The Relationship Between Some Anemia Parameters and Hepcidin Level in Anaplasma phagocytophilum Seropositive Dogs

Year 2020, , 90 - 97, 31.12.2020

Menekşe Deniz Şima Şahinduran

https://doi.org/10.24998/maeusabed.801923

Abstract

Anaplasmosis in dog is caused by Anaplasma phagocytophilum, a gram-negative, mandatory intracellular bacteria. Although this bacterium is not contagious, it is transmitted through vector tick. Clinically, the acute bacterial phase is the most common in dogs. Animals with clinical disease due to acute infection often have vague symptoms of the disease, including fever, drowsiness, weakness, loss of appetite, and muscle pain. Hepcidin, on the other hand, is a peptide hormone and also plays a role as a type II acute phase reactant and regulator of iron metabolism. The aim of the study was to evaluate the relationship between hepcidin and some anemia parameters in Anaplasma phagocytophilum seropositive dogs and to learn about the use of hepcidin as a biomarker. Our study group was composed of 20 positive Anaplasma phagocytophilum dogs, and our control group consisted of 10 healthy dogs. In both groups, complete blood counts were performed. Hepcidin, iron, ALT, AST and ALP values were also measured in serum samples collected. As a result, hepcidin values between the two groups were statistically significant (p<0.05) and it was concluded that hepcidin could be used as a biomarker in the diagnosis of anaplasma infection in dogs with other parameters.

Keywords

Hepcidin, anaplasma, anemia

Project Number

0572-YL-19

References

• Bexfield, N.H., Villiers, E.J., Herrtage, M.E., 2005. Immune‐mediated haemolytic anaemia and thrombocytopenia associated with Anaplasma phagocytophilum in a dog. Journal of Small Animal Practice 46, 543-548.
• Cai, H.J., Wang, N.L., Liu, K.K., Chu, J.H., Wang, Y., Yang, L.H., Wu, Z.Y., 2016. Clinical Significance of Hepcidin in the Diagnosis of Infant Iron Deficiency Anemia. Zhongguo shi yan xue ye xue za zhi 24, 546-550.
• Chirek, A., Silaghi, C., Pfister, K., Kohn, B., 2018. Granulocytic anaplasmosis in 63 dogs: clinical signs, laboratory results, therapy and course of disease. Journal of Small Animal Practice 59, 112-120.
• Cockwill, K.R., Taylor, S.M., Snead, E.C., Dickinson, R., Cosford, K., Malek, S., Lindsay, L.R., Diniz, P.P., 2009. Granulocytic anaplasmosis in three dogs from Saskatoon, Saskatchewan Can. Veterinary Journal 50, 835-840.
• Costa, M.M., França, R.T., Da Silva, A.S., Paim, C.B., Paim, F., Amaral, C.H.D., Dornelles, G.L., Cunha, J., Soares, J.F., Labruna, M.B., Mazzanti, C.M.A., Silvia, G., Monteiro, G.G., Lopes, S., 2012. Rangelia vitalii: changes in the enzymes ALT, CK and AST during the acute phase of experimental infection in dogs. Revista Brasileira De Parasitologia Veterinaria 21, 243-248.
• Coyne, D.W., 2011. Hepcidin: clinical utility as a diagnostic tool and therapeutic target. Kidney International 80 (3), 240-244.
• Eberts, M.D., Vissotto de, P., Diniz, P.P., Beall, M.J., Stillman, B.A., Chandrashekar, R., Breitschwerdt, E.B., 2011. Typical and atypical manifestations of Anaplasma phagocytophilum infection in dogs. Journal of the American Animal Hospital Association 47, 86-94.
• Falzacappa, M.V.V., Muckenthaler, M.U., 2005. Hepcidin: iron-hormone and anti-microbial peptide. Gene 364, 37-44.
• Frazer, D.M., Wilkins, S.J., Becker, E.M., Vulpe, C.D., Mckie, A.T., Trinder, D., Anderson, G.J., 2002. Hepcidin expression inversely correlates with the expression of duodenal iron transporters and iron absorption in rats. Gastroenterology 123, 835-844.
• Fry, M.M., Liggett, J.L., Baek, S.J., 2004. Molecular cloning and expression of canine hepcidin, Veterinary Clinical Pathology 33, 223-227.
• Ganz, T., 2006. Hepcidin—a peptide hormone at the interface of innate immunity and iron metabolism. In Antimicrobial Peptides and Human Disease, Berlin: Heidelberg Springer, pp: 183-198.
• Granick, J.L., Armstrong, P.J., Bender, J.B., 2009. Anaplasma phagocytophilum infection in dogs: 34 cases (2000–2007). Journal of the American Veterinary Medical Association 1559-1565.
• Huang, P., Wang, J., Lin, X., Yang, F.F., Tan, J.H., 2017. Effects of IL-10 on iron metabolism in LPS-induced inflammatory mice via modulating hepcidin expression. European Review for Medical and Pharmacological Sciences 21, 3469-3475.
• Jensen, J., Simon, D., Escobar, H.M., Soller, J.T., Bullerdiek, J., Beelitz, P., Nolte, I., 2007. Anaplasma phagocytophilum in dogs in Germany. Zoonoses Public Health 54, 94-101. Kali, A., Charles, M.V.P., Seetharam, R.S.K., 2015. Hepcidin-A novel biomarker with changing trends. Pharmacognosy Reviews 9, 35.
• Kemna, E., Pickkers, P., Nemeth, E., van, d., Hoeven, H., Swinkels, D., 2005. Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS. Blood 106, 1864-1866.
• Kohn,. B, Galke, D., Beelitz, P., Pfister, K., 2008. Clinical features of canine granulocytic anaplasmosis in 18 naturally infected dogs. Journal of Veterinary Internal Medicine 22, 1289-1295.
• Krause, A., Neitz, S., Mägert, H.J., Schulz, A., Forssmann, W.G., Schulz-Knappe, P., Adermann, K., 2000. LEAP‐1, a novel highly disulfide‐bonded human peptide, exhibits antimicrobial activity. FEBS Letters 480, 147-150.
• Lai, T.H., Kumagai, Y., Hyodo, M., Hayakawa, Y., Rikihisa, Y., 2009. The Anaplasma phagocytophilum PleC histidine kinase and PleD diguanylate cyclase two-component system and role of cyclic Di-GMP in host cell infection. Journal of Bacteriology 191, 693-700.
• Lee, S.H., Lee, J.H., Jang, W.J., Koh, S.E., Yang, Y.M., Kim, B.J., Kook, Y.H., Park, K.H., 2003. Differentiation of Borrelia burgdorferi sensu lato through groEL gene analysis. FEMS Microbiology Letters 222, 51-57.
• Melter, O., Stehlik, I., Kinska, H., Volfova, I., Ticha, V., Hulinska, D., 2007. Infection with Anaplasma phagocytophilum in a young dog: a case report. Veterinarni Medicina 52, 207-212.
• Murata, H., Shimada, N., Yoshioka, M., 2004. Current research on acute phase proteins in veterinary diagnosis. The Veterinary Journal 168, 28-40.
• Nemeth, E., Valore, E.V., Territo, M., 2003. Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood 101, 2461-2463.
• Nicolas, G., Viatte, L., Bennoun, M., Beaumont, C., Kahn, A., Vaulont, S., 2002. Hepcidin, a new iron regulatory peptide. Blood Cells, Molecules and Diseases 29, 327-335.
• Orro, T., Jacobsen, S., LePage, J.P., Niewold, T., Alasuutari, S., Soveri, T., 2008. Temporal changes in serum concentrations of acute phase proteins in newborn dairy calves. The Veterinary Journal 176, 182-187.
• Park, C.H., Valore, E.V., Waring, A.J., Ganz, T., 2001. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. The Journal of Biological Chemistry 276, 7806-7810.
• Petersen, H.H., Nielsen, J.P., Heegaard, P.M., 2004. Application of acute phase protein measurements in veterinary clinical chemistry. Veterinary Research 35, 163-187.
• Plier, M.L., Breitschwerdt, E.B., Hegarty, B.C., Kidd, L.B., 2009. Lack of evidence for perinatal transmission of canine granulocytic anaplasmosis from a bitch to her offspring. Journal of the American Animal Hospital Association 45, 232-238.
• Prak, M., Lopez, M.A., Gabayan, V.,,Ganz, T., Rivera, S., 2006. Suppression of hepcidin during anemia requires erythropoietic activity. Blood 108, 3730-3735.
• Rikihisa, Y., 2006. New findings on members of the family Anaplasmataceae of veterinary importance. Annals of the New York Academy of Sciences 1078, 438-445.
• Sahinduran, S., Albay, M.K., Karakurum, M.C., Ozmen, O., Kale, M., 2016. Investigation of some cytokines, acute phase proteins and hepcidin levels before and after treatment in dogs with parvoviral gastroenteritis. Pakıstan Veterınary Journal 36, 487-492.
• Sainz, Á., Roura, X., Miró, G., Estrada-Peña, A., Kohn, B., Harrus, S., Solano-Gallego, L., 2015. Guideline for veterinary practitioners on canine ehrlichiosis and anaplasmosis in Europe. Parasites Vectors 8, 75.
• Shaw, S.E., Day, M.J., Birtles, R.J., Breitschwerdt, E.B., 2001. Tick-borne infectious diseases of dogs. Trends Parasitol 17, 74-80.
• Tunç, H.Ö., Aktaş, M.S., 2016. Türkiye’de Köpeklere Kene Aracılığıyla Bulaşan Hastalıklar. Erciyes Üniversitesi Veteteriner Fakültesi Dergisi 13, 223-230.
• Weinstein, D.A., Roy, C.N., Fleming, M.D., Loda, M.F., Wolfsdorf, J.I., Andrews, N.C., 2002. Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. Blood 100, 3776-3781.
• Wessling-Resnick, M., 2010. Iron homeostasis and the inflammatory response. Annual Review of Nutrition 30, 105-122.
• Zhang, D.L., Hughes, R.M., Ollivierre-Wilson, H., Ghosh, M.C., Rouault, T.A., 2009. A ferroportin transcript that lacks an iron-responsive element enables duodenal and erythroid precursor cells to evade translational repression. Cell Metabolism 9, 461-473.