User:Marvin O'Neal/VlsE: Difference between revisions

The variable regions undergo a recombination event stimulated by the host’s cytokines and absence of those cytokines results in a decreased bacterial burden <ref>PMID:11544329</ref>.  This leads to variation with an estimated 10³⁰ possible combinations, far exceeding the number of antibodies found in the human immune system.  While the VR does exhibit antigenicity, this recombination makes it unlikely that enough of a single VR variation will be present in large enough supply to lead to an immunodominant variable region <ref>PMID:10553085</ref>.  IR₆, however, exhibits immunodominance while IR₁-IR₅ are primarily nonantigenic in humans.  Thus, shielding of the immunodominant IR₆ by VR regions not subject to antibody response allows for IR₆ to elicit an immune response while remaining inaccessible to antibody binding.  Research suggests that the 26 amino residues of IR₆ may function as a single epitope with a central alpha helical core <ref>PMID:11923306</ref> <ref>PMID:11544329</ref> <ref>PMID:10722641</ref>.   

VlsE is essential to the persistence and virulence of Lyme disease <ref>PMID:17714442</ref>.  This rapid recombination event is stimulated by the host’s cytokines and absence of those cytokines results in a decreased bacterial burden <ref>PMID:11544329</ref>.  In addition, VlsE is upregulated under humoral immune pressure <ref>PMID:15385475</ref>.  The variable regions undergo the a recombination event leading to variation with an estimated 10³⁰ possible combinations, far exceeding the number of antibodies found in the human immune system.  This makes it unlikely that enough of a single VR variation will be present in large enough supply to lead to an immunodominant variable region <ref>PMID:10553085</ref>.  Thus, shielding of the immunodominant IR₆ by regions not subject to antibody response allows for IR₆ to elicit an immune response while remaining inaccessible to antibody binding <ref>PMID:11923306</ref> <ref>PMID:11544329</ref> <ref>PMID:10722641</ref>. <br>

 

While the exact mechanism for immune evasion remains unknown several theories have been put forth.  One popular theory is that VlsE masks other surface antigens by coating the surface of the bacteria, thereby sterically blocking the antigens from antibody binding.  This is similar to other pathogens with variable regions, such as the [http://en.wikipedia.org/wiki/Trypanosoma_brucei protozoa] responsible for African sleeping sickness and also the [http://en.wikipedia.org/wiki/Neisseria_gonorrhoeae bacterium] that causes gonorrhea.  However, recent studies have cast doubt on this theory.  An alternate theory provides that VlsE directly stimulates B cell antibody production independent of T-cells.  The robust response elicited is thought to override antibody production against other antigens <ref>PMID:17714442</ref>.   

Throughout the course of the disease IR₆ produces a strong antibody response that can be identified from early to late phases, and which lasts for months to years following treatment.  Applications in diagnostic testing have been identified as a result of this strong immune response and IR₆’s relative invariability across strains <ref>PMID:10565920</ref> <ref>PMID:10722641</ref>.  A C₆ ELISA test has been developed which uses a 26-mer synthetic peptide with the IR₆ sequence.  Results show 99% specificity and 100% precision with high sensitivity. <scene name='Studio:G5SecL01/Ir6_with_epitope/1'>PINK</scene> In fact, OspA vaccination does not influence C6 specificity; therefore, C₆ ELISA tests are valuable diagnostic tools for patients vaccinated against OspA.  The [http://www.cdc.gov/lyme/healthcare/clinician_twotier.html CDC]  currently recommends a two-step test incorporating first an ELISA followed by a Western blot to eliminate false positives.  Therefore, this one-step ELISA test presents an economical and more accurate improvement over the current two-step model <ref>PMID:10565920</ref>. <br>

[http://en.wikipedia.org/wiki/Lyme_disease_microbiology Lyme Disease Microbiology]

[http://www.cdc.gov/lyme/ CDC Lyme Disease Page]

[http://en.wikipedia.org/wiki/Lyme_disease Lyme Disease]

[http://www.cdc.gov/about/grand-rounds/archives/2011/pdfs/PHGRLymeMay2011.pdf Ecology, Epidemiology, and Prevention of Lyme Disease- CDC]

[http://en.wikipedia.org/wiki/Antigenic_variation Antigenic Variation]