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

Sci Transl Med. 2019 Feb 6;11(478):eaau3776. doi: 10.1126/scitranslmed.aau3776.


"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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alleles
  • Antibodies, Bacterial / immunology*
  • B-Lymphocytes / immunology
  • Cell Differentiation
  • Child
  • Disease Susceptibility
  • Female
  • Germinal Center / immunology
  • Granzymes / metabolism
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Immunoglobulin G / metabolism
  • Male
  • Recurrence
  • Streptococcus / physiology*
  • Superantigens / metabolism
  • T-Lymphocytes, Helper-Inducer / immunology
  • Tonsillitis / immunology*
  • Tonsillitis / microbiology*


  • Antibodies, Bacterial
  • Histocompatibility Antigens Class II
  • Immunoglobulin G
  • Superantigens
  • Granzymes