR5∗ was significantly reduced in patients with severe asthma (0.91) compared with mild-moderate (1.58) asthma and control groups (1.55; p 〈 0.001). CONCLUSIONS: There are phenotypic differences in nTreg lymphocytes between patients with severe and mild-moderate asthma. This fact may confirm nTreg cell dysfunction and indicate that the potential markers (FoxP3, CD152, CCR5), can be used to monitor the effectiveness of treatment of bronchial asthma, especially severe disease.

Evaluation of the relationship between leptin, resistin, adiponectin and natural regulatory T cells in relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Data suggest that adipocytokines and natural regulatory T (nTreg) cells play a pivotal role in the immunopathogenesis of multiple sclerosis and the associated inflammation. The purpose of this study was to evaluate selected adipocytokines and nTreg cells and to assess their relationship with relapsing-remitting multiple sclerosis (RRMS). MATERIAL AND METHODS: The study was conducted among 25 patients with RRMS and 25 healthy individuals. Blood samples were collected within two weeks after the beginning of acute relapse of RRMS. The body mass index (BMI) of each patient was calculated. Serum adipocytokine concentrations were determined by ELISA and nTreg cells were evaluated using multicolour flow cytometry. RESULTS: Patients and controls had similar BMI, regardless of gender. Significantly higher leptin and resistin levels and significantly lower adiponectin levels were found in patients with RRMS in comparison to the control group (p < 0.0001). The percentage of nTreg cells (p < 0.01) and the mean fluorescence channel (MFC) of FoxP3 were significantly reduced in patients with RRMS (p < 0.001). There was an inverse correlation be-tween leptin concentration and MFC of the transcription factor Foxp3 nTreg in patients with RRMS (r = -0.7, p < 0.05). CONCLUSIONS: Proinflammatory adipocytokine profile and decreased percentage of nTreg cells suggest their implication in the inflammatory response in RRMS regardless of corticosteroid therapy. The correlation between leptin and the MFC of the transcription factor Foxp3 in nTreg cells in patients with RRMS suggests its inhibitory effect on FoxP3 expression.

The patents on glucocorticosteroids and selected new therapies for the management of asthma in children.

Despite the continuous increase in the prevalence of asthma in the most underdeveloped parts of the world, nowadays, we can generally speak of a better understanding and management of this disease. The remarkable role played by the inflammatory process in asthmatic patients is well known. The aim of most asthma guidelines is to suppress inflammatory process with a combination of anti-inflammatory drugs and immunotherapy. The management of asthma in children is a challenge because of their inability to express warning signs and seek medical attention in a timely manner. Unlike adults, asthmatic children must rely on their parents or caregivers for the administration of asthma medications. This inability to carry and self-administer asthma drugs may increase the risk of non-compliance. Glucocorticosteroids, the most important drugs for patients with asthma, are associated with an increased level of side effects and compliance issues mostly in children. In an attempt to solve that dilemma, emphasis is being placed on the modification of current management tactics and the introduction of other drugs. This review presents more recent patent therapies for the management of asthma in children.

Manganese superoxide dismutase (MnSOD) gene (Ala-9Val, Ile58Thr) polymorphism in patients with age-related macular degeneration (AMD).

BACKGROUND: Oxidative stress is involved in the pathogenesis of many chronic disorders including cancer, inflammation, and neurologic diseases. Reactive oxygen species (ROS) may play a major role in age-related macular degeneration (AMD). This study investigated the mRNA and protein profiles of manganese superoxide dismutase MnSOD in patients with AMD and healthy controls, while examining its genetic sequence polymorphism (Ala-9Val, Ile58Thr). Our intent was to find a correlation between the expression of MnSOD genes and nucleotide sequence polymorphisms encoded in the gene of the dry and wet form of AMD. MATERIAL/METHODS: We examined 300 unrelated AMD patients and 300 unrelated healthy controls who gave free consent to participate in the study. The MnSOD gene polymorphisms were determined by PCR/RFLP method. We also used real-time RT-PCR and ELISA methods to estimate expression of MnSOD mRNA and protein. RESULTS: There were statistically significant differences in the genotype distribution between patients with AMD and controls. Our results showed positive correlations between gene sequence polymorphism and the level of MnSOD mRNA and protein expression. The Ala-9Ala genotype and alanine allele (Ala-9Val sequence polymorphism) is much more frequent in AMD patients than in healthy subjects. Healthy controls who are homozygotes Val/Val and heterozygotes Ala/Val showed lower expression of the MnSOD gene as compared to homozygote Ala/Ala. The lowest expression of MnSOD (homozygotes Val/Val and heterozygotes Ala/Val for wet and dry form of AMD) was noted in patients with AMD. CONCLUSIONS: These data suggest a genetic role of MnSOD polymorphism in the development of age-related degeneration.