Liza Breckler

Clinical effects of probiotics are associated with increased interferon‐γ responses in very young children with atopic dermatitis

Background We recently demonstrated that administration of probiotics resulted in significant clinical improvement in very young children with moderate‐to‐severe atopic dermatitis (AD). The purpose of this study was to determine the underlying immunological effects that are associated with these apparent clinical benefits.

Presymptomatic differences in Toll-like receptor function in infants who have allergy.

BACKGROUND Microbial exposure might play a key role in allergy development, but little is known about the role of Toll-like receptors (TLRs). OBJECTIVE This study explored the association between neonatal TLR microbial recognition/function, allergy risk (maternal allergy), and prospective allergy development. METHODS Cord blood mononuclear cells (n = 111) were cultured either alone or with optimal concentrations of TLR ligands: lipoteichoic acid (TLR2), polyinosinicpolycytidylic acid (TLR3), LPS with IFN-gamma (TLR4), flagellin (TLR5), imiquimod R837 (TLR7), or CpG (TLR9). Cytokine responses were assessed in relation to allergy risk (maternal allergy) and allergy outcomes (sensitization, food allergy, and atopic dermatitis) at 12 months of age. RESULTS Maternal allergy (n = 59) was associated with significantly higher neonatal IL-12 and IFN-gamma responses to TLR2, TLR3, and TLR4 activation, whereas TNF-alpha and IL-6 responses to TLR2, TLR4, and TLR5 activation were significantly higher in newborns who subsequently had allergic disease (n = 32). Notably, consistent with previous reports, newborns who had disease had lower T(H)1 IFN-gamma response to mitogens (PHA). CONCLUSION Allergic disease was associated with increased (rather than decreased) perinatal TLR responses. Further studies are needed to determine how these responses track in the postnatal period and whether this relative hyperresponsiveness is a product of intrauterine influences, including maternal atopy, functional genetic polymorphisms, or both.

Atopic dermatitis in young children is associated with impaired interleukin‐10 and interferon‐γ responses to allergens, vaccines and colonizing skin and gut bacteria

Background A significant proportion of children with food allergy and more severe forms of atopic dermatis (AD) go on to develop persistent forms of allergic disease such asthma. Defining immune dysregulation in these children will be of great value in understanding disease pathogenesis.

Supplementation with vitamins C, E, β‐carotene and selenium has no effect on anti‐oxidant status and immune responses in allergic adults: a randomized controlled trial

Background Anti‐oxidants are of growing interest in early treatment and prevention of allergic diseases in early life, but the effects on allergen‐specific immune responses need to be documented further before intervention studies in infants are undertaken. The aim of this study in adults was to determine the effects of dietary anti‐oxidants on allergen‐specific immune responses in sensitized individuals.

The effects of maternal smoking on early mucosal immunity and sensitization at 12 months of age

With the dramatic rise in asthma and respiratory disease, there is an urgent need to determine the effects of common environmental exposures on early immune development. In this study, we examined the effects of maternal smoking as a major adverse exposure in early life, on mucosal immune function and allergen sensitization in the first year of life. A cohort of 60 smokers and 62 non‐smokers was recruited in pregnancy, and followed prospectively at 3 and 12 months of age for saliva collection [for immunoglobulin (Ig) A measurements], urine collection (for cotinine levels) and clinical assessments (for allergy and infection history). Allergen skin‐prick tests were also performed at 12 months of age. Specific IgA to common colonizing bacteria was measured on saliva samples, including pneumococcal polysaccharide (PS) serotype 14 and non‐typeable Haemophilus influenza (NTHI) outer membrane protein 6 (OMP6). Eighty‐two mothers and their infants completed the 12‐month follow‐up period – 56 in the maternal non‐smoking group and 26 in the maternal smoking group. Maternal smoking was associated with significantly higher total infant salivary IgA at 12 months of age (p = 0.026), and more chronic upper respiratory tract symptoms (p = 0.012). However, there were no differences in the level of specific IgA antibodies to common colonizing bacteria (pneumococcal PS serotype 14 and NTHI OMP6). In general, the IgA levels at 12 months were higher in children who had more chest infections in the first year (Kendalls tau b, 0.282; p = 0.003). There was also a trend of lower respiratory tract symptoms (wheeze) (p = 0.142) in infants of smokers. There were no effects of maternal smoking on the rates of allergen sensitization, atopic dermatitis and food allergy at 12 months of age. In conclusion, maternal smoking did not inhibit the production of anti‐microbial IgA, suggesting that other factors are responsible for the increased susceptibility to infection in these infants. The increased mucosal inflammation in these children was not associated with effects on early allergy propensity.

Associations between antioxidant status, markers of oxidative stress and immune responses in allergic adults

Background There has been growing interest in the role of antioxidant function in controlling inflammatory disease states, such as allergy. This study investigated the relationship between antioxidant status, markers of airways inflammation [exhaled nitric oxide (eNO)], oxidative stress (F2 isoprostanes) and immune responses in allergic adults.

Pregnancy IFN‐γ responses to foetal alloantigens are altered by maternal allergy and gravidity status

Background:  During pregnancy, variations in maternal–foetal cellular interactions may influence immune programming. This study was carried out to determine if maternal responses to foetal alloantigens are altered by maternal allergic disease and/or previous pregnancies.

Modulation of in vivo and in vitro cytokine production over the course of pregnancy in allergic and non-allergic mothers.

Breckler LA, Hale J, Jung W, Westcott L, Dunstan JA, Thornton CA, Prescott SL. Modulation of in vivo and in vitro cytokine production over the course of pregnancy in allergic and non‐allergic mothers.
Pediatr Allergy Immunol 2010: 21: 14–21.
© 2009 The Authors
Journal compilation

Allergic women show reduced T helper type 1 alloresponses to fetal human leucocyte antigen mismatch during pregnancy.

Low‐level alloreactivity between mother and fetus may provide stimulation for fetal T helper type 1 (Th1) cell immune maturation. This study explored the effects of human leucocyte antigen (HLA) mismatch on materno–fetal interactions detected as cytokine responses and lymphoproliferation in mixed lymphocyte reactions, and whether this was altered in allergic women (n = 62) who have a Th2 propensity compared with non‐allergic women (n = 65). HLA‐DRβ1 mismatch was associated with significantly increased Th1 interferon (IFN)‐γ, Th2 interleukin (IL)‐13 and lymphoproliferative responses by both mothers and fetuses. Allergic women showed significantly lower IFN‐γ Th1 production in response to HLA‐DRβ1 mismatch. The infants of these women also showed significantly lower IL‐10 and lower IFN‐γ production relative to IL‐13. Both HLA‐DRβ1 mismatch and maternal allergy had significant independent effects on maternal IFN‐γ Th1 responses. Maternal allergy modifies HLA‐mediated alloreactivity between the mother and the fetus, reducing Th1 activation. This may affect the cytokine milieu at the materno–fetal interface and could be implicated in the attenuated Th1 responses observed commonly in infants of atopic mothers.