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The association between IgG4 antibodies to dietary factors, islet autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young.

Lamb MM, Simpson MD, Seifert J, Scott FW, Rewers M, Norris JM - PLoS ONE (2013)

Bottom Line: In addition, mean antigen-specific IgG4 concentrations in infancy (age <2 years) were not associated with risk of IA nor progression to T1D.Higher ovalbumin IgG4 at first IA positive visit was marginally associated with progression to T1D (Hazard Ratio: 1.39, 95% Confidence Interval: 1.00, 1.92).We found no association between the IgG4 response to β-lactoglobulin, gluten, and the development of either IA or T1D.

View Article: PubMed Central - PubMed

Affiliation: Colorado School of Public Health, University of Colorado, Aurora, Colorado, United States of America.

ABSTRACT

Background: Infant dietary exposures have been linked to type 1 diabetes (T1D) development. IgG4 antibody responses to food antigens are associated with food intolerances but have not been explored prospectively in the period preceding T1D.

Methods: Using a case-cohort design, IgG4 antibodies to ß-lactoglobulin, gluten, and ovalbumin were measured in plasma collected annually from 260 DAISY participants. Of those, 77 developed islet autoimmunity (IA), defined as positive for either insulin, GAD65 or IA-2 autoantibodies on two consecutive visits, and 22 developed T1D.

Results: In mixed model analysis adjusting for HLA-DR status, T1D family history, age and ethnicity, higher ß-lactoglobulin IgG4 concentrations were associated with shorter breastfeeding duration (beta = -0.03, 95% Confidence Interval: -0.05, -0.006) and earlier first cow's milk exposure (beta = -0.04, 95% Confidence Interval: -0.08, 0.00). Higher gluten IgG4 was associated with older age at gluten introduction (beta = 0.06, 95% Confidence Interval: 0.00, 0.13). In proportional hazards analysis adjusting for HLA-DR status, T1D family history and ethnicity, IgG4 against individual or multiple dietary antigens throughout childhood were not associated with IA. In addition, mean antigen-specific IgG4 concentrations in infancy (age <2 years) were not associated with risk of IA nor progression to T1D. Higher ovalbumin IgG4 at first IA positive visit was marginally associated with progression to T1D (Hazard Ratio: 1.39, 95% Confidence Interval: 1.00, 1.92).

Conclusion: We found no association between the IgG4 response to β-lactoglobulin, gluten, and the development of either IA or T1D. The association between higher ovalbumin and progression to T1D in children with IA should be explored in other populations.

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Related in: MedlinePlus

Selection of the analysis cohorts.
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pone-0057936-g001: Selection of the analysis cohorts.

Mentions: Based on availability of biological samples and timing of entry into the study, 1,433 DAISY children were eligible for selection into a representative sub-cohort of 192 children (Figure 1). The sub-cohort was selected from the DAISY cohort via stratified random sampling based on HLA-DR genotype and T1D family history. This representative sub-cohort was used to test the internal consistency of the IgG4 antibodies by correlating them with infant diet exposures.


The association between IgG4 antibodies to dietary factors, islet autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young.

Lamb MM, Simpson MD, Seifert J, Scott FW, Rewers M, Norris JM - PLoS ONE (2013)

Selection of the analysis cohorts.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585253&req=5

pone-0057936-g001: Selection of the analysis cohorts.
Mentions: Based on availability of biological samples and timing of entry into the study, 1,433 DAISY children were eligible for selection into a representative sub-cohort of 192 children (Figure 1). The sub-cohort was selected from the DAISY cohort via stratified random sampling based on HLA-DR genotype and T1D family history. This representative sub-cohort was used to test the internal consistency of the IgG4 antibodies by correlating them with infant diet exposures.

Bottom Line: In addition, mean antigen-specific IgG4 concentrations in infancy (age <2 years) were not associated with risk of IA nor progression to T1D.Higher ovalbumin IgG4 at first IA positive visit was marginally associated with progression to T1D (Hazard Ratio: 1.39, 95% Confidence Interval: 1.00, 1.92).We found no association between the IgG4 response to β-lactoglobulin, gluten, and the development of either IA or T1D.

View Article: PubMed Central - PubMed

Affiliation: Colorado School of Public Health, University of Colorado, Aurora, Colorado, United States of America.

ABSTRACT

Background: Infant dietary exposures have been linked to type 1 diabetes (T1D) development. IgG4 antibody responses to food antigens are associated with food intolerances but have not been explored prospectively in the period preceding T1D.

Methods: Using a case-cohort design, IgG4 antibodies to ß-lactoglobulin, gluten, and ovalbumin were measured in plasma collected annually from 260 DAISY participants. Of those, 77 developed islet autoimmunity (IA), defined as positive for either insulin, GAD65 or IA-2 autoantibodies on two consecutive visits, and 22 developed T1D.

Results: In mixed model analysis adjusting for HLA-DR status, T1D family history, age and ethnicity, higher ß-lactoglobulin IgG4 concentrations were associated with shorter breastfeeding duration (beta = -0.03, 95% Confidence Interval: -0.05, -0.006) and earlier first cow's milk exposure (beta = -0.04, 95% Confidence Interval: -0.08, 0.00). Higher gluten IgG4 was associated with older age at gluten introduction (beta = 0.06, 95% Confidence Interval: 0.00, 0.13). In proportional hazards analysis adjusting for HLA-DR status, T1D family history and ethnicity, IgG4 against individual or multiple dietary antigens throughout childhood were not associated with IA. In addition, mean antigen-specific IgG4 concentrations in infancy (age <2 years) were not associated with risk of IA nor progression to T1D. Higher ovalbumin IgG4 at first IA positive visit was marginally associated with progression to T1D (Hazard Ratio: 1.39, 95% Confidence Interval: 1.00, 1.92).

Conclusion: We found no association between the IgG4 response to β-lactoglobulin, gluten, and the development of either IA or T1D. The association between higher ovalbumin and progression to T1D in children with IA should be explored in other populations.

Show MeSH
Related in: MedlinePlus