The Potential of Omics Technologies in Lyme Disease Biomarker Discovery and Early Detection

Abstract

Lyme borreliosis (LB) is the most prevalent arthropod-borne infectious disease in North America and many countries of the temperate Northern Hemisphere. It is associated with local and systemic manifestations and has persistent post-treatment health complications in some individuals. Innate and acquired immunity-related inflammation is likely to play a critical role in both host defense against Borrelia burgdorferi and disease severity. Large-scale analytical approaches to quantify gene expression (transcriptomics), proteins (proteomics) and metabolites (metabolomics) in LB have recently emerged with a potential to advance the development of disease biomarkers in early, disseminated and posttreatment disease stages. These technologies may permit defining the disease stage and facilitate its early detection to improve diagnosis. They will also likely allow elucidating the underlying molecular pathways to aid in identifying molecular targets for therapy. This article reviews the findings within the field of omics relevant to LB and its prospective utility in developing an array of biomarkers that can be employed in LB diagnosis and detection particularly at the early disease stages.

Risk of Severe Influenza Infection: Hypercytokinemia Gene Polymorphisms and Related Plasma Proteome in Canadian Young Adults

“…In addition, the AT genotype at rs4073 in IL8 [16] and the AG at rs909253 in LTα, also known as TNF-β [16,26], were associated with the inflammatory response [13]. In the present study, the genotypes identified to play a role in IAV, were also rep- compared to those with "no-risk" genotype.…”

“…Such polymorphisms in hypercytokinemia genes are associated with an increased potential to synthesize cytokines and chemokines and influence the nature and effectivness of the inflammatory immune response [13,27]. Overall, risk alleles of IL8 and TNF-β were associated with a 1.5 to 3-fold increased risk of IAV infection and with a 1.2 to 2.4 increased risk of death [16,28]. This observation may facilitate the characterization of genetic factors and downstream protein biomarkers that can be employed in identifying individuals at high risk of disease severity upon and during infection.…”

“…Furthermore, elevated levels of the resultant pro-inflammatory cytokines and chemokines were found in the plasma of patients with acute respiratory distress syndrome caused by IAV [14,15]. Previous studies examining the relationship between infectious diseases and cytokine markers suggest that host genetic factors may indeed influence these biomarkers and the subsequent disease severity [16], as was also noted in severe IAV infection [14,15,17,18]. Advances in proteomics enable the simultaneous detection of multiple proteins in plasma that assist in understanding the interactions within and between pathways.…”

Metabolites of prostaglandin synthases as potential biomarkers of Lyme disease severity and symptom resolution

“…Infected tissues typically display a mononuclear-type inflammation, with predominating macrophages, dendritic cells, and plasma cells [12, 16]. However, the underlying mechanisms of this inflammatory response and resolution are not clear [13, 14]. The initial innate immune response begins with a signaling cascade which is promoted by cytokines, eicosanoids and related lipid mediators [17, 18].…”

“…Although the role of cytokines in the mediation of the inflammatory process in LB has been well described [13], no study has systematically evaluated the role of PGs and related lipid mediators in the induction and resolution of inflammation in LB. Given the high level of inflammation-related long-term effects of LB as well as the widespread use of COX-specific inhibitors and non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of LB [21], it is critical to understand the role of bioactive lipid mediators in LB to provide better approach for symptoms resolution and LB treatment.…”