Cytotoxicity is the ability of a cell to damage another cell. Natural killer (NK) cells use this ability to destroy infected and diseased cells – a function that is crucial in the immune system.
Research has previously found that the most consistent immune-related finding in ME/CFS research is reduced NK cell cytotoxicity. This suggests that NK cells in individuals with ME/CFS potentially have impaired killing ability, supporting the broader hypothesis of immune system dysfunction in the disease.
Killer-cell immunoglobulin-like receptors (KIRs) are receptors, expressed on the cell membrane of NK cells. KIRs regulate cell activity through the interaction of inhibitory and activating KIRs with major histocompatibility (MHC) class I molecules (found on the surface of all nucleated cells). Inhibitory KIRs send a “don’t kill” signal, whereas activating KIRs do the opposite. Each has an important role.
A study using DNA samples from 418 people with ME/CFS (diagnosed according to Canadian Consensus Criteria) and 473 health controls examined the genes encoding for KIRs, specifically looking at alleles (different versions of the same gene). The researchers did not find any difference in the KIR gene content (which KIR genes people carry) or the number of copies of each gene, but they did find differences at the allele level. Three alleles – KIR3DL3*002, KIR3DL1*020, KIR3DL2*009 – encoding inhibitory KIRs were more frequent in individuals with ME/CFS compared to healthy controls.
Essentially, the participants with ME/CFS did not have more inhibitory KIR genes, but they were more likely to carry certain inhibitory alleles. The study does not explicitly show that these alleles weaken NK function (e.g. through sending stronger “don’t kill” signals), but the authors do state that the data supports the role of NK cells in ME/CFS.
This is the “Largest KIR genetic association study in ME/CFS to date.”
