The Epidemiology and Clinical Presentations of Atopic Diseases in Selective IgA Deficiency

Morawska, Izabela; Kurkowska, Sara; Bębnowska, Dominika; Hrynkiewicz, Rafał; Becht, Rafał; Michalski, Adam; Piwowarska-Bilska, Hanna; Birkenfeld, Bożena; Załuska-Ogryzek, Katarzyna; Grywalska, Ewelina; Roliński, Jacek; Niedźwiedzka-Rystwej, Paulina

doi:10.3390/jcm10173809

Cited by 17 publications

(21 citation statements)

References 175 publications

(243 reference statements)

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“…Despite the importance of IgA for protection against pathogens, a certain fraction of the human population is characterized by IgA deficiency ( 98 , 99 ). Only 10%–15% of IgA deficient individuals are susceptible to recurrent sino-pulmonary and gastrointestinal infections/disorders, whereas the vast majority remain asymptomatic and are often accidentally identified among healthy blood donors.…”

Section: Discussionmentioning

confidence: 99%

Intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2 induces neutralizing salivary IgA

et al. 2023

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Intramuscularly administered vaccines stimulate robust serum neutralizing antibodies, yet they are often less competent in eliciting sustainable “sterilizing immunity” at the mucosal level. Our study uncovers a strong temporary neutralizing mucosal component of immunity, emanating from intramuscular administration of an mRNA vaccine. We show that saliva of BNT162b2 vaccinees contains temporary IgA targeting the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus-2 spike protein and demonstrate that these IgAs mediate neutralization. RBD-targeting IgAs were found to associate with the secretory component, indicating their bona fide transcytotic origin and their polymeric multivalent nature. The mechanistic understanding of the high neutralizing activity provided by mucosal IgA, acting at the first line of defense, will advance vaccination design and surveillance principles and may point to novel treatment approaches and new routes of vaccine administration and boosting.

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Section: Discussionmentioning

confidence: 99%

Intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2 induces neutralizing salivary IgA

et al. 2023

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“…In spite of the importance of IgA for protection against pathogens, a certain fraction of the human population is characterized by IgA deficiency (Brandtzaeg et al, 1999; Morawska et al, 2021). Only 10-15% of IgA deficient individuals are susceptible to recurrent sino-pulmonary and gastrointestinal infections/disorders, while the vast majority remains asymptomatic and are often incidentally identified among healthy blood donors.…”

Section: Discussionmentioning

confidence: 99%

Intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2 induces robust neutralizing salivary IgA

Stolovich-Rain

Kumari

Friedman

et al. 2022

Preprint

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Intramuscularly administered vaccines stimulate robust serum neutralizing antibodies, yet they are often less competent in eliciting sustainable 'sterilizing immunity' at the mucosal level. Our study uncovers, strong neutralizing mucosal component (NT50 ≤ 50pM), emanating from intramuscular administration of an mRNA vaccine. We show that saliva of BNT162b2 vaccinees contains temporary IgA targeting the Receptor-Binding-Domain (RBD) of SARS-CoV-2 spike protein and demonstrate that these IgAs are key mediators of potent neutralization. RBD-targeting IgAs were found to associate with the Secretory Component, indicating their bona-fide transcytotic origin and their dimeric tetravalent nature. The mechanistic understanding of the exceptionally high neutralizing activity provided by mucosal IgA, acting at the first line of defence, will advance vaccination design and surveillance principles, pointing to novel treatment approaches, and to new routes of vaccine administration and boosting.

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“…FLG and DSG1 are marked in italics, as they are not necessarily associated with IEI but are monogenic defects supporting the pathogenic category. We have grouped thymic development disorders and decreased T cell repertoire diversity [4 ▪ ,5,6 ▪ ,26,28–41].…”

Section: Methodsmentioning

confidence: 99%

Atopic manifestations of inborn errors of immunity

Sams,

Wijetilleka,

Ponsford

et al. 2023

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of review Allergy and atopic features are now well recognized manifestations of many inborn errors of immunity (IEI), and indeed may be the hallmark in some, such as DOCK8 deficiency. In this review, we describe the current IEI associated with atopy, using a comprehensive literature search and updates from the IUIS highlighting clinical clues for underlying IEI such as very early onset of atopic disease or treatment resistance to enable early and accurate genetic diagnosis. Recent findings We focus on recently described genes, their categories of pathogenic mechanisms and the expanding range of potential therapies. Summary We highlight in this review that patients with very early onset or treatment resistant atopic disorders should be investigated for an IEI, as targeted and effective therapies exist. Early and accurate genetic diagnosis is crucial in this cohort to reduce the burden of disease and mortality.

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The Epidemiology and Clinical Presentations of Atopic Diseases in Selective IgA Deficiency

Cited by 17 publications

References 175 publications

Intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2 induces neutralizing salivary IgA

Intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2 induces neutralizing salivary IgA

Intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2 induces robust neutralizing salivary IgA

Atopic manifestations of inborn errors of immunity

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