Research ArticlePEDIATRICS

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

See allHide authors and affiliations

Science Translational Medicine  06 Feb 2019:
Vol. 11, Issue 478, eaau3776
DOI: 10.1126/scitranslmed.aau3776

Teasing apart tonsillitis

Although exposure to group A Streptococcus is prevalent, only some children develop recurrent tonsillitis, which can lead to tonsillectomy. To discern why some children are susceptible and others are resistant, Dan et al. examined tonsil samples from two cohorts. They found that children with a history of recurrent tonsillitis had smaller germinal centers and reduced antibacterial antibodies. Moreover, the T follicular helper cells from those subjects may actually have been cytotoxic toward B cells. Class II HLA analysis also identified protective and risk alleles. Together, these results reveal that altered adaptive immune responses to group A Streptococcus may differentiate those at risk of recurrent infection.


“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.

View Full Text

Stay Connected to Science Translational Medicine