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Recurrent group A tonsillitis is an immunosusceptibility disease involving antibody deficiency and aberrant TFH cells

Recurrent group A tonsillitis is an immunosusceptibility disease involving antibody deficiency and aberrant TFH cells
Recurrent group A tonsillitis is an immunosusceptibility disease involving antibody deficiency and aberrant TFH cells

"Strep throat" is highly prevalent among children, yet it is unknown why only some children develop recurrent tonsillitis (RT), a common indication for tonsillectomy. To gain insights into this classic childhood disease, we performed phenotypic, genotypic, and functional studies on pediatric group A Streptococcus (GAS) RT and non-RT tonsils from two independent cohorts. GAS RT tonsils had smaller germinal centers, with an underrepresentation of GAS-specific CD4+ germinal center T follicular helper (GC-TFH) cells. RT children exhibited reduced antibody responses to an important GAS virulence factor, streptococcal pyrogenic exotoxin A (SpeA). Risk and protective human leukocyte antigen (HLA) class II alleles for RT were identified. Lastly, SpeA induced granzyme B production in GC-TFH cells from RT tonsils with the capacity to kill B cells and the potential to hobble the germinal center response. These observations suggest that RT is a multifactorial disease and that contributors to RT susceptibility include HLA class II differences, aberrant SpeA-activated GC-TFH cells, and lower SpeA antibody titers.

Journal Article
1946-6234
Dan, Jennifer M.
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Havenar-Daughton, Colin
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Kendric, Kayla
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Al-Kolla, Rita
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Kaushik, Kirti
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Rosales, Sandy L.
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Anderson, Ericka L.
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LaRock, Christopher N.
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Vijayanand, Pandurangan
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Seumois, Grégory
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Layfield, David
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Cutress, Ramsey I.
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Ottensmeier, Christian H.
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Lindestam Arlehamn, Cecilia S.
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Sette, Alessandro
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Nizet, Victor
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Bothwell, Marcella
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Brigger, Matthew
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Crotty, Shane
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Dan, Jennifer M.
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Havenar-Daughton, Colin
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Kendric, Kayla
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Al-Kolla, Rita
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Kaushik, Kirti
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Rosales, Sandy L.
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Anderson, Ericka L.
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LaRock, Christopher N.
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Vijayanand, Pandurangan
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Seumois, Grégory
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Layfield, David
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Cutress, Ramsey I.
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Ottensmeier, Christian H.
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Lindestam Arlehamn, Cecilia S.
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Sette, Alessandro
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Nizet, Victor
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Bothwell, Marcella
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Brigger, Matthew
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Crotty, Shane
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Dan, Jennifer M., Havenar-Daughton, Colin, Kendric, Kayla, Al-Kolla, Rita, Kaushik, Kirti, Rosales, Sandy L., Anderson, Ericka L., LaRock, Christopher N., Vijayanand, Pandurangan, Seumois, Grégory, Layfield, David, Cutress, Ramsey I., Ottensmeier, Christian H., Lindestam Arlehamn, Cecilia S., Sette, Alessandro, Nizet, Victor, Bothwell, Marcella, Brigger, Matthew and Crotty, Shane (2019) Recurrent group A tonsillitis is an immunosusceptibility disease involving antibody deficiency and aberrant TFH cells. Science Translational Medicine, 11 (478). (doi:10.1126/scitranslmed.aau3776).

Record type: Article

Abstract

"Strep throat" is highly prevalent among children, yet it is unknown why only some children develop recurrent tonsillitis (RT), a common indication for tonsillectomy. To gain insights into this classic childhood disease, we performed phenotypic, genotypic, and functional studies on pediatric group A Streptococcus (GAS) RT and non-RT tonsils from two independent cohorts. GAS RT tonsils had smaller germinal centers, with an underrepresentation of GAS-specific CD4+ germinal center T follicular helper (GC-TFH) cells. RT children exhibited reduced antibody responses to an important GAS virulence factor, streptococcal pyrogenic exotoxin A (SpeA). Risk and protective human leukocyte antigen (HLA) class II alleles for RT were identified. Lastly, SpeA induced granzyme B production in GC-TFH cells from RT tonsils with the capacity to kill B cells and the potential to hobble the germinal center response. These observations suggest that RT is a multifactorial disease and that contributors to RT susceptibility include HLA class II differences, aberrant SpeA-activated GC-TFH cells, and lower SpeA antibody titers.

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Accepted/In Press date: 11 January 2019
Published date: 6 February 2019
Additional Information: Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Keywords: Journal Article

Identifiers

Local EPrints ID: 430007
URI: https://eprints.soton.ac.uk/id/eprint/430007
ISSN: 1946-6234
PURE UUID: d8e7e62b-fe73-4ad3-a233-02dd904b714e

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Date deposited: 09 Apr 2019 16:30
Last modified: 14 Aug 2019 16:34

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Contributors

Author: Jennifer M. Dan
Author: Colin Havenar-Daughton
Author: Kayla Kendric
Author: Rita Al-Kolla
Author: Kirti Kaushik
Author: Sandy L. Rosales
Author: Ericka L. Anderson
Author: Christopher N. LaRock
Author: Pandurangan Vijayanand
Author: Grégory Seumois
Author: David Layfield
Author: Cecilia S. Lindestam Arlehamn
Author: Alessandro Sette
Author: Victor Nizet
Author: Marcella Bothwell
Author: Matthew Brigger
Author: Shane Crotty

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