Korean scientists have produced evidence supporting the role of inhibitory and activating natural killer (NK) cell receptor genes in determining susceptibility to rheumatoid arthritis (RA).
NK cell receptors “regulate the innate and adaptive immune systems related to cytotoxicity and cytokine production that are involved in the pathogenesis of RA,” Park Kyung Sook (Sungshin Women’s University, Seoul) and co-workers explain in the journal Tissue Antigens.
The investigators therefore examined whether NK cell receptor genotype could be implicated in susceptibility to RA. They recruited 210 patients with RA from the Seoul National University Hospital, along with 298 healthy controls. All patients with RA had been diagnosed with the condition at least 2 years previously.
Participants were genotyped for the inhibitory NK cell receptor gene NKG2A and the activating NK cell receptor genes NKG2C and NKG2D.
The analysis revealed a number of significant associations. The homozygous A/A genotype for an A/G single nucleotide polymorphism on intron 4 of NKG2A was significantly less common among patients with RA than in the control group (38.6% versus 49.7%), indicating a possible protective effect against RA.
However, the strongest effects were observed in relation to two variants of the NKG2C and NKG2D genes. Specifically, the combined presence of the Ser/Ser genotype of a Ser/Phe polymorphism of NKG2C and the Thr/Thr genotype of an Ala/Thr polymorphism of NKG2D was observed in 7.7% of patients with RA, compared with just 0.7% of those in the control group, conferring an odds ratio of 12.3 for RA.
Conversely, 13.1% of the control group carried both the Phe/Phe genotype of the NKG2C polymorphism and the Ala/Ala genotype of the NKG2D polymorphism, compared with only 2.9% of patients with RA, indicating significant protection against RA (odds ratio=0.2).
The authors conclude that the NK cell receptor gene polymorphisms investigated in their study are “strongly associated with susceptibility to RA.”
Discussing the potential mechanisms underlying the results, they suggest that the genes may influence RA susceptibility via “recruitment of macrophages and other immune cells, differentiation, and secretion of proinflammatory cytokines that attract more inflammatory cells.”
Free abstract