Pancreatic Stone Protein for Early Sepsis Detection: Diagnostic Performance & Clinical Implications

Pancreatic stone protein (PSP) is an emerging biomarker that enables early detection of sepsis, often rising before clinical signs of organ dysfunction appear. PSP demonstrates diagnostic accuracy and consistent performance across patient subgroups, with higher levels strongly associated with sepsis. Its rapid point-of-care measurement allows timely clinical decision-making, particularly within the first 24 hours of ICU admission. When combined with C-reactive protein, PSP significantly improves diagnostic specificity, enhancing confidence in identifying high-risk patients.

Introduction

Sepsis remains a leading cause of morbidity and mortality in intensive care units (ICUs). Despite advances in supportive care, early diagnosis remains a major clinical challenge. Prompt administration of antimicrobial therapy improves survival, whereas delays significantly increase mortality. On the other hand, unnecessary antibiotic use contributes to antimicrobial resistance, underscoring the importance of accurate and timely diagnosis.

Traditional biomarkers, including C-reactive protein (CRP) and procalcitonin, have not demonstrated sufficient sensitivity or specificity to serve as definitive diagnostic tools for sepsis. Hence, there is a need for biomarkers that can detect sepsis earlier and with greater reliability. Pancreatic stone protein (PSP) has emerged as a promising candidate in this context, offering both early predictive capability and practical applicability at the point of care.

Biological Characteristics and Clinical Relevance of PSP

PSP is a C-type lectin protein synthesised primarily in the pancreas and intestine, with diverse biological functions. Initially associated with pancreatic pathology, PSP has gained attention for its role in infection and inflammation. In sepsis, PSP production may derive from both pancreatic and intestinal sources, reflecting systemic activation of host defence mechanisms.

A defining feature of PSP is its early elevation during infection. Evidence indicates that PSP levels may increase several days before the clinical diagnosis of sepsis, preceding changes observed with other biomarkers such as CRP. PSP can predict sepsis onset up to 72 hours before the appearance of organ dysfunction, suggesting its value as a predictive rather than purely diagnostic biomarker.

PSP also demonstrates specificity for infection-related processes. Studies show that PSP does not increase in patients experiencing non-infectious inflammatory stress, such as trauma or burns, in the absence of infection. This characteristic distinguishes PSP from many conventional inflammatory markers and supports its potential to differentiate infectious from non-infectious conditions.

Study Design and Investigative Framework

A recent study by Shorr et al. (2026) evaluates the diagnostic performance of a rapid point-of-care PSP immunoassay in ICU patients. Conducted across six ICUs in the United States, the study included 466 adult patients expected to require at least 24 hours of ICU care.

PSP levels were measured within the first 24 hours of ICU admission using a rapid immunofluorescence assay that delivers results in approximately 7 minutes. Patients were followed for up to three days to determine whether sepsis developed, allowing assessment of PSP as an early predictive biomarker.

Diagnostic Performance of PSP

At the optimal threshold of 117 ng/mL, PSP demonstrated a sensitivity of 74.2% and specificity of 67.8%, with an overall diagnostic accuracy of 71.0%. Positive and negative predictive values were 70.3% and 71.9%, respectively, indicating balanced performance in identifying and excluding sepsis.

PSP levels differed significantly between patients with and without sepsis. Median PSP concentrations were markedly higher in septic patients (237.5 ng/mL) compared with non-septic patients (79.5 ng/mL), supporting its discriminatory capacity. The diagnostic utility of PSP was approximately 75.6% (area under the curve). These findings indicate that PSP provides moderate but clinically meaningful diagnostic accuracy for early sepsis detection.

Threshold-Dependent Risk Stratification

A key advantage of PSP is its ability to support risk stratification via adjustable thresholds. Lower thresholds enhance sensitivity, making PSP suitable for screening purposes, whereas higher thresholds improve specificity, helping confirm sepsis.

At a threshold of 100 ng/mL, sensitivity was 79%, while specificity was 61%. In contrast, at a threshold of 600 ng/mL, specificity increased to 97%, while sensitivity decreased to 23%. These variations allow clinicians to interpret PSP results in the context of the clinical setting and the desired balance between sensitivity and specificity.

The associated changes in post-test probabilities further illustrate clinical utility. For example, at 100 ng/mL, a positive result increased the probability of sepsis from 51% to 68%, whereas at 600 ng/mL, this probability rose to 90%. This suggests that higher PSP concentrations are associated with very high positive predictive values, reinforcing its role in identifying high-risk patients.

Subgroup Performance and Clinical Consistency

PSP demonstrated consistent diagnostic performance across several important patient subgroups. Sensitivity and specificity were comparable between male and female patients, indicating no significant sex-related differences.

Age-based analysis revealed similar sensitivity across age groups but reduced specificity among patients older than 60 years. Younger patients showed higher specificity, suggesting that age-related factors may influence baseline PSP levels or inflammatory responses.

PSP also maintained diagnostic utility in both febrile and afebrile patients. In febrile individuals, specificity was higher, whereas in non-febrile patients, sensitivity was greater. This finding is particularly relevant because afebrile sepsis often presents with subtle clinical features and may be difficult to recognise. PSP's ability to detect sepsis in such cases enhances its clinical value.

Overall, these findings demonstrate that PSP maintains stable performance across diverse clinical presentations, supporting its broad applicability in ICU populations.

Combined Use of PSP and C-Reactive Protein

The combination of PSP with CRP represents a complementary diagnostic strategy that leverages distinct inflammatory pathways. PSP is primarily associated with early infection signalling, whereas CRP reflects systemic inflammatory response mediated by interleukin-6.

Using predefined thresholds of PSP ≥ 200 ng/mL and CRP ≥ 100 mg/L, the combined approach significantly improved diagnostic specificity to 95.2% and positive predictive value to 88.9%. This represents a substantial improvement over either biomarker alone.

However, this increase in specificity was accompanied by a reduction in sensitivity to 37.3%, indicating that the combined approach is most useful for confirming sepsis rather than excluding it. Thus, combining PSP with CRP can increase diagnostic confidence and improve identification of patients at high risk of sepsis progression.

Clinical Utility in Point-of-Care Settings

The rapid measurement of PSP using a point-of-care immunoassay represents a significant practical advantage. The assay requires only a small blood sample and provides results within approximately seven minutes, enabling real-time clinical decision-making.

This rapid turnaround is particularly valuable in the ICU, where early intervention is critical. By identifying patients at risk of developing sepsis within the first 24 hours of admission, PSP facilitates earlier monitoring and treatment, potentially improving outcomes.

The predictive capability of PSP represents a shift in clinical practice, enabling clinicians to anticipate sepsis rather than react to established organ dysfunction. Such an approach aligns with current efforts to improve early recognition and timely intervention in sepsis management.

Implications for Clinical Practice and Future Directions

The findings of this study position PSP as a valuable addition to the diagnostic toolkit for sepsis in critical care settings. Its ability to provide early, rapid, and clinically relevant information supports its integration into routine ICU practice.

PSP may serve as an early screening tool to identify patients at high risk of developing sepsis, particularly when clinical signs are nonspecific or absent. Its use in combination with CRP further enhances diagnostic precision, particularly for confirming sepsis in high-risk patients.

Conclusion

Pancreatic stone protein is a promising biomarker for early sepsis detection in critically ill patients. The evidence demonstrates that PSP provides moderate diagnostic accuracy, consistent performance across patient subgroups, and the ability to identify sepsis before clinical manifestation. Its rapid point-of-care availability and predictive capacity make it particularly valuable in time-sensitive ICU environments. When combined with CRP, PSP offers significantly improved specificity, enhancing confidence in identifying high-risk patients.

Overall, PSP has the potential to improve early sepsis recognition and support more timely and informed clinical decision-making. Its integration into clinical practice may improve the management of sepsis.

Key Points

• Pancreatic stone protein (PSP) can predict sepsis up to 72 hours before clinical diagnosis, supporting earlier recognition.
• In ICU patients, PSP demonstrated moderate diagnostic performance, with approximately 74% sensitivity and 68% specificity.
• PSP levels are significantly higher in patients who develop sepsis, demonstrating clear discriminatory value.
• Diagnostic performance remains consistent across sex, age groups, and febrile or afebrile presentations.
• Combining PSP with C-reactive protein markedly improves specificity to over 95%, strengthening diagnostic confidence.
• Rapid point-of-care testing allows PSP to support real-time clinical decisions and earlier intervention in critical care.

Disclaimer

Point-of-view articles are the sole opinion of the author(s) and are part of the ICU Management & Practice Corporate Engagement or Educational Community Programme.