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Evidence that recurrent Group A streptococcus tonsillitis is an immunosusceptibility disease involving antibody deficiency and aberrant Tfh cells

By Jennifer M Dan, Colin Havenar-Daughton, Kayla Kendric, Kirti Kaushik, Sandy L. Rosales, Erika Anderson, Christopher LaRock, Pandurangan Vijayanand, Gregory Seumois, David Layfield, Ramsey Cutress, Christian Ottensmier, Cecilia S. Lindestam Arlehamn, Alessandro Sette, Victor Nizet, Marcella Bothwell, Matthew Brigger, Shane Crotty

Posted 27 Jun 2018
bioRxiv DOI: 10.1101/356741 (published DOI: 10.1126/scitranslmed.aau3776)

Recurrent Group A Streptococcus (GAS) tonsillitis (RT) is a common indication for pediatric tonsillectomy. Strep throat is highly prevalent among children; yet, it is unknown why some children develop RT. To gain insights into this classic childhood disease, we performed phenotypic, genotypic, and functional studies on pediatric GAS RT and non-RT tonsils. We observed significantly smaller germinal centers in GAS RT tonsils, and underrepresentation of GAS-specific germinal center follicular helper (GC Tfh) CD4+ T cells. RT children exhibited reduced antibody responses to GAS virulence factor SpeA. Risk and protective HLA Class II alleles for RT were identified. Finally, SpeA induced granzyme B+ GC Tfh cells in RT tonsils that had capacity to kill B cells. Together, these observations suggest that RT susceptibility can occur due to genetic differences that can result in aberrant GC Tfh cells and poor antibody responses to GAS SpeA.

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