HMGB1 shows promise, but not proof, in canine SIRS prognosis
Bottom line
A new Veterinary Evidence Knowledge Summary concludes that HMGB1 is an intriguing, but still unproven, prognostic biomarker for dogs with systemic inflammatory response syndrome, or SIRS. Reviewing three prospective observational studies, author Hannah Abrahams found weak overall evidence that higher HMGB1 concentrations may be associated with mortality in canine SIRS, with two studies supporting that link and one failing to show clear prognostic value. The signal is biologically plausible: HMGB1 is a late inflammatory mediator, and earlier canine studies have found it elevated in dogs with SIRS and other inflammatory diseases, behaving differently from C-reactive protein. But the underlying studies were small, used different populations and sampling approaches, and didn’t establish a consistent clinical cutoff that could be applied confidently in practice. (pubmed.ncbi.nlm.nih.gov)
Why it matters: For veterinary professionals, the takeaway is less about adding another assay today and more about avoiding overconfidence in a marker that hasn’t been validated well enough for triage or prognosis decisions. That caution fits the broader direction of sepsis and SIRS research in small animals: a 2026 consensus paper noted that SIRS-based frameworks are sensitive but often nonspecific, and emphasized the need for better outcome-linked tools, especially those tied to organ dysfunction and serial assessment rather than a single inflammatory snapshot. In other words, HMGB1 may still prove useful, but current evidence doesn’t support using it alone to guide conversations with pet parents or major treatment decisions. (onlinelibrary.wiley.com)
What to watch: The next step is whether larger, prospective studies can standardize HMGB1 timing, define actionable thresholds, and compare it head-to-head with better-established prognostic tools in canine critical care. (pubmed.ncbi.nlm.nih.gov)
Key facts
- Topic
- HMGB1 as a prognostic biomarker for mortality in canine systemic inflammatory response syndrome (SIRS)
- Review type
- Knowledge Summary in Veterinary Evidence
- Studies reviewed
- Three prospective observational studies
- Overall conclusion
- Evidence is weak and not ready for routine clinical use
- Main finding
- Higher HMGB1 concentrations may be associated with mortality in canine SIRS
- Mixed results
- Two studies supported the mortality link, and one did not show clear prognostic value
- Key limitation
- Small sample sizes, heterogeneous case mixes, and inconsistent timing of measurement
- Clinical takeaway
- HMGB1 should not be used alone to guide prognosis or major treatment decisions
A new Knowledge Summary in Veterinary Evidence takes a measured view of HMGB1 as a mortality biomarker in canine systemic inflammatory response syndrome, concluding that the evidence is weak and not ready for routine clinical use. The review, by Hannah Abrahams, assessed three prospective observational studies and found a mixed picture: two suggested elevated HMGB1 was associated with death in dogs with SIRS, while another found HMGB1 rose with inflammatory disease but left its added clinical value uncertain. (pubmed.ncbi.nlm.nih.gov)
That conclusion lands in a field that has been searching for better prognostic tools for years. HMGB1 is a nuclear protein that, once released extracellularly during tissue injury or inflammation, acts as a damage-associated signal and has long been studied in sepsis biology. In dogs, one of the earlier prospective studies, published in 2010, reported that admission HMGB1 concentrations, and the HMGB1-to-IL-10 ratio, were higher in nonsurvivors than survivors among 28 dogs with naturally occurring SIRS. A subsequent 2011 study found HMGB1 concentrations were elevated in dogs with SIRS and other diseases, and that HMGB1 followed a different time course from CRP, peaking later after surgery, which reinforced the idea that it may reflect a different part of the inflammatory cascade. (pubmed.ncbi.nlm.nih.gov)
Still, the case for HMGB1 as a practical prognostic test remains unsettled. The studies reviewed in the Knowledge Summary were all prospective and observational, but they were also limited by small sample sizes, heterogenous case mixes, and inconsistent timing of measurement. That matters because HMGB1 appears to behave as a relatively late mediator, so a single sample taken at presentation may not mean the same thing across patients. Later work in septic dogs also showed that HMGB1 is elevated in sepsis compared with healthy controls and dogs with noninfectious systemic inflammation, but that study emphasized broader cytokine profiling rather than establishing HMGB1 as a standalone mortality test. (pubmed.ncbi.nlm.nih.gov)
The wider evidence base in veterinary critical care also helps explain the cautious tone. A 2026 consensus statement on sepsis definitions in dogs and cats said SIRS-based approaches are sensitive but nonspecific, and argued that sepsis recognition should move beyond SIRS alone toward better characterization of organ dysfunction and host response. The same paper noted that available veterinary evidence remains limited and that clinicians still need to interpret abnormalities in context rather than lean on rigid cutoffs. That broader uncertainty makes it harder for any single inflammatory biomarker, including HMGB1, to carry much decision-making weight on its own. (onlinelibrary.wiley.com)
There doesn’t appear to be much published expert reaction yet to Abrahams’ summary specifically, but the surrounding literature points in a consistent direction: HMGB1 is scientifically interesting, and possibly complementary to markers like CRP, but not yet clinically settled. Earlier reviews of veterinary sepsis immunopathology have described HMGB1 as a late inflammatory mediator and noted that circulating concentrations in dogs may correlate with mortality in SIRS, while also underscoring that translational findings from human medicine have been inconsistent. That’s important context for clinicians deciding whether a promising biomarker is ready to move from research bench to cage-side use. (academic.oup.com)
Why it matters: For veterinarians in emergency and critical care, the practical message is restraint. HMGB1 may eventually help refine prognosis, especially if paired with illness-severity scoring, organ dysfunction measures, or serial biomarker trends, but the current literature doesn’t support using it in isolation to estimate survival or to shape major treatment recommendations. For general practitioners and specialists alike, that means standard clinical assessment, hemodynamic monitoring, and established prognostic indicators remain more reliable than a single HMGB1 result. It also matters for communication with pet parents: when evidence is weak, precision language around uncertainty is part of good care. (pubmed.ncbi.nlm.nih.gov)
The bigger opportunity is research design. If HMGB1 is going to become useful clinically, future studies will need larger cohorts, clearer separation of infectious versus noninfectious inflammation, standardized sampling windows, and predefined outcome thresholds. Comparative work against CRP, lactate, troponin, qSOFA-style tools, and organ dysfunction scoring would be especially useful, because clinicians need to know not just whether HMGB1 changes, but whether it improves decisions beyond the tools already available. (pubmed.ncbi.nlm.nih.gov)
What to watch: Watch for prospective multicenter studies that test HMGB1 alongside newer sepsis definitions and organ dysfunction frameworks, because that’s the kind of evidence that could determine whether HMGB1 becomes a niche research marker or a clinically useful prognostic tool. (onlinelibrary.wiley.com)