New technologies for autoimmune disease monitoring

Abstract

Purpose of review This article will review new technologies used to characterize the immune phenotype of cells and serum for potential use in studies of autoimmunity. Recent findings One area of recent development in studies of immune phenotyping is the contrast between cells of the immune system at rest and following activation. This simply involves comparing these cells at rest and following ligand-induced activation and measuring signaling system activation (phosphoepitope identification) or intracellular cytokine production or activation-induced gene expression. Preliminary data using these techniques have begun to identify signatures of disease (biomarkers) that are only seen when using these activation-induced assays. One of the most exciting new technologies, cytometry by time-of-flight mass spectrometry, couples a flow cytometer to a mass spectrometer, allowing many more parameters to be analyzed per cell, and without spillover between assay reagents, compared to conventional optical flow cytometry (heavy ions, mass, replaces fluorophore readout). Another new technology to analyze soluble proteins, bead-based immunoassays, can simultaneously measure up to 75 soluble analytes in a multiplexed array. Other technologies provide similar innovations in terms of analytical content, throughput, and miniaturization. Summary We believe that new cellular genomic and protein-based technologies can provide key insights into autoimmune disease pathogenesis, progression, and therapy, and that these assays need to be applied in a systematic way to samples from patients with autoimmune diseases.

Immunomonitoring Lymphocyte Subpopulations in Multiple Sclerosis Patients

“…Studies in the animal model of MS, experimental autoimmune encephalomyelitis (EAE), have shown that the effector CD4 + T-subpopulations, Th1 and Th17, play an important role in the pathogenesis of the disease. These subpopulations have been found increased in the CNS of patients with MS, mainly in CSF and the perivascular space (3,4). In addition, oligoclonal expansions of activated CD8 + T-cells in CNS lesions of MS patients have been described, indicating their participation in CNS damage (5,6).…”

“…It has been demonstrated that immunomodulatory treatments decrease the percentage of these cell populations, alter the expression of their surface markers, and modify their functionality (i.e., cytokine production, proliferation, and induction of apoptosis). For these reasons, it has been hypothesized that systematic analyses of peripheral blood immune cells could serve as surrogate biomarkers of activity of the disease and/or response to therapy, leading to the development of personalized medicine (1)(2)(3)(4).…”

Computationally efficient multidimensional analysis of complex flow cytometry data using second order polynomial histograms

“…In the first step, the range of each parameter is scaled to the same interval, typically [0,5], which allows division into the same number of bins, b, of equal size or binwidth, resulting in a total of b d d-dimensional volumes or bins, where d is the number of dimensions. This initial step mimics the idea of histogram estimators, which are efficient, and allows the elimination of empty bins in later calculations.…”

“…For notational convenience, and for easier comparison of results, the cluster center or mode of each cluster is identified with the centre of its bin. Figures show the center of each modal bin in the scaled range [0,5].…”

Immunodiagnostics and immunosensor design (IUPAC Technical Report)

“…The system is efficient but not perfect. As a consequence of disturbance of the self-tolerance mechanisms, the immune system may treat self-molecules as if they were foreign, causing immune reactions that result in autoimmune disease [154][155][156]. This is often directed towards only one or a few types of molecules of just one organ.…”