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

Abstract

Background Infants who develop house dust mite (HDM) allergy and HDM-sensitised children with severe persistent asthma have low antibody responses to the P6 antigen of Haemophilus influenzae. Objective To measure the development of antibody to two ubiquitous bacteria of the respiratory mucosa in a prospective birth cohort at high risk of allergic disease and to assess which responses are associated with asthma and atopy. Methods IgG1 and IgG4 antibody to H influenzae (P4 and P6) and Streptoccocus pneumoniae (PspA and PspC) surface antigens was measured in yearly blood samples of children aged 1e5 years. IgE to the P6 antigen was examined for the 5-year group. The children were stratified based on HDM sensitisation and asthma at 5 years of age. Results HDM-sensitised children had lower IgG1 antibody titres to the bacterial antigens, and early responses (<3 years and before the development of HDM sensitisation and asthma) corrected for multiple antigens were significantly reduced for P4, P6 and PspC (p¼0.008, p¼0.004 and p¼0.028, respectively). Similar associations with asthma were also found (p¼0.008, p¼0.004 and p¼0.032 for P4, P6 and PspC, respectively). The IgG4 antibody titre and prevalence were similar in both HDM-sensitised and non-sensitised groups, but sensitised children had a slower downregulation of the IgG4 response. Children with asthma (27/145 at 5 years) had lower anti-P6 IgE responses (p<0.05). Conclusions HDM-sensitised children have early defective antibody responses to bacteria that are associated with asthma. Surprisingly, antibacterial IgE was associated with a reduced risk for asthma.

Asthma Status and Waning of Measles Antibody Concentrations after Measles Immunization

“…Children with house-dust mite (HDM) sensitization had lower pneumococcal surface protein A titers at three years of age as well as lower anti-P6 antibody for H. influenza 16 and lower pneumococcal antibody titers. 30,39 We recently reported that HDM-stimulated IL-5 secretion was inversely correlated with pneumococcal antibody values in asthmatics.…”

“…This concern becomes especially relevant considering asthma has been reported to be associated with an increased risk of microbial infections 12-14 and suboptimal innate 15 and adaptive immune functions. 16-18 Also, a few recent papers demonstrated evidence of waning of pertussis, mumps, and measles vaccine-induced immunity in children and its potential impact on public health. 8, 19,20 Despite the public health concerns over the outbreaks of vaccine preventable diseases in the United States and elsewhere, currently there are scant data about factors influencing waning of vaccine-induced humoral immunity.…”

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.…”

Elucidation of Pathways Driving Asthma Pathogenesis: Development of a Systems-Level Analytic Strategy

“…It is therefore relevant to question whether variations in antibacterial host defense mechanisms may also contribute to asthma susceptibility in young children. Preliminary evidence from the CAS birth cohort (134, 136) suggests that the efficiency of immune surveillance for common nasopharyngeal bacterial species during infancy as measured via specific IgG1 antibody titers is inversely related to risk for subsequent development of atopic asthma in children, and this may reflect the role of this antibody in bacterial clearance. Moreover, we have recently reported that Th2-polarized immunity in school children against these bacterial species is protective against expression of asthma symptoms (137).…”