Evaluation of the CD14/-260 polymorphism and house dust entotoxin exposure in the Barbados Asthma Genetics Study

BACKGROUND: Both a functional promoter polymorphism in the gene encoding CD14 (C-260T) and exposure to endotoxin are believed to play key roles in modulating the immune response and expression of atopic disease. OBJECTIVE: We aimed to evaluate the role of the CD14 C-260T polymorphism in a population of African descent and to test for interaction between this genotype and house dust endotoxin (HDE) exposure on atopic phenotypes. METHODS: Asthmatic probands and their families were recruited as part of the Barbados Asthma Genetics Study. The C-260T polymorphism and two additional CD14 promoter markers (G-1461T, C-1721T) were genotyped. Endotoxin was measured in house dust samples. RESULTS: Using a Family-Based Association Test, the C-260T allele appeared to be protective against asthma (z=−2.444; P=.015) and asthma severity (z=−2.615; P=.009) under a recessive model. No significant associations were observed for the G-1461T and C-1721T markers both individually and in haplotypes. In a case-control analysis, the CD14 TT genotype was found to reduce risk of asthma compared with the CD14 CC/CT genotypes (odds ratio [OR], 0.26; 95% CI, 0.14-0.49) and was associated with lower asthma severity scores (P < .002). The TT genotype might protect against asthma for individuals with low HDE (OR, 0.09; 95% CI, 0.03-0.24), but may be a risk factor for individuals with high HDE (OR, 11.66; 95% CI, 1.03-131.7), suggesting a gene-environment interaction. CONCLUSION: These data suggest that the CD14-260 polymorphism may play a role in controlling risk to atopic disease and underscore the importance of incorporating key environmental exposures into studies of genetic risk factors.

Short report: long-term serum antibody isotype responses to Strongyloides stercoralis filariform antigens in eight patients treated with ivermectin

The enzyme-linked immunosorbant assay was used to investigate long term changes in serum immunoglobulin G1 (IgG1), IgG4, IgE, and IgA against Strongyloides stercoralis phosphate-buffered saline-soluble filariform larval antigens in eight Jamaican patients treated with ivermectin. Patients were followed for periods of between 170 and 542 days. Based on repeated formalin-ether concentration and agar plate culture, all patients were found to be uninfected up to 18 months following chemotherapy. Generally, all antibody isotype levels decreased following treatment, although there was considerable heterogeneity among patients. In a single patient with hyperinfection, the decrease in IgG4 was marginal and may represent a treatment failure. Reduction in serum antibody isotype responses to S. stercoralis following treatment may be used to assess the effectiveness of ivermectin in treating endemic strongyloides (AU)

Linkage of asthma and total serum IgE concentration to markers on chromosome 12q: evidence from Afro-Caribbean and Caucasian population

To identify genes potentially relevant in atopic asthma, we analyzed markers in chromosome 12q15-q24.1 for linkage to asthma and total serum Ige concentration. Sib-pair analyses of 10 markers in 345 full- and 219 half-sib pairs from 29 multiplex Afro-Caribbean families provided evidence for linkage to his region for both asthma and total serum IgE. Certain alleles at these loci showed significant evidence of transmission disequilibrium with both asthma and high IgE. Using 6 of these markers and 11 additional markers, evidence for linkage of total IgE to 12q was also found in 12 Caucasian Amish kindreds (24 nuclear families) by both sib-pair and transmission disequilibrium analyses. These findings suggest that the 12q15-q24.1 region may contain a gene(s) contolling asthma and the associated high total IgE. trait.(AU)

The role of total IgE as a predictor of asthma in Barbadian subjects - abstract

Assessment of the epidemiology of asthma requires that the asthma phenotype be characterized. A study was conducted in Barbados among 24 families (n = 175 persons). The geometric mean serum total IgE (tIgE) was 559.8 ng/ml, and was significantly higher in asthmatic subjects (n = 88; means = 1352.1) than in non-asthmatic subjects (n = 87; means = 229.6; t-test, p < 0.001). Asthma subjects reported shortness of breath (80.7 percent), cough (77.3 percent), wheezing (72.7 percent). An index of asthma severity was created based on questionnaire data. Shortness of breath, cough and wheeze were similarly correlated with the index of severity; however, none of the symptoms were significantly correlated with tIgE. Similarly, tIgE was not correlated with the severity score of any of the individual variables that comprised the severity score. The findings in this study of Afro-Caribbean subjects living in a tropical setting concur with those of Caucasian subjects living in developed, temperate locales, whereby tIgE is a good means of classifying the presence or absence of asthma. The poor association between tIgE and severity of asthma and asthma symptoms warrants further investigation into the validation of the severity scale, but raises the question regarding the absence of a relationship between tIgE and asthma severity (AU)

Year-round total serum IgE and IgG4 levels in allergic and non-allergic West Indian medical students

Twenty-four allergic and non-allergic West Indian medical students and pathology technologists had repeated serum IgE an dIgG4 levels determined over a one-year period. Contrary to previously published reports on this type of population, total serum IgE levels were usually consistently normal (18 of 24 subjects) with little variation throughout the year. The remaining six subjects, all allergic and non-allergic elevated levels (620-1096 kU/1). Total serum IgG4 was elevated in most of the allergic and non-allergic subjects (18 0f 24). Perennial exposure to molds and house dust mite in this tropical environment could possibly produce the chronic antigenic stimulation reponsible for the elevation in serum IgG4 levels found in this study (AU)

The significance of serum IgE levels in Trinidad and Tobago - abstract

In Trinidad, normal non-atopic children, mean age 2.5 years, had serum IgE's of 133 Ku/l whereas in the northern hemisphere the corresponding value for 9-month to 3-year-old children is 33 Ku/1 and the adult mean is 100 Ku/1. However, childhood asthmatics with helminthic infestation had a mean serum IgE of 1,432 Ku/l. On the other hand, childhood asthmatics whose stools were negative for helminths had significantly (840 Ku/l) less serum IgE, confirming the additive effect of helminths upon the type I hypersensitivity response in children. Those children who were diagnosed as having atopic dermatitis had the highest mean serum IgE concentrations (1,892 Ku/l). Blood Donors had a mean serum IgE of 231 Ku/l. It is concluded that serum IgE is of significant importance in identifying the atopic state, even in countries with endemic helminthic infestation. However, local normal and abnormal ranges need to be established before the results can be correctly interpreted (AU)

Total serum IgE and IgG4 levels in allergic and non-allergic West Indian medical students - abstract

Despite high prevalence rates of allergic illnesses in the region, the laboratory indices of these disorders have not been documented. This prospective controlled study was undertaken to determine the levels of sensitizing antibodies (IgE and IgG4) and their variation over a one-year period. The subjects, 17 allergic and 7 non-allergic pre-clinical medical students and laboratory technologists, were selected by questionnaire. Blood samples were collected at approximately 3-monthly intervals and a stool sample at the beginning of the study. Routine haematological and microbiological investigations were carried out on blood and stool samples respectively. IgE was measured by enzyme immunoassay and IgG4 by radial immunodiffusion. Haematological and coprological investigations were normal in all subjects. Total serum IgE levels were higher in allergic subjects than in controls (geometric means 192ñ4.5 and 77ñ3.5 Ku/1 respectively) and there were no seasonal fluctuations in either group. Both groups had similar IgG4 levels which also showed no seasonal variation (geometric means 0.88ñ2.18 and 1.01ñ1.89g/L respectively). These IgG4 values were elevated in comparison with those reported for Europeans (mean 0.6g/1). The total IgE levels in our study, which were within the normal range for temperate populations, were much lower than those reported for tropical populations. Total serum IgE levels in isolation were unable to distinguish between allergic and non-allergic individuals. There was no evidence of a seasonal allergen. The elevation in IgG4 levels in control and allergic subjects has not been previously reported. Chronic antigenic stimulation is thought to produce elevated IgG4 levels. It is possible that chronic perennial allergenic stimulation may contribute to the raised IgG4 levels found in this study (AU)

Plasma protein response in children with trichuris dysentry syndrome - abstract

In Trichuris Dysentry Syndrome (TDS), we have elsewhere shown an IgE-mediated mucosal mast cell inflammatory response and infiltration of the colonic lamina propria by macrophages with evidence of the cellular production to TNF O. There is an increased concentration of this cytokine in the systemic circulation: both this and the correlation of finger-clubbing with worm load are evidence of an inflammatory response which is systemic as well as local to the intestine. We therefore assayed the plasmas of 53 TDS children, 16 "disease control" (DC) and 20 "normal control" (NC) children for plasma protein changes. DC children were Trichuris negative patients who had clinical indications for colonoscopy, mainly chronic diarrhoea; NC were trichuris-negative asymptomatic children of similar background to the TDS patients who were subjected to venepuncture and non-invasive tests of intestinal permeability and intestinal protein clearance (normal). There was a significant increase (p<0.05) in the means of C-Reactive protein (CRP) and antitrypsin in the TDS compared with the NC group. The mean increase in the DC group was significantly differernt from the NC. The reduction in the mean albumin concentration in TDS compared with NC children was not quite significant (p=0.05). Caeruloplasmin showed a significant difference only between the DC and NC children (p < 0.05). The other plasma proteins assayed, transferrin and fibrinogen, showed no significant difference in their means among the three groups. These changes in plasma protein concentrations are indicative of a generalized sytemic response to Trichuris trichuria and correspond to a continuous, mile "acute phase response" to this chronic infection (AU)