Plasma HMGB-1 and Nucleosome Concentrations in Horses with Colic and Healthy Horses

Abstract

Background: Acute gastrointestinal disease occurs commonly in horses. Novel biomarkers might improve the understanding of SIRS and aid diagnosis and determination of prognosis.

Hypotheses: Increased plasma concentrations of the biomarkers HMGB-1 and nucleosomes are associated with severity of gastrointestinal lesions in horses; concentrations of these biomarkers will be greater in horses with lesions more likely to cause SIRS; and will provide additional information compared with standard biomarkers fibrinogen and SAA.

Animals: Thirty horses with gastrointestinal disease, 22 healthy horses.

Methods: Prospective study. Plasma samples taken on admission were used for measurement of HMGB-1, nucleosomes, fibrinogen, and SAA. Values were compared between healthy horses and those with gastrointestinal disease, and between horses with gastrointestinal disease grouped by lesion type (inflammatory, strangulating, and nonstrangulating). Correlations between biomarkers were assessed.

Results: Plasma concentrations of all biomarkers were significantly higher in horses with gastrointestinal disease compared to healthy horses (P ≤ .001). HMGB-1 and nucleosomes were significantly higher in inflammatory and strangulating groups compared to healthy horses (3.5-fold and 5.4-fold increases, respectively, for HMGB-1 (P < .05) and 4.8-fold and 5.6-fold increases for nucleosomes (P < .05)), but concentrations in the group with nonstrangulating disease did not differ from healthy horses. There was significant correlation between HMGB-1 and nucleosomes (Spearman's r = 0.623; P < .001), and fibrinogen and SAA (Spearman's r = 0.801; P < .001) but not between other biomarkers.

Conclusions and clinical importance: High mobility group box-1 and nucleosomes might have use as biomarkers for horses with gastrointestinal disease. Further studies are required to determine kinetics and prognostic value of serial measurements of these biomarkers in horses.

Keywords: HMGB-1; Horse; Nucleosomes; Systemic inflammatory response syndrome.

Figure 1

Plasma concentrations of HMGB‐1 in all horses with gastrointestinal disease (colic, n = 30) compared to healthy horses (n = 22), A; and between healthy (n = 22), inflammatory (n = 11), strangulating (n = 12), and nonstrangulating (n = 7) groups; B. Data are expressed as the median and interquartile range (boxes), with the whiskers representing the range. Asterisks show significant differences from the healthy group. HMGB‐1 concentrations were significantly higher in horses with gastrointestinal disease compared to healthy horses (P < .001; A). HMGB‐1 concentrations were significantly higher in the inflammatory and strangulating groups compared to the healthy horses (P < .05; B).

Figure 2

Plasma concentrations of nucleosomes in all horses with gastrointestinal disease (colic, n = 30) compared to healthy horses (n = 22), A; and between healthy (n = 22), inflammatory (n = 11), strangulating (n = 12), and nonstrangulating (n = 7) groups; B. Data are expressed as the median and interquartile range (boxes), with the whiskers representing the range. Asterisks show significant differences from the healthy group. Nucleosome absorbance was significantly higher in horses with gastrointestinal disease compared to healthy horses (P < .001; A). As for HMGB‐1, nucleosome concentrations were significantly higher in the inflammatory and strangulating groups compared to the healthy horses (P < .05; B).

Figure 3

Plasma concentrations of fibrinogen in all horses with gastrointestinal disease (colic, n = 28) compared to healthy horses (n = 6), A; and between healthy, inflammatory (n = 10), strangulating (n = 11), and nonstrangulating (n = 7) groups; B. Data are expressed as the median and interquartile range (boxes), with the whiskers representing the range. Asterisks show significant differences from the healthy group, or between groups where indicated. Fibrinogen concentrations were significantly higher in horses with gastrointestinal disease compared to healthy horses (P = .001; A). Unlike the other two biomarkers, fibrinogen was only significantly higher in the inflammatory group compared to healthy horses (P < .05, B). Fibrinogen was also significantly higher in the inflammatory group compared to the nonstrangulating group (P < .05, B).

Figure 4

Plasma concentrations of Serum amyloid A (SAA) in all horses with gastrointestinal disease (colic, n = 30) compared to healthy horses (n = 22), A; and between healthy, inflammatory (n = 11), strangulating (n = 12) and nonstrangulating (n = 7) groups; B. Data are expressed as the median and interquartile range (boxes), with the whiskers representing the range. Asterisks show significant differences from the healthy group. Plasma concentrations of SAA were significantly higher in horses with gastrointestinal disease compared to healthy horses (P < .001; A). Serum amyloid A was significantly higher in all groups compared to healthy horses (P < .05, B), but not significantly different between groups of horses with gastrointestinal disease (P > .05; B).

Figure 5

Correlation between HMGB‐1 and nucleosomes (n = 30), and fibrinogen and SAA (n = 28). There was significant correlation between HMGB‐1 and nucleosome concentrations (Spearman's r = 0.623, P < .001; A). There was also significant correlation between fibrinogen and SAA (Spearman's r = 0.801, P < .001; B).