Modular Immune Profile (MIP) Test Kit

DxTerity`s MIP Test measures the relative gene expression immune system related genes. The MIP Test is composed of 12 immune system expression modules, including Type I and Type II Interferon, plasma and plasmablast cells, neutrophils, B cells, T cells, and T cell exhaustion. MIP is being developed for longitudinal monitoring of a patient’s immune health and for characterization of therapy response in clinical trials and investigational studies.

Type I Interferon (IFN-1) Module
Type I interferon (IFN-1) is primarily related to innate immunity and how a body responds to viral attacks. IFN-1 status has been shown to be a prognostic factor for disease severity in SLE 4 and IFN-1 high patients are more likely to progress to lupus nephritis5. Many current and developmental therapeutics have mechanisms of action that impact IFN-1 and the JAK/STAT pathway3.

Type II Interferon (IFN-γ) Module
Type II Interferons or IFN-γ is primarily involved in adaptive response and the development of long-term immunity, but also plays a role in innate immunity. IFN-γ plays a key role in T-cell differentiation immunoregulatory, antiviral and anti-tumor activity. This 3-gene module is being evaluated for therapy response and disease activity in SLE6, subtyping in RA, and immunotherapy response prediction in cancer.

B-Cell Module
B cells or B lymphocytes are a type of white blood cell. They are primarily responsible for the generation of antibodies after being activated by helper T cells and antigens. B cells differentiate into short lived plasmablast cells and long-lived plasma cells, which are both antibody secreting. Many common immunosuppressive therapies function through a B-cell depletion mechanism including Rituximab, Ocrevus, and Benlysta. The B-cell module can be used to monitor therapeutic response for B cell depleting therapies.

Plasmablast/Plasma Cell Module
Plasmablast cells are short lived antibody producing cells that further differentiate into long lived, antibody producing plasma cells. This module has been shown to positively correlate with disease activity in SLE7, and it is also impacted by B-cell depleting therapies, however with a more delayed response. Measuring these changes may aid clinicians in the early identification of changes in disease activity or potential disease flare, providing the opportunity for early intervention.

Neutrophils/Low Density Granulocytes (LDGs) Module
Neutrophils are a type of white blood cell that protect the body from infection. Low density granulocytes are a subset of neutrophils that have been implicated in SLE inflammation and disease progression including promoting organ damage and increased production of Type I Interferon8,9.   Increases in this module may be predictive of disease progression and increased kidney involvement .

T Cells Module
T cells play a key role in immune response10.  There are several different types of T cells including cytotoxic T cells or “Killer cells”, helper T cells which assist B cells in identification of antigens/antibody response, memory T cells for building up adaptive immunity, and regulatory T cells which play a major role in tolerance or recognition of “self”.  The T cell genes in MIP are looked at individually to help better understand the underlying mechanism of a patient’s autoimmune disease or cancer.

T Cell Exhaustion Module
In chronic autoimmune disease like SLE, the process of T-cell exhaustion helps inhibit immune response, and exhausted T cell responses have been associated with better outcomes 10.  T cell exhaustion mechanisms and markers also play a major role in cancer and how tumors hide from the immune system.  The measurement of T-cell exhaustion may help clarify the underlying mechanism of poor T cell function and its importance in autoimmunity. Therapeutics that successfully exhaust the T-cell response may be good candidates for autoimmune diseases. The measurement of T-cell gene expression profiles may provide a method to determine future outcomes of targeted therapies.  Additionally, the lack of T-cell exhaustion signals may indicate a risk of relapse or occurrence, or in the context of targeted therapy, may result in dose escalation.

The DxTerity Modular Immune Profile (MIP) assay uses Chemical Ligation Dependent Probe Amplification (CLPA) on PAXgene® and DxCollect® stabilized whole blood. The 51 genes are separated by capillary electrophoresis and the gene expression levels are calculated relative to the average of three control genes. The results are grouped into Modules which demonstrate correlation to immune pathways and therapeutic targets.  Below are the sample collection methods for the MIP test.