Long-term changes in milk component immunoglobulins reflect milk oral immunotherapy outcomes in Finnish children

Background Milk oral immunotherapy (OIT) may increase the amount of milk protein that can be ingested without triggering an allergic reaction. It is important to understand why some patients benefit from the treatment while others do not. Objective The aim was to define the differences in the milk allergen component-specific (casein, alpha-lactalbumin, ss-lactoglobulin) immunoglobulin (sIg [sIgE, sIgG4, and sIgA]) levels relative to the long-term outcomes of milk OIT. Methods In this long-term, open-label follow-up study, 286 children started milk OIT between 2005 and 2015. Follow-up data were collected at two points: the post-buildup phase and long term (range 1-11 years, median 6 years). Comparisons of sIg levels were made among three outcome groups of self-reported long-term milk consumption (high-milk dose, low-milk dose, and avoidance). Results A total of 168 (59%) of the 286 patients on OIT participated. Most patients (57%) were in the high-dose group; here, 80% of these patients had a baseline casein sIgE value less than 28 kUA/L, they had the lowest casein sIgE levels at all time (p < .001), their casein sIgG4/IgE levels increased, and long-term casein sIgA was highest compared with the low-dose and avoidance groups (p = .02). Low-milk dose group had the highest casein sIgG4/IgE levels in long term (p = .002). Conclusion The baseline Ig profiles and responses to milk OIT differed depending on long-term milk consumption. Lower casein sIgE levels were associated with better outcome. Milk casein sIgA differed in the long term among high-milk consumers.Peer reviewe

Inhalation of rod-like carbon nanotubes causes unconventional allergic airway inflammation

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Serum chitinase-like protein YKL-40 is linked to small airway function in children with asthmatic symptoms

Background Lung function impairment among asthmatic children begins in early life, and biomarkers for identifying this impairment are needed. The chitinase-like protein YKL-40 has been associated with asthma and lung function in adults, but studies in children have yielded conflicting results. We evaluated the potential of YKL-40 and other systemic biomarkers for identifying lung function deficits in children with asthmatic symptoms. Methods We determined the levels of serum YKL-40, periostin, and high-sensitivity C-reactive protein (hs-CRP) from the blood samples of 49 children with asthmatic symptoms. Lung function was assessed with impulse oscillometry (IOS) and spirometry, combined with an exercise challenge and a bronchodilator test. Fractional exhaled nitric oxide was measured at multiple flow rates. Results Serum levels of YKL-40 showed significant correlations with most IOS indices at baseline (P = .008-.039), but there was no association between YKL-40 and spirometry parameters. Neither periostin nor hs-CRP were associated with baseline lung function. Children with a significant response in either the exercise challenge or the bronchodilator test had increased serum levels of YKL-40 (P = .003) and periostin (P = .035). YKL-40 correlated significantly with the blood neutrophil count (r(s) = .397, P = .005) but was not associated with biomarkers of eosinophilic inflammation. Conclusion Serum YKL-40 is a potential biomarker for lung function deficits in children with asthmatic symptoms. These deficits appear to be focused on small airways and may remain undetected with spirometry.Peer reviewe

Functional beta2-integrins restrict skin inflammation in vivo

Beta2-integrins and the important integrin regulator kindlin-3 are essential for leukocyte trafficking, but the role of beta2-integrins in regulating inflammation is still incompletely understood. Here, we have investigated skin inflammation in a mouse model where the kindlin-3 binding site in the beta2-integrin has been mutated (TTT/AAA-beta2-integrin knock-in), leading to expressed but dysfunctional integrins. We show that, surprisingly, neutrophil trafficking into the inflamed skin in a contact hypersensitivity model is normal in these mice, although trafficking of T cells and eosinophils into the skin is reduced. Instead, expression of dysfunctional integrins leads to increased mast cell and dendritic cell numbers in the skin, increased inflammatory cytokine production in the inflamed skin in vivo, and in mast cells in vitro. Furthermore, expression of dysfunctional integrins leads to increased dendritic cell activation and migration to lymph nodes and increased Th1 responses in vivo. Therefore, the kindlin-3/integrin interaction is important for trafficking of T cells and eosinophils but not absolutely required for neutrophil trafficking into the inflamed skin. Functional beta2-integrins also have a major role in restricting the immune response in the inflamed skin and lymph nodes in vivo, likely through effects on mast cell and dendritic cell numbers and activation

Long-term changes in milk component immunoglobulins reflect milk oral immunotherapy outcomes in Finnish children

Background Milk oral immunotherapy (OIT) may increase the amount of milk protein that can be ingested without triggering an allergic reaction. It is important to understand why some patients benefit from the treatment while others do not. Objective The aim was to define the differences in the milk allergen component-specific (casein, alpha-lactalbumin, ss-lactoglobulin) immunoglobulin (sIg [sIgE, sIgG4, and sIgA]) levels relative to the long-term outcomes of milk OIT. Methods In this long-term, open-label follow-up study, 286 children started milk OIT between 2005 and 2015. Follow-up data were collected at two points: the post-buildup phase and long term (range 1-11 years, median 6 years). Comparisons of sIg levels were made among three outcome groups of self-reported long-term milk consumption (high-milk dose, low-milk dose, and avoidance). Results A total of 168 (59%) of the 286 patients on OIT participated. Most patients (57%) were in the high-dose group; here, 80% of these patients had a baseline casein sIgE value less than 28 kUA/L, they had the lowest casein sIgE levels at all time (p < .001), their casein sIgG4/IgE levels increased, and long-term casein sIgA was highest compared with the low-dose and avoidance groups (p = .02). Low-milk dose group had the highest casein sIgG4/IgE levels in long term (p = .002). Conclusion The baseline Ig profiles and responses to milk OIT differed depending on long-term milk consumption. Lower casein sIgE levels were associated with better outcome. Milk casein sIgA differed in the long term among high-milk consumers.Peer reviewe

Pets, furry animal allergen components, and asthma in childhood

Abstract Background The use of component‐resolved allergy diagnostics has provided a clearer understanding of the species‐specific sensitization and severity of potential allergic reactions. This cross‐sectional study aimed to determine whether sensitization to allergen components in furry animals is indicative of blood eosinophilia, a positive fractional exhaled nitric oxide (FeNO) test, abnormal lung function, and asthma symptoms in children. Additionally, we investigated whether having pets during childhood affects the development of asthma or allergic sensitization to furry animals. Methods We recruited 203 children aged 4–17 years with asthma diagnosis based on abnormal lung function and 33 controls. IgE‐sensitization to allergen components for dogs, cats, and horses was analyzed using a multiplex microarray. Children were tested with FeNO, impulse oscillometry, spirometry, methacholine challenge, and skin prick test. A questionnaire was used to investigate pet ownership and symptom profile. Results FeNO results and blood eosinophilia revealed a correlation with sensitization to all furry animal allergens, particularly lipocalins (r = 0.203–0.560 and 0.206–0.560, respectively). Can f 3 was found to correlate with baseline R5 (r = 0.298). No association between methacholine challenge results and sensitization to furry animal allergens was found. Children with asthma who were sensitized to Can f 1, Can f 6, or both frequently reported asthma symptoms. Dog ownership was associated with a lower level of IgE‐sensitization to lipocalins, fewer asthma symptoms, and less blood eosinophilia. Conclusion Furry animal allergen component IgE‐sensitization is a risk factor for type 2‐inflammation and asthma symptoms