Modular Immune Profile (MIP) Test
The investigational use MIP assay is designed to measure activity of 12 autoimmune disease related biological pathways.
The Modular Immune Profile (MIP) Test
About Modular Immune Profiling
Autoimmune diseases need analysis tools that go beyond superficial symptoms to recognize the distinct immune system activity of each patient. Modular transcriptome repertoire analysis 1, also known as modular genomics, shows tremendous promise for improving the characterization of patients with autoimmune diseases such as Systemic Lupus Erythematosus (SLE)7, Multiple Sclerosis (MS), Inflammatory Bowel Disease (IBD), and Rheumatoid Arthritis (RA) by providing biological insight into the underpinnings of a patient’s disease and how interrelated immune pathways change in response to treatment.
Description of the MIP Test
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) 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 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.
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 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 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.
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.
DxTerity DxCollect MCD
(16x100 mm / 100 uL)
Tube Material Plastic
Tube Size 19x90 mm
Draw Volume 100 uL
Regulatory Status IUO
PAXgene® Blood RNA Tube
(16x100 mm / 2.5 mL)
Tube Material Plastic
Tube Size 16x100 mm
Draw Volume 2.5 mL
Regulatory Status IVD
MIP Modular Immune Profile Test
The DxTerity Modular Immune Profile (MIP) Test is available for Investigational Use Only (IUO). The performance characteristics of this product have not been established.
Please contact us to learn more.
MIP Modular Immune Profile Test
1. Chaussabel D et al, A Modular Analysis Framework for Blood Genomics Studies: Application to Systemic Lupus Erythematosus, Immunity, 29(1):150-164 (2008)
2. Altman MC et al, A Transcriptome Fingerprinting Assay for Clinical Immune Monitoring, bioRxiv The Preprint Server for Biology – Cold Spring Harbor Laboratory, doi: https://doi.org/10.1101/587295 (2019)
3. Comabella M et al. A type I interferon signature in monocytes is associated with poor response to interferon beta in multiple sclerosis. Brain 132: 3353—3365 (2009)
4. Baechler E et al., "Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus.," Proc Natl Acad Sci U S A., pp. Mar 4;100(5):2610-5. Epub 2003 Feb 25., (2003)
5. Arriens C et al, Increased Risk of Progression to Lupus Nephritis for Lupus Patients with Elevated Interferon Signature[abstract], Arthritis Rheumatol. 2019; 71 (suppl 10) https://acrabstracts.org/abstract/increasedrisk-of-progression-to-lupus-nephritis-for-lupus-patients-with-elevated-interferon-signature/
6. Chiche L et al. and D. Chaussabel, "Modular transcriptional repertoire analyses of adults with systemic lupus erythematosus reveal distinct type I and type II interferon signatures.," Arthritis Rheumatol., pp. Jun;66(6):1583-95. doi: 10.1002/art.38628., 2014
7. Banchereau R. et al, "Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients.," Cell, pp. Apr 21;165(3):551-65. doi: 10.1016/j.cell.2016.03.008. Epub 2016 Mar 31., 2016
8. Kaplan MJ, Neutrophils in the pathogenesis and manifestations of SLE, Nature Reviews Rheumatology, 7: 691-699 (2011)
9. Jourde-Chiche N et al, Modular transcriptional repertoire analyses identify a blood neutrophil signature as a candidate biomarker for lupus nephritis, Rheumatology, 56(3):477-487 (2017)
10. McKinney EF et al, T cell exhaustion, costimulation and clinical outcome in autoimmunity and infection, Nature, 523(7562):612-616 (2015)
11. Angela R Jones-Leone et al, Efficacy Analysis of Patients with Systemic Lupus Erythematosus Treated with Belimumab or Placebo Plus Standard Therapy in Phase 3 Trials by Baseline Levels of BLyS mRNA and Type 1 Interferon Inducible Gene Signature Status [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/efficacy-analysis-of-patients-with-systemic-lupus-erythematosus-treated-with-belimumab-or-placebo-plus-standard-therapy-in-phase-3-trials-by-baseline-levels-of-blys-mrna-and-type-1-interferon-inducibl/
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