Immune responses to stress after stress management training in patients with rheumatoid arthritis

Introduction

Psychological stress may alter immune function by activating physiological stress pathways. Building on our previous study, in which we report that stress management training led to an altered self-reported and cortisol response to psychological stress in patients with rheumatoid arthritis (RA), we explored the effects of this stress management intervention on the immune response to a psychological stress task in patients with RA.

Methods

In this study, 74 patients with RA, who were randomly assigned to either a control group or a group that received short stress management training, performed the Trier Social Stress Test (TSST) 1 week after the intervention and at a 9-week follow-up. Stress-induced changes in levels of key cytokines involved in stress and inflammatory processes (for example, interleukin (IL)-6 and IL-8) were assessed.

Results

Basal and stress-induced cytokine levels were not significantly different in patients in the intervention and control groups one week after treatment, but stress-induced IL-8 levels were lower in patients in the intervention group than in the control group at the follow-up assessment.

Conclusions

In line with our previous findings of lower stress-induced cortisol levels at the follow-up of stress management intervention, this is the first study to show that relatively short stress management training might also alter stress-induced IL-8 levels in patients with RA. These results might help to determine the role of immunological mediators in stress and disease.

Trial registration

The Netherlands National Trial Register (NTR1193)     

Genome-wide association study using deregressed breeding values for cryptorchidism and scrotal/inguinal hernia in two pig lines

Background

Cryptorchidism and scrotal/inguinal hernia are the most frequent congenital defects in pigs. Identification of genomic regions that control these congenital defects is of great interest to breeding programs, both from an animal welfare point of view as well as for economic reasons. The aim of this genome-wide association study (GWAS) was to identify single nucleotide polymorphisms (SNPs) that are strongly associated with these congenital defects. Genotypes were available for 2570 Large White (LW) and 2272 Landrace (LR) pigs. Breeding values were estimated based on 1 359 765 purebred and crossbred male offspring, using a binary trait animal model. Estimated breeding values were deregressed (DEBV) and taken as the response variable in the GWAS.

Results

Heritability estimates were equal to 0.26 ± 0.02 for cryptorchidism and to 0.31 ± 0.01 for scrotal/inguinal hernia. Seven and 31 distinct QTL regions were associated with cryptorchidism in the LW and LR datasets, respectively. The top SNP per region explained between 0.96% and 1.10% and between 0.48% and 2.77% of the total variance of cryptorchidism incidence in the LW and LR populations, respectively. Five distinct QTL regions associated with scrotal/inguinal hernia were detected in both LW and LR datasets. The top SNP per region explained between 1.22% and 1.60% and between 1.15% and 1.46% of the total variance of scrotal/inguinal hernia incidence in the LW and LR populations, respectively. For each trait, we identified one overlapping region between the LW and LR datasets, i.e. a region on SSC8 (Sus scrofa chromosome) between 65 and 73 Mb for cryptorchidism and a region on SSC13 between 34 and 37 Mb for scrotal/inguinal hernia.

Conclusions

The use of DEBV in combination with a binary trait model was a powerful approach to detect regions associated with difficult traits such as cryptorchidism and scrotal/inguinal hernia that have a low incidence and for which affected animals are generally not available for genotyping. Several novel QTL regions were detected for cryptorchidism and scrotal/inguinal hernia, and for several previously known QTL regions, the confidence interval was narrowed down.

Electronic supplementary material

The online version of this article (doi:10.1186/s12711-015-0096-6) contains supplementary material, which is available to authorized users.     

Modern evolution of a single-copy gene: the immunoglobulin C kappa locus in wild mice

The immunoglobulin kappa light-chain constant region gene (C kappa) has been cloned and sequenced from five wild mouse species. Analysis of these data has permitted an assessment of single-copy gene evolution during a limited time period as defined by the genus Mus. Sequence conservation was found to be as high (or higher) in the 5' and enhancer regions as in the coding region. The pattern of substitutions throughout these genes suggests that parallel evolution has occurred frequently and that substitutions at replacement sites have not decreased significantly, owing to saturation during this period of approximately 10 Myr. Phylogenetic relationships have been determined among these wild species as well as among members of the genus Rattus.      

Construction and expression of an adenosine deaminase::lacZ fusion gene

A eukaryotic expression vector was constructed in which the coding nucleotide sequences (ADA) of human adenosine deaminase (ADA) were fused in frame with the coding sequences of the bacterial gene lacZ encoding beta-galactosidase (beta Gal). This ADA::lacZ fusion gene was anticipated to encode a hybrid protein that has retained the biological functions of both proteins. Transfection of mammalian cells with the fusion gene resulted in the synthesis of both ADA and beta Gal. Cells expressing the gene could therefore be detected with the histochemical staining procedure that relies on the conversion of the indicator, XGal, by beta Gal. In addition, the transfected cells could be sorted on a fluorescence-activated cell sorter with the use of a vital staining procedure described for the selection of beta Gal-producing cells. Cell lines that harbored the fusion gene were tested for ADA overexpression by exposing them to the cytotoxic adenosine analog 9-beta-D-xylofuranosyl adenine (Xyl-A), in the presence of the ADA inhibitor deoxycoformycin (dCF). Resistance to Xyl-A/dCF was observed in the lines carrying ADA::lacZ and moreover, the fraction of cells that survived a stringent selection for ADA overexpression also exhibited significantly increased levels of beta Gal, which confirmed the direct linkage between ADA and lacZ expression. The use of this and other fusion genes might be useful in the development of gene-therapy protocols where they could help to meet the demand for versatile methods to detect and select cells with newly introduced genes.