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Immune Function and Disease

Decoding the metabolic pathways in immune function and diseases.

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Immune Function

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Immune Function

Metabolomics in Immunology

Immunology research is continually challenged by the need to decipher complex immune responses and their variations in different pathological conditions. Researchers grapple with the heterogeneity of immune responses, particularly  how they manifest in various immune-related diseases such as autoimmune disorders, allergies, and immunodeficiencies. Identifying specific biomarkers and understanding the nuanced interactions within the immune system requires methods that go beyond traditional approaches to provide a more granular and dynamic view of immune function.

Metabolomics has the potential to greatly benefit immunology research by offering insights into the metabolic changes that occur during immune responses. It aids in the identification of metabolites involved in immune cell activation and differentiation, shedding light on the mechanisms behind immune responses. Additionally, metabolomics facilitates the discovery of biomarkers associated with various immune-related conditions, enabling early disease detection and personalized treatment approaches. It plays a crucial role in drug development, helping assess the metabolic effects of immunomodulatory drugs and contributing to personalized immunotherapy strategies. Metabolomics also unravels the intricate crosstalk between the immune system and metabolism, influences vaccine development, and enhances our understanding of host-pathogen interactions during infectious diseases. By integrating metabolomics with other omics technologies, researchers can adopt a holistic systems biology approach to advance immunology research and develop targeted therapies for immune-related disorders.

Immune Function

Uncover Functional, Actionable Insights with Metabolomics

More research is needed to understand the complex mechanisms of the human immune system and how it both impacts and is impacted by various factors in disease. Metabolon can help researchers gain the phenotypic resolution needed to understand and leverage immune responses. Global and untargeted metabolite panels can provide actionable insight into novel biomarkers to aid in the development of effective therapies for immune disorders.

Patient Stratification
Characterization of Treatment Response
Diagnostic Biomarker Discovery

​Patient Stratification

Metabolomics provides insights to help characterize phenotypes. Understanding phenotypic difference helps with patient stratification and reveals factors contributing to the phenotype to elucidate mechanisms of disease. For example, in a study published in iScience, metabolomics was used to profile HIV-1-positive elite controllers, which are HIV-1-infected individuals who can suppress viral replication in the absence of antiretroviral therapy.

The results of the metabolomics analysis highlighted the role of low-level inflammation and oxidative stress at physiological levels as important factors contributing to the elite control phenotype.

Sperk M, Mikaeloff F, Svensson-Akusjärvi S, et al. Distinct lipid profile, low-level inflammation, and increased antioxidant defense signature in HIV-1 elite control status. iScience. 2021;24(2):102111. doi:10.1016/j.isci.2021.102111

Characterization of Treatment Response

Metabolomics can identify metabolic changes in response to  drug therapy to inform better treatment regimens and support personalized medicine approaches. For example, metabolomics was performed on plasma samples from patients with relapsed remitting multiple sclerosis who received dimethyl fumarate. The results showed that DMF treatment altered lipid metabolism by increasing levels of multiple phospholipids and reducing the levels of several fatty acids, changes that were associated with immunological parameters such as absolute lymphocyte count.

Bhargava P, Fitzgerald KC, Venkata SLV, et al. Dimethyl fumarate treatment induces lipid metabolism alterations that are linked to immunological changes. Ann Clin Transl Neurol. 2019;6(1):33-45. doi: 10.1002/acn3.676

Diagnostic Biomarker Discovery

Metabolomics can reveal novel dysregulated metabolic pathways in various immune diseases. For example, adenomyosis is a gynecologic condition in which the endometrium grows into the uterine wall.  A study published in iScience used non-invasive cervicovaginal lavage sampling combined with metabolomics to identify metabolic biomarkers that could be used to detect adenomyosis and help understand how it dysregulates the immune system. In fact, enrichment analysis showed how pyrimidine metabolism, carnitine synthesis, and histidine/histamine metabolism were significantly upregulated pathways in adenomyosis.

Lorentzen GM, Łaniewski P, Cui H, et al. Immunometabolic profiling of cervicovaginal lavages identifies key signatures associated with adenomyosis. iScience. 2022;25(12):105508.  doi:10.1016/j.isci.2022.105508

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Metabolomics Applications for Immune Function and Disease Research

  • EBiomarker discovery
  • EPersonalized medicine research
  • EPrecision medicine research
  • EMonitoring treatment response
  • EEarly detection of altered pathways
  • EDrug discovery and development
  • EUnderstanding molecular mechanisms of disease
  • EPatient stratification
  • EIdentification of metabolism-immune associations
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“Whilst it is clear that microbes within the gut can themselves induce changes to host immunity, microbial metabolites are emerging to play a critical role.”

Simpkins DA, Downton P, Gray KJ, et al.
Consequences of collagen induced inflammatory arthritis on circadian regulation of the gut microbiome. FASEB J. 2023;37(1):e22704. doi:10.1096/fj.202201728R

Metabolomics Insights into Immune Function

HIV elite controllers are a rare but heterogeneous group of HIV-infected individuals who can suppress viral replication despite not being on antiretroviral therapy (ART). They are a rare population that maintains low levels of HIV in their blood for a prolonged period without showing any clinical symptoms of HIV infection and progression to acquired immunodeficiency syndrome (AIDS). Researchers believe this population might hold the key to developing novel HIV therapies; however, the mechanisms of how HIV elite controllers achieve viral suppression remain unclear. It is thought that a major part of maintaining undetectable viral loads can be attributed to host factors rather than viral factors. Metabolomics offers a unique opportunity to uncover how HIV elite controllers remain symptom-free without ART.

Researchers used the Global Discovery Panel to identify 950 metabolites in the plasma samples of HIV elite controllers, viremic progressors (VP), and healthy control (HC) subjects. Most of these metabolites belonged to the class of lipids (49%), followed by amino acids (21%). VP had lower levels of several lipids compared with HIV elite controllers and HC, including metabolites belonging to polyunsaturated fatty acids, lysophospholipids, phospholipid metabolism, or lysoplasmalogen. In contrast, diacylglycerol levels were highest in VP and unchanged in HIV elite controllers compared with HC. The levels of acylcholines and choline were increased in HIV elite controllers relative to HC and VP, making these biomarkers unique to HIV elite controllers.

Untargeted metabolomics also demonstrated that HIV elite controllers exhibit reduced oxidative stress. Glutathione is an antioxidant that helps resist oxidative stress. Relative to VP, HIV elite controllers showed a significant increase in S-adenosylhomocysteine (SAH), the glutathione precursors cysteine and glycine; the cysteine-derived antioxidants hypotaurine and taurine, as well as the glutathione cycle intermediates cysteinylglycine, 5-oxoproline, glutamate, methionine, and several gamma-glutamyl amino acids. These data suggest that HIV elite controllers exhibit greater antioxidant defense activity than VP. The data also show that HC and HIV elite controllers have similar oxidative stress levels and antioxidant defense. This signature suggests that HIV elite controllers, but not VP, can keep redox homeostasis at levels seen in HIV-uninfected (HC) individuals.

Sperk M, Mikaeloff F, Svensson-Akusjärvi S, et al. Distinct lipid profile, low-level inflammation, and increased antioxidant defense signature in HIV-1 elite control status. iScience. Feb 19 2021;24(2):102111. doi:10.1016/j.isci.2021.102111. Available under CC BY 4.0

Immune Function and Disease Publications and Citations

Metabolon has contributed extensively to publications ranging from basic research to clinical trials.

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Immune Function and Disease Knowledge Base

Dive deeper by viewing our case studies and webinars. Learn more about how Metabolon furthers immune function and disease research and check back for more to stay up to date on the latest developments in metabolomics in immune function and disease.

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References

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