Inflammation, immunity, and gastric ulcer — clinical insights from routine haematology

Abstract

Gastric ulcer remains a common cause of morbidity, yet marked clinical variability suggests contributors beyond established risk factors such as Helicobacter pylori, non-steroidal anti-inflammatory drug exposure, and excess gastric acid. To clarify the role of systemic inflammation, Shen et al evaluated six complete blood count (CBC)-derived inflammatory indices in patients with gastric ulcer. All indices showed significant associations, with the systemic inflammatory response index demonstrating the strongest discriminatory value. Given that CBC testing is routine, inexpensive, and widely accessible, these indices may offer practical adjunctive markers for identifying individuals at increased risk. However, the cross-sectional design and lack of adjustment for major confounders limit causal interpretation. Prospective validation is required to determine whether these indices predict ulcer development, recurrence, or clinical outcomes, and to assess their potential integration with established risk factors.

Key Words: Inflammation; Immunity; Gastric ulcer; Systemic immune-inflammation index; Routine haematology

Core Tip: Gastric ulcer remains a significant health concern with serious complications. This study shows that six complete blood count (CBC)-derived inflammatory indices—neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, systemic inflammatory response index (SIRI), and aggregate index of systemic inflammation—are associated with gastric ulcer, with SIRI demonstrating the strongest predictive value (area under the curve = 0.868). As CBC is widely available, inexpensive, and reproducible, these indices may serve as practical, non-invasive tools for identifying at-risk patients and supplementing traditional risk factors. The findings emphasise the role of systemic inflammation in gastric ulcer pathogenesis and warrant prospective validation.

TO THE EDITOR

Gastric ulcer, a common form of peptic ulcer disease, remains a significant global health concern. Beyond discomfort and impaired quality of life, gastric ulcer can lead to serious complications such as bleeding, perforation, and obstruction. Classic risk factors—including Helicobacter pylori (H. pylori) infection[1], non-steroidal anti-inflammatory drug (NSAID) use, and excess gastric acid—are well established. Yet clinical experience shows marked variability in susceptibility, severity, and recurrence, suggesting additional contributors. Growing evidence implicates systemic inflammation and immune dysregulation as central to ulcer pathogenesis[2].

In this context, Shen et al[3] offer timely insights by investigating the relationship between complete blood count (CBC)-derived inflammatory indices and gastric ulcer. Six markers were evaluated: Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI), and aggregate index of systemic inflammation (AISI). Shen et al[3] performed a case–control study demonstrating that all indices were significantly associated with gastric ulcer, with SIRI emerging as the strongest predictor (area under the curve = 0.868)[3].

These findings carry notable clinical implications[3]. CBC is among the most routinely performed and widely accessible laboratory tests, including in resource-limited settings. Indices derived from it are inexpensive, reproducible, and non-invasive. If validated prospectively, they could help identify patients at higher risk of gastric ulcer or stratify those with established disease, supplementing traditional risk assessment without the need for additional specialized tests. The results also align with broader evidence linking systemic inflammatory indices to cardiovascular disease, metabolic disorders[4], and malignancy[5], underscoring inflammation as a unifying mechanism across disease processes.

Mechanistically, the associations are biologically plausible. NLR elevation reflects neutrophil predominance over lymphocytes[6]. Neutrophils mediate mucosal injury via reactive oxygen species, proteases, and pro-inflammatory cytokines, while lymphocytes support inflammation regulation and tissue repair. Increased MLR indicates sustained monocyte activity and macrophage-mediated cytokine production[7], again in the context of relative lymphopenia. Higher PLR emphasizes platelet involvement: Activated platelets release inflammatory mediators, interact with leukocytes, and may induce microvascular thrombosis, impairing mucosal perfusion and healing[8].

Composite indices provide further integrative insight. SII combines neutrophil and platelet activity against lymphocyte suppression, capturing acute tissue injury, vascular compromise, and immune dysregulation[9]. SIRI, which integrates neutrophil and monocyte counts relative to lymphocytes, reflects the intersection of acute oxidative damage, chronic cytokine-driven inflammation, and diminished adaptive immunity, mirroring the pathophysiological milieu of gastric ulcer[10]. AISI, incorporating neutrophils, monocytes, and platelets relative to lymphocytes, offers a measure of total systemic inflammatory burden[11]. The strong predictive performance of SIRI underscores the pathogenic significance of neutrophil–monocyte activation coupled with lymphocyte depletion in shaping the gastric mucosal environment[9].

Nevertheless, caution is warranted. The cross-sectional design limits causal inference; elevated indices may reflect ongoing ulceration rather than predispose to it. Key confounders—including H. pylori status, NSAID use[12], smoking, and alcohol consumption—were not adjusted for, though each can independently influence systemic inflammatory indices and ulcer risk. Systemic indices were also not correlated with local mucosal immune or histological features, leaving the mechanistic link indirect. Moreover, systemic inflammation may be influenced by comorbidities such as cardiovascular disease, diabetes, or infection, reducing ulcer-specific specificity. The absence of longitudinal outcomes precludes assessment of whether these indices predict ulcer recurrence, complications, or healing trajectories[13].

Future research should prioritise prospective, longitudinal validation to clarify whether dynamic changes in CBC-derived indices predict gastric ulcer onset, persistence, or recurrence. Mechanistic studies linking systemic indices with mucosal immune activity—neutrophil and monocyte infiltration, cytokine profiles, oxidative stress—would strengthen causal inference. Integration of these indices with established risk factors could determine independent predictive value, while evaluating their utility in predicting complications or monitoring response to anti-inflammatory or mucosal-protective therapies would enhance clinical relevance.

In summary, Shen et al[3] provide compelling evidence that CBC-derived inflammatory indices, particularly SIRI, are strongly associated with gastric ulcer. These indices combine clinical accessibility with mechanistic credibility, reflecting the inflammatory–immune imbalance central to ulcer pathogenesis. If validated in prospective and mechanistic studies, they could enhance risk stratification, guide management, and deepen our understanding of gastric ulcer immunobiology, bridging routine haematology with personalised gastrointestinal care.