EDITORIAL published: 26 October 2020 doi: 10.3389/fvets.2020.587741 Editorial: Factors Influencing Biomarker Range Intervals in Farm Animals Ana M. Gutiérrez 1*, Anna Bassols 2 , Laura Soler 3 and Matilde Piñeiro 4 1 Department of Animal Medicine and Surgery, BioVetMed Research Group, University of Murcia, Murcia, Spain, 2 Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Autonomous University of Barcelona, Barcelona, Spain, 3 Institut National de la Recherche Agronomique, Toulouse, France, 4 Acuvet Biotech, Zaragoza, Spain Keywords: biomarkers, reference values, biological fluids, farm animals, values variation Editorial on the Research Topic Factors Influencing Biomarker Range Intervals in Farm Animals A wide variety of biomarkers are used in farm animals for different purposes such as diagnostic testing, animal health monitoring, and serological surveillance and management of a farm. However, the presence of non-pathologic factors represents a challenge for valid and reliable biomarker use. These factors will influence reference interval (RI) and interpretation of biomarker test results. They are defined by intra-species genetic variability, and different physiological and environmental conditions, and their impact might be biological and/or analytical. In this special issue, our contributors have addressed some of the problems related with these factors. Harmonization of veterinary biomarker calibration procedures and reagents is also a must for the rationale use of biomarkers, as pointed out in one of the articles. Yu et al. studied the effects of several variables on the serum biochemical RIs in young animals: Edited and reviewed by: Tracy Stokol, age, season of birth and sex in calves and age and sex in piglets. The study comprised unweaned Cornell University, United States calves (at 24 h and 2, 5, and 7 weeks of age) and piglets from weaning at 21 days old to 35 days of life. In calves, season of birth did not affect the distribution of values of the studied analytes *Correspondence: Ana M. Gutiérrez while age-biased differences were noticed. The authors showed that hepatic enzymes, renal markers, agmontes@um.es antioxidant enzymes (glutatione peroxidase and superoxide dismutase) and some metabolism analytes [non-esterified fatty acids (NEFAs), triglycerides, glucose and total proteins] are increased Specialty section: at 24 h after birth in comparison with other ages (2, 5, and 7 weeks of age). They also showed that, This article was submitted to in pigs, the concentrations of cholesterol, triglycerides, and NEFAs are increased just after weaning Veterinary Experimental and compared to 28 and 35 days of life and this may be explained by a dietary change from milk, with Diagnostic Pathology, high fat content, to a solid feed. An increase in cortisol and pig major acute phase protein (Pig- a section of the journal MAP) concentrations was also observed the day after weaning and could be reflecting a stressful Frontiers in Veterinary Science condition. Yu et al. also provided the age at which each analyte reached RIs for adult animals. Received: 27 July 2020 Henning-Pauka et al. studied how season influences the level of serum acute phase proteins Accepted: 28 September 2020 (APP) in piglets in the nursery period (from 3 to 11 weeks of life) and found higher values Published: 26 October 2020 in autumn compared to winter. The experiment was performed in two indoor-outer nursery Citation: compartments of a farrow-to-finishing farm with space for 180 piglets each, in which a new Gutiérrez AM, Bassols A, Soler L and ammonia sensory technology connected to a forced ventilation system was evaluated. No Piñeiro M (2020) Editorial: Factors Influencing Biomarker Range Intervals direct influence of ammonia levels on APP concentrations could be confirmed. However, the in Farm Animals. authors recommend that low ammonium levels and optimal temperatures should be maintained, Front. Vet. Sci. 7:587741. particularly during periods in which outside temperatures are extreme, to improve production doi: 10.3389/fvets.2020.587741 parameters and preserve a good health status of piglets. Frontiers in Veterinary Science | www.frontiersin.org 1 October 2020 | Volume 7 | Article 587741 Gutiérrez et al. Editorial: Range Intervals in Farm Animals Sánchez et al. evaluated how other intrinsic biological factors Serological and molecular tests are the best choice for the such as production stage, breed and sex, could influence the detection of a wide variety of infectious diseases using different RIs of the APP, inflammation biomarker adenosine deaminase biological specimens such as serum, saliva, urine, or feces. (ADA), and total antioxidant capacity (TAC), measured in saliva. Some chronic infections result in multisystemic disease that The level of these biomarkers in saliva samples from clinically may affect animal production. Therefore, detection of specific healthy conventional and Iberian pigs were studied in male and chronic infections has been postulated to be a predictor of female animals at different production stages (post-weaning, production losses. Echeverría et al. analyzed the association nursery, fattening, and finishing). In conventional pigs, sex and between seroprevalence of Small Ruminal Lentivirus infection production stage influenced the concentration of all the studied (SRLV) and production losses in two different sheep breeds biomarkers with higher values in females compared to males at (Navarra and Latxa Navarra) and production systems (dairy or finishing, while the opposite was observed in younger animals, meat). The authors present antigenic heterogeneity as the main at post-weaning. On the contrary, no sex and production stage factor influencing the seroprevalence analysis excluding breed, differences on the aforementioned biomarkers were observed in age, production system or animal management effects. However, Iberian pigs that could be associated with the routine castration the possible influence of lentivirus infection on the production of males in this breed. However, ADA levels appeared higher in status of the studied animals was not evaluated. The results Iberian males in comparison to females at finishing. Additional did highlight the importance of combining different detection studies should be performed to improve our knowledge on methods (ELISAs against different antigen preparations and saliva biomarkers. genetic-based test) for determining the SRLV infection status at When establishing RIs for biomarkers, it is important to use the herd level in SRLV. well-established calibrators to obtain equivalent results between In conclusion, more research must be carried out on the laboratories. Several analytes such as enzymes (enzymatic effects of interfering factors before establishing reliable RIs activity), total protein, ions or metabolites (such as urea for diagnostic/prognostic analytes in farm animals, especially or glucose) are measured by chemical reactions which are in alternative body fluids such as saliva. Saliva, as biological common for all species and do not present a problem with fluid, can allow for routine monitoring of animal health status calibrators. However, protein biomarkers, usually measured due to its minimally invasive and non-stressful collection by immunoassays, need special attention due to changes in method that could be performed by personnel with minimal amino acid sequence between the different animal species, training. However, the use of saliva biomarkers in the clinical or other protein modifications, that result in differences assessment of farm animals is still far from being routinely in epitopes recognized by antibodies in the assay. These applied and requires further validation and research, including differences in protein structure or content usually require the RI establishment. Continued effort should be invested in the use of species-specific calibrators in such biomarker assays. implementation of novel biomarkers in clinical veterinary Thus, an international harmonization of veterinary biomarker practice, including assay standardization, publications of RIs with calibration has been proposed (Eckersall) consisting of two various methods and reagents used globally, and establishment of important stages. First, an international consortium would defined guidelines for result interpretation. be established to define how to approach the harmonization process and establish a plan of action that should include the AUTHOR CONTRIBUTIONS following activities: identify biomarkers where standardized calibration is needed, define the protocols for preparation and AG, AB, LS, and MP contributed to writing this editorial of the distribution of reference materials, identify the participating Research Topic Factors Influencing Biomarker Range Intervals in laboratories and find funding opportunities from industry Farm Animals. and academia. The working group should include members from the main international/regional societies covering Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a veterinary pathology, and members from industry and potential conflict of interest. experts in the field of study. Second, reference preparations, consisting of a pool of species-specific serum containing the Copyright © 2020 Gutiérrez, Bassols, Soler and Piñeiro. This is an open-access article analyte being measured would be prepared and a consensus distributed under the terms of the Creative Commons Attribution License (CC BY). value assigned for the selected biomarker (Eckersall). The The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original preparations will be available to laboratories and diagnostic kits publication in this journal is cited, in accordance with accepted academic practice. manufacturers for use as a primary standard to calibrate their No use, distribution or reproduction is permitted which does not comply with these working standards. terms. Frontiers in Veterinary Science | www.frontiersin.org 2 October 2020 | Volume 7 | Article 587741