Surfactant protein D alters allergic lung responses in mice and human subjects
inflammation; asthma; Immunology; polymorphism; lung; Allergy; endotoxin; Aspergillus; deficient mice; Allergy; aspergillus-fumigatus; d gene; emphysema; eosinophil; hygiene hypothesis; IL-13; sftpd gene; sp-a; surfactant protein D
Background: Surfactant protein (SP) D has been proposed to be protective in allergic airway responses. Objective: We aimed to determine the effect of SP-D deficiency on murine and human airway allergy. Methods: Immunologic responses of SP-D gene-deficient mice (Sftpd(-/-)) at baseline and after 4 intranasal Aspergillus fumigatus exposures were assessed. In addition, the significance of a single nucleotide polymorphism (Met(11)Thr) in the human SP-D gene (known to decrease SP-D function) was investigated. Results: Macrophage and neutrophil bronchoalveolar lavage fluid levels and large airway mucus production were increased in naive Sftpd(-/-) mice in association with increased lung CCL17 levels and CD4(+) T cell numbers. T(H)2-associated antibody levels (IgG1 and IgE) were significantly lower in 4- to 5-week-old Sftpd(-/-) mice (P <.05). Accordingly, naive Sftpd(-/-) splenocytes released significantly less IL-4 and IL-13 on anti-CD3/CD28 stimulation (P <.01). After intranasal allergen exposures, a modest decrease in bronchoalveolar lavage fluid eosinophilia and IL-13 levels was observed in Sftpd(-/-) mice compared with values seen in wild-type mice in association with decreased airway resistance (P <.01). A single nucleotide polymorphism in the SFTPD gene, affecting SP-D levels and pathogen binding, was associated with decreased atopy in black subjects and potentially lower asthma susceptibility in white subjects. Conclusion: Sftpd(-/-) mice have an impaired systemic T(H)2 response at baseline and reduced inflammation and airway responses after allergen exposure. Translational studies revealed that a polymorphism in the SFTPD gene was associated with lower atopy and possibly asthma susceptibility. Taken together, these results support the hypothesis that SP-D-dependent innate immunity influences atopy and asthma.
Brandt E B; Mingler M K; Stevenson M D; Wang N; Hershey G K K; Whitsett J A; Rothenberg M E
Journal of Allergy and Clinical Immunology
2008
2008-05
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/j.jaci.2008.02.011" target="_blank" rel="noreferrer noopener">10.1016/j.jaci.2008.02.011</a>
Aeroallergen sensitization in healthy children: racial and socioeconomic correlates.
Female; Male; Socioeconomic Factors; Incidence; Child; Risk Factors; Sensitivity and Specificity; Odds Ratio; Health Status; Probability; Confidence Intervals; Human; Adolescence; Logistic Regression; Case Control Studies; Immunization; Preschool; Population; Air Pollutants – Immunology; Allergens – Immunology; Hypersensitivity – Diagnosis; Hypersensitivity – Epidemiology; Hypersensitivity – Immunology; Respiratory Hypersensitivity – Diagnosis; Respiratory Hypersensitivity – Ethnology; Respiratory Hypersensitivity – Immunology; Skin Tests – Methods
Objective: Allergic sensitization is very prevalent and often precedes the development of allergic disease. This study examined the association of race with allergic sensitization among healthy children with no family history of atopy.Study Design: Two hundred seventy-five children, predominantly from lower socioeconomic strata, from Cincinnati, Ohio, ages 2 to 18 years without a family or personal history of allergic diseases, underwent skin prick testing to 11 allergen panels. The Pediatric Allergic Disease Quality of Life Questionnaire (PADQLQ) was used to examine the impact of sensitization on quality of life.Results: Thirty-nine percent of healthy children were sensitized to 1 or more allergen panels. Multivariate logistic regression showed increased risk among African-American children for any sensitization (OR, 2.17; [95% CI: 1.23, 3.84]) and sensitization to any outdoor allergen (OR, 2.96 [95% CI: 1.52, 5.74]). Eighty-six percent of children had PADQLQ scores of 1 or less (0 to 6 scale).Conclusions: Allergic sensitization is prevalent even among children who do not have a personal or family history of asthma, allergic rhinitis, or atopic dermatitis and who have no evidence of current, even subtle effects from this sensitization on allergic disease-related quality of life. African-American children are at greater risk for presence of sensitization, especially to outdoor allergens.
Stevenson MD; Sellins S; Grube E; Schroer K; Gupta J; Wang N; Khurana Hershey GK; Stevenson Michelle D; Sellins Stacey; Grube Emilie; Schroer Kathy; Gupta Jayanta; Wang Ning; Khurana Hershey Gurjit K
Journal of Pediatrics
2007
2007-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.jpeds.2007.03.001" target="_blank" rel="noreferrer noopener">10.1016/j.jpeds.2007.03.001</a>