# Integrated Molecular and Hematobiochemical Biomarkers for the Detection of Bovine Babesiosis in Holstein Calves

**Authors:** Haifa Ali Alqhtani, Mohamed Marzok, Rasha Yassin Elkhidr, Ahmed A. Elsayed, Safaa M. Barghash, Ahmed L. El-Naggar, Mohamed T. Ragab, Ahmed I. Ateya, Fatmah Ahmed Safhi, Wafaa A. Osman

PMC · DOI: 10.3390/vetsci13020176 · Veterinary Sciences · 2026-02-10

## TL;DR

This study identifies molecular and blood-based biomarkers that can help detect and monitor bovine babesiosis in Holstein calves.

## Contribution

The study integrates immune and antioxidant gene expression with hematobiochemical markers for early detection of bovine babesiosis.

## Key findings

- Infected calves showed upregulated immune genes and downregulated antioxidant genes.
- Hematobiochemical changes included elevated liver/kidney markers and reduced antioxidants.
- Combining molecular and blood indicators improves disease detection and monitoring.

## Abstract

Bovine babesiosis is a tick-borne parasitic disease that impairs the health and productivity of Holstein calves. This study investigated the link between immune- and antioxidant-related gene expression and blood and serum biochemical changes in naturally infected calves. Infected animals showed increased expression of immune genes and decreased expression of antioxidant genes, reflecting strong inflammatory responses and increased oxidative stress. These molecular changes coincided with hematological disturbances and altered biochemical markers of liver and kidney function, metabolism, mineral balance, and antioxidant status in the calves. The results highlight a close relationship between gene expression dynamics and blood-based indicators during B. bovis infection and suggest that combining immune and antioxidant genes with hematobiochemical biomarkers can serve as effective tools for disease detection, monitoring, and control in livestock.

Bovine babesiosis is a widespread tick-borne parasitic disease that compromises calf health and productivity, causing substantial economic losses. This study evaluated the potential of molecular and hematobiochemical biomarkers for the detection of babesiosis in Holstein calves by analyzing the expression dynamics of selected immune and antioxidant genes and their association with blood-based indicators. Blood samples were collected from 243 fattening calves, classified as healthy (n = 180) or naturally infected (n = 63). Transcriptional levels of immune-related genes (IL-2, IL-6, TNF-α, and MCP-1) and antioxidant genes (SOD3, CAT, GPX, and GST) were measured alongside hematological, biochemical, immunological, and oxidative stress assessments. Infected calves exhibited significant upregulation (p < 0.05) of immune and pro-inflammatory genes, indicating strong immune activation, while antioxidant gene expression was markedly downregulated, reflecting impaired redox balance. These molecular changes were accompanied by hematobiochemical alterations, including elevated liver and kidney markers, serum lipids, inflammatory mediators, and oxidative stress indices. Conversely, reductions were observed in glucose, serum proteins, thyroid hormones, essential minerals, total antioxidant capacity, and endogenous antioxidant enzymes. The coordinated assessment of immune and antioxidant gene expression with hematobiochemical profiles provides a robust biomarker-based approach for the early detection and monitoring of bovine babesiosis. These integrated molecular and blood-based indicators may support effective diagnosis, disease management, and control strategies in livestock production systems.

## Linked entities

- **Genes:** IL2 (interleukin 2) [NCBI Gene 3558], IL6 (interleukin 6) [NCBI Gene 3569], TNF (tumor necrosis factor) [NCBI Gene 7124], CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347], SOD3 (superoxide dismutase 3) [NCBI Gene 6649], CAT (catalase) [NCBI Gene 847], GPX (probable phospholipid hydroperoxide glutathione peroxidase) [NCBI Gene 103970350], SLCO6A1 (solute carrier organic anion transporter family member 6A1) [NCBI Gene 133482]

## Full-text entities

- **Genes:** SOD1 (superoxide dismutase 1) [NCBI Gene 281495] {aka SOD1L1}, ASB16 (ankyrin repeat and SOCS box containing 16) [NCBI Gene 539253], CRP (C-reactive protein) [NCBI Gene 527553], FPGT (fucose-1-phosphate guanylyltransferase) [NCBI Gene 100138313], TLR2 (toll like receptor 2) [NCBI Gene 281534], PRDX6 (peroxiredoxin 6) [NCBI Gene 282438] {aka AOP2, LPCAT-5}, OXSR1 (oxidative stress responsive kinase 1) [NCBI Gene 526949], RASGRP1 (RAS guanyl releasing protein 1) [NCBI Gene 533125], IL10 (interleukin 10) [NCBI Gene 281246] {aka IF2A}, LOC517016 (interleukin 6 (interferon, beta 2)) [NCBI Gene 517016] {aka IF1DA6}, CMPK2 (cytidine/uridine monophosphate kinase 2) [NCBI Gene 784304], NDUFS5 (NADH:ubiquinone oxidoreductase subunit S5) [NCBI Gene 338057], IFNG (interferon gamma) [NCBI Gene 281237], ALB (albumin) [NCBI Gene 280717], KEAP1 (kelch like ECH associated protein 1) [NCBI Gene 532791], MARCHF3 (membrane associated ring-CH-type finger 3) [NCBI Gene 520348] {aka MARCH3}, TNNI3K (TNNI3 interacting kinase) [NCBI Gene 535940], LPCAT1 (lysophosphatidylcholine acyltransferase 1) [NCBI Gene 788450], NOS2 (nitric oxide synthase 2) [NCBI Gene 282876] {aka NOS2A, iNOS}, CCL2 (chemokine (C-C motif) ligand 2) [NCBI Gene 281043] {aka MCP-1, MCP-1A, MCP1, MCP1A, SCYA2}, SOD3 (superoxide dismutase 3) [NCBI Gene 532481] {aka EC-SOD, ECSOD}, EPS15L1 (epidermal growth factor receptor pathway substrate 15 like 1) [NCBI Gene 506374], TNF (tumor necrosis factor) [NCBI Gene 280943] {aka TNF-a, TNF-alpha, TNFa}, CAT (catalase) [NCBI Gene 531682], GPHN (gephyrin) [NCBI Gene 535194], SAA2 (serum amyloid A2) [NCBI Gene 506412] {aka SAA, SAA1}, IL1B (interleukin 1 beta) [NCBI Gene 281251], Glyceraldehyde-3-phosphate dehydrogenase [NCBI Gene 786101], PPIE (peptidylprolyl isomerase E) [NCBI Gene 787681], TLR5 (toll like receptor 5) [NCBI Gene 444870] {aka TLR-5}, IL6 (interleukin 6) [NCBI Gene 280826], TNNI3 (troponin I3, cardiac type) [NCBI Gene 511094], GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 281181] {aka GAPD}, DIO3 (iodothyronine deiodinase 3) [NCBI Gene 494549], NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 497024] {aka NRF2}, IL2 (interleukin 2) [NCBI Gene 280822] {aka IL-2, TCGF}, IL17A (interleukin 17A) [NCBI Gene 282863] {aka IL-17, IL17}, LDH (Muscle lactate dehydrogenase activity) [NCBI Gene 101409728]
- **Diseases:** renal impairment (MESH:D007674), depression (MESH:D003866), degeneration (MESH:D009410), aggressiveness (MESH:D010554), tick infestation (MESH:D013984), parasitic infection (MESH:D010272), hemolytic anemia (MESH:D000743), hepatic injury (MESH:D056486), clinical abnormalities (MESH:D013568), premature labor (MESH:D007752), sepsis (MESH:D018805), infectious diseases (MESH:D003141), hypochromic anemia (MESH:D000747), hypoproteinemia (MESH:D007019), anemia (MESH:D000740), glomerulonephritis (MESH:D005921), tremors (MESH:D014202), hematological disturbances (MESH:D006402), nutritional deficiencies (MESH:D044342), Neutropenia (MESH:D009503), abortion (MESH:D000026), trypanosomiasis (MESH:D014352), hypoglycemia (MESH:D007003), Infected (MESH:D007239), hemoglobinuria (MESH:D006456), weight loss (MESH:D015431), hyperesthesia (MESH:D006941), organ dysfunction (MESH:D009102), ruminal atony (MESH:D000079562), leukopenia (MESH:D007970), Anaplasma marginale infection (MESH:D000712), diarrhea (MESH:D003967), hypoalbuminemia (MESH:D034141), jaundice (MESH:D007565), paralysis (MESH:D010243), nystagmus (MESH:D009759), fever (MESH:D005334), convulsions (MESH:D012640), hemolysis (MESH:D006461), anemic hypoxia (MESH:D000860), Babesia (MESH:D001404), injury to (MESH:D014947), inflammation (MESH:D007249), muscle atrophy (MESH:D009133), hepatic and renal dysfunction (MESH:D008107), atony (MESH:D014593), skin damage (MESH:D012871), lameness (MESH:D007794), myxomatous mitral valve disease (MESH:C564326), necrosis of renal convoluted tubules (MESH:D007673), Lymphopenia (MESH:D008231), cancers (MESH:D009369), chromosomal abnormalities (MESH:D002869), unconsciousness (MESH:D014474), dyspnea (MESH:D004417), anorexia (MESH:D000855), tick-borne parasitic disease (MESH:D017282)
- **Chemicals:** GSH (MESH:D005978), SYBR Green (MESH:C098022), agarose (MESH:D012685), lipid (MESH:D008055), T3 (MESH:D014284), ice (MESH:D007053), ROS (MESH:D017382), calcium (MESH:D002118), creatinine (MESH:D003404), glucose (MESH:D005947), T4 (MESH:D013974), H2O2 (MESH:D006861), O2 (MESH:D013481), EK0418 (-), Sodium (MESH:D012964), K (MESH:D011188), urea (MESH:D014508), oil (MESH:D009821), MDA (MESH:D008315), carbohydrates (MESH:D002241), Cytosine (MESH:D003596), water (MESH:D014867), Trizol (MESH:C411644), iron (MESH:D007501), Adenine (MESH:D000225), Cu (MESH:D003300), hydroxyl radicals (MESH:D017665), blood glucose (MESH:D001786), NO (MESH:D009569), cholesterol (MESH:D002784), methanol (MESH:D000432), Zn (MESH:D015032), EDTA (MESH:D004492), bilirubin (MESH:D001663), Guanine (MESH:D006147), Thymine (MESH:D013941), triglyceride (MESH:D014280)
- **Species:** Rhipicephalus annulatus (species) [taxon 34611], Ixodida (ticks, order) [taxon 6935], Odocoileus virginianus (white-tailed deer, species) [taxon 9874], Bos taurus (bovine, species) [taxon 9913], Ixodes (genus) [taxon 6944], Babesia divergens (species) [taxon 32595], Capra hircus (domestic goat, species) [taxon 9925], Hyalomma (genus) [taxon 34625], Babesia bigemina (species) [taxon 5866], Homo sapiens (human, species) [taxon 9606], Ovis aries (domestic sheep, species) [taxon 9940], Rhipicephalus microplus (cattle tick, species) [taxon 6941], Babesia sp. (species) [taxon 35084], Canis lupus familiaris (dog, subspecies) [taxon 9615], Babesia bovis (species) [taxon 5865]
- **Mutations:** C330T, A137G, G224A, G488A, T270C, A93G, G448A, A205G, G328A, C396G, T152C, T180C, T45C, T333C, G147A

## Full text

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## Figures

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## References

114 references — full list in the complete paper: https://tomesphere.com/paper/PMC12945156/full.md

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Source: https://tomesphere.com/paper/PMC12945156