Inflammatory biomarkers across a

range of human diseases

Olink panels targeting inflammation-related proteins suggest new pathophysiological mechanisms across diverse disease areas. This brief
review shows how cytokines, chemokines and other immune- and inflammatory proteins are integrally involved with infectious disease
(COVID-19 response), neurology (traumatic brain injury), digestive disorders (ulcerative colitis) and skin disease (atopic dermatitis).

Inflammation can be chronic Name of cohort #of Cases Olink®Target or Olink® Sample Matrix Inactivation, tubes
Explore panels
Mass General n=306 Olink® Explore 1536 Plasma Triton, EDTA
Inflammation is characterized by the activation of immune and non-
immune cells to protect the host organism against pathogens and Imperial College A n=55 Infl., Immune, CVD II, CVD III Plasma N/ A, EDTA

related toxins by eliminating these infections, establishing immune Imperial College B n=46 Infl., Immune, CVD II, CVD III Serum N/ A, EDTA

memory and promoting tissue repair and recovery. Recent research Weill Cornell Int Med n=177 Infl., CVD II, CVD III Serum 56C

has uncovered differences between a normal acute inflammatory Weill Cornell ICU n=49 Infl., CVD II, CVD III Plasma 56C in EDTA

responses (where inflammatory activity is up-regulated for a short
period of time) and low-grade, non-resolving “systemic chronic
inflammation” that is characterized by activation of immune
components but is persistent, breaking down immune tolerance and
leading to major changes across tissues and organs.(1)
To study a complex and pervasive inflammation-related
pathogenesis, Olink Proteomics offers the broadest and most
comprehensive set of multiplexed inflammation biomarker assays on
the market. These sensitive biomarker panels scale from the Olink®
Target 48 Cytokine panel (simultaneous analysis of 26 cytokines,
12 chemokines and other immune-related biomarkers totaling 45
protein targets), through the Olink® Target 96 Inflammation panel
(simultaneous analysis of 92 protein biomarkers), up to the Olink®
Explore 384 Inflammation I and Olink® Explore 384 Inflammation II
panels, each with approximately 370 inflammatory or inflammation-
related biomarkers each. Here we highlight four diverse disease
areas where Olink panels revealed a central role for inflammation-
related proteins: severe COVID-19, traumatic brain injury, ulcerative
colitis and atopic dermatitis.
Figure 1: The five cohorts used in the meta-analysis from Suhre et al. (2)
Inflammation markers involved in
severe COVID-19 and cytokine release
storms
A recent meta-analysis across five independent COVID-19 studies
analyzed 253 unique proteins (contained in the Olink® Target
Inflammation, Cardiovascular II and Cardiovascular III panels)
that were common to all.2 The number of cases, and the fourteen
proteins differentially expressed, are shown in Figure 1. Thirteen of
the proteins were overexpressed in COVID-19 patients across all five
studies (CCL7, CXCL10, CCL8, LGALS9, CXCL11, IL1RN, CCL2, CD274,
IL6, IL18, MERTK, IFNg, and IL18R1) with only one (CCL16) that
was higher in healthy controls. Figure 2 shows the heatmap with the
five studies listed on x-axis and the fourteen differentially expressed
proteins on the y-axis.
 Study
Mass General Imperial College Imperial College Weil Cornell General Weill Cornell
Source
Hospital MA NHS Cohort A NHS Cohort B Int Med Ward NY ICU NY
Biomarker
IL-18R1 ** * * * *
IFNG ** ** – ** ** Beta
MERTK ** ** ** – – 1-
IL-18 * ** *** – **
IL-6 – ** ** – **
CD-274 ** ** ** * **
CCL2 – ** ** – ** 0-
IL-1RN * ** ** * **
CXCL11 ** ** ** ** *
LGALS9 ** ** ** ** **
CCL8 ** ** * ** – -1
CXCL10 ** ** ** ** **
CCL7 ** ** ** ** **
CCL16 ** ** – ** –

Figure 2: Heatmap analysis of 13 statistically increased and decreased levels of protein biomarkers in COVID-19 patients out of a total of 253 measured across studies.
Significance “**” (p<0.05/253/5 = 4x10-5, Bonferroni level), “*” (P<0.05/115 = 0.00043, replication level), “–” (p<0.05, nominal significance). Adapted from Suhre et al.
Figure 5a. (2)

In this meta-analysis they noted that several immune pathways

were activated, including viral protein interaction with cytokine and
cytokine receptors, and the COVID-19 adverse outcome pathway,
with particular emphasis on CCL2, CSCL10 and IL6. Another
interesting point to make is that in spite of the diversity of settings,
sample type (serum or plasma) and sample handling from three
different clinical settings, all of the data could be combined and
statistically-significant findings be derived.
If you are interested in seeing a webinar on how high-throughput
proteomics is a keystone in multiomics approaches to COVID-19
research, you can access it here.
Severe traumatic brain injury and
Inflammation markers and early
immune activation in ulcerative colitis
In ulcerative colitis (UC), immune dysregulation is dependent upon
both genetic and environmental factors. Shifts in the microbiome
and subclinical inflammation are defined by NFκB activity, and early
detection markers are needed.
Plasma samples from patients up to 15 years pre-diagnosis (n=72)
were tested along with patients with UC (n=101) with the Olink®
Target 96 Inflammation panel, identifying a six-protein signature
with excellent discrimination (AUC = 0.92).4 These pro-inflammatory
and tissue-repair pathway proteins can detect UC several years
before conventional diagnosis.

markers of mortality
Traumatic brain injury (TBI) is a major cause of death and disability
Inflammatory protein responses to a
and is diagnosed clinically on a scale from mild to severe. In a study JAKi/SYKi for atopic dermatitis
that measured 1,161 plasma proteins from the Olink® Target 96 In an example from drug development, a new dual inhibitor
panels in patients with severe TBI and known clinical outcomes, compound called ASN002 (from Asana Biosciences) for the
the top 15 differentially expressed proteins in the patients with sTBI condition atopic dermatitis was evaluated for efficacy, safety,
mainly involved vascular pathology, immunity/inflammation, and cell pharmacokinetics, dosage and effects on systemic biomarkers.(5)
survival.[3]
In a clinical trial (NCT03139981), a total of 36 patients were
The researchers identified two protein biomarker pairs (vWF/WIF-1 randomized and given three different doses or placebo, and
or vWF/CSF-1) as potential disease severity or outcome biomarkers, patient samples were analyzed with four Olink® Target 96 panels
as they were able to predict ICU mortality with 100% accuracy (~360 total proteins). ASN002 significantly downregulated several
(Figure 3). serum biomarkers involved in Th1, Th2, and Th17/Th22 immunity,
showing strong efficacy with not only rapid onset of action but also
Protein AUC S.E. p-value 95% CI (lower) 95% CI (upper)
improvements in overall systemic inflammation.
vWF 0.917 0.096 0.033 0.728 1.000
In addition, their dosage trial indicated that a lower dose could be
WIF-1 0.833 0.137 0.088 0.565 1.000
selected for optimal effect and decreased risk for adverse events.
CSF-1 0.833 0.158 0.088 0.524 1.000

C1QTNF1 0.750 0.160 0.201 0.437 1.000

Information about our Olink Target 96 Inflammation panels can be
IL15 0.750 0.170 0.201 0.417 1.000
accessed here.
NID1 0.708 0.178 0.286 0.360 1.000

PROK1 0.667 0.182 0.394 0.311 1.000

References
1. JFullerton JN and Gilroy DW. Resolution of inflammation: a new therapeutic
frontier. Nat Rev Drug Discov. (2016) 15(8):551-567. doi:10.1038/
nrd.2016.39
2. Suhre K and Schmidt F et al. Identification of Robust Protein Associations
With COVID-19 Disease Based on Five Clinical Studies. Front Immunol.
2022 12:781100. doi:10.3389/fimmu.2021.781100
3. Fraser DD and Prassas I et al. Novel severe traumatic brain injury blood
outcome biomarkers identified with proximity extension assay. Clin Chem
Lab Med. 2021 59(10):1662-1669. doi:10.1515/cclm-2021-0103
4. Bergemalm D and Halfvarson J et al. Systemic Inflammation in Preclinical
Ulcerative Colitis. Gastroenterology. 2021 161(5):1526-1539.e9.
doi:10.1053/j.gastro.2021.07.026.
5. Bissonnette R and Guttman-Yassky E et al. The oral Janus kinase/spleen
tyrosine kinase inhibitor ASN002 demonstrates efficacy and improves
associated systemic inflammation in patients with moderate-to-severe
atopic dermatitis: results from a randomized double-blind placebo-
controlled study. Br J Dermatol. 2019; 181(4):733-742. doi:10.1111/
bjd.17932

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v1.0, 2022-11-01