Abstract
BackgroundKIR genes coding for natural killer cell immunoglobulin-like receptors, KIR, influence the effector and regulatory function of NK cells as well as some subpopulations of T lymphocytes (e.g. CD4+CD28-KIR+) depending on presence of ligands (particularly HLA-C molecules). KIR-KIR ligand interaction may lead to the development of autoimmune disorders, including rheumatoid arthritis (RA). However, their role in the response of RA patients to methotrexate therapy is not known.MethodsKIR genes and KIR-ligand (HLA-C C1/C2 allomorphs) genotyping was performed using the PCR-SSP method in 312 RA patients (179 classified as good responders and 133 as poor responders using DAS28 criteria). Thus, we evaluated the association of KIR genes and HLA-C allomorphs with the response to methotrexate (MTX) treatment.ResultsWe observed that patients possessing the full-length KIR2DS4 (KIR2DS4f) gene had a lower chance of responding in comparison to KIR2DS4f-negative cases. This phenomenon was observed both in erosive disease (ED) and rheumatoid factor (RF) positive and in ED- and RF-negative patients. Interestingly, the observed effect of the KIR2DS4f gene was strongest in individuals possessing medium values (20-33 mm/h) of the erythrocyte sedimentation rate (ESR). Patients with high ESR values had low probability and, in contrast, patients with low ESR had a high probability of MTX response, and the presence of KIR2DS4f did not affect their outcome. Additionally, we show that the KIR2DS4f effect did not depend on the presence of either C1 or C2 allomorphs.ConclusionOur results suggest that the response of RA patients with medium ESR values to MTX treatment may be dependent on the full-length KIR2DS4 gene.
Highlights
KIR genes coding for natural killer cell immunoglobulin-like receptors, KIR, influence the effector and regulatory function of Natural killer (NK) cells as well as some subpopulations of T lymphocytes (e.g. CD4+CD28-KIR+) depending on presence of ligands ( human leukocyte antigen (HLA)-C molecules)
When the frequencies of the KIR genes were compared between good responders and poor responders of rheumatoid arthritis (RA) patient groups, we observed an effect of only one KIR gene, full-length KIR2DS4 (KIR2DS4f ), on the response to MTX therapy
Patients with erosive disease (ED) and rheumatoid factor (RF) were less likely to respond to MTX, and those positive for KIR2DS4f had an even lower chance than those who were negative for KIR2DS4f but positive for both ED and RF (36.2% and 43.6% of good responders, respectively; Table 3)
Summary
KIR genes coding for natural killer cell immunoglobulin-like receptors, KIR, influence the effector and regulatory function of NK cells as well as some subpopulations of T lymphocytes (e.g. CD4+CD28-KIR+) depending on presence of ligands ( HLA-C molecules). KIR-KIR ligand interaction may lead to the development of autoimmune disorders, including rheumatoid arthritis (RA). The most polymorphic receptors of NK cells are encoded by killer cell immunoglobulin-like receptor (KIR) genes distributed differently in unrelated individuals Since these receptors, depending on their structure, are either inhibitory or activating, their repertoire in a genotype affects activity of NK cells (and T cell subpopulations which express KIRs, including T lymphocyte CD4 + CD28KIR+) and, in consequence, susceptibility to different diseases including autoimmune disorders such as RA [4,5,6]. The whole KIR region was divided into centromeric (A or B) and telomeric (A or B) halves, depending on the KIR gene content [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
