By Sam LaBrie
Developing precision medicines for COPD is an important goal, as the disease is the third most common cause of death in the developed world and there are relatively few effective therapies. A recent study published in PLOS, Common Genetic Polymorphisms Influence Blood Biomarkers Measurements in COPD, explores the massive datasets from two cohorts, SPIROMICS and COPDGene, in a search for biomarkers linked to various aspects of COPD. Scientists combined single nucleotide polymorphisms (SNPs) and a custom MAP (Multi-Analyte Profile) of Myriad RBM’s serum biomarker assays to identify protein quantitative trait loci (pQTLs), i.e. genetic features that are correlated with variations in protein expression).
Data analysis revealed 527 SNPs that are associated with 38 protein biomarkers (pQTLs). For 13 of these proteins, the pQTL could explain >10% of the variation in expression levels seen in the 2 cohorts, with the strongest influence being ~75% of the change in expression of vitamin D binding protein. Several of the pQTLs show significant associations with disease phenotypes, including the pQTL linked to sRAGE, which has been previously associated with emphysema. A striking finding was that SNPs in the ABO blood group region of the genome are strongly associated with many protein biomarker levels. Interestingly, the ABO blood group and COPD have been linked in earlier studies, confirming that ABO status should be taken into consideration for future COPD studies.
The authors conclude that multi-omics studies like this one are important for understanding complex diseases like COPD.
Let your kids get dirty; it’s good for them!
In the current issue of the New England Journal of Medicine researchers explore the mechanism behind the effect of endotoxin exposure on asthma and allergies in children. The researchers used Myriad RBM’s TruCulture® tubes to collect and stimulate whole blood in order to study differences in the innate and adaptive immune response in Amish and Hutterite children. The authors also investigated cellular changes and allergy biomarkers in serum. Amish and Hutterite people are similar in genetic make-up and lifestyle, but differ in exposure to microbial antigen which has been shown to be protective for asthma and allergies in other studies.
The results show that Amish children, who –through their families’ dairy farms– are more exposed to endotoxins then their Hutterite counterparts, have a reduced incidence of asthma and allergies coinciding with lower serum IgE levels. Stimulating the innate immune system with LPS resulted in lower cytokine release in Amish then Hutterite children, but there were no differences when using a T cell specific stimulant. This data and changes in immune cell populations suggests that lower asthma incidence in children exposed to microbial antigen and their endotoxin is mediated by changes in innate immunity.
VentiRx, the developers of motolimod, a TLR8 agonist, have published preclinical and clinical results that indicate effective immune system stimulation in human whole blood cultures, non-human primates, healthy subjects, and late-stage cancer patients. Immune system stimulation in all of these settings is dose-dependent, characterized by similar biomarkers, and consistent with stimulation via the TLR8 pathway. The rapid translation and development of motolimod clearly benefited from the use of standardized immune monitoring systems and validated biomarker assays.
Researchers at Brigham and Women’s Hospital, Harvard Medical School demonstrate the utility of a blood-based panel for identifying Interstitial Lung Disease (ILD) in Rheumatoid Arthritis (RA) patients. The comorbidity of RA-ILD is prevalent and is associated with negative patient outcomes: ILD is the second leading cause of death in patients with RA. When combined with existing clinical risk factors, the biomarker panel (MMP7, PARC and SP-D) has considerable potential as an early diagnostic, which could improve clinical outcomes in patients with RA-ILD.
Researchers at Philip Morris used Myriad RBM’s RodentMAP (Multi-Analyte Profiling) immunoassay service and other histological and functional assessments to demonstrate that prototypic modified risk tobacco product (pMRTP) aerosol stops emphysema progression and eliminates most inflammatory processes when compared to mice exposed to cigarette smoke. The pMRTP investigated is based on a distillation technology with a controlled heating of tobacco rather than burning, yielding a smoke aerosol with reduced concentrations of combustion related constituents. The study provides a framework for future research aiming to identify clinical endpoints and examine the safety of using pMRTPs instead of traditional tobacco alternatives.
A new paper from Peter Schafer, et al, of Celgene shows how biomarkers can be used to monitor treatment response in an inflammatory disease setting. The early timepoints show a dose-dependent biomarker response while the later timepoints show a more normalized response, possibly correlated with reduced disease severity.