rs2072135, a low‐penetrance variant for chronic lymphocytic leukaemia?

Recent multi‐stage genome‐wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) that are robustly associated with chronic lymphocytic leukaemia (CLL) risk. Given that most of these SNPs map to non‐coding regions of the genome, it suggests that the functional basis of many GWAS signals will be through differential gene expression. By referencing publically accessible expression quantitative trait loci (eQTL) data on lymphoblastoid cells lines (LCLs) we have globally demonstrated an association between GWAS P‐values and eQTLs, consistent with much of the variation in CLL risk being defined by variants impacting on gene expression. To explore using eQTL data to select GWAS SNPs for replication, we genotyped rs2072135 (GWAS P‐value = 0·0024, eQTL P‐value = 1·510^?19) in five independent case‐control series totalling 1968 cases and 3538 controls. While not attaining statistical significance (combined P‐value = 1 × 10^?4), rs2072135 defines a promising risk locus for CLL. Incorporating eQTL information offers an attractive strategy for selecting SNPs from GWAS for validation.     

Role of molecular mimicry and polyclonal cell activation in the induction of pathogenic β2-glycoprotein I–directed immune response in Balb/c mice upon hyperimmunization with tetanus toxoid

It is known that tetanus toxoid (TTd)-hyperimmunization induces increased titer of sera β2-glycoprotein I (β2GPI)-specific antibodies (Abs) in Balb/c mice. The concentrations of such induced anti-β2GPI Abs as well as their pathogenic potential are strongly influenced by the context of TTd application. β2GPI-specific immune response is established as a part of TTd-specific immune response by molecular mimicry mechanism due to structural homology between TTd and β2GPI. This finding is supported by the following facts: (1) cross-reactive Abs that recognize both TTd and β2GPI epitopes are present in Balb/c mice sera; (2) anti-TTd Abs secretion in splenic cultures is induced after β2GPI stimulation and vice versa. However, analyses of (1) IL-10 production following in vitro stimulation of immunized Balb/c mice splenocytes by TTd, β2GPI or glutaraldehyde-treated β2GPI and (2) specific impact of ConA and agonists of TLR2, TLR4, and TLR9 on anti-TTd and autoreactive Abs secretion strongly imply that these two branches of the TTd-induced immune response do not use identical cell populations and are regulated in a different way. Results presented in this paper describe that structural homology between foreign and self-antigens could focus mounted autoreactive immune response toward specific self-structure, but the context of antigen application, including a history of previous immune stimulations and adjuvants applied together with the antigen, are the main factors which determine the outcome of the induced immune response.     

Intra-bone nuclear DNA variability in Second World War metatarsal and metacarpal bones

International Journal of Legal Medicine - DNA analysis of Second World War skeletal remains is challenging because of the limited yield of DNA that is usually recovered. Recent forensic research...     

Hyper-dense foreign bodies found in the bowel during IGRT following brachytherapy

A 28-year-old female with locally advanced adenocarcinoma of the cervix was undergoing treatment with external beam radiation therapy (EBRT), concurrent chemotherapy and high dose rate brachytherapy (BT). On-board imaging obtained prior to one of her external beam treatments revealed four radiopaque foreign bodies in her abdomen. The patient's treatment was delayed for further work-up of this new finding. Upon further investigation, it was discovered that the patient had recently started taking bismuth subsalicylate tablets (brand name: Pepto-Bismol, Procter & Gamble Co., Cincinnati, OH). A computed tomography (CT) scan of the tablets confirmed the size and Hounsfield Unit (HU) values coincided with the foreign object properties seen on the patient's scan. This unexpected finding is important to recognize as it consequently lead to a delay in treatment, additional imaging, and patient anxiety.