A Rapid Blood Test to Monitor the Immune Status Change of Dairy Cows and to Evaluate their Disease Risk during the Periparturient Period

Abstract

BackgroundDairy cows are at the highest risk of developing clinical and subclinical diseases and disorders in the first few weeks following parturition. During the periparturient period, from approximately 30 days before calving to 30 days postpartum, the immune system of the dairy cows undergoes a multitude of changes to prepare for parturition, colostrum production and lactation. One such change is the transfer of a large amount of immunoglobulin G proteins, especially subclass IgG1 to colostrum, leading to a reduction of IgG1 in the blood. As IgG1 and IgG2 need to maintain a balance to protect animals from intracellular and extracellular pathogens, a disruption of this balance compromises the immune protection of the animals. Rapid tests that can detect these immunological changes may be potentially useful for predicting the risk of dairy cows developing infectious diseases and other adverse health conditions following parturition. ResultsWe report here a new rapid test to detect certain immune status changes in the blood serum of dairy cows. This test uses a nanoparticle probe to evaluate the relative quantity of IgG1 and IgG2 in a sample. The nanoparticle probes are aggregated together upon interaction with bovine IgG2, while bovine IgG1 inhibits such interactions. The nanoparticle aggregates are detected by monitoring the color change of the assay solution using a handheld device. We tested the serum samples from 230 dairy cows collected during periparturient period, from 14-7 days before calving to 7-14 days postpartum. Results show that the test clearly detected an immune status change associated with IgG1/IgG2 relative quantity change around the time of parturition. Data analysis using mixed liner model in SAS (Statistical Analysis System) revealed a significant difference (P value = 0.042) in their test responses between healthy cows and cows with mastitis and/or lameness. ConclusionThe new rapid test we report here can be used to detect and monitor certain immune status change in dairy cows during the periparturient period. The test results may be potentially used to evaluate and predict the health risk of the dairy cows following parturition.

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“…To give a few examples, we found that the D2Dx immunity test score of mouse models and young calves is correlated directly to the humoral immunity development of the animals from neonates to adults ( 28 ). We found the D2Dx immunity test score changes dramatically in animals during pregnancy and parturition, and these changes reflect precisely the type of immunity changes that are expected during the reproduction process ( 29, 30 ). We also observed clearly the test score change in animals with virus infections compared to non-infected controls, and these test score changes mirror almost exactly the humoral immune responses in animals upon infection ( 28, 31 ).…”

“…We named this new test as D2Dx (from diameter to diagnostics) because the test is based on AuNP aggregate formation and we initially used particle size measurement for detection (28,(30)(31)(32). More recently, we have changed the detection method to a lower cost, and more convenient colorimetry method (29).…”

“…Specifically, our studies found that when the AuNP is mixed with a blood plasma or serum sample, blood proteins, especially the three most important proteins from the immune system, immunoglobulin protein IgG, IgM, and complement proteins, will react with the AuNP as if it is a virus pathogen encountered in vivo ( 28 ). Depending on whether the immune response is type 1 or type 2-biased immunity, these interactions will lead to different degrees of AuNP aggregate formation ( 29 ). Type 1-biased immune response leads to more extensive AuNP aggregation, and type 2-biased immune response leads to lesser degree of AuNP aggregation (Figure 1A).…”

“…Our laboratory has recently developed a rapid blood test, D2Dx immunity test, to monitor the humoral immune status and responses in humans and animals (28)(29)(30)(31)(32). The test uses a gold nanoparticle (AuNP) as a pseudo virus pathogen to probe the humoral immunity in blood plasma or serum samples, as illustrated in Figure 1.…”

“…The copyright holder for this preprint this version posted October 2, 2020. ; https://doi.org/10.1101/2020.09.30.20203844 doi: medRxiv preprint aggregation, and type 2-biased immune response leads to lesser degree of AuNP aggregation (Figure 1A). The reaction product can be detected by measuring the average particle size of the assay solution using a dynamic light scattering technique (28,(30)(31)(32), or by monitoring the surface plasma resonance absorption change of the AuNPs using a UV-Vis spectrophotometer or colorimeter such as shown in Figure 1B (29). Both detection techniques have been well-established and routinely used for detecting AuNP aggregate formation for sensing and bioassay applications (37)(38)(39)(40).…”