Genetic ‘risk’ for atopy is associated with delayed postnatal maturation of T‐cell competence

Holt, Patrick G.; Clough, Joanne; Holt, Barbara J.; Baron‐Hay, M. J.; Rose, Alison H.; Robinson, B. W.; Thomas, Wayne R.

doi:10.1111/j.1365-2222.1992.tb00135.x

Cited by 256 publications

(168 citation statements)

References 29 publications

Supporting

Mentioning

157

Contrasting

Order By: Relevance

“…This phenotype of low Th1/Th2 cytokine production observed in an unselected community cohort was also seen in infants at high genetic risk for atopy, who show delayed maturation of T-cell competence (13). Noakes and coworkers (14) examined the relationship between MSP and cord blood mononuclear cell cytokine responses and found that IL-13 production in response to house dust mite (HDM) or ovalbumin was higher in infants exposed to MSP (n = 17) than in unexposed (n = 40) neonates.…”

Section: At a Glance Commentarymentioning

confidence: 56%

Persistent Effects of Maternal Smoking during Pregnancy on Lung Function and Asthma in Adolescents

Hollams¹,

Klerk

Holt³

et al. 2014

Am J Respir Crit Care Med

108

View full text Add to dashboard Cite

Rationale: The extent to which maternal smoking in pregnancy (MSP) has persisting effects on respiratory health remains uncertain and the mechanisms involved are not fully understood. Alterations in immune function have been proposed as a mechanism contributing to respiratory disease.Objectives: To determine whether MSP increases risk of respiratory disorders in adolescence and, if so, whether this occurs by decreased lung function, altered immune function, and/or enhanced atopy.Methods: Data on spirometry, bronchial responsiveness, respiratory symptoms, total and allergen-specific IgE and IgG4, immune function, and inflammatory markers were obtained from 1,129 participants in the 14-year follow-up of the Western Australian Pregnancy (Raine) Cohort and related to MSP using regression analyses.Measurements and Main Results: MSP was reported for 21.0% (237 of 1,129) of participants, with 92 (8.1%) reporting current smoking. MSP was associated with some altered immune measures at age 14. MSP was strongly related to reduced lung function in current nonsmokers (forced expiratory flow midexpiratory phase ], P = 0.016; FEV 1 /FVC, P = 0.009) and increased risk for current asthma (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.16-2.92; P = 0.01), current wheeze (OR, 1.77; 95% CI, 1.14-2.75; P = 0.011), and exercise-induced wheeze (OR, 2.29; 95% CI, 1.37-3.85; P = 0.002), but not for bronchial hyperresponsiveness or atopy. Adjustment for immune measures and/or lung function in multivariate models did not greatly alter these associations and the increased risks for asthma and wheeze were not modified by sex, atopy, or maternal history of asthma or atopy.Conclusions: MSP increases risk of asthma and wheezing in adolescence; mechanisms go beyond reducing lung function and exclude altering immune function or enhancing atopy.Keywords: atopy; immune function; bronchial hyperresponsiveness; Raine study At a Glance CommentaryScientific Knowledge on the Subject: The impact of maternal smoking during pregnancy on lung function and asthma risks in children is well known. However, how long these effects persist and how they are mediated is not clearly understood.What This Study Adds to the Field: The data from the present study show that maternal smoking during pregnancy increases risk for asthma and wheeze that persist into adolescence independent of effects on lower lung function, immune function, or allergic sensitization in adolescents.

show abstract

Section: At a Glance Commentarymentioning

confidence: 56%

Persistent Effects of Maternal Smoking during Pregnancy on Lung Function and Asthma in Adolescents

Hollams¹,

Klerk

Holt³

et al. 2014

Am J Respir Crit Care Med

108

View full text Add to dashboard Cite

show abstract

“…The capacity to induce protective Th1 immune responses develops early in life, primarily over the first year (37), but appears to be delayed in children predisposed to atopy (38). In fact, Th2 polarization appears to be more prominent and to persist until a greater age in such children (39,40).…”

Section: Age Atopy and Defense Against Viral Respiratory Infectionmentioning

confidence: 99%

Microbial Manipulation of Immune Function for Asthma Prevention: Inferences from Clinical Trials

Yoo

Tcheurekdjian

Lynch

et al. 2007

Proceedings of the American Thoracic Society

View full text Add to dashboard Cite

The "hygiene hypothesis" proposes that the increase in allergic diseases in developing countries reflects a decrease in infections during childhood. Cohort studies suggest, however, that the risks of asthma are increased in children who suffer severe illness from a viral respiratory infection in infancy. This apparent inconsistency can be reconciled through consideration of epidemiologic, clinical, and animal studies. The elements of this line of reasoning are that viral infections can predispose to organ-specific expression of allergic sensitization, and that the severity of illness is shaped by the maturity of immune function, which in turn is influenced by previous contact with bacteria and viruses, whether pathogenic or not. Clinical studies of children and interventional studies of animals indeed suggest that the exposure to microbes through the gastrointestinal tract powerfully shapes immune function. Intestinal microbiota differ in infants who later develop allergic diseases, and feeding Lactobacillus casei to infants at risk has been shown to reduce their rate of developing eczema. This has prompted studies of feeding probiotics as a primary prevention strategy for asthma. We propose that the efficacy of this approach depends on its success in inducing maturation of immune function important in defense against viral infection, rather than on its effectiveness in preventing allergic sensitization. It follows that the endpoints of studies of feeding probiotics to infants at risk for asthma should include not simply tests of responsiveness to allergens, but also assessment of intestinal flora, immune function, and the clinical response to respiratory viral infection.Keywords: asthma; gastrointestinal; lactobacilli; microbes; prevention The purpose of this review is to sketch the rationale for a theory of asthma's pathogenesis. The proposed theory is that asthma is caused, at least in part, by infection, especially in infancy, by a respiratory virus, most likely a human rhinovirus (HRV). The development of asthma may thus be a function of the "asthmagenic" pathogenicity of the strains of RV causing asthma in infancy and of the efficacy of antiviral immune function at the time of infection. This review notes how the validity of this theory might be examined by adding additional outcomes to ongoing trials of feeding a "probiotic," like Lactobacillus casei, to infants as a primary prevention strategy for allergic disease. Space constraint does not permit more than a brief, partial review

show abstract

“…More recently, the authors9 laboratory has sought to extend these findings to allergic disease in general. The key findings, based upon quantitative T-cell cloning studies and cytokine analyses on extensive panels of isolated clones, indicate that an important element of genetic susceptibility to atopy involves delayed postnatal maturation of Th1 function [20]. The present authors showed that the capacity of CD4z Th-cells from infants at high risk (HR) of atopy to produce both Th1 and Th2 cytokines was reduced relative to their low risk (LR) counterparts; however, the reduction in IFN-c was greatest, resulting in a relative Th2 "skewing" of responsiveness in the HR children.…”

Section: T-cell Immunity To Inhalant Allergens: the Basis Of Variatiomentioning

confidence: 99%

“…4) The earlier that Th2-polarized memory against inhalant allergens develops, the more severe are the long-term consequences in relation to AHR [59,60], implying that repeated cycles of airway inflammation during rapid lung growth may establish some form of "matrix" for development of subsequent changes associated with airway remodelling. 5) Genetic risk for atopy is associated with sluggish postnatal maturation of adaptive immune function, in particular, Th1 function [20,27].…”

Section: The Apparent Dualistic Effects Of Respiratory Tract Infectiomentioning

confidence: 99%

Interactions between respiratory tract infections and atopy in the aetiology of asthma

Holt

Sly²

2002

European Respiratory Journal

View full text Add to dashboard Cite

The prevalence of asthma, in particular atopic asthma, has markedly increased in recent years. Accumulating evidence suggests that environmental factors associated with allergic sensitization and exposure to microbial stimuli during infancy and early childhood, are associated with these changes in prevalence. However, considerable controversy surrounds the role of microbial agents, as evidence has been presented for both positive and negative effects in this context.The review below focuses upon interactions between immune competence during infancy, the development of T-helper (Th)1-polarized versus Th2-polarized memory against inhalant allergens, and susceptibility to virus infection. In particular, recent finding are highlighted which suggest that delayed postnatal maturation of Th1 function is associated with increased risk for early postnatal sensitization to inhalant allergens, and also with risk for viral bronchiolitis during infancy.Variations in the kinetics of postnatal maturation of T-helper 1 function may in part be attributable to polymorphisms in the CD14 gene, which influence host responsiveness both to bacterial as well as viral stimuli. It is evident from a wide range of studies carried out in different geographical areas, that the prevalence of allergic diseases, and in particular atopic asthma, has increased markedly over the last 2-3 decades. Moreover, the increases become evident in successive birth cohorts during early childhood. It is also generally accepted that "diagnostic shift" is not a significant factor in these changes. Accordingly, given the timeframe over which the changes have occurred, the responsible factor(s) must be environmental, presumably interacting with one or more susceptibility genes.The search for the relevant genetic and environmental factors continues, and a variety of potential candidates have been identified. Prominent amongst these are factors related to respiratory infections, particularly those occurring in childhood. Paradoxically, these infections have been invoked both as potential protective factors in relation to asthma/ allergy development, and as triggers of asthma exacerbations in atopic asthmatics. The mechanisms by which these effects may be mediated are incompletely understood; however, recent findings suggest some intriguing new possibilities, which are discussed in this review. T-cell immunity to inhalant allergens: the basis of variations in responder phenotype within the adult populationThe epithelial surface of the upper and lower respiratory tract are continuously exposed to an array of pathogenic and nonpathogenic airborne antigens, and the induction and local expression of local T-cell immunity must accordingly be tightly controlled, in order to avoid the pathological consequences of chronic T-cell-driven inflammation. While it is highly plausible that resistance to airborne pathogens is a direct function of the speed of mobilization and the intensity of expression of local innate and adaptive immune mechanisms in the lung, the conve...

show abstract

Genetic ‘risk’ for atopy is associated with delayed postnatal maturation of T‐cell competence

Cited by 256 publications

References 29 publications

Persistent Effects of Maternal Smoking during Pregnancy on Lung Function and Asthma in Adolescents

Persistent Effects of Maternal Smoking during Pregnancy on Lung Function and Asthma in Adolescents

Microbial Manipulation of Immune Function for Asthma Prevention: Inferences from Clinical Trials

Interactions between respiratory tract infections and atopy in the aetiology of asthma

Contact Info

Product

Resources

About