Serum Health Biomarkers in African and Asian Elephants: Value Ranges and Clinical Values Indicative of the Immune Response

Edwards, Katie L.; Miller, Michele; Siegal-Willott, Jessica L.; Brown, Janine L.

doi:10.3390/ani10101756

Cited by 16 publications

(43 citation statements)

References 82 publications

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“…SAA was also higher in cases of EEHV1 compared to EEHV5, and both APPs were higher during fatal cases than in individuals that survived a bout of viremia exceeding 5000 vge/ml. Although concentrations for three (IFN-γ, IL-6 and IL-10) of the five cytokines validated for elephants [ 46 ] were undetectable in longitudinal samples, results for TNF-α and IL-2 may show potential as diagnostic tools for studying the immune response to EEHV. Continued studies are needed to determine if increasing assay sensitivity would be beneficial, or if the low-level responses actually are indicative of sub-optimal immune activation.…”

Section: Discussionmentioning

confidence: 99%

“…lameness and temporal swelling) that upon testing were not associated with EEHV. We recently published reference intervals for several biomarkers in African and Asian elephants and found SAA to be elevated in 83% of active clinical cases, including both infectious and traumatic etiologies, and in 50% of deaths studied [ 46 ]. The lack of specificity to EEHV viremia should not preclude the use of APPs as diagnostic tools, however.…”

Section: Discussionmentioning

confidence: 99%

“…SAA and HP concentrations were measured using a RX Daytona automated clinical chemistry analyzer (Randox Industries-US Ltd., Kearneysville, WV, USA). Commercially available reagents, calibrators, and two-level controls were used for each assay (Eiken Chemical Co. Ltd, Tokyo, Japan and Tridelta Tri-DD, Boonton, NJ, USA, respectively), which have previously been validated for elephants [ 29 , 46 , 47 ]. The technical ranges were 0.1–500 mg/l and 0.01–2.5 mg/ml, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Cytokines were measured by enzyme immunoassay as described in Edwards et al [ 46 ]. In brief, TNF-α was measured using a commercially available equine TNF-α ELISA reagent kit (ESS0017; Thermo Fisher Scientific, Frederick, MD, USA), with anti-equine TNF-α coating antibody and biotinylated anti-equine TNF-α detection antibody both diluted 1:100, and recombinant equine TNF-α standards (3.9 to 1000 pg/ml).…”

Section: Methodsmentioning

confidence: 99%

“…Interleukin 2 (IL-2) was measured using a commercially available equine Duoset ELISA development kit (DY1613) with modifications, incorporating anti-equine IL-2 coating (2.0 μg/ml) and biotinylated detection (0.2 μg/ml) antibodies and recombinant equine IL-2 standards (15.6 to 4000 pg/ml). Preliminary testing of samples from three individuals on other cytokine assays that have been validated for elephants (IFN-γ, IL-6, IL-10; [ 46 ]) were all below assay detection limits, and so were excluded from the remainder of the study. High and low controls within the standard range for each assay were maintained within an inter-assay CV of 15%.…”

Section: Methodsmentioning

confidence: 99%

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Patterns of serum immune biomarkers during elephant endotheliotropic herpesvirus viremia in Asian and African elephants

et al. 2021

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Hemorrhagic disease (HD) caused by a group of elephant endotheliotropic herpesviruses (EEHV) is one of the leading causes of death for young elephants in human care. These viruses are widespread and typically persist latently in adult elephants with no negative effects; however, in juvenile Asian and more recently young African elephants, the onset of disease can be rapid and the mortality rate high. Measuring biomarkers associated with the immune response could be beneficial to understanding underlying disease processes, as well as the management of infection and HD. The goal of this study was to measure acute phase proteins and cytokines in serum collected from elephants infected with EEHV (13 Asian and 1 African) and compare concentrations according to presence, severity and outcome of disease. Serum amyloid A (SAA) and haptoglobin (HP) were higher in elephants with EEHV viremia than those without; concentrations increased with increasing viral load, and were higher in fatal cases compared to those that survived. In Asian elephants, SAA was also higher during EEHV1 viremia compared to EEHV5. Cytokine concentrations were typically low, and no statistical differences existed between groups. However, in individuals with detectable levels, longitudinal profiles indicated changes in tumor necrosis factor alpha (TNF-α) and interleukin-2 (IL-2) that may reflect an immune response to EEHV infection. However, the overall low concentrations detected using previously validated assays do not support the presence of a ‘cytokine storm’ and suggest more work is needed to understand if sub-optimal immune responses could be involved in disease progression. These results highlight the potential benefit of measuring circulating biomarker concentrations, such as APPs and cytokines, to improve our understanding of EEHV viremia and HD, assist with monitoring the progression of disease and determining the impact of interventions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%