Differences in the antibody response to a mucosal bacterial antigen between allergic and non-allergic subjectsSmoke-free legislation reduces exposure in children

Abstract

Background: The immune response to bacterial antigens on mucosal surfaces may be modified in individuals allergic to aeroallergens due to a maturational or genetic difference or from the interaction between inhaled allergens and bacteria at the mucosa. Methods: Plasma from children and adults allergic (n = 97) and non-allergic (n = 54) to aeroallergens were initially tested for IgG1 (Th1) and IgG4 (Th2) reactivity to P6, a conserved outer membrane protein of Haemophilus influenzae. IgE binding was measured for some allergic donors. The development of the antibody responses to P6 was subsequently examined in the plasma from 35 children aged 1, 2 and 5 years taken from a prospective birth cohort. Results: IgG4 antibodies to P6 were more readily detected in allergic subjects than in non-allergic subjects (p,0.001), with a strong bias to the male gender. Some allergic subjects (35%) also had IgE antibody (1-10 ng/ ml) that was not associated with IgG4 or gender. In the cohort study of infants, subjects who developed skin prick test positivity to mite allergens by 5 years of age had an 85% reduction in the IgG1 anti-P6 antibody at year 2 (p,0.05) and, unlike skin test negative infants, this group had IgG4 anti-P6 antibodies at 5 years of age. Conclusions: The antibodies of subjects allergic to a bacterial antigen included IgE and IgG4 (particularly for males) compared with the almost exclusive IgG1 response of non-allergic subjects. The IgG1 responses of 2-year-old children who became skin test positive was markedly reduced and P6-specific IgG4 became detectable at 5 years of age.The T cell responses of children who develop allergic sensitisation have been shown to mature slowly. The late maturation has been demonstrated in T cell precursor analyses, 1 responses to mitogens 2 3 and in the production of Th1 and Th2 cytokines induced by allergens.4 5 Both Th1 and Th2 responses are lower in allergic infants, 4 but the Th1 cytokine production has been a centre of focus because interferon-c (IFNc) responses are very slow to mature in children, 6 leaving the possibility that Th2 imprinting in the neonatal period can persist into infancy. Most of the studies of cytokine regulation of allergic sensitisation have examined the response to allergens. An effect on responses to other antigens could also be expected. This could result from a genetic or environmentally-induced predisposition to producing Th2 responses in general, or be mediated via bystander interactions with the responses to allergens. The latter possibility has been demonstrated by experiments with viral and bacterial infections of sensitised mice.7-9 A greater involvement of the Th2 component of the response of children with aeroallergies to childhood vaccines has been observed. [10][11][12] The responses to mucosal antigens where co-presentation could occur with allergens would therefore be of interest.To study immune responses to an antigen presented at the respiratory mucosa, the IgE and IgG subclass antibodies induced by a conserved outer membrane p...

Antibacterial antibody responses associated with the development of asthma in house dust mite-sensitised and non-sensitised children

“…In keeping with these associations, IgG1 antibody responses to the protective P6 antigen of H influenzae have been found to be decreased in 2-year-old children who developed atopy at 5 years 4. House dust mite (HDM)-sensitised children with frequent or persistent asthma exacerbations were also shown to have lower anti-P6 IgG1 titres than children with infrequent episodic asthma 5.…”

“…It is becoming apparent that the development of allergy and asthma is associated with deviated immune responses to respiratory viruses2 3 and mucosal bacteria4 5 which, through several proposed mechanisms, could increase susceptibility to sensitisation and disease 6 7. In keeping with this, children with atopic asthma experience more frequent and severe rhinovirus-induced illnesses8 and children who develop wheeze have increased bacterial colonisation of the nasopharynx as neonates 9.…”

“…House dust mite (HDM)-sensitised children with frequent or persistent asthma exacerbations were also shown to have lower anti-P6 IgG1 titres than children with infrequent episodic asthma 5. One-third of atopic children and adults had the Th2-dependent IgG4 anti-P6 antibody 4. Antibacterial IgE antibody has also been found in both atopic and non-atopic subjects4 13 and, counterintuitively, for atopic subjects was inversely related to the risk of asthma 13…”

“…One-third of atopic children and adults had the Th2-dependent IgG4 anti-P6 antibody 4. Antibacterial IgE antibody has also been found in both atopic and non-atopic subjects4 13 and, counterintuitively, for atopic subjects was inversely related to the risk of asthma 13…”

The mechanism or mechanisms driving atopic asthma initiation: The infant respiratory microbiome moves to center stage

“…Relevant to this possibility, it has recently been demonstrated that infants and schoolchildren with atopic asthma symptoms display aberrant patterns of humoral immunity against common respiratory bacterial pathogens. This includes reduced production of specific IgG 1 antibody levels that are central to bacterial clearance 84,85 and also reduced levels of specific IgE directed against particulate antigens on bacterial pathogens, which are produced in relatively high titers by nonatopic and asymptomatic atopic subjects. 86 Collectively, these findings emphasize the necessity of obtaining an accurate picture at the population level of the full spectrum of bacterial strains that constitute the respiratory tract microbiome and their population dynamics across the age range during which asthma development is most commonly initiated.…”