Toll-like receptor 3 increases antigen-presenting cell responses to a pro-apoptotic stimulus, yet does not contribute to systemic lupus erythematosus genetic susceptibility.

Objectives: TLR3 mediates skin solar injury by binding nuclear material released from apoptotic keratinocytes, resulting in the production of pro-inflammatory cytokines. Because the TLR3 gene is located in 4q35, a known systemic lupus erythematosus (SLE) susceptibility locus, we wondered whether TLR3 single nucleotide polymorphisms (SNPs) were associated with inflammatory mechanisms relevant to the development of SLE, and disease susceptibility.

Methods: Functional assays were carried out in TLR3-transfected HEK293 cells and in monocyte-derived dendritic cells (moDCs).

Replication study of polymorphisms associated with response to methotrexate in patients with rheumatoid arthritis.

About 70 genetic studies have already addressed the need of biomarkers to predict the response of patients with rheumatoid arthritis (RA) to methotrexate (MTX) treatment. However, no genetic biomarker has yet been sufficiently validated. Here, we aimed to replicate a selection of 25 SNPs in the largest collection of patients up to date, which consisted of 915 patients treated with MTX.

Evaluation of a clinical pharmacogenetics model to predict methotrexate response in patients with rheumatoid arthritis.

Variability of response to treatment hinders successful management of rheumatoid arthritis (RA). Consequently, a clinical pharmacogenetics model for predicting response to methotrexate (CP-MTX) has been previously proposed that includes four clinical variables (disease activity, sex, the presence of rheumatoid factor and smoking status) and four SNPs (rs2236225, rs17602729, rs1127354, and rs2372536) in genes of the folate pathway. It showed good performance, but failed to attract attention, likely, in relation with lack of clear clinical benefit.

Anti-carbamylated protein autoantibodies associated with mortality in Spanish rheumatoid arthritis patients.

Patients with rheumatoid arthritis (RA) have an increased mortality rate that is associated with the presence of RA-specific autoantibodies in many studies. However, the relative role of rheumatoid factor (RF), anti-CCP antibodies and the most recently established RA-autoantibodies, directed against carbamylated proteins (anti-CarP antibodies), is unclear. Here, we have assessed the role of these three antibodies in 331 patients with established RA recruited from 2001 to 2009 and followed until November 2015.

Corrigendum: Simplified Assay for Epigenetic Age Estimation in Whole Blood of Adults.

[This corrects the article on p. 126 in vol. 7, PMID: 27471517.

Specific premature epigenetic aging of cartilage in osteoarthritis.

Osteoarthritis (OA) is a disease affecting multiple tissues of the joints in the elderly, but most notably articular cartilage. Premature biological aging has been described in this tissue and in blood cells, suggesting a systemic component of premature aging in the pathogenesis of OA. Here, we have explored epigenetic aging in OA at the local (cartilage and bone) and systemic (blood) levels.

Simplified Assay for Epigenetic Age Estimation in Whole Blood of Adults.

Biological age is not always concordant with chronological age and the departures are of interest for understanding how diseases and environmental insults affect tissue function, organismal health, and life expectancy. The best-known biological age biomarker is telomere length, but there are more accurate biomarkers as the recently developed based in epigenetic, transcriptomic, or biochemical changes. The most accurate are the epigenetic biomarkers based on specific changes in DNA methylation referred as DNA methylation age measures (DmAM).

A combined large-scale meta-analysis identifies COG6 as a novel shared risk locus for rheumatoid arthritis and systemic lupus erythematosus.

Objectives: During the last years, genome-wide association studies (GWASs) have identified a number of common genetic risk factors for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, the genetic overlap between these two immune-mediated diseases has not been thoroughly examined so far. The aim of the present study was to identify additional risk loci shared between RA and SLE.

The genetic legacy of the pre-colonial period in contemporary Bolivians.

Only a few genetic studies have been carried out to date in Bolivia. However, some of the most important (pre)historical enclaves of South America were located in these territories. Thus, the (sub)-Andean region of Bolivia was part of the Inca Empire, the largest state in Pre-Columbian America.