PURPOSE OF THE STUDY.
The goal of this study was to determine if maternal production of anti-HLA antibodies arising from mismatch between mother and fetus is associated with allergic outcomes at 8 years of age. Previous studies have suggested that the prevalence of atopy is lower in children of higher birth order. Higher numbers of pregnancies are associated with increased antibodies against paternal HLA antigens and maternal interferon-γ production (Th1) in response to fetal cells. The authors postulated that the raised levels of interferon-γ secondary to HLA mismatch may be another factor associated with lower risk of allergic disease.
A total of 269 maternal blood samples from the Asthma in Ashford Study (Ashford, Kent, UK) were analyzed for anti-HLA antibodies. Retrospective anti-HLA antibody analysis was restricted to mothers who had no additional births in the 4-year interval between birth of the child and collection of the blood sample. Parity at the time of birth of the index child ranged from 0 to >4.
Maternal sera were tested for antibodies to HLA class I and II molecules. Associations between the presence or absence of maternal anti-HLA antibodies and allergic outcomes at age 8 years were made by using χ2 tests. Logistic regression was used to investigate the association between maternal HLA antibodies and birth order with the child’s allergic status. Skin prick testing to pollen mixture, Dermatophagoides pteronyssinus, and cat fur were conducted on the mothers during pregnancy and on children at age 8 years. Allergic outcomes in children were measured by using questionnaires and results of skin prick testing.
The detection of maternal anti-HLA class II antibodies was associated with less positivity to allergens on skin prick testing and less seasonal rhinitis in children at age 8 years. Nonatopic children had a higher birth order and increased presence of maternal anti-HLA class II antibodies. Atopic children did not have a statistically significant difference in maternal HLA antibodies when analyzed for birth order.
Maternal anti-HLA class II antibodies are associated with birth order and increased protection from allergy in offspring in nonatopic children. Increasing parity-related Th1 cytokine maternal immune responses may contribute to the birth order effect regardless of maternal atopic status.
This study suggests another mechanism for decreased allergy prevalence in children who have older siblings. This difference has been attributed to the predominance of Th1 cytokines over Th2 cytokines secondary to higher exposure to infections in younger children in many previous studies. The authors of this study offer an alternative explanation based on the presence of anti-HLA antibodies in women with multiple pregnancies. This interesting alternative explanation for decreased allergy in younger siblings has no practical implications at this point.
- Copyright © 2014 by the American Academy of Pediatrics