Biomarkers of Multiple Sclerosis

The search for an ideal multiple sclerosis biomarker with good diagnostic value, prognostic reference and an impact on clinical outcome has yet to be realized and is still ongoing. The aim of this review is to establish an overview of the frequent biomarkers for multiple sclerosis that exist to date. The review summarizes the results obtained from electronic databases, as well as thorough manual searches. In this review the sources and methods of biomarkers extraction are described; in addition to the description of each biomarker, determination of the prognostic, diagnostic, disease monitoring and treatment response values besides clinical impact they might possess. We divided the biomarkers into three categories according to the achievement method: laboratory markers, genetic-immunogenetic markers and imaging markers. We have found two biomarkers at the time being considered the gold standard for MS diagnostics. Unfortunately, there does not exist a single solitary marker being able to present reliable diagnostic value, prognostic value, high sensitivity and specificity as well as clinical impact. We need more studies to find the best biomarker for MS.

Inter-Pathogen Peptide Sharing and the Original Antigenic Sin: Solving a Paradox

Aims:To analyse the peptide commonality among viral, bacterial, and protozoan pathogens, and the immunopathologic consequences in the human host.Methods:HPV16, HCMV,C. diphtheriae, B. pertussis, C. tetani, T. gondii,andT. cruziwere analysed for common amino acid sequences that are additionally shared with the human host. The pentapeptide, a minimal immune determinant in humoral and cellular immune recognition, was used as a measurement unit of the peptide similarity level. Molecular modeling was applied to compare the amino acid contexts containing common minimal determinants.Results:Twenty-nine pentapeptides were found to occur, even hundreds of times, throughout the analyzed pathogen proteomes as well as in the human proteome. Such vast peptide commonalities together with molecular modeling data support the possibility that a pre-existing immune response to a first pathogen can be boosted by a successive exposure to a second different pathogen,i.e., the primary response to a pathogen can be transformed into a secondary response to a previously encountered different pathogen. Two possible consequences emerge. Firstly, no responses might be elicited against the pathogen lastly encountered either by infection or active immunization, but reactions could occur only with the early sensitizing pathogen, which is no more present in the organism. Secondly, the immune response boosted by the pathogen lastly encountered will find a way out by cross-reacting with human proteins.Conclusion:This study might explain the “original antigenic sin” phenomenon described seven decades ago [Francis T. Jr. Ann Intern Med 1953;39:203], thus providing explanations for vaccine failures and offering possible clues for designing successful vaccines.

Tracing Aluminium-based Adjuvants: Their Interactions with Immune Competent Cells and their Effect on Mitochondrial Activity

Background: Studies revealing the immune stimulatory properties of aluminium-based adjuvants (ABAs) have been impaired by the absence of simple and reliable methods of tracing the adjuvants and their effect on biochemical processes upon endocytosis. Objective: To verify that labelling of ABAs with lumogallion doesn’t affect the physicochemical properties of the adjuvant; tracing cellular interaction with aluminium adjuvants; explore their effect on metabolic activity upon endocytosis. Methods: Physicochemical characterization by Z-potential and size distribution of ABAs labelled with lumogallion. Cellular interactions with ABAs by flow cytometry and confocal microscopy. Metabolic activity explored by measuring transformation of tetrazolium into formazan. Results: No or minor change of zeta potential and average particle size of lumogallion labelled aluminium oxyhydroxide, AlO(OH) and aluminium hydroxyphosphate, Al(OH)x(PO4)y. Both phagocytosing and non-phagocytosing leukocytes became associated with ABAs at concentrations expected after in vivo administration of a vaccine. The ABAs were relatively toxic, affecting both lymphocytes and monocytes, and Al(OH)x(PO4)y was more toxic than AlO(OH). Endocytosed aluminium adjuvant particles were not secreted from the cells and remained intracellular throughout several cell divisions. The presence of ABAs increased the mitochondrial activity of the monocytic cell line THP-1 and peripheral monocytes, as based on the transformation of tetrazolium into formazan. Conclusion: Lumogallion labelled ABAs is a valuable tool tracing interactions between ABAs and cells. Labelled ABAs can be traced intracellularly and ABAs are likely to remain intracellular for a long period of time. Intracellular ABAs increase the mitochondrial activity and the presence of intracellular Al ions is suggested to cause an increased mitochondrial activity.