Chapter 193
The Path Forward — 5
A second composite of immune cells and their proteins (cytokines and chemokines) is iAge score. Its increase correlates with chronological age, frailty, cognitive decline, and the number of coexisting conditions. Of note, centenarians had a low iAge score compared with people aged fifty to seventy-nine years old. A third immunome based on CD4+ helper T cells, CD8+ cytotoxic T cells, and gene expression predicted the best survival over a decade of follow-up for the group with markers of high immunocompetence and low inflammation.
More recently, a stab at another immunome called the immune health metric was developed from blood proteins, RNA sequencing, immune cells, and clinical data, integrated with multimodal AI. It can differentiate marked aging in clinically heathy people, track the immune response to diseases, and predict the age-dependent antibody response to vaccines. Like the prior study, there is marked heterogeneity for the metric from one individual to another (fig. 13.3).
Ben Larman, a scientist who runs the Laboratory of Precision Immunology at Johns Hopkins, started a company called Infinity Bio that, amazingly, can take a small amount of blood (a drop) on filter paper and through extensive panels of DNA-barcoded proteins and protein fragments determine a person’s exposure to over five hundred viruses via their antibodies. In the same assay, the new technology can detect hundreds of autoimmune antibodies. The test, which has a ring of the Theranos fraud debacle except that it is real, is currently only available for research projects since the company is taking a rigorous stepwise approach—which makes sense given the promises of Theranos’s fake tests. Hopefully Infinity Bio’s test will become commercially available for clinicians and consumers in the next couple of years. For a preview, my results for this test are presented in figure 13.4.
Figure 13.3. Marked variability between individuals for aging of their cellular immune response, two different immunomes. Adapted from Ayelet Alpert et al., “A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring,” Nature Medicine 25, no. 3 (March 2019): 487–95, https://doi.org/10.1038/s41591-019-0381-y (panel A); and Rachel Sparks et al., “A unified metric of human immune health,” Nature Medicine (July 2024), https://doi.org/10.1038/s41591-024-03092-6 (panel B).
We need to build on these potential immunomes so they can be readily available, inexpensive, and useful in routine clinical checkups. Why?
Well beyond tracking age, such immune system assessments may be fundamental to promoting health span. As we’ve seen with cancer, our inability to quash it early helps explain how cancer cells can spread. By the same token, the immune system reaction to misfolded proteins in our brain is central to degenerative diseases of our brain and the atherosclerosis of our arteries. If we could get an immunome on a periodic basis, it could help to pinpoint our arc to immunosenescence and guide our decisions about potential interventions such as a vaccine or some other treatment (senolytic, gut microbiome manipulation, or partial epigenetic reprogramming) to rejuvenate our immune system. That would enhance our defense against many age-related diseases. The flip side is that supercharging our immune system could prove to be unsafe, if it results in a pro-inflammatory state from stimulating release of cytokines or chemokines or fosters autoimmunity. Sure, it may be a Goldilocks strategy with the need for just the right level of immune response in the right person at the right time, but that is the approach nature seems to be demanding.