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

BACKGROUND: 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 int...

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Autores principales: Majorczyk, Edyta, Pawlik, Andrzej, Gendosz, Daria, Kuśnierczyk, Piotr
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4118653/
https://www.ncbi.nlm.nih.gov/pubmed/25069714
http://dx.doi.org/10.1186/1471-2474-15-256
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author Majorczyk, Edyta
Pawlik, Andrzej
Gendosz, Daria
Kuśnierczyk, Piotr
author_facet Majorczyk, Edyta
Pawlik, Andrzej
Gendosz, Daria
Kuśnierczyk, Piotr
author_sort Majorczyk, Edyta
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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spelling pubmed-41186532014-08-02 Presence of the full-length KIR2DS4 gene reduces the chance of rheumatoid arthritis patients to respond to methotrexate treatment Majorczyk, Edyta Pawlik, Andrzej Gendosz, Daria Kuśnierczyk, Piotr BMC Musculoskelet Disord Research Article BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. BioMed Central 2014-07-28 /pmc/articles/PMC4118653/ /pubmed/25069714 http://dx.doi.org/10.1186/1471-2474-15-256 Text en Copyright © 2014 Majorczyk et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
spellingShingle Research Article
Majorczyk, Edyta
Pawlik, Andrzej
Gendosz, Daria
Kuśnierczyk, Piotr
Presence of the full-length KIR2DS4 gene reduces the chance of rheumatoid arthritis patients to respond to methotrexate treatment
title Presence of the full-length KIR2DS4 gene reduces the chance of rheumatoid arthritis patients to respond to methotrexate treatment
title_full Presence of the full-length KIR2DS4 gene reduces the chance of rheumatoid arthritis patients to respond to methotrexate treatment
title_fullStr Presence of the full-length KIR2DS4 gene reduces the chance of rheumatoid arthritis patients to respond to methotrexate treatment
title_full_unstemmed Presence of the full-length KIR2DS4 gene reduces the chance of rheumatoid arthritis patients to respond to methotrexate treatment
title_short Presence of the full-length KIR2DS4 gene reduces the chance of rheumatoid arthritis patients to respond to methotrexate treatment
title_sort presence of the full-length kir2ds4 gene reduces the chance of rheumatoid arthritis patients to respond to methotrexate treatment
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4118653/
https://www.ncbi.nlm.nih.gov/pubmed/25069714
http://dx.doi.org/10.1186/1471-2474-15-256
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