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Open Access Research article

Presence of the full-length KIR2DS4 gene reduces the chance of rheumatoid arthritis patients to respond to methotrexate treatment

Edyta Majorczyk12*, Andrzej Pawlik3, Daria Gendosz1 and Piotr Kuśnierczyk1*

Author Affiliations

1 Laboratory of Immunogenetics and Tissue Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland

2 Biochemistry and Physiology, Institute of Physiotherapy, Faculty of Physical Education and Physiotherapy, Opole University of Technology, Proszkowska 76, 45-758 Opole, Poland

3 Pharmacokinetics and Therapeutic Drug Monitoring, Pomeranian University of Medicine, Powstańców Wlkp. 72, 70-111 Szczecin, Poland

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BMC Musculoskeletal Disorders 2014, 15:256  doi:10.1186/1471-2474-15-256

Published: 28 July 2014



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 (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.


KIR 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.


We 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.


Our results suggest that the response of RA patients with medium ESR values to MTX treatment may be dependent on the full-length KIR2DS4 gene.

Rheumatoid arthritis; Treatment response; Methotrexate; KIR; KIR ligand