Evidence map›Paper›PMID 26350950›Full record

ArticleArthritis research & therapy2015

IL2RA is associated with persistence of rheumatoid arthritis.

H W van Steenbergen, J A B van Nies, A Ruyssen-Witrand, T W J Huizinga, Al Cantagrel, F Berenbaum, A H M van der Helm-van Mil

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Article in Arthritis research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
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  12. Rheumatoid Arthritis: The Stride from Research to Clinical Practice.International journal of molecular sciences · 2016
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

H W van SteenbergenDepartment of Rheumatology, Leiden University Medical Center, P.O. Box 9600, 2300, RC, Leiden, The Netherlands. h.w.van_steenbergen@lumc.nl.
J A B van NiesDepartment of Rheumatology, Leiden University Medical Center, P.O. Box 9600, 2300, RC, Leiden, The Netherlands. j.a.b.van_nies@lumc.nl.
A Ruyssen-WitrandDepartment of Rheumatology, Toulouse University Hospital, Toulouse, 31059 Toulouse cedex 9, France. adruyssen@hotmail.com.
T W J HuizingaDepartment of Rheumatology, Leiden University Medical Center, P.O. Box 9600, 2300, RC, Leiden, The Netherlands. t.w.j.huizinga@lumc.nl.
Al CantagrelDepartment of Rheumatology, Toulouse University Hospital, Toulouse, 31059 Toulouse cedex 9, France. cantagrel.a@chu-toulouse.fr.
F BerenbaumUniversity of Paris 06 UPMC, UMR_S-938, 75005 Paris France, Department of Rheumatology, AP-HP, Saint-Antoine Hospital, 184, rue du Faubourg-Saint-Antoine, 75012, Paris, France. francis.berenbaum@sat.aphp.fr.
A H M van der Helm-van MilDepartment of Rheumatology, Leiden University Medical Center, P.O. Box 9600, 2300, RC, Leiden, The Netherlands. a.h.m.van_der_helm@lumc.nl.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionAlthough rheumatoid arthritis (RA) is generally a chronic disease, a proportion of RA-patients achieve disease-modifying antirheumatic drug (DMARD)-free sustained remission, reflecting loss of disease-persistence. To explore mechanisms underlying RA-persistence, we performed a candidate gene study. We hypothesized that variants associating with lack of radiographic progression also associate with DMARD-free sustained remission.

methods645 Dutch RA-patients were studied on DMARD-free sustained remission during a maximal follow-up duration of 10-years. Variants associated with radiographic progression under an additive model in the total RA-population (Human Leukocyte Antigens (HLA)-DRB1-shared epitope (SE), Dickkopf-1 (DKK1)-rs1896368, DKK1-rs1896367, DKK1-rs1528873, C5Orf30-rs26232, Interleukin-2 receptor-α (IL2RA)-rs2104286, Matrix metalloproteinase-9 (MMP-9)-rs11908352, rs451066 and Osteoprotegerin (OPG)-rs1485305) were studied. Cox-regression analyses were performed and Bonferroni correction applied. Soluble IL2Rα (sIL2Rα)-levels were studied. For replication, 622 RA-patients included in the French Evaluation et Suivi de POlyarthrites Indifférenciées Récentes cohort (ESPOIR)-cohort were investigated. Results were combined in inverse-variance weighted meta-analysis.

resultsSimilar as previously reported, the SE-alleles associated with less remission (hazard ratio (HR) = 0.57, 95 % confidence interval (95 % CI) = 0.42-0.77, p = 2.72×10(-4)). Variants in DKK-1, C5orf30, MMP-9 and OPG were not associated with remission. The IL2RA-rs2104286 minor allele associated with a higher chance on remission (HR = 1.52, 95 % CI = 1.16-1.99, p = 2.44×10(-3)). The rs2104286 minor allele associated with lower sIL2Rα-levels (p = 1.44×10(-3)); lower sIL2Rα-levels associated with a higher chance on remission (HR per 100 pg/L = 0.81, 95 % CI = 0.68-0.95, p = 0.012). When including rs2104286 and sIL2Rα-levels in one analysis, the HR for rs2104286 was 2.27 (95 % CI = 1.06-4.84, p = 0.034) and for sIL2Rα 0.83 (95 % CI = 0.70-0.98, p = 0.026). Within ESPOIR, the HR of rs2104286 was 1.31 (95 % CI = 0.90-1.90). The meta-analysis revealed a p-value of 1.01×10(-3).

conclusionIL2RA-rs2104286 and sIL2Rα-level associated with RA-persistence. IL2RA variants are known to protect against multiple sclerosis, diabetes mellitus and RA. Besides HLA-SE, IL2RA-rs2104286 is thus far the only known genetic variant associated with both joint destruction and RA-persistence. This underlines the relevance of IL2RA for RA.

Indexed as

Polymorphism, Single NucleotideAdultAgedAllelesAntirheumatic AgentsArthritis, RheumatoidCohort StudiesDisease ProgressionFemaleFollow-Up StudiesGene FrequencyGenetic Predisposition to DiseaseGenotypeHumansInterleukin-2 Receptor alpha SubunitMaleAntirheumatic AgentsInterleukin-2 Receptor alpha Subunit

Identifiers

PMID26350950
PMCPMC4563834

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