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

JM Dan, C Havenar-Daughton, K Kendric… - Science translational …, 2019 - science.org
JM Dan, C Havenar-Daughton, K Kendric, R Al-Kolla, K Kaushik, SL Rosales, EL Anderson…
Science translational medicine, 2019science.org
“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 …
“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.
AAAS