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.