Isoplexis_July2021_AcceleratingDevelopmentCurativeMedicines - 7

ACCELERATING THE DEVELOPMENT OF CURATIVE MEDICINES WITH FUNCTIONAL IMMUNE PROFILING
IsoPlexis' Walk-Away Proteomics
Reveals Critical Therapeutic Targets
and Predictive Biomarkers
While previous studies have investigated patient's
innate and adaptive immune responses to COVID19,
the role of these COVID-19-specific immune
responses in disease pathogenesis has still been
unclear. A comprehensive understanding of how
airway and blood immune cells function together
to drive COVID-19 pathogenesis is needed. The
study identified protective T cell signatures in the
respiratory tract that were associated with younger
age and survival from severe COVID-19. Conversely,
the study also identified airway myeloid cells,
primarily macrophages and monocytes, that drove
immune cell recruitment and lung inflammation,
and were associated with older age and mortality.
CCL2 was noted as a potential therapeutic target
due to its role in recruiting monocytes into the lung.
The identification of elevated airway chemotactic
mediators suggests that targeting these attractors
of circulating monocytes and macrophages may
help improve COVID-19 outcomes. Airway T cell
frequencies, which correlated with younger age and
survival, may be useful as a predictive biomarker for
monitoring patients and stratifying risk.1
Overall, the study by Szabo, et al. elucidated the
roles of airway cells and plasma in both protective
and inflammatory responses to COVID-19,
providing novel insights which may aid in the
development of improved methods for monitoring
and treating COVID-19. n
Identifying prognostic
biomarkers of inflammation
in COVID-19 with functional
immune landscaping
Learn about another study in which
IsoPlexis' immune profiling revealed key
mechanisms of COVID-19 pathogenesis
and inflammation.
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P
redicting COVID-19 progression in patients is
a challenge. The virus affects numerous organ
systems and patients display a large range of
symptoms, making each case unique. The ability to
detect COVID-19 immune biomarkers associated with
disease severity and progression will aid in identifying the
appropriate treatments at early disease stages. A major
hurdle in immune biomarker identification is the complex
nature of the immune system. In a recent Cell publication,
an interdisciplinary team led by James R. Heath from the
Institute for Systems Biology employed a unique multiomics
approach to dissect the coordinated immune
responses in mild to severe SARS-CoV-2 infections and to
detect COVID-19 biomarkers.
Functional immune landscaping to map the immune
response in COVID-19
To understand how the immune system changes in mild
to severe COVID-19, Heath and his team analyzed blood
samples from hundreds of COVID-19 patients and healthy
donors. Through the deep immune profiling of plasma and
PBMCs, the researchers established a disease severity-based
correlation network for COVID-19.
Using single-cell functional proteomics, Heath's team assessed
immune cell composition in the PBMC samples.
Deep immune profiling revealed that healthy donors and
patients with mild disease had similar percentages of monocytes,
CD8+
T cells, CD4+ T cells, and NK cells. In contrast,
there was a drop in the relative lymphocyte percentage and
an increase in the monocyte percentage as patients transitioned
from mild to moderate disease.
Decoding the immune cell response in COVID-19 with
functional proteomics
The researchers further investigated major immune cell
populations via functional proteomics using a unique
single-cell secretome analysis of 32 cytokines. In the transition
from mild to moderate disease, they discovered an
increase in polyfunctional T cells; however, CD8+
T cells
from patients with severe COVID-19 demonstrated a significant
drop in function, indicating a potentially stressed
immune environment.
When circulating monocytes were analyzed using single-cell
proteomics, it was discovered that the polyfunctionality
of peripheral monocytes increased with disease
severity, including severe cases. This finding suggests
1
GENengnews.com | 7
https://www.isoplexis.com/literature/identifying-prognostic-biomarkers-of-inflammation-in-covid-19-with-functional-immune-landscaping/ http://www.GENengnews.com

Isoplexis_July2021_AcceleratingDevelopmentCurativeMedicines

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