Longitudinal atopic dermatitis endotypes: An atopic march paradigm that includes Black children

Biagini, Jocelyn M.; Kroner, John; Kyzy, Asel Baatyrbek; Gonzales, Alexandra; He, Hua; Stevens, Mariana L.; Grashel, Brittany; Spagna, Daniel; Samuel, Paul; Patel, Rahul P.; Bucci, Ángelo; Sherenian, Michael G.; Murrison, Liza Bronner; Martin, Lisa J.; Hershey, Gurjit K. Khurana

doi:10.1016/j.jaci.2021.09.036

Cited by 34 publications

(23 citation statements)

References 60 publications

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“…It is possible that genetic admixture is not fully accounted for by self-described race and could have added bias to our results. However, it is important to note that we have previously shown that in an evaluation of a similar population, self-described race was highly concordant with an assessment of genetic ancestry (Margolis et al, 2012;Abuabara et al, 2020;Biagini et al, 2022). In addition, many of our findings had similar effect estimates in both races.…”

Section: Discussionsupporting

confidence: 73%

A combination of HLA-DP α and β chain polymorphisms paired with a SNP in the DPB1 3’ UTR region, denoting expression levels, are associated with atopic dermatitis

et al. 2023

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Introduction: Components of the immune response have previously been associated with the pathophysiology of atopic dermatitis (AD), specifically the Human Leukocyte Antigen (HLA) Class II region via genome-wide association studies, however the exact elements have not been identified.Methods: This study examines the genetic variation of HLA Class II genes using next generation sequencing (NGS) and evaluates the resultant amino acids, with particular attention on binding site residues, for associations with AD. The Genetics of AD cohort was used to evaluate HLA Class II allelic variation on 464 subjects with AD and 384 controls.Results: Statistically significant associations with HLA-DP α and β alleles and specific amino acids were found, some conferring susceptibility to AD and others with a protective effect. Evaluation of polymorphic residues in DP binding pockets revealed the critical role of P1 and P6 (P1: α31M + (β84G or β84V) [protection]; α31Q + β84D [susceptibility] and P6: α11A + β11G [protection]) and were replicated with a national cohort of children consisting of 424 AD subjects. Independently, AD susceptibility-associated residues were associated with the G polymorphism of SNP rs9277534 in the 3’ UTR of the HLA-DPB1 gene, denoting higher expression of these HLA-DP alleles, while protection-associated residues were associated with the A polymorphism, denoting lower expression.Discussion: These findings lay the foundation for evaluating non-self-antigens suspected to be associated with AD as they potentially interact with particular HLA Class II subcomponents, forming a complex involved in the pathophysiology of AD. It is possible that a combination of structural HLA-DP components and levels of expression of these components contribute to AD pathophysiology.

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Section: Discussionsupporting

confidence: 73%

A combination of HLA-DP α and β chain polymorphisms paired with a SNP in the DPB1 3’ UTR region, denoting expression levels, are associated with atopic dermatitis

et al. 2023

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“…Black children had higher asthma risk and lower risk of allergic rhinitis and food allergy, while white children were most likely to progress to allergic rhinitis and food allergy, despite a lower asthma risk. These differences may be partly explained by ancestral genetic variabilities but also by different exposure to various race-specific environmental risk factor [107]. Overall, the presence of extracutaneous atopic manifestations suggest a prominent role of the type 2 inflammation in all ethnic groups.…”

Section: Discussionmentioning

confidence: 94%

Pathophysiology of Atopic Dermatitis in Different Ethnic Groups

Chiricozzi¹,

Maurelli²,

Calabrese³

et al. 2023

Preprint

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Atopic dermatitis (AD) is a common chronic inflammatory skin disease with high prevalence worldwide, including countries from Asia, Africa and Latin America, and in different ethnic groups. In recent years, more attention on AD heterogeneity associated on multiple factors, including patient’s ethnic background, has been posed, resulting in an increasing body of clinical, genetic, epidemiologic, and immune-phenotypic evidence that delineate differences among racial groups with AD. Filaggrin (FLG) mutations, the strongest genetic risk factor for the development of AD, are detected in up to 50% of European and 27% of Asian AD patients, while very rarely in Africans. The Th2 activation is a common attribute of all ethnic groups, though the Asian endotype of AD is also characterized by an increased Th17-mediated signal whereas African Americans own a strong Th2/Th22 signature and the absence of Th1/Th17 skewing. In addition, the ethnic heterogeneity may own important therapeutic implications as the genetic predisposition may affect treatment response and, thereby, a tailored strategy that better targets the dominant immunologic pathways in each ethnic subgroup may be envisaged. Nevertheless, white patients with AD represent the largest ethnicity enrolled and tested in clinical trials and the most treated in a real-world setting, limiting the investigation about safety and efficacy across different ethnicities. The purpose of this review is to describe the heterogeneity of pathophysiology across ethnicities and its potential therapeutic implications.

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“…Black children had higher risk of asthma and lower risk of allergic rhinitis and food allergy, while white children were most likely to progress to allergic rhinitis and food allergy, despite a lower asthma risk. These differences may be partly explained by ancestral genetic variabilities but also by different exposure to various race-specific environmental risk factors [ 118 ]. Overall, the presence of extracutaneous atopic manifestations suggest a prominent role of the type 2 inflammation in all ethnic groups.…”

Section: Discussionmentioning

confidence: 99%

Overview of Atopic Dermatitis in Different Ethnic Groups

Chiricozzi

Maurelli

Calabrese

et al. 2023

JCM

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Atopic dermatitis (AD) is a common chronic inflammatory skin disease with a high prevalence worldwide, including countries from Asia, Africa, and Latin America, and in different ethnic groups. In recent years, more attention has been placed on the heterogeneity of AD associated with multiple factors, including a patient’s ethnic background, resulting in an increasing body of clinical, genetic, epidemiologic, and immune-phenotypic evidence that delineates differences in AD among racial groups. Filaggrin (FLG) mutations, the strongest genetic risk factor for the development of AD, are detected in up to 50% of European and 27% of Asian AD patients, but very rarely in Africans. Th2 hyperactivation is a common attribute of all ethnic groups, though the Asian endotype of AD is also characterized by an increased Th17-mediated signal, whereas African Americans show a strong Th2/Th22 signature and an absence of Th1/Th17 skewing. In addition, the ethnic heterogeneity of AD may hold important therapeutic implications as a patient’s genetic predisposition may affect treatment response and, thereby, a tailored strategy that better targets the dominant immunologic pathways in each ethnic subgroup may be envisaged. Nevertheless, white patients with AD represent the largest ethnicity enrolled and tested in clinical trials and the most treated in a real-world setting, limiting investigations about safety and efficacy across different ethnicities. The purpose of this review is to describe the heterogeneity in the pathophysiology of AD across ethnicities and its potential therapeutic implications.

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Longitudinal atopic dermatitis endotypes: An atopic march paradigm that includes Black children

Cited by 34 publications

References 60 publications

A combination of HLA-DP α and β chain polymorphisms paired with a SNP in the DPB1 3’ UTR region, denoting expression levels, are associated with atopic dermatitis

A combination of HLA-DP α and β chain polymorphisms paired with a SNP in the DPB1 3’ UTR region, denoting expression levels, are associated with atopic dermatitis

Pathophysiology of Atopic Dermatitis in Different Ethnic Groups

Overview of Atopic Dermatitis in Different Ethnic Groups

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