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Dipeptidyl Peptidase 3 (DPP3) has emerged as a highly promising biomarker for shock, attracting significant attention in the medical community. Circulating DPP3 (cDPP3) predicts shock development triggered via the DPP3 pathway in critically ill patients.

Biomarker background & pathophysiology
DPP3 Background

Aspect

Details

Basic Properties

EC-Number:
3.4.14.4

Size:
83-kDa

Enzyme class:
Zinc-dependent aminopeptidase

Structure:
Two main domains forming a central cleft.

Conservation:
Highly conserved among species

Distribution:
Ubiquitously expressed across various cell types

Biochemical properties

Enzymatic activity:
Cleaves dipeptides from the N-terminus of tetra- to decapeptides. Involved in the activation and degradation of signaling peptides.

Optimal conditions:  
At physiological pH (7.0-7.5)

Preferred substrates:  
N-terminal dipeptides: Arg-Arg, Ala-Arg, Asp-Arg, and Tyr-Gly

Key substrates⁶

Angiotensin II, Angiotensin III, Angiotensin IV, Angiotensin 1-5, Angiotensin 1-7
Endogenous opioids (Met/Leu-Enkephalin / Endomorphin-1 and 2)
Other bioactive peptides

Physiological roles

Intracellular:

Oxidative stress
Inflammation
Pain perception
Protein turnover

In the blood stream (cDPP3):
Regulation of the renin-angiotensin-aldosterone system (RAAS)

Concentration in plasma

Healthy individuals:
10 ng/mL, with the 97.5th percentile reaching 22 ng/mL

97.5th percentile of ambulatory population:
40 ng/mL⁶

DPP3 pathophysiology

Aspect

Details

RAAS-dysregulation

Degrades angiotensin II and other AT1R agonists
Impairs AT1R signaling
Contributes to systemic vasodilation and hypotension
Increases the angiotensin I/angiotensin II ratio

Renal impact

Decreases glomerular efferent arteriole tone
Reduces glomerular capillary pressure and decreases glomerular filtration rate
Triggers renin-release due to attenuated AT1R stimulation on juxtaglomerular cells

Hemodynamic impact in shock

cDPP3 is released during tissue hypoperfusion and cell death
Exacerbates vasodilation and hypotension in shock states
Contributes to vasodilatory component in various shock states
Acts as a secondary insult that perpetuates circulatory failure
Present in circulatory failure of diverse etiologies

Clinical prognosis marker: Cut-off value

The 40 ng/mL cut-off:

More selective, identifying ~50% of patients with DPP3-driven circulatory failure
Associated with increased need for cardiovascular support (vasopressors, inotropes, mechanical circulatory support)
Linked to requirement for renal replacement therapy
Linked to requirement of mechanical ventilation
Correlates with impaired survival rates

cDPP3: A new biomarker for predicting shock

Clinically, high cDPP3 levels are a robust indicator of severe organ dysfunction and predict an increased need for aggressive cardiovascular support, often correlating with higher short-term mortality. DPP3 stands out as both a drug target and a biomarker, making it a unique and powerful tool in medical research and treatment. This dual role is truly remarkable, opening up exciting possibilities for developing targeted therapies and improving shock prognosis:

Early recognition of patients at high risk of developing in-hospital shock starting at ED
Additional and objective criterion for admission and discharge decision between ward stations and ICU
Potential to reduce the number of assessment errors and inappropriate admission/discharge of patients
Informed decision-making complementing the risk scores of early warning systems (EWS)

What the experts say

“We need to implement DPP3 in clinical routine and thus close the gap in diagnosis, prognosis and therapy guidance in circulatory shock. With the DPP3 POC, patient stratification and ICU bed utilization could be optimized on a risk-based approach.”

Prof. Dr. med. Hüseyin Ince

Chief Physician for Internal Medicine – Cardiology / Vivantes Klinikum am Urban

"To say that DPP3 has potential is a huge understatement. A biomarker that might guide therapeutic choices, predict the risk of decompensation or assure clinical stability? That is a tool we need at the bedside as soon as humanly possible."

Nathan Nielsen, M.D.

Professor of Medicine and of Pathology / The University Of New Mexico School of Medicine

DPP3-Diagnostic products
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cDPP3-Testing of cohorts

Test your biobank samples with our cDPP3 cohort analysis service. We provide reliable quantification of DPP3 protein concentration with the LIA assay.