To the editor

We read with great interest the research letter by Suski et al¹ puslished recently in Polish Archives of Internal Medicine, reporting early serum proteomic profiling in acute pancreatitis (AP) using a data‑independent acquisition–based mass spectrometry workflow. The identification of candidate markers, such as the S100A7 protein and V‑set and immunoglobulin domain–containing 4 (VSIG4), along with the demonstration of neutrophil‑related and insulin‑like growth factor–signaling pathways, represents an important step toward refining early severity assessment in AP. This work addressed a clinically relevant, unmet need for timely triage of patients at a risk of severe AP (SAP). While the proteomic approach offers novel insights, 3 methodological concerns warrant discussion regarding the clinical applicability of these findings.

First, the exclusion of patients with moderately severe AP (MSAP) introduces significant spectrum bias. The authors compared only the polar ends of the disease spectrum—mild AP (MAP) vs SAP—while excluding the intermediate MSAP group, which constituted a large portion of their initial cohort (n = 31/70). In clinical practice, distinguishing SAP from MSAP is the primary diagnostic dilemma, as both can present with local complications or transient organ failure. By removing this “grey zone,” the study likely overestimated the discriminatory power of markers such as S100A7 and VSIG4.²

Second, biological specificity is compromised by nonpancreatic sources and oncogenic overlap. S100A7 (psoriasin), an epidermal peptide, raises concerns regarding skin contamination; crucially, recent data also identify it as a driver of invasion in pancreatic adenocarcinoma.^3,4 Similarly, VSIG4 expression extends to tissue‑resident macrophages (Kupffer cells), suggesting hepatic involvement or systemic activation.⁵ Furthermore, VSIG4 characterizes tumor‑associated macrophages and predicts poor prognosis in aggressive malignancies.^6-8 Consequently, elevated levels of VSIG4 in SAP may reflect systemic stress or occult premalignant changes rather than exclusive acute inflammatory severity. Without noncancerous septic controls, the diagnostic precision remains uncertain.

Third, therapeutic heterogeneity confounds the day 2 proteomic profiles. The authors reported robust proteomic divergence on day 2 postadmission. However, according to the data presented in Supplementary material, Table S1, 75% of the SAP patients received antibiotics, as compared with only 8.3% of the MAP patients (P = 0.004). Consequently, the observed signals on day 2 likely capture the metabolic response to antimicrobial intervention rather than the natural disease trajectory alone.

We believe addressing these issues in future validation studies—specifically by including MSAP patients, appropriate disease control groups (for example, patients with nonpancreatitic sepsis or nonsevere AP with systemic inflammation), and adjusting for treatment exposure—will be essential to establish the role of S100A7 and VSIG4 as viable clinical tools.