Oral Presentation 20th Lancefield International Symposium on Streptococci and Streptococcal Diseases 2017

Is the concept of rheumatogenic Group A Streptococcus a myth? A systematic literature review from 1944 to 2016 and a molecular analysis of the M-protein (#103)

Gabrielle J de Crombrugghe de Looringhe 1 2 , Noemie Baroux 3 , Deborah A Williamson 4 , Nikki (Nicole) J Moreland 5 , Andrew C Steer 3 , Pierre R Smeesters 1 2 3
  1. Academic Children Hospital Queen Fabiola, Université Libre de Bruxelles, Brussels, Belgium
  2. Molecular Bacteriology Laboratory, Université Libre de Bruxelles, Brussels, Belgium
  3. Group A Streptococcus Research Group, Murdoch Childrens Research Institute, Melbourne, Victoria, Australia
  4. Microbiological Diagnostic Unit (MDU) Public Health Laboratory, Doherty Institute, University of Melbourne, Victoria, Australia
  5. Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand

Background and Objective:

The concept that a minority of Group A streptococcus (GAS) emm-types are more “rheumatogenic” than others is widely disseminated. The objective of this study is to provide a comprehensive list of ARF-associated strains and analyze their genetic diversity. 


All articles reporting ARF-associated strains or ARF-associated emm-type-specific antibody responses were identified in Pubmed from 01/01/1944 (first publication of Jones criteria) to 31/12/2016. The revised Jones Criteria (American Heart Association, 2015) were used to define ARF and a maximum time-period of four weeks between microbiological characterization and ARF onset was accepted. A database of 175 M-protein sequences was used to analyze the genetic diversity of ARF-associated strains in a PhyML phylogenetic tree. Geneious software was used to search for the presence of putative ARF-associated motifs (PARF motif and two proposed rheumatogenic peptides).


Thirty-six relevant studies were identified among 677 publications. 440 ARF-associated isolates belonging to 66 different emm-types were included in the analysis. The classical “rheumatogenic” emm-types represented 41% of the 440 ARF-associated isolates and 14% of the 66 identified emm-types. When the classical rheumatogenic emm-type were mapped by specific clade onto the emm-cluster-type phylogenetic tree, ARF-associated emm-types were disseminated along the tree suggesting ARF-associated strains belong to various genetic backgrounds. ARF-associated motifs (PARF or rheumatogenic peptides) were present in only 20 and 12% of the ARF-associated strains and emm-types, respectively.


The concept of ”rheumatogenicity” should probably be extended to include strains other than those classically described. Further work is needed to understand the physiopathology of ARF.