CXCL16 - Routes to Personalized Medicine
Yates, Andrew. “Overview of White Blood Cell Disorders: Symptoms, Diagnosis, Treatment.” Verywell Health, 2016, www.verywellhealth.com/white-blood-cell-disorders-overview-4013280.
Our response to nearly everything from diseases to drugs vary based on a plethora of factors, including comorbidities, socioeconomic status, and genetics. Understanding this immune response is important as it may determine if an individual will obtain, survive, and even respond to treatment of a disease. Hence, determining certain genetic markers that can indicate susceptibility and response, may pave the way towards personalized medicine, consisting of more accurate diagnoses, increasingly effective treatment based on an individual’s genotype, detection and preventative actions for at-risk individuals early on, and more appropriate allocation of resources. Overall, this can increase efficiency and lower medical costs by overcoming the limitations of traditional medicine and uniquely treating and focusing on every patient rather than the disease. This article provides a background on CXCL16 of which current laboratories are testing for potential use in targeting gene therapies.
Cytokines are membrane-bound proteins assisting cell communication to signal an immune response. During a normal immune response to an infection such as COVID-19, the cytokines signal white blood cells (WBC) to the affected location to clear the virus. However, during a severe immune response, there is an uncontrolled secretion of cytokines, known as a cytokine storm which can instigate a hyperactive immune system leading to respiratory complications and death from the deterioration of the lining of the lung and blood vessels .
The CXCR6 gene at the chromosome region 3p21.31, a respiratory failure susceptibility locus previously determined by Genome-Wide Association Study (GWAS), encodes for a chemokine receptor most commonly found on T-cells and natural killer cells of lung tissue. C-X-C chemokine ligand 16 (CXCL16), a surface-bound chemokine found on the surface of splenic red pulp, antigen-presenting cells (such as B cells, macrophages, and dendritic cells), and the thymic medulla, may help determine the migration of various T-cell subsets by aiding in cell-to-cell communication during an immune response and T-cell recruitment and trafficking. If there are elevated levels of CXCL16, this has been associated with a multitude of diseases discussed below.
After collecting and analyzing serum from moderate to severe COVID-19 patients as well as comparing morbidity among patients, Yasmine Boukhalfa et al. found that CXCL16 counts were approximately eight times higher in patients who developed severe symptoms and ultimately died from COVID-19, conveying that heightened levels of CXCL16 are significantly associated with death (p < 0.0001). In regards to breast, ovarian, prostate, and colorectal cancer, researchers discovered that sCXCL16 aided in tumor migration and proliferation. In contrast, membrane forms of CXCL16 play a suppressor role in BrCa cells by inducing apoptosis.
Other diseases associated with elevated levels of CXCL16 include atherosclerosis, renal fibrosis, diabetes mellitus, sepsis morbidity, non-alcoholic fatty liver disease (NAFLD), and coronary disease.
Genotyping is the process of identifying differences in the genetic makeup of individuals by examining their genetic sequence. By probing for SNPs, the frequency of the polymorphism within a population can be determined and data can be stratified into wild type (SNP present in neither allele), heterozygous (SNP present in one allele), and homozygous (SNP present in both alleles). By determining factors that can contribute to disease susceptibility, SNP genotyping can lead to more effective treatment tailored to one’s genome.
Overall, understanding specific functions of genes and eventually testing for their association to disease and disease response will lead to a new era of medicine where individualized treatment will be possible by catering treatment options to a person’s genetic makeup. Once an SNP has been identified as related to a particular disease or trait, specific risk profiling tools can be created and personal treatments can be given to have maximum benefit, with minimum side effects.
