VIENNA — A polymorphism in the gene coding for toll-like receptor 2 appears to constitute a powerful susceptibility gene for acute rheumatic fever, H. Hakan Aydin, M.D., Ph.D., said at the annual European Congress of Rheumatology.
Indeed, 56 of 61 unselected Turkish children who met diagnostic criteria for acute rheumatic fever were heterozygous for the simple polymorphism, in which arginine is replaced by glutamine at position 753 in the toll-like receptor 2 (TLR-2) gene, according to Dr. Aydin of Ege University, Izmir, Turkey.
In contrast, 9 of 91 ethnically matched healthy pediatric controls and 12 of 116 healthy adult controls were heterozygous for TLR-2 Arg753Gln. Not one patient or control was homozygous for Arg753Gln.
Genetic differences in host susceptibility to acute rheumatic fever as reflected in the TLR-2 polymorphism go a long way toward explaining why only 0.3%–3.0% of patients with acute group A streptococcal pharyngitis go on to develop acute rheumatic fever, he said at the meeting sponsored by the European League Against Rheumatism. TLRs play a key role in host immunity, initiating the full range of both adaptive and innate immune responses against all manner of foreign microbes. Thus, a polymorphism in TLR-2 rendering affected individuals hyporesponsive to bacteria which contain TLR-2 agonists—as do gram-positive group A strep—could have important clinical consequences.
The finding that a TLR-2 polymorphism is strongly associated with increased susceptibility to rheumatic fever should eventually lead to a simple genetic test to risk-stratify patients for a disorder the World Health Organization says is still a major health problem, particularly in developing countries. It also opens the door to pharmacologic manipulation of TLR-2 for therapeutic purposes, Dr. Aydin predicted.