Blood and nasal epigenetics correlate with allergic rhinitis symptom development in the environmental exposure unit.

BACKGROUND: Epigenetic alterations may represent new therapeutic targets and/or biomarkers of allergic rhinitis (AR). Our aim was to examine genome-wide epigenetic changes induced by controlled pollen exposure in the environmental exposure unit (EEU). METHODS: 38 AR sufferers and eight nonallergic controls were exposed to grass pollen for 3 hours on two consecutive days. We interrogated DNA methylation at baseline and 3 hours in peripheral blood mononuclear cells (PBMCs) using the Infinium Methylation 450K array. We corrected for demographics, cell composition, and multiple testing (Benjamini-Hochberg) and verified hits using bisulfite PCR pyrosequencing and qPCR. To extend these findings to a clinically relevant tissue, we investigated DNA methylation and gene expression of mucin 4 (MUC4), in nasal brushings from a separate validation cohort exposed to birch pollen. RESULTS: In PBMCs of allergic rhinitis participants, 42 sites showed significant DNA methylation changes of 2% or greater. DNA methylation changes in tryptase gamma 1 (TPSG1), schlafen 12 (SLFN12), and MUC4 in response to exposure were validated by pyrosequencing. SLFN12 DNA methylation significantly correlated with symptoms (P < 0.05), and baseline DNA methylation pattern was found to be predictive of symptom severity upon grass allergen exposure (P = 0.029). Changes in MUC4 DNA methylation in nasal brushings in the validation cohort correlated with drop in peak nasal inspiratory flow (Spearman's r = 0.314, P = 0.034), and MUC4 gene expression was significantly increased (P < 0.0001). CONCLUSION: This study revealed novel and rapid epigenetic changes upon exposure in a controlled allergen challenge facility, and identified baseline epigenetic status as a predictor of symptom severity.

[Knowledge, attitudes and practices about blood donation. A sociological study among the population of Lomé in Togo]. / Etude des connaissances, attitudes et pratiques en matière de don de sang. Enquête sociologique dans la population de Lomé (Togo).

GOALS: 1) analyse the knowledge, attitudes and practices of Lome population about blood donation; 2) identify obstacles to blood donation among the population of Lome; 3) suggest some solutions to improve the performance of the National Blood Transfusion Centre (CNTS). METHODOLOGY: We have conducted a sample survey among the population of Lome from the 6th to 21st October 2003. Three hundred persons filled a questionnaire. RESULTS: In the sample, 183 (61%) were males. Their age ranged from 18 to 67 years with 2/3 of young peoples between 18 and 37 years. Pupils/students were 24,33%, wage-earners, 55% and the unemployed, 17,67%. More than the half of the investigated persons (54,67%) were unmarried and 96, 33% persons were literate. Nearly all the people (96,33%) knew about blood donation in Lome and they have received information mainly from friends, media and sensitization by the CNTS. Sixty-one percent of the investigated knew where blood is donated. All the investigated were unanimous about the vital role of blood. Whatever their religion, they recognized its sacred nature. The majority of the investigated (85%) were willing to donate blood. Only 95 people were donors. The reasons for non-donation were mainly related to the fear of catching diseases (31,71%) especially the HIV (9,76%), the lack of information (25,37%), the religious beliefs (19,51%) and the fear of knowing the result of one's HIV test. 277 people (92,33%) said that blood should be donated without remuneration. CONCLUSION: There is a growing interest in the blood donation among the population of Lome but new strategies must be elaborated to inform the population and motivate blood donors.

[Assessment of 32 months of continuous control of detection kits for anti-HIV and anti-HTLV antibodies and Hbs antigen used most commonly in transfusion biology. Retrovirus Study Group and Viral Hepatitis Study Group]. / Bilan de 32 mois de contrôle continu des trousses de dépistage des anticorps anti-VIH, anticorps anti-htlv et antigène hbs les plus utilisées en biologie transfusionnelle. Rétrovirus et Hépatites Virales de la SFTS.

Controls were performed using a common internal panel specific for anti-HIV, anti-HTLV and HBs Ag. During the past 32 months, 5 anti-HIV1 + 2 antibody kits (Abbott, Behring, Biotest, Murex D. and Organon T., total of 199 lots), 4 anti-HTLV I/II antibody kits (Abbott, Murex D., Organon T. and Ortho C.D., total of 153 lots) and 5 HBs Ag kits (Abbott, S.D. Pasteur, Murex D., Organon T. and Ortho C.D., total of 244 lots) were used and controlled by the 14 participating laboratories. Analysis of the results showed the values obtained for the most representative sample of each panel to be within the limits m +/- 2 SD in 95 to 100% of the HIV1 + 2 kits, in 94 to 97% of the HTLV kits and in 92 to 100% of the HBs Ag kits. The specificity of the kits evaluated was on an average equal or superior to 99.5%, as required by the French Drug Agency in a blood donor population.

[Hepatitis B virus, serological markers of viral infections and humoral immunity in alcoholic cirrhosis]. / Virus de l'hépatite B, marqueurs sérologiques d'infections virales et immunité humorale au cours de la cirrhose alcoolique.

In order to define the role of hepatitis B virus (HBV) in alcoholic liver disease and to study the relationship between HBV and other common viruses, the serological markers of viral disease (HBV, Rubella, Polio, Herpes, and Cytomegalovirus-CMV) were compared in 163 patients with alcoholic cirrhosis (group C), 100 patients with alcoholic steatosis (group S) and in 168 non-alcoholic control subjects (group NA). A significantly increased prevalence of HBV markers in group C was related to the presence of anti-HBc antibodies, in 10.5 p. 100 of cirrhotic patients, vs. 1.2 p. 100 in group S and 1 p. 100 in group NA (p less than 0.01). In cirrhotic patients with HBV markers (HBV +) incidence of alcoholic hepatitis was 4 times lower and the total duration of alcohol overconsumption was significantly lower than in cirrhotic patients without these markers (HBV-). Hepatic function tests were not different in HBV + and HBV- cirrhotic patients, excepted for the ASAT/ALAT ratio (1.55 +/- 0.10 vs. 1.92 +/- 0.12; p less than 0.05). Prevalence of anti-CMV antibodies, and anti-herpes greater than 1/100 antibodies, was significantly increased in S and C groups (p less than 0.01). Anti-Rubella, Polio, and CMV antibody titers were higher (p less than 0.05) in HBV + than in HBV- cirrhotic patients. In cirrhotic subjects, titers of these 3 anti-virus antibodies were not related to alcoholic hepatitis or to IgG and IgM concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

[Determination of sub-populations of circulating T lymphocytes in alcoholic cirrhosis using monoclonal antibodies OKT3, 4, 5, Leu 2 and Leu 15. Effect of hepatitis B virus infection]. / Détermination des sous-populations lymphocytaires T circulantes au cours de la cirrhose alcoolique par les anticorps monoclonaux OKT3, 4, 8, Leu 2 et Leu 15. Influence de l'infection par le virus de l'hépatite B.

Peripheral T lymphocyte subpopulations were quantified in 24 alcoholic cirrhotic patients, 11 of them having anti-HBs and/or anti-HBc antibodies, and were compared with 35 healthy control subjects, 10 of them having anti-HBs and/or anti-HBc antibodies. The monoclonal antibodies utilized (OKT3, OKT4, OKT8 in simple staining, Leu 2 and Leu 15 in double staining) are considered as markers of mature (CD3), helper (CD4), cytotoxic/suppressor (CD8, Leu 2), suppressor (Leu [2+ 15+), and cytotoxic (Leu 2+ 15-) T cells. In cirrhotics, when compared to controls, the number of CD3 cells was reduced (p less than 0.01); the proportion of CD4 cells was within normal range, and that of CD8 cells diminished (p less than 0.001), contrasting with an increased proportion of Leu 2+ cells (p less than 0.01), related to an increased proportion of Leu 2+ 15+ cells. Leu 2+ 15- lymphocytes were within normal range. In control subjects, a decreased proportion of Leu 2+ 15+ cells was found (p less than 0.05) when Ac HBs and/or Ac HBc were present. In cirrhotics having at least one serologic marker of hepatitis B virus infection, when compared with negative ones, increased proportions of Leu 2+ (p less than 0.05) and Leu 2+ 15+ (p less than 0.05) cells were found. These results show that data concerning T lymphocyte subpopulations are conflicting when various types of antibodies are used. However, they suggest abnormalities of immune regulation, possibly a defect of T suppressor cell function. Hepatitis B virus infection probably modifies immune regulation in alcoholic cirrhosis, and perhaps in normal subjects.

[Hemoglobin abnormalities diagnosis in the clinical laboratory (author's transl)]. / Les anomalies de l'hémoglobine: leur diagnostic en biologie clinique.

For routine detection of hemoglobin abnormalities, a number of tests are necessary including hemoglobin electrophoresis at alkaline pH, the study of hemoglobin molecular stability, possibly assay for hemoglobin A2 and hemoglobin F, as well as tests for reduced hemoglobin solubility in cases where hemoglobin S is suspected. Among the complementary techniques required for identification of abnormal hemoglobin or electrophoretically "silent" mutants, isoelectrofocalization is the method of choice and is easily set up in the clinical laboratory.

[Assay of plasma fibronectin in clinical biology: comparison of nephelometric and turbidimetric technics]. / Dosage de la fibronectine plasmatique en biologie clinique: comparaison des techniques néphélométrique et turbidimétrique.

The aim of this study was to determine the optimal conditions for the assay of plasma Fn by laser nephelometry, to compare the nephelometric and turbidimetric techniques and to confirm the influence of various parameters on the Fn concentration. The results reveal that both techniques are sensitive (threshold of sensitivity: 20 mg/l with laser nephelometry, 125 mg/l with turbidimetry), reproducible (coefficient of variation of less than 10 p. cent), specific, simple and rapid. The interpretation of the results must take into account the influence of various factors on the Fn concentration. Fn is present in lower concentrations in the serum and the percentage of serum Fn to the plasma concentration varies from one sample to another in the same patient. The optimal conditions for the assay include collection of the plasma on EDTA, storage of the samples at - 20 degrees C and incubation of the sample at 37 degrees C prior to the assay. There is a relationship between the concentration of Fn and the sex and age of the subject. There is a significant difference between the sexes between the ages of 18 and 40, which is no longer seen after the age of 50. The ability to assay plasma Fn by rapid, specific and sensitive techniques enables us to evaluate the capacity of response of the reticulo-endothelial system in conditions of severe sepsis.

[Cooley's syndrome in a Togolese nursing infant. Clinical and biological considerations]. / La maladie de Cooley chez un nourrisson togolais. Considérations cliniques et biologiques.

Several possible diagnoses are proposed to explain the symptomatology observed in a slightly jaundiced 10 month-old suckling infant suffering from fever and anaemia. Major beta-thalassaemia in its most severe form (Cooley's syndrome) proved to be the correct diagnosis. The importance of family background is stressed for these haemolytic cases.

[Determination of synovial fibronectin by laser nephelometry. Its diagnostic value in rheumatology]. / Dosage de la fibronectine synoviale par néphélométrie laser. Son intérêt diagnostique en rhumatologie.

The object of the present study was to define the optimal conditions for the quantitative determination of fibronectin in synovial fluid by laser nephelometry and to determine the diagnostic importance of this analysis in rheumatology. The results show that this technique is sensitive (threshold sensitivity is 70 mg/l if the sample is diluted 1/30 and 5 mg/l for a sample diluted to 1/2), accurate, reproducible (coefficient of variation less than 10%), specific, simple and rapid. The response is linear for dilutions from 1/30 to 1/240. Fibronectin P and fibronectin S were determined in 104 subjects who had contracted an arthropathy; 26 cases of rheumatoid polyarthritis, 43 mechanical arthropathies and 35 cases of non-rheumatoid arthritis. the plasma fibronectin does not vary significantly from one group of arthropathies to another but the mean value for the total population of arthropathies is significantly lower than that for a control group. In the synovial fluid the mean value for fibronectin in the patients with rheumatoid arthritis (583 + 76 mg/l) is very considerably higher than that in non-rheumatoid (379 + 58 mg/l) or mechanical (367 + 32 mg/l) arthritis patients. Thus, the determination of synovial fibronectin may provide useful information for the etiological diagnosis of inflammatory arthropathies.

[Good practices for the study of hemoglobin]. / Bonnes pratiques de l'étude de l'hémoglobine.

Hemoglobinopathies have become a significant national health problem in France. The biologists have a pivotal role in the genetic diagnoses. Although sickle cell disease (SCD) is the most frequent abnormality found: not less than 200 new cases are observed each year at birth, many other globin gene variations are found in the various ethnic groups. Since 1995 a neonatal sickle cell screening program has been established for at risk newborns. This programme is supported by the "Association française de dépistage et prévention des handicaps de l'enfant" (AFDPHE). The characterization of hemoglobin genetic variations requires a comprehensive set of laboratory techniques for which we specify here main clinical and technical recommendations.

[Beta-thalassemia in metropolitan France]. / Les beta-thalassémies en France métropolitaine.

OBJECTIVES: Update the data collected in 1990 in order to assess the distribution and management of thalassemic patients presently living in Metropolitan France. METHODS: A survey conducted in France in the clinical and biological departments of haematology permitted collection of epidemiological, clinical and biological data in a population of thalassemic patients followed-up in metropolitan France. RESULTS: Analysis of the replies revealed a total of 362 thalassemia with 249 beta-thalassemia major, 81 beta-thalassemia intermedia and 32 E-beta thalassemia. These patients predominated in the East of France and in the large cities. The total number of patients has remained stable over the last decade and new cases are decreasing. Among the 249 patients presenting with a ss-thalassemia major, 42 had received a bone marrow graft, whereas 207 were systematically transfused and 189 regularly underwent iron chelating. COMMENTS: Management is standardised and efficient but could be improved on with regard to iron chelating therapy.

[Hemoglobin A1c and its variations in pregnancy]. / L'hémoglobine A1c et ses variations au cours de la grossesse.

Variations in haemoglobin A1c were studied at different stages of pregnancy in 306 non-diabetic women, using a specific method. It was found that HbA1c levels progressively decreased during the first 25 weeks of pregnancy, then remained stable. No correlation was noted between carbohydrate metabolis and Hb A1c levels. The new assay provides additional information on glucose tolerance in pregnant women and could be used to detect gestational diabetes.

[Evaluation of malnutrition and immunity in alcoholic liver diseases]. / Evaluation de la dénutrition et de l'immunité au cours des maladies alcooliques du foie.

Disorders of immunity and nutritional status are known to be present in alcohol-induced diseases of the liver, but their significance is still debated. Nutrition and immunity were evaluated at different stages of the disease in 58 alcoholic patients with steatosis (n = 20), alcoholic hepatitis (n = 14) or cirrhosis (n = 24). Most of the anthropometric data and biochemical values relating to nutrition were altered to the same degree in these 3 groups. Only patients with cirrhosis had significantly lower blood albumin and zinc levels (P less than 0.01). Humoral immunity was altered in cirrhosis only and cellular immunity in all 3 liver diseases. There was no correlation between immunity and nutrition (except for blood zinc and E rosettes; P less than 0.01) or between these and alcohol consumption. Like several nutritional parameters, blood lymphocyte values correlated negatively with a liver disease severity index. It is concluded that disorders of nutrition and immunity are broadly comparable in alcohol-induced liver diseases; there is no direct statistical correlation between these disorders which seem to be independent of the type of liver disease.

[Epidemiology of genetic hemoglobin diseases in metropolitan France]. / Epidémiologie des maladies génétiques de l'hémoglobine en France métropolitaine.

The number of subjects with heterozygous beta-thalassaemia and sickle-cell anaemia in metropolitan France can be evaluated by the distribution of populations originating from countries with a high prevalence of genetic haemoglobinopathies. Taking into account the movements of these populations observed since the 1982 census, the current prevalences of beta-thalassaemic and drepanocytic traits are higher than the figures of 180,000 and 130,000 respectively found at that date. On the other hand, it appears from episodic screenings performed during the last few years that the percentage of subjects with heterozygous beta-thalassaemia is 3.09% in Corsica, 0.77% in school-age population in the Marseille area, and 0.72% in the general population of Marseille, Toulon and Nice. In 1992, the number of patients with heterozygous beta-thalassaemia and with major sickle-cell syndrome is estimated at 250-350 and 1000-3000 respectively. Patients with sickle-cell anemia predominate in the Paris area, whereas those with heterozygous beta-thalassemia predominate in the provinces, notably in the Provence-Côte d'Azur and Corsica regions.