Early recovery from cow's milk allergy is associated with decreasing IgE and increasing IgG4 binding to cow's milk epitopes  Emma M. Savilahti, MD, Ville.

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Early recovery from cow's milk allergy is associated with decreasing IgE and increasing IgG4 binding to cow's milk epitopes  Emma M. Savilahti, MD, Ville Rantanen, MSc, Jing S. Lin, PhD, Sirkku Karinen, MSc, Kristiina M. Saarinen, MD, PhD, Marina Goldis, MD, Mika J. Mäkelä, MD, PhD, Sampsa Hautaniemi, DTech, Erkki Savilahti, MD, PhD, Hugh A. Sampson, MD  Journal of Allergy and Clinical Immunology  Volume 125, Issue 6, Pages 1315-1321.e9 (June 2010) DOI: 10.1016/j.jaci.2010.03.025 Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Differences in IgE binding to CM peptides (black curve) between children with persisting CMA at the age of 8 to 9 years (P, red) and those recovering early by the age of 3 years (E, green) at 3 time points: A, T:0, the time of diagnosis; B, T:1, 1 year later; C, T:9, follow-up at the age of 8 to 9 years. Arrows point to regions with significant (>0.1 or <−0.1) differences between groups. The x-axis depicts amino acid sequences of the 5 proteins, and the y-axis depicts relative signal strength. The temporal differences in IgE-binding intensity are shown within study groups (D) and between groups (E); red denotes regions with significantly (>0.1) increased binding intensity, and blue denotes regions with significantly (<−0.1) decreased binding intensity. β-LG, β-Lactoglobulin. Journal of Allergy and Clinical Immunology 2010 125, 1315-1321.e9DOI: (10.1016/j.jaci.2010.03.025) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Differences in IgG4 binding to CM peptides (black curve) between children with persisting CMA at the age of 8 to 9 years (P, red) and those recovering early by the age of 3 years (E, green) at 3 time points: A, T:0, the time of diagnosis; B, T:1, 1 year later; C, T:9, follow-up at the age of 8 to 9 years. Arrows point to regions with significant (>0.1 or <−0.1) differences between groups. The x-axis depicts amino acid sequences of the 5 proteins, and the y-axis depicts relative signal strength. The temporal differences in IgG4-binding intensity are shown within study groups (D) and between groups (E); red denotes regions with significantly (>0.1) increased binding intensity, and blue denotes regions with significantly (<−0.1) decreased binding intensity. β-LG, β-Lactoglobulin. Journal of Allergy and Clinical Immunology 2010 125, 1315-1321.e9DOI: (10.1016/j.jaci.2010.03.025) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 A, Differences in IgA binding to CM peptides (black curve) between children with persisting CMA at the age of 8 to 9 years (P, red) and those recovering early by the age of 3 years (E, green) at the time of follow-up at the age of 8 to 9 years (T:9). Arrows point to regions with significant (>0.1 or <−0.1) differences between groups. The x-axis depicts amino acid sequences of the 5 proteins, and the y-axis depicts relative signal strength. The temporal differences in IgA-binding intensity are shown within study groups (B) and between groups (C); red denotes regions with significantly (>0.1) increased binding intensity, and blue denotes regions with significantly (<−0.1) decreased binding intensity. β-LG, β-Lactoglobulin. Journal of Allergy and Clinical Immunology 2010 125, 1315-1321.e9DOI: (10.1016/j.jaci.2010.03.025) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Differences in overlap of antibody-binding intensity to CM peptides between children with persisting CMA at the age of 8 to 9 years (P) and those recovering early by the age of 3 years (E). Time points are denoted as follows: T:0, the time of diagnosis; T:1, 1 year later; T:9, follow-up at the age of 8 to 9 years. Red denotes regions where the difference of binding intensity between IgE and IgG4 (A) or between IgE and IgA (B) is greater (less overlap) in group P compared with that in group E, and blue denotes the opposite. Differences of greater than 0.1 or less than −0.1 are considered significant. β-LG, β-Lactoglobulin. Journal of Allergy and Clinical Immunology 2010 125, 1315-1321.e9DOI: (10.1016/j.jaci.2010.03.025) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

A theoretical situation in which only a single peptide is active A theoretical situation in which only a single peptide is active. The Gaussian convolution kernel is shown as a dashed line. Journal of Allergy and Clinical Immunology 2010 125, 1315-1321.e9DOI: (10.1016/j.jaci.2010.03.025) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

The signal of one single active peptide after convolution with a Gaussian function. Journal of Allergy and Clinical Immunology 2010 125, 1315-1321.e9DOI: (10.1016/j.jaci.2010.03.025) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

A theoretical situation where four peptides are active A theoretical situation where four peptides are active. The Gaussian convolution kernel is shown as a dashed line. Journal of Allergy and Clinical Immunology 2010 125, 1315-1321.e9DOI: (10.1016/j.jaci.2010.03.025) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

The signal of four active peptides after convolution with a Gaussian function. Note that the peptides closer to each other form a higher signal. Journal of Allergy and Clinical Immunology 2010 125, 1315-1321.e9DOI: (10.1016/j.jaci.2010.03.025) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

The individual sample signal strengths after convolution (thin blue line) and their averages (thick black line). Journal of Allergy and Clinical Immunology 2010 125, 1315-1321.e9DOI: (10.1016/j.jaci.2010.03.025) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Differences (black curve) between IgE (orange) and IgG4 (blue) binding to CM peptides in children recovering early by the age of 3 years from CMA at 3 time points: A, T:0, the time of diagnosis; B, T:1, 1 year later; C, T:9, follow-up at the age of 8 to 9 years. Arrows point to regions with significant (>0.1 or <−0.1) differences between IgE and IgG4 binding. The x-axis depicts amino acid sequences of the 5 proteins, and the y-axis depicts relative signal strength. β-LG, β-Lactoglobulin. Journal of Allergy and Clinical Immunology 2010 125, 1315-1321.e9DOI: (10.1016/j.jaci.2010.03.025) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Differences (black curve) between IgE (orange) and IgG4 (blue) binding to CM peptides in children with persisting CMA at the age of 8 to 9 years at 3 time points: A, T:0, the time of diagnosis; B, T:1, 1 year later; C, T:9, follow-up at the age of 8 to 9 years. Arrows point to regions with significant (>0.1 or <−0.1) differences between IgE and IgG4 binding. The x-axis depicts amino acid sequences of the 5 proteins, and the y-axis depicts relative signal strength. β-LG, β-Lactoglobulin. Journal of Allergy and Clinical Immunology 2010 125, 1315-1321.e9DOI: (10.1016/j.jaci.2010.03.025) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions